Home Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
Article Open Access

Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C

  • Daquan Zhang , Lu Wang , Zhigao Wang , Xiaohui Shi , Wen Tang , Long Jiang , Ba Yin Cha Han Bo Ran Yi , Xinwei Lv , Congyu Hu and Dong Xiao EMAIL logo
Published/Copyright: February 7, 2023
Download Article (PDF)
Open Life Sciences
From the journal Open Life Sciences Volume 18 Issue 1

Abstract

This study investigated the effect of combined thymosin α1 and vitamin C (Tα1 + VitC) on the immunological responses of septic rats. Five groups were designed. The septic model was established by the cecal ligation puncture (CLP) method. The sham group did not undergo CLP, the model group was given normal saline solution, the Tα1 group was given Tα1 (200 µg/kg), the VitC group was given VitC (200 mg/kg), and the Tα1 + VitC group was given Tα1 + VitC. Specimens for immunological analyses were collected at 6, 12, 24, and 48 h posttreatment in each group except for the sham group (only at 48 h). CD4 + CD25 + T cells in the peripheral blood and dendritic cell (DC) proportions in the spleen were analyzed by flow cytometry. Tumor necrosis factor α (TNF-α), interleukin 6 (IL-6), transforming growth factor-β (TGF-ß1), and nuclear factor kappa-B (NF-κB) were measured by ELISA. CD4 + CD25 + T cells and OX62 + DCs levels significantly increased in the model group and decreased in the Tα1 and/or VitC treatment groups. Similarly, the levels of TNF-α, IL-6, TGF-ß1, and NF-κB significantly increased in the model group and decreased in the Tα1, VitC, and Tα1 + VitC groups, indicating that combined Tα1 and VitC therapy may help regulate the immunological state of patients with sepsis, thereby improving prognosis.

Keywords: sepsis; thymosin α1; vitamin C; immune response; inflammatory response

1 Introduction

Sepsis is a series of immune response dysregulation syndromes that occur after infection with pathogenic microorganisms, and sepsis-related infectious shock and multiorgan dysfunction syndrome are the main causes of patient death [1,2,3,4]. The high incidence and lethality of sepsis is a serious threat to human health. Statistically, the annual incidence of sepsis is 0.149–0.24%, while the annual mortality rate is 28–50% [5,6]. Each case of sepsis is costly and imposes a huge economic burden on society.

Sepsis has long been thought to be divided into two distinct phases: the proinflammatory response phase and the anti-inflammatory response phase. The proinflammatory phase typically occurs first. The intrinsic immune system releases systemic inflammatory factors that fight infection; the adaptive immune system is simultaneously recruited and increases the intensity of the immune response. The anti-inflammatory response phase refers to systemic inflammatory response syndrome (SIRS), which begins immediately after the proinflammatory response phase and is generally considered an irresponsive phase of infection [7]. When pathogens infect the body, the pathogen antigens are recognized by receptors on the surface of inflammatory effector cells. Nuclear factor kappa-B (NF-κB) is activated through an antigen-antibody response and enzyme activation, promoting the generation and release of various proinflammatory factors and inflammatory mediators, such as interleukin 6 (IL-6), tumor necrosis factor α (TNF-α), and transforming growth factor-β (TGF-β). NF-κB was first discovered by David Baltimore and is a transcription factor that can aggravate the tissue inflammatory response. NF-κB activation or phosphorylation can transactivate cyclooxygenase-2 or allograft inflammatory factor-1 expressed in inflammatory or malignant tumors, and NF-κB can activate multiple inflammatory factors, such as TNF-α, IL-6, IL-8, and matrix metallopeptidase-9 [26]. IL-6 is a cytokine involved in multiple immune responses and is associated with several diseases [25]. TNF-α is a potent proinflammatory cytokine with deleterious effects in several autoimmune diseases that also mediates paradoxical anti-inflammatory and immunomodulatory effects. TGF-β belongs to a newly identified TGF-β superfamily that regulates cell growth and differentiation. In recent years, TGF-β has been shown to play important regulatory roles in cell growth, differentiation, and immune function. TGF-β inhibits the proliferation of immunologically active cells and the differentiation of lymphocytes and suppresses cytokine production. TGF-β can synergistically activate mouse thymic MHC nonrestricted killer cells via IL-2 and IL-6. TGF-β can also inhibit the production of interferon gamma (IFN-γ) and TNF-α in peripheral blood mononuclear cells. Numerous anti-inflammatory immunomodulatory treatments have been used to combat the proinflammatory phase of sepsis; however, these immunomodulatory agents (TNF-α, IL-1β, toll-like receptor-4, etc.) have failed in clinical trials [8,9,10]. This failure has led to the recognition that the pathogenesis of sepsis is not simply the result of an excessive proinflammatory response to infection, suggesting that the pathophysiological process of sepsis is a more complex condition.

Data suggest that the proinflammatory and anti-inflammatory phases occur simultaneously during the host immune response to severe trauma or sepsis [11]. The magnitude of the initial proinflammatory phase appears depending on many factors, including the virulence of the pathogen, pathogen load, and the patient’s underlying disease state. While the accumulation of proinflammatory factors in patients is associated with early morbidity and mortality, the number of chronic sepsis-related deaths appears clearly associated with immunosuppression and immune dysfunction. In fact, most sepsis-related deaths occur after 3 days, and some occur several weeks after the onset of disease [10]. Patients with sepsis pass through an early proinflammatory phase followed by a prolonged period of immunosuppression and immune paralysis. Numerous studies have led to a deeper and broader understanding of sepsis and the gradual recognition that its pathogenesis is complex. There is an excessive inflammatory response, immunosuppression, a second strike, oxidative stress, apoptosis, and coagulation disorders caused by the invasion of pathogenic microorganisms that participate in organ damage in septic patients [12,13]. Although many basic and clinical studies have been conducted on the pathogenesis and treatment of sepsis, no breakthroughs have been made. Immune disorders manifest as a disruption of the balance between excessive inflammatory responses and immunosuppression, which occur simultaneously, and the dynamic balance between excessive inflammatory responses and immunosuppression in the organism is restored through immunomodulation. Research reports on achieving immune regulation and restoring balance in sepsis and the related mechanisms are gradually increasing.

Thymidine α1 (Tα1) can have antimicrobial effects by increasing the release of IL-12, IL-2, IFN-α, and IFN-γ, and it also increases IL-10 secretion and the ratio of regulatory T cells (Tregs), controlling inflammatory responses [14,15]. Tα1 is widely used to regulate immune disorders in sepsis and is a new direction for sepsis treatment. Vitamin C (VitC) has anti-inflammatory and immunomodulatory effects on sepsis, and Fisher et al. [16] showed that VitC significantly attenuated the expression of proinflammatory chemokines and NF-kB activity in septic mice and prolonged their survival time. In addition, high mobility group protein B1 (HMGBl) triggers the inflammatory response by increasing the release of inflammatory factors (such as TNF-α, IL-1, IL-6, IL-8, and macrophage inflammatory protein 1B), and changes in HMGBl levels are significantly correlated with the prognosis of patients with sepsis [17,18]. High doses of VitC induce the expression of heme oxygenase-1, which reduces the release of HMGBl, attenuates the inflammatory response, and significantly increases the survival rate of septic mice [19]. VitC improves brain function and increases the survival rate of septic rats [20].

The mechanism of sepsis is complex and relies on a single drug with limited therapeutic efficacy, and outcomes may be improved by a combination of drugs. VitC combined with hydrocortisone and vitamin B1 has been tested clinically in the early stages of sepsis [21,22], and these agents can reduce the inflammatory response and decrease morbidity and mortality rates. Our group showed that combining Tα1 and hydrocortisone could improve immune function, regulate the inflammatory response, and increase the survival rate of mice with endotoxin-induced sepsis. There have been many studies on the effects of VitC on septic mice, but few have reported the immune response to thymidine α1 combined with VitC.

Based on the aforementioned information, this study investigated changes in the immune response in septic rats treated with Tα1 and VitC alone or in combination, analyzed the effect on the immunity of septic rats, and provided a theoretical basis for the study of immune regulation therapy in septic rats. The results of this study might shed new light on the treatment of sepsis and deepen the understanding of this condition.

2 Materials and methods

2.1 Animal modeling and groupings

A total of 85 male Sprague Dawley (SD) rats (weighing 220 ± 20 g) were provided by the Experimental Animal Center of the First Teaching Hospital of Xinjiang Medical University. The septic rat model was established by the cecal ligation puncture (CLP) method. The rats were randomly divided into the sham, sepsis model, Tα1, VitC, and Tα1 + VitC groups. (1) In the sham group (n = 5), after the rats were disinfected, a 1.5 cm-long longitudinal incision was made in the main midline of the lower abdomen, which was stratified into the abdominal cavity, completely exposing the cecum, and the mesenteric membrane was separated. The abdominal wall incision was stitched layer by layer. After the surgery, an equal amount of normal saline was injected into the abdomen. (2) The sepsis model group (n = 20) was established by using the CLP method. After the surgery, an equal amount of normal saline was injected into the abdomen. (3) In the Tα1 group (n = 20), the rat sepsis model was established by CLP, and 200 μg/kg Tα1 was dissolved in saline and injected into the abdomen. (4) In the VitC group (n = 20), the rat sepsis model was established by CLP, and 200 mg/kg VitC was dissolved in saline and injected into the abdomen. (5) In the Tα1 + VitC group (n = 20), the rat sepsis model was established by CLP, 200 μg/kg Tα1 was dissolved in saline and injected into the abdomen, and 200 mg/kg VitC was dissolved in saline and injected into the abdomen.

All groups except for the sham group were further divided into four groups, with five animals per group, according to the time points (6, 12, 24, and 48 h after treatment) for sample collection.

  1. Ethical approval: The research related to animal use has been complied with all the relevant national regulations and institutional policies for the care and use of animals and has been approved by the Institute of Animal Ethics of Xinjiang Medical University (SYXK 2018-0001).

2.2 Sample collection

All rats in each group survived until the designated experimental time points.

At the designated experimental time point, the rats in the model, Tα1, VitC, and Tα1 + VitC groups were weighed and anesthetized with 5% chloral hydrate at 8 ml/kg by intraperitoneal administration, and the limbs were immobilized and photographed. At 48 h, the same procedure was performed on the rats in the sham group.

Blood was collected from the heart. The blood sampling needle was inserted into the left chest where the heartbeat was most obvious, and the anticoagulant tube/nonanticoagulation tube was connected. The needle was inserted slowly, and the tube was clamped when full. One anticoagulant tube was collected per rat. The anticoagulant tube was shaken gently and immediately refrigerated at 4°C. A nonanticoagulation tube was used to facilitate the separation of clear serum from blood, minimizing shaking as much as possible.

Then, the rat abdomen was opened to expose the spleen under the stomach and separated into two parts with five samples taken from each part, for a total of ten splenic tissue samples. Six samples were fixed in 4% formaldehyde and stored in 5–10 ml tubes at room temperature. The other four samples were frozen at −80℃ for grouping and labeling, and testing was performed 1–2 days later. Three samples were stained with hematoxylin-eosin (HE), enzyme-linked immunosorbent assay (ELISA) was performed on three samples, and the remaining four samples were analyzed by flow cytometry.

2.3 Flow cytometry

Flow cytometry was performed in rigorous accordance with the instructions of the kit (Solarbio, Beijing, China; article no., P8630), and five repetitions were performed for each group.

The rat blood samples were centrifuged to prepare a cell suspension, and 50 μl of direct-labeled mouse anti-CD4/FITC (Bioss, bsm-33076M-FITC) and direct-labeled Rb IL2RA/CD25/PE (BioLegend, 303504) antibodies in PBS were added, mixed well, and incubated at 4°C for 30 min. Then, 1 ml of PBS was added to wash the samples, which were centrifuged at 1,000 rpm for 5 min. The supernatant was discarded and 200 μl of PBS was added to resuspend the cells, which were then placed in a specific flow cytometer for analysis. FlowJo software was used for image processing, and GraphPad Prism 7.00 software was used for analysis and graph construction.

The rat spleen was ground until no obvious tissue clumps were seen, and the obtained suspension was passed through a 200-mesh filter screen. The culture dish was rinsed with PBS to collect the remaining cells and wash the screen, and the filtrate was placed in a centrifuge tube. The tube was centrifuged at 1,500 rpm for 8 min at 4°C, and the supernatant was discarded. Then, 1 ml of erythrocyte lysis buffer (ten times the cell volume ratio) was added to the centrifuge tube, and the sample was mixed thoroughly. After standing at room temperature for 5 min, 8 ml of precooled PBS was added, and the mixture was centrifuged at 1,500 rpm at 4°C for 8 min. The supernatant was discarded, an appropriate amount of precooled PBS was added, and the suspension was mixed well. A small volume of the suspension was taken for proper dilution, and the number of cells was adjusted to approximately 500,000 per tube. Then, 1 ml of PBS was used to wash the sample, which was centrifuged at 1,000 rpm for 5 min at 4°C, and the supernatant was discarded. Next 50 μl of antibody-containing PBS was added, and the sample was mixed well and incubated at 4°C for 30 min. The samples were washed with 1 ml of PBS and centrifuged at 1,000 rpm for 5 min, the supernatant was discarded, 50 μl of staining solution containing secondary antibody was added to resuspend the cells, and the samples were incubated at 4°C for 30 min. The samples were washed with 1 ml of PBS and centrifuged at 1,000 rpm for 5 min, and the cell supernatant was discarded. The cells were resuspended in 200 μl of PBS, placed in a specific test tube, and analyzed by a flow cytometer. FlowJo software was used for image processing, and GraphPad Prism 7.00 software was used for analysis and graph construction.

2.4 ELISA

Serum samples were collected at 48 h by centrifugation. The TNF-α, IL-6, TGF-β1, and NF-κB levels in the serum samples were measured with an ELISA kit (Shanghai Enzyme-linked Biotechnology, Shanghai, China) according to the manufacturer’s instructions.

Spleen tissue was ground by adding prechilled PBS. The TNF-α, IL-6, and TGF-β levels in the spleen samples were measured with an ELISA kit (Shanghai Enzyme-linked Biotechnology, China) according to the manufacturer’s instructions.

2.5 HE staining

The rat spleen tissues were soaked in 10% formaldehyde for 7 days, embedded in paraffin, sliced, and deparaffinized in a xylene solution. After full hydration, 100 µl of hematoxylin staining solution was added dropwise for 10 min, and then the sections were differentiated with 1% hydrochloric acid in ethanol. A weakly basic blue-stimulating solution was added to the tissue section to stain the nuclei blue. Eosin staining solution was added, and after 3 min, the tissue sections were dehydrated by a gradient. The dehydrated tissue sections were soaked in xylene twice for 4 min each, and then the tissue sections were dried and sealed with neutral gum. Images were taken with an upright microscope with a 100× field of view.

2.6 Statistical analysis

The data are expressed as the mean value ± standard deviation (SD). Statistical analysis was performed using SPSS 22.0 software. ANOVA was used to analyze the pairwise comparison after Bartlett’s homogeneity of variance test, and differences between the groups were compared by the least significant difference (LSD)-t method. P < 0.05 was considered statistically significant.

3 Results

3.1 Flow cytometry

The proportions of CD4 + CD25 + double-positive T cells in peripheral blood and OX62 + dendritic cells (DCs) in the spleen were counted by flow cytometry to investigate the effect of Tα1 and/or VitC treatment on the immune response in septic rats.

Compared with those in the sham group, the proportions of CD4 + CD25 + T cells in the remaining groups were significantly increased (P < 0.001; Figure 1a, Figure A1a). Compared with that in the model group, the proportion in the Tα1 group, VitC group, and Tα1 + VitC group was significantly decreased at 12, 24, and 48 h (P < 0.001), with the most noticeable decrease observed in the Tα1 + VitC group.

Figure 1 Comparison of the flow cytometry results among different groups. (a) CD4 + CD25 + T cells in serum. (b) OX62 + DCs in the spleen. Note: **P < 0.01 and ***P < 0.001 vs the sham group; #P < 0.05, ##P < 0.01, and ###P < 0.001 vs the sepsis model group; $P < 0.05 and $$$P < 0.001 vs the Tα1 group; &&P < 0.01 vs the VitC group.
Figure 1

Comparison of the flow cytometry results among different groups. (a) CD4 + CD25 + T cells in serum. (b) OX62 + DCs in the spleen. Note: **P < 0.01 and ***P < 0.001 vs the sham group; #P < 0.05, ##P < 0.01, and ###P < 0.001 vs the sepsis model group; $P < 0.05 and $$$P < 0.001 vs the Tα1 group; &&P < 0.01 vs the VitC group.

Flow cytometry of the spleen samples showed consistent outcomes (Figure 1b, Figure A1b). The proportion of OX62 + DCs in the model group, Tα1 group, VitC group, and Tα1 + VitC group was significantly increased compared with that in the sham group (P < 0.001). Compared with that in the model group, the proportion of OX62 + DCs in the Tα1 group, VitC group, and Tα1 + VitC group was significantly decreased at 12, 24, and 48 h (P < 0.001). Compared with that in the Tα1 group, the proportion of OX62 + DCs in the Tα1 + VitC group was significantly decreased (P < 0.05).

3.2 ELISA

3.2.1 Blood samples

Compared with that in the sham group, the serum level of TNF-α in the model group was significantly increased at 6, 12, and 24 h (P < 0.001, P < 0.01, and P < 0.05, respectively). Compared with that in the model group, the expression level of TNF-α in the Tα1 group, VitC group, and Tα1 + VitC group was significantly decreased at 6, 12, and 24 h (P < 0.05, P < 0.01, and P < 0.01, respectively) (Figure 2a).

Figure 2 Comparison of the levels of serum cytokines among different groups according to ELISA. (a) TNF-α, (b) IL-6, (c) TGF-β1, and (d) NF-κB (P65).
Figure 2

Comparison of the levels of serum cytokines among different groups according to ELISA. (a) TNF-α, (b) IL-6, (c) TGF-β1, and (d) NF-κB (P65).

Compared with that in the sham group, the expression level of IL-6 was significantly upregulated in the model group at 12, 24, and 48 h (P < 0.01). At 6 h, compared with that in the model group, the expression level of IL-6 was significantly downregulated in both the VitC group and the Tα1 + VitC group (P < 0.01 and P < 0.05, respectively). At 12 h, compared with that in the model group, the expression level of IL-6 was significantly downregulated in the Tα1, VitC, and Tα1 + VitC groups (P < 0.01, P < 0.001). At 48 h, compared with that in the model group, the expression level of IL-6 in the Tα1 + VitC group was significantly downregulated (P < 0.05) (Figure 2b).

Compared with that in the sham group, the TGF-β1 expression level was significantly upregulated in the model group at 6, 12, and 24 h (P < 0.001). Compared with that in the model group, TGF-1 expression was significantly downregulated in the Tα1, VitC, and Tα1 + VitC groups at these time points (P < 0.001). Compared with that in the model group, the TGF-β1 expression level was downregulated in the Tα1, VitC, and Tα1 + VitC groups, but there was no significant difference at 48 h (Figure 2c).

Compared with that in the sham group, NF-κB expression was significantly upregulated in the model group at 6, 12, and 24 h (P < 0.001). At these time points, NF-κB expression levels were significantly downregulated in all treatment groups compared with the model group (P < 0.01, P < 0.001). At 48 h, a significant decrease was still observed in the VitC group and Tα1 + VitC group (P < 0.05) (Figure 2d).

3.2.2 Spleen samples

In spleen samples, compared with that in the sham group, the expression level of TNF-α in the model group was significantly upregulated at 12, 24, and 48 h (P < 0.01). Compared with that in the model group, the expression level of TNF-α was significantly downregulated in the Tα1 group, VitC group, and Tα1 + VitC group at 6, 12, and 24 h, with the most noticeable change observed in the combined group (P < 0.001). Compared with that in the model group, at 48 h, the expression level of TNF-α was downregulated in the VitC group, and the difference was statistically significant (P < 0.01). However, the expression level of TNF-α was upregulated in the Tα1 + VitC group, and the difference was statistically significant (P < 0.001). Combining the results of TNF-α in serum and the results of the Tα1 group and VitC group, we consider that the increase may have been caused by an experimental error (Figure 3a).

Figure 3 Comparison of the levels of spleen cytokines among different groups. (a) TNF-α, (b) IL-6, and (c) TGF-β1.
Figure 3

Comparison of the levels of spleen cytokines among different groups. (a) TNF-α, (b) IL-6, and (c) TGF-β1.

After modeling, the expression level of IL-6 increased in the model group at 12 and 24 h (P < 0.01 and P < 0.001, respectively). At these time points, all treatment groups exhibited significantly increased IL-6 levels compared with the model group (P < 0.001) (Figure 3b).

The TGF-β1 expression level also significantly increased at 6, 12, and 24 h after modeling. Compared with that in the model group, the TGF-β1 expression level was significantly downregulated in all treatment groups at 6, 12, 24, and 48 h (P < 0.01, P < 0.001) (Figure 3c).

3.3 HE staining

The results of HE staining are shown in Figure 4.

Figure 4 HE staining of the spleen tissue. (a) HE staining of spleen tissue in the 6 h subgroup (×200) (A1: Model group at 6 h; A2: Tα1 group at 6 h; A3: VitC group at 6 h; A4: Tα1 + VitC group at 6 h), (b) HE staining of spleen tissue in the 12 h subgroup (×200) (B1: Model group at 12 h; B2: Tα1 group at 12 h; B3: VitC group at 12 h; B4: Tα1 + VitC group at 12 h), (c) HE staining of spleen tissue in the 24 h subgroup (×100) (C1: Model group at 24 h; C2: Tα1 group at 24 h; C3: VitC group at 24 h; C4: Tα1 + VitC group at 24 h), and (d) HE staining of spleen tissue in the 48 h subgroup (×100) (D1: Model group at 48 h; D2: Tα1 at 48 h; D3: VitC group at 48 h; D4: Tα1 + VitC group at 48 h; D5: Sham group at 48 h). Reactive hyperplasia of the white pulp is indicated by a black hollow arrow, infiltration of inflammatory cells between red pulp by a black solid arrow, and interstitial fibrous tissue hyperplasia by a white arrow.
Figure 4

HE staining of the spleen tissue. (a) HE staining of spleen tissue in the 6 h subgroup (×200) (A1: Model group at 6 h; A2: Tα1 group at 6 h; A3: VitC group at 6 h; A4: Tα1 + VitC group at 6 h), (b) HE staining of spleen tissue in the 12 h subgroup (×200) (B1: Model group at 12 h; B2: Tα1 group at 12 h; B3: VitC group at 12 h; B4: Tα1 + VitC group at 12 h), (c) HE staining of spleen tissue in the 24 h subgroup (×100) (C1: Model group at 24 h; C2: Tα1 group at 24 h; C3: VitC group at 24 h; C4: Tα1 + VitC group at 24 h), and (d) HE staining of spleen tissue in the 48 h subgroup (×100) (D1: Model group at 48 h; D2: Tα1 at 48 h; D3: VitC group at 48 h; D4: Tα1 + VitC group at 48 h; D5: Sham group at 48 h). Reactive hyperplasia of the white pulp is indicated by a black hollow arrow, infiltration of inflammatory cells between red pulp by a black solid arrow, and interstitial fibrous tissue hyperplasia by a white arrow.

No abnormal changes were observed in the spleen tissue of the sham group (Figure 4D5). Unlike those in the sham group, the rats in the model group showed reactive hyperplasia of the white pulp (indicated by the black hollow arrow in Figure 4A1) and infiltration of inflammatory cells within the red pulp (indicated by the black solid arrow in Figure 4A1) in spleen tissue 6 h after modeling. Interstitial fibrous tissue hyperplasia appeared (indicated by the white arrow in Figure 4B1–D1, respectively) at 12, 24, and 48 h due to the white and red pulp changes.

In the Tα1 group, white pulp hyperplasia and intermedullary inflammatory cell infiltration were observed in the spleen tissue at 6, 12, 24, and 48 h (indicated by the black hollow and solid arrows in Figure 4A2–D2, respectively). In the VitC group, white pulp hyperplasia and intermedullary inflammatory cell infiltration were observed at 6 h (indicated by the black hollow and solid arrow in Figure 4A3), and interstitial fibrous tissue hyperplasia appeared after 12 h (indicated by the white arrow in Figure 4B3–D3).

The rats in the Tα1 + VitC group only showed infiltration of inflammatory cells in the red pulp in spleen tissue at 6–48 h (indicated by the black solid arrow in Figure 4A4–D4). This group exhibited no white pulp hyperplasia or interstitial fibrous tissue hyperplasia, and the infiltration of inflammatory cells in the red pulp was slight.

4 Discussion

Tregs express CD4 and CD25. CD4 + CD25 + T cells are a recently recognized class of immunomodulatory cells that originate in the thymus and exert suppressive immunomodulatory effects. In this study, at 6, 12, 24, and 48 h after modeling, the proportion of CD4 + CD25 + T cells in the Tα1, VitC, and Tα1 + VitC groups was significantly reduced compared with that in the model group, and we also found that the proportion in the Tα1 + VitC group was more significantly reduced than that in the Tα1 group and the VitC group. According to the literature [23], Treg numbers and TNF-α levels in the peripheral blood of septic rats are decreased by Tα1 compared with the CLP group after 3 days of modeling. Our finding in the Tα1 group was consistent with that reported in the literature. A subset of CD4 + CD25 + T cells expresses CD45RO isoforms, GITC, and CD152 on the cell surface and the transcription factor Foxp3 in the nucleus. There is growing evidence that CD4 + CD25 + Foxp3 + Tregs play an active role in reducing sepsis-induced inflammation through TGF-β-dependent and TGF-β-independent pathways [24,25,26,27,28]. Presumably, Tα1 and/or VitC reduce the expression of CD4 + CD25 + T cells and reduce the proliferation of Treg cells that inhibit T cells, thereby mitigating the early stage of sepsis-induced rapid inflammation due to an excessive inflammatory response and the associated damage to the body.

DCs are named for the many dendritic or pseudopod-like protrusions that extend at maturity and are the most powerful antigen-presenting cells observed to date. The only function of DCs is antigen presentation. Our results showed that at all observed time points after modeling, the proportion of OX62 + DCs in the Tα1, VitC, and Tα1 + VitC groups was significantly reduced compared with that in the model group, and the proportion in the Tα1 + VitC group was more significantly reduced than that in the Tα1 and VitC groups. Despite the effectiveness of Tα1 + VitC, our findings have not been previously reported. We hypothesized that the combination of Tα1 and VitC reduced the levels of Tregs and DCs, thereby reducing the activation of NF-κB and the expression level of inflammatory factors.

In the course of sepsis, DCs first transfer to the antigen epitopes of neutrophils, macrophages, and T helper lymphocytes (Th), activate NF-κB, enter the nucleus and form a complex with DNA, induce cell apoptosis, and release numerous proinflammatory cytokines and chemokines, such as TNF-α and IL-6. Therefore, inflammatory factors serve as indicators of the degree of the inflammatory response and can also be used as indicators of sepsis patient prognosis. Numerous studies have shown that during sepsis, the massive release of cytokines and the dysregulation of the inflammatory response due to tissue damage are among the origins of the pathophysiology leading to vascular endothelial damage [29,30]. According to a clinical study involving 81 patients with severe pneumonia complicated with sepsis, the expression levels of TNF-α, IL-6, IL-8, and other inflammatory factors in the group that received Tα1 under the basal epithelium were significantly reduced compared with those in the control group [31]. The efficacy of VitC in the treatment of sepsis has also been reported in numerous studies [32,33]. In this study, the Tα1 and VitC groups both exhibited reduced relevant inflammatory factors, consistent with the abovementioned results. The antisepsis effect of VitC is possibly realized by suppressing immune dysfunction and inflammation-associated functional processes [34].

The spleen is the largest lymphoid organ in the human body, with the functions of blood storage, hematopoiesis, removal of aging red blood cells, and immune responses. The spleen comprises three parts, the white pulp, red pulp, and marginal area. The white pulp is composed of dense lymphocytes and is the main location of specific immunity. Our experimental results showed no abnormal changes in the spleen tissue of rats in the sham group. At 6–48 h after modeling, compared with the sham group, the spleen tissue of the rats in the model group showed pathological changes, such as white myeloid reactive hyperplasia, fibrous tissue hyperplasia, and infiltration of red medullitis cells. Compared with the model group, the spleen tissue of rats in the Tα1 and VitC groups still demonstrated white myeloid reactive hyperplasia, but the infiltration of red medullitis cells decreased. Spleen tissue infiltration in rats in the Tα1 + VitC group showed red medullitis cell infiltration, but there was no interstitial fibrous tissue hyperplasia, and no pathological changes were seen in the white pulp. These results suggest that the combination of Tα1 + VitC has a therapeutic effect on septic rats and can effectively reduce the organ damage caused by sepsis and regulate the body’s immune response. Simultaneous intergroup comparisons suggest that Tα1 or VitC alone may not be as effective as Tα1 + VitC combination therapy.

The mechanism of action of sepsis is complex, including an excessive inflammatory response, immunosuppression, a second strike, apoptosis, oxidative stress and coagulation disorders, which are jointly involved in organ damage. Carlson et al. [35] reported that the combined use of VitC and VitE in septic rats prevented the activation of NF-κB and caspase and improved myocardial contractile function, suggesting that the combined use of these antioxidants has an important protective effect on sepsis-related myocardial dysfunction. In contrast, a high dose of VitC (1,000 m/8 h) combined with α-tocopherol (1,000 IU/8 h) significantly reduced the duration of mechanical ventilation in mechanically ventilated patients [36]. In addition, the combination of VitC and VitE significantly reduced the levels of oxidative stress and lipid peroxidation, downregulated the expression of hepatic cytochrome p450 enzymes in sepsis and prevented the dysfunction of hepatic drug metabolism in sepsis [37]. These results suggest that the combined use of VitC and VitE can exert a better antioxidant effect than individual treatment, which is clearly beneficial for improving the patient’s condition and prognosis. The use of Tα1 in the early stages of sepsis regulates immune function, attenuates overreaction, prevents immunosuppression, and avoids or mitigates secondary strikes, while the use of VitC, which inhibits the expression of superoxides in microvascular endothelial cells, reduces endothelial oxidative stress and improves endothelial dysfunction and microcirculatory disorders [38]. Furthermore, VitC can inhibit the expression of TNF-α-induced intracellular adhesion molecule 1, which mediates the production of oxidative stress via reactive oxygen species and nitric oxide synthase (NOS) [39], preventing platelet and leukocyte adhesion to the microvascular endothelium and improving microvascular blood flow. In addition, VitC prevents endothelial-type nitric oxide synthase (eNOS) production, reduces protein phosphatase 2A activity, inhibits vascular leakage, and attenuates vascular endothelial barrier dysfunction by preventing eNOS uncoupling (superoxide anion production), reducing inducible nitric oxide synthase, and neural-type nitric oxide synthase activity and endothelial permeability [40], and reversing vascular hyporesponsiveness and hypotension in patients with sepsis [41].

Tα1 is produced by thymic epithelial cells and thymic endocrine cells and is an endogenous regulator of the innate and acquired immune systems [42]. Tα1 mainly enhances T-cell function, in addition to acting through different toll-like receptors (type I transmembrane proteins, TLRs) on different DC subpopulations and myeloid differentiation protein antigen (MyD88)-dependent signaling pathways, thus playing a unique role in balancing pro- and anti-inflammatory cytokines. The therapeutic effects and mechanisms of thymidine α1 in chronic viral hepatitis, malignant tumors, and acquired immune deficiency syndrome (AIDS) have been clearly established, while the therapeutic effects in severe infections, especially sepsis, have been confirmed in several clinical studies. However, the mechanisms of action are still not well understood. The most commonly used immunomodulatory drugs in clinical treatments are Tα1 and ustekin, and the results of one study showed that immunotherapy reduced the incidence of 28 days death in patients with severe sepsis but had no effect on the length of ICU stay, duration of mechanical ventilation, or use of vasoactive drugs and antibiotics [43]. Tα1 significantly increased the expression of serum monocyte human leukocyte antigen (mHLA)-DR in patients with severe sepsis, indicating that this treatment may help improve the clinical prognosis of patients with severe sepsis.

VitC, also known as ascorbic acid, is a water-soluble antioxidant and cofactor for some enzymes [44] and is an important cofactor for iron- and copper-containing enzymes [45]. VitC is absorbed in the small intestine via sodium-dependent VitC transporters and excreted via the kidneys [46]. Plasma VitC levels are significantly lower in patients with sepsis, and plasma VitC levels are 1/3 to 1/2 of the normal level in patients with severe sepsis [47,48,49]. In a study of the acute inflammatory response induced by intravenous administration of low-dose Escherichia coli endotoxin (LPS) in healthy subjects, a 37% decrease in plasma VitC concentrations was observed after 4 h [50], and reduced plasma VitC concentrations were significantly associated with inflammatory infection, the severity of organ failure, morbidity, and mortality [51]. VitC is also a potent antioxidant and cofactor of biosynthetic and gene regulatory enzymes [52], and severe VitC deficiency can lead to the potentially fatal disease scurvy [53]. Scurvy is characterized by a weakened collagen structure leading to poor wound healing and impaired immune function. Patients with scurvy are highly susceptible to fatal infectious diseases, such as pneumonia, and conversely, infections significantly affect VitC levels due to enhanced inflammation and metabolic demands [54]. Recent studies have shown the beneficial effects of VitC on multiple pathways associated with sepsis. VitC deficiency has been shown to worsen pulmonary pathology following influenza infection. In addition, VitC levels are significantly reduced in critically ill patients, especially those with proinflammatory diseases (e.g., sepsis and SIRS) [55]. In addition, there is a dysregulated host immune response in sepsis, and immunosuppression can occur early in the course of the disease [56]. The immunosuppressed state and the imbalance in the pro- and anti-inflammatory responses can lead to an increased mortality rate [57]. VitC is an important immune response factor that can improve host defenses by regulating the proliferation and differentiation of immune cells, regulating the balance of helper T lymphocyte 1/helper T lymphocyte 2, and improving the functions of macrophages, T lymphocytes, and B lymphocytes. In the present study, the inflammatory response to sepsis in rats was differentially reduced and immune function was differentially modulated after Tα1 and/or VitC intervention, and these outcomes were accompanied by reductions in the proportions of CD4 + CD25 + T cells and DCs and reductions in the inflammatory cytokines IL-6, TNF-α, TGF-β1, and NF-κB (P65).

The accumulation of proinflammatory factors in patients is associated with early morbidity and mortality, and the number of chronic sepsis-related deaths appears significantly associated with immunosuppression and dysfunction; most sepsis-related deaths occur after 3 days, and some occur several weeks after the onset of disease [10]. Our findings suggest that Tα1, VitC, and Tα1 + VitC treatment in the early proinflammatory phase of sepsis may improve immune function in rats with sepsis, attenuating the overly dysregulated inflammatory response, reducing inflammatory damage, and protecting organ function. The effective treatment effect was particularly reflected in the Tα1 + VitC group, in which no noticeable white pulp hyperplasia or interstitial fibrous tissue hyperplasia was observed at different time points. In patients with sepsis, in addition to traditional active anti-infection and proper shock treatment, combined Tα1 and VitC treatment may help modulate the harmful immune proinflammatory state in the early stages. However, the synergistic action between Tα1 and VitC remains to be explored.

There are some limitations in the present study. First, animal experimental studies are sometimes incomplete, and the extrapolation of results obtained through animal experimental models to other species is sometimes unreliable. Second, animal experiments are sometimes misleading, and many of the apparent abnormalities observed between animal tests and humans may be due to normal biological characteristic responses that are specific to the species or changes caused by unnatural means or stress reactions in the laboratory environment. These abnormalities are unrelated to pathological changes in humans. In our study, the small sample size was a major experimental limitation, and the number of blank controls was too small to allow for blank comparisons at each time point.

5 Conclusion

Our results suggest that Tα1 + VitC treatment can improve immune function, reduce inflammatory damage, and protect organ function in septic rats. In patients with sepsis, in addition to traditional active anti-infection and proper shock treatment, the combination of Tα1 and VitC can be considered a treatment and may help regulate the immune state and improve prognosis.

  1. Funding information: This study was financially supported by the Natural Science Foundation of Xinjiang Uygur Autonomous Region (grant no. 2019D01C152). The funder had no role in the preparation of data, the study design, or the writing and submission of the manuscript.

  2. Conflict of interest: Authors state no conflict of interest.

  3. Data availability statement: The datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request.

Appendix

Figure A1 Flow cytometry results. (a) CD4 + CD25 + T cells in serum. (b) OX62 + DCs in the spleen.
Figure A1

Flow cytometry results. (a) CD4 + CD25 + T cells in serum. (b) OX62 + DCs in the spleen.

References

[1] Angus DC, van der Poll T. Severe sepsis and septic shock. N Engl J Med. 2013;369(9):840–51.10.1056/NEJMra1208623Search in Google Scholar PubMed

[2] Cawcutt KA, Peters SG. Severe sepsis and septic shock: Clinical overview and update on management. Mayo Clin Proc. 2014;89(11):1572–8.10.1016/j.mayocp.2014.07.009Search in Google Scholar PubMed

[3] Martin GS. Sepsis, severe sepsis and septic shock: changes in incidence, pathogens and outcomes. Expert Rev Anti Infect Ther. 2012;10(6):701–6.10.1586/eri.12.50Search in Google Scholar PubMed PubMed Central

[4] Puskarich MA. Emergency management of severe sepsis and septic shock. Curr Opin Crit Care. 2012;18(4):295–300.10.1097/MCC.0b013e328354dc16Search in Google Scholar PubMed

[5] Jawad I, Luksic I, Rafnsson SB. Assessing available information on the burden of sepsis: global estimates of incidence, prevalence and mortality. J Glob Health. 2012;2(1):010404.10.7189/jogh.01.010404Search in Google Scholar

[6] Zhang XH, Dong Y, Chen YD, Zhou P, Wang JD, Wen FQ. Serum N-terminal pro-brain natriuretic peptide level is a significant prognostic factor in patients with severe sepsis among Southwest Chinese Population. Eur Rev Med Pharmacol Sci. 2013;17(4):517–21.Search in Google Scholar

[7] Ward NS, Casserly B, Ayala A. The compensatory anti-inflammatory response syndrome (CARS) in critically ill patients. Clin Chest Med. 2008;29(4):617–22.10.1016/j.ccm.2008.06.010Search in Google Scholar PubMed PubMed Central

[8] Abraham E, Glauser MP, Butler T, Garbino J, Gelmont D, Laterre PF, et al. p55 Tumor necrosis factor receptor fusion protein in the treatment of patients with severe sepsis and septic shock. A randomized controlled multicenter trial. Ro 45-2081 Study Group. JAMA. 1997;277(19):1531–8.10.1001/jama.277.19.1531Search in Google Scholar

[9] Opal SM, Laterre PF, Francois B, LaRosa SP, Angus DC, Mira JP, et al. Effect of eritoran, an antagonist of MD2 TLR4, on mortality in patients with severe sepsis: the ACCES randomized trial. JAMA. 2013;309(11):1154–62.10.1001/jama.2013.2194Search in Google Scholar PubMed

[10] Panacek EA, Marshall JC, Albertson TE, Johnson DH, Johnson S, MacArthur RD, et al. Efficacy and safety of the monoclonal antitumor necrosis factor antibody F(ab') 2 fragment afelimomab in patients with severe sepsis and elevated interleukin 6 levels. Crit Care Med. 2004;32(11):2173–82.10.1097/01.CCM.0000145229.59014.6CSearch in Google Scholar PubMed

[11] Arina P, Singer M. Pathophysiology of sepsis. Curr Opin Anaesthesiol. 2021;34(2):77–84.10.1097/ACO.0000000000000963Search in Google Scholar PubMed

[12] Andrades MÉ, Morina A, Spasić S, Spasojević I. Bench-to-bedside review: Sepsis-from the redox point of view. Crit Care. 2011;15(5):230.10.1186/cc10334Search in Google Scholar PubMed PubMed Central

[13] Berger MM, Chiolero RL. Antioxidant supplementation in sepsis and systemic inflammatory response syndrome. Crit Care Med. 2007;35(9):S584–90.10.1097/01.CCM.0000279189.81529.C4Search in Google Scholar PubMed

[14] Romani L, Bistoni F, Gaziano R, Bozza S, Montagnoli C, Perruccio K, et al. Thymosin alpha1 activates dendritic cells for antifungal Th1 resistance through toll-like receptor signaling. Blood. 2004;103(11):4232–9.10.1182/blood-2003-11-4036Search in Google Scholar PubMed

[15] Bozza S, Gaziano R, Bonifazi P, Zelante T, Pitzurra L, Montagnoli C, et al. Thymosin alpha1 activates the TLR9/MyD88/IRF7 dependent murine cytomegalovirus sensing for induction of antiviral responses in vivo. Int Immunol. 2007;19(11):1261–70.10.1093/intimm/dxm097Search in Google Scholar PubMed

[16] Fisher BJ, Seropian IM, Kraskauskas D, Thakkar JN, Voelkel NF, Fowler AA, et al. Ascorbic acid attenuates lipopolysaccharide-induced acute lung injury. Crit Care Med. 2011;39(6):1454–60.10.1097/CCM.0b013e3182120cb8Search in Google Scholar PubMed

[17] Blumental-Perry A, Bonfield TL. Editorial: Modulation of HMGBl holds promise for managing Sepsis immune paralysis. J Leukoc Biol. 2017;101(6):1273–5.10.1189/jlb.3CE1216-510RSearch in Google Scholar PubMed

[18] Yang W, Zhang PA, Han RL. Dynamic expression level of plasma HMGB1 and clinical significance in patients with sepsis shock. Int J Lab Med. 2017;38(4):433–5, 8.Search in Google Scholar

[19] Kim SR, Ha YM, Kim YM, Park EJ, Kim JW, Park SW, et al. Ascorbic acid reduces HMGB1 secretion in lipopolysaccharide-activated RAW 264.7 cells and improves survival rate in septic mice by activation of Nrf2/HO-1 signals. Biochem Pharmacol. 2015;95(4):279–89.10.1016/j.bcp.2015.04.007Search in Google Scholar PubMed

[20] Lyu JJ, Chen ZJ, Chen JF. Improvement of Vitamin C on septic brain injury in rats. Chin J Appl Clin Pediatr. 2018;33(18):1415–8.Search in Google Scholar

[21] Marik PE, Khangoora V, Rivera R, Hooper MH, Catravas J. Hydrocortisone, vitamin C, and thiamine for the treatment of severe sepsis and septic shock: A retrospective before-after study. Chest. 2017;151(6):1229–38.10.1016/j.chest.2016.11.036Search in Google Scholar PubMed

[22] Chen JY, Wu JL, Liang QG, Liang JT, Yao HW. Study of vitamin C combined with hydrocortisone and vitamin B1 treatment for the early stage of sepsis. Shanxi Med J. 2018;47(20):2400–3.Search in Google Scholar

[23] Wang HB, Dong F, Xu LW. Effect of thymosin α1 on sepsis in rats. Chin J Anesthesiol. 2019;39(7):877–80.Search in Google Scholar

[24] McFadyen JD, Zeller J, Potempa LA, Pietersz GA, Eisenhardt SU, Peter K. C-Reactive protein and its structural isoforms: An evolutionary conserved marker and central player in infammatory diseases and beyond. Subcell Biochem. 2020;94:499–520.10.1007/978-3-030-41769-7_20Search in Google Scholar PubMed

[25] Yende S, Kellum JA, Talisa VB, Peck Palmer OM, Chang CH, Filbin MR, et al. Long-term host immune response trajectories among hospitalized patients with sepsis. JAMA Netw Open. 2019;2(8):e198686.10.1001/jamanetworkopen.2019.8686Search in Google Scholar PubMed PubMed Central

[26] Huang X, Zhao M. High expression of long non-coding RNA MALAT1 correlates with raised acute respiratory distress syndrome risk, disease severity, and increased mortality in sepstic patients. Int J Clin Exp Pathol. 2019;12(5):1877–87.Search in Google Scholar

[27] Mikacenic C, Hahn WO, Price BL, Harju-Baker S, Katz R, Kain KC, et al. Biomarkers of endothelial activation are associated with poor outcome in critical illness. PLoS ONE. 2015;10(10):e0141251.10.1371/journal.pone.0141251Search in Google Scholar PubMed PubMed Central

[28] Ehler J, Petzold A, Wittstock M, Kolbaske S, Gloger M, Henschel J, et al. The prognostic value of neuroflament levels in patients with sepsis-associated encephalopathy-a prospective, pilot observational study. PLoS ONE. 2019;14(1):e0211184.10.1371/journal.pone.0211184Search in Google Scholar PubMed PubMed Central

[29] Ghanemi A, St-Amand J. Interleukin-6 as a “metabolic hormone.” Cytokine. 2018;112:132–6.10.1016/j.cyto.2018.06.034Search in Google Scholar PubMed

[30] Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.10.1101/cshperspect.a016295Search in Google Scholar PubMed PubMed Central

[31] Chen Y, Zhou LJ, Wang J, Gu TH, Li SQ. Clinical effect of Xuebijing combined with thymosin α1 on patients with severe pneumonia complicated with sepsis and its effect on serum inflammatory factors. Cell Mol Biol (Noisy-le-grand). 2022;67:228–35.10.14715/cmb/2021.67.6.30Search in Google Scholar PubMed

[32] Muhammad M, Jahangir A, Kassem A, Sattar SBA, Jahangir A, Sahra S, et al. The role and efficacy of vitamin C in sepsis: A systematic review and meta-analysis. Adv Respir Med. 2022;90:281–99.10.3390/arm90040038Search in Google Scholar PubMed PubMed Central

[33] Zhao B, Li MJ, Sun WW, Li J, Liu LS, Wang YH, et al. High-dose vitamin C on sepsis: Protocol of a prospective, multi-centered, double-blinded, randomized, and placebo-controlled superiority study. Front Med (Lausanne). 2022;9:950246.10.3389/fmed.2022.950246Search in Google Scholar PubMed PubMed Central

[34] Li R, Guo C, Li Y, Qin Z, Huang W. Therapeutic targets and signaling mechanisms of vitamin C activity against sepsis: A bioinformatics study. Brief Bioinform. 2021;22(3):bbaa079.10.1093/bib/bbaa079Search in Google Scholar PubMed PubMed Central

[35] Carlson D, Maass DL, White DJ, Tan J, Horton JW. Antioxidant vitamin therapy alters sepsis-related apoptotic myocardial activity and inflammatory responses. Am J Physiol Heart Circ Physiol. 2006;291(6):H2779–89.10.1152/ajpheart.01258.2005Search in Google Scholar PubMed

[36] Howe KP, Clochesy JM, Goldstein LS, Owen H. Mechanical ventilation antioxidant trial. Am J Crit Care. 2015;24(5):440–5.10.4037/ajcc2015335Search in Google Scholar PubMed

[37] Kim JY, Lee SM. Vitamins C and E protect hepatic cytochrome P450 Dysfunction induced by polymicrobial sepsis. Eur J Pharmacol. 2006;534(1–3):202–9.10.1016/j.ejphar.2006.01.015Search in Google Scholar PubMed

[38] Pang TS, Liu DR, Cao LP. Progress of antioxidant therapy in sepsis. Int J Surg. 2013;40(6):402–4.Search in Google Scholar

[39] Mo SJ, Son EW, Rhee DK, Pyo S. Modulation of TNF-alpha-induced IEAM-l expression, NO and H202 production by alginate, alliein and ascorbic acid in human endothelial cells. Arch Pharm Res. 2003;26(3):244–51.10.1007/BF02976837Search in Google Scholar PubMed

[40] Zhou G, Kamenos G, Pendem S, Wilson JX, Wu F. Ascorbate protects against vascular leakage in cecal ligation and puncture-induced septic peritonitis. Am J Physiol Regul Integr Comp Physiol. 2012;302(4):R409–16.10.1152/ajpregu.00153.2011Search in Google Scholar PubMed PubMed Central

[41] Tyrol K. Vitamin C and microvascular dysfunction in systemic inflammation. Antioxid-ants. 2017;6(3):1–11.10.3390/antiox6030049Search in Google Scholar

[42] Romani L, Bistoni F, Montagnoli C, Gaziano R, Bozza S, Bonifazi P, et al. Thymosin alpha1: an endogenous regulator of inflammation, immunity, and tolerance. Ann NY Acad Sci. 2007;1112:326–38.10.1196/annals.1415.002Search in Google Scholar PubMed

[43] Giamarellos-Bourboulis EJ. What is the pathophysiology of the septic host upon admission? Int J Antimicrob Agents. 2010;36(Suppl 2):S2–5.10.1016/j.ijantimicag.2010.11.003Search in Google Scholar PubMed

[44] Oudemans-van Straaten HM, Spoelstra-de Man AM, de Waard MC. Vitamin C revisited. Crit Care. 2014;18(4):460.10.1186/s13054-014-0460-xSearch in Google Scholar PubMed PubMed Central

[45] Denhis JM, Witting PK. Protective role for antioxidants in acute kidney disease. Nutrients. 2017;9(7):E718.10.3390/nu9070718Search in Google Scholar PubMed PubMed Central

[46] May JM, Harrison FE. Role of vitamin C in the function of the vascular endothelium. Antioxid Redox Signal. 2013;19(17):2068–83.10.1089/ars.2013.5205Search in Google Scholar PubMed PubMed Central

[47] May JM. Vitamin C transport and its role in the central nervous system. Subcell Biochem. 2012;56:85–103.10.1007/978-94-007-2199-9_6Search in Google Scholar PubMed PubMed Central

[48] Fowler AA, Syed AA, Knowlson S. Phase I safety trial of intravenous ascorbic acid inpatients with severe sepsis. J Transl Med. 2014;12:32.10.1186/1479-5876-12-32Search in Google Scholar PubMed PubMed Central

[49] Schorah CJ, Downing C, Piripitsi A, Gallivan L, Al-Hazaa AH, Sanderson MJ, et al. Total vitamin C, ascorbie acid, and dehydroascorbic acid concentrations in plasma of critically ill patients. Am J Clin Nutr. 1996;63(5):760–5.10.1093/ajcn/63.5.760Search in Google Scholar PubMed

[50] Pleiner J, Mittermayer F, Schaller G, MacAllister RJ, Wolzt M. High doses of vitamin C reverse Escheriehia coli endotoxin-induced hyporeactivity to acetylcholine in the human forearm. Circulation. 2002;106(12):1460–4.10.1161/01.CIR.0000030184.70207.FFSearch in Google Scholar PubMed

[51] De Grooth HM. Spoelstra-de Man AME, Oudemans-van Straaten HM. Early plasma vitamin C concentration, organ dysfunction and ICU mortality. Intensive Care Med. 2014;40(1):S199–200.Search in Google Scholar

[52] Carr AC, Maggini S. Vitamin C and immune function. Nutrients. 2017;9(11):1211.10.3390/nu9111211Search in Google Scholar PubMed PubMed Central

[53] Bsoul SA, Terezhalmy GT. Vitamin C in health and disease. J Contemp Dent Pract. 2004;5(2):1–13.10.5005/jcdp-5-2-1Search in Google Scholar

[54] Hemila H. Vitamin C and infections. Nutrients. 2017;9(4):339.10.3390/nu9040339Search in Google Scholar PubMed PubMed Central

[55] McIlwain DR, Berger T, Mak TW. Caspase functions in cell death and disease. Cold Spring Harb Perspect Biol. 2013;5(4):a008656.10.1101/cshperspect.a008656Search in Google Scholar PubMed PubMed Central

[56] Hiraki S, Ono S, Tsujimoto H, Kinoshita M, Takahata R, Miyazaki H, et al. Neutralization of interleukin-10 or transforming growth factor-beta decreases the percentages of CD4 + CD25 + Foxp3 + regulatory T cells in septic mice, thereby leading to an improved survival. Surgery. 2012;151(2):313–22.10.1016/j.surg.2011.07.019Search in Google Scholar PubMed

[57] Feng Z, Shi Q, Fan Y, Wang Q, Yin W. Ulinastatin and/or thymosin alpha1 for severe sepsis: A systematic review and meta-analysis. J Trauma Acute Care Surg. 2016;80(2):335–40.10.1097/TA.0000000000000909Search in Google Scholar PubMed

Received: 2022-07-02
Revised: 2022-12-09
Accepted: 2022-12-14
Published Online: 2023-02-07

© 2023 the author(s), published by De Gruyter

This work is licensed under the Creative Commons Attribution 4.0 International License.

Articles in the same Issue

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
  6. A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection
  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
  8. Isoimperatorin alleviates lipopolysaccharide-induced periodontitis by downregulating ERK1/2 and NF-κB pathways
  9. Immunoregulation of synovial macrophages for the treatment of osteoarthritis
  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
  11. Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms
  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
https://doi.org/10.1515/biol-2022-0551
Keywords for this article
sepsis; thymosin α1; vitamin C; immune response; inflammatory response
Creative Commons
BY 4.0

Articles in the same Issue

  1. Biomedical Sciences
  2. Systemic investigation of inetetamab in combination with small molecules to treat HER2-overexpressing breast and gastric cancers
  3. Immunosuppressive treatment for idiopathic membranous nephropathy: An updated network meta-analysis
  4. Identifying two pathogenic variants in a patient with pigmented paravenous retinochoroidal atrophy
  5. Effects of phytoestrogens combined with cold stress on sperm parameters and testicular proteomics in rats
  6. A case of pulmonary embolism with bad warfarin anticoagulant effects caused by E. coli infection
  7. Neutrophilia with subclinical Cushing’s disease: A case report and literature review
  8. Isoimperatorin alleviates lipopolysaccharide-induced periodontitis by downregulating ERK1/2 and NF-κB pathways
  9. Immunoregulation of synovial macrophages for the treatment of osteoarthritis
  10. Novel CPLANE1 c.8948dupT (p.P2984Tfs*7) variant in a child patient with Joubert syndrome
  11. Antiphospholipid antibodies and the risk of thrombosis in myeloproliferative neoplasms
  12. Immunological responses of septic rats to combination therapy with thymosin α1 and vitamin C
  13. High glucose and high lipid induced mitochondrial dysfunction in JEG-3 cells through oxidative stress
  14. Pharmacological inhibition of the ubiquitin-specific protease 8 effectively suppresses glioblastoma cell growth
  15. Levocarnitine regulates the growth of angiotensin II-induced myocardial fibrosis cells via TIMP-1
  16. Age-related changes in peripheral T-cell subpopulations in elderly individuals: An observational study
  17. Single-cell transcription analysis reveals the tumor origin and heterogeneity of human bilateral renal clear cell carcinoma
  18. Identification of iron metabolism-related genes as diagnostic signatures in sepsis by blood transcriptomic analysis
  19. Long noncoding RNA ACART knockdown decreases 3T3-L1 preadipocyte proliferation and differentiation
  20. Surgery, adjuvant immunotherapy plus chemotherapy and radiotherapy for primary malignant melanoma of the parotid gland (PGMM): A case report
  21. Dosimetry comparison with helical tomotherapy, volumetric modulated arc therapy, and intensity-modulated radiotherapy for grade II gliomas: A single‑institution case series
  22. Soy isoflavone reduces LPS-induced acute lung injury via increasing aquaporin 1 and aquaporin 5 in rats
  23. Refractory hypokalemia with sexual dysplasia and infertility caused by 17α-hydroxylase deficiency and triple X syndrome: A case report
  24. Meta-analysis of cancer risk among end stage renal disease undergoing maintenance dialysis
  25. 6-Phosphogluconate dehydrogenase inhibition arrests growth and induces apoptosis in gastric cancer via AMPK activation and oxidative stress
  26. Experimental study on the optimization of ANM33 release in foam cells
  27. Primary retroperitoneal angiosarcoma: A case report
  28. Metabolomic analysis-identified 2-hydroxybutyric acid might be a key metabolite of severe preeclampsia
  29. Malignant pleural effusion diagnosis and therapy
  30. Effect of spaceflight on the phenotype and proteome of Escherichia coli
  31. Comparison of immunotherapy combined with stereotactic radiotherapy and targeted therapy for patients with brain metastases: A systemic review and meta-analysis
  32. Activation of hypermethylated P2RY1 mitigates gastric cancer by promoting apoptosis and inhibiting proliferation
  33. Association between the VEGFR-2 -604T/C polymorphism (rs2071559) and type 2 diabetic retinopathy
  34. The role of IL-31 and IL-34 in the diagnosis and treatment of chronic periodontitis
  35. Triple-negative mouse breast cancer initiating cells show high expression of beta1 integrin and increased malignant features
  36. mNGS facilitates the accurate diagnosis and antibiotic treatment of suspicious critical CNS infection in real practice: A retrospective study
  37. The apatinib and pemetrexed combination has antitumor and antiangiogenic effects against NSCLC
  38. Radiotherapy for primary thyroid adenoid cystic carcinoma
  39. Design and functional preliminary investigation of recombinant antigen EgG1Y162–EgG1Y162 against Echinococcus granulosus
  40. Effects of losartan in patients with NAFLD: A meta-analysis of randomized controlled trial
  41. Bibliometric analysis of METTL3: Current perspectives, highlights, and trending topics
  42. Performance comparison of three scaling algorithms in NMR-based metabolomics analysis
  43. PI3K/AKT/mTOR pathway and its related molecules participate in PROK1 silence-induced anti-tumor effects on pancreatic cancer
  44. The altered expression of cytoskeletal and synaptic remodeling proteins during epilepsy
  45. Effects of pegylated recombinant human granulocyte colony-stimulating factor on lymphocytes and white blood cells of patients with malignant tumor
  46. Prostatitis as initial manifestation of Chlamydia psittaci pneumonia diagnosed by metagenome next-generation sequencing: A case report
  47. NUDT21 relieves sevoflurane-induced neurological damage in rats by down-regulating LIMK2
  48. Association of interleukin-10 rs1800896, rs1800872, and interleukin-6 rs1800795 polymorphisms with squamous cell carcinoma risk: A meta-analysis
  49. Exosomal HBV-DNA for diagnosis and treatment monitoring of chronic hepatitis B
  50. Shear stress leads to the dysfunction of endothelial cells through the Cav-1-mediated KLF2/eNOS/ERK signaling pathway under physiological conditions
  51. Interaction between the PI3K/AKT pathway and mitochondrial autophagy in macrophages and the leukocyte count in rats with LPS-induced pulmonary infection
  52. Meta-analysis of the rs231775 locus polymorphism in the CTLA-4 gene and the susceptibility to Graves’ disease in children
  53. Cloning, subcellular localization and expression of phosphate transporter gene HvPT6 of hulless barley
  54. Coptisine mitigates diabetic nephropathy via repressing the NRLP3 inflammasome
  55. Significant elevated CXCL14 and decreased IL-39 levels in patients with tuberculosis
  56. Whole-exome sequencing applications in prenatal diagnosis of fetal bowel dilatation
  57. Gemella morbillorum infective endocarditis: A case report and literature review
  58. An unusual ectopic thymoma clonal evolution analysis: A case report
  59. Severe cumulative skin toxicity during toripalimab combined with vemurafenib following toripalimab alone
  60. Detection of V. vulnificus septic shock with ARDS using mNGS
  61. Novel rare genetic variants of familial and sporadic pulmonary atresia identified by whole-exome sequencing
  62. The influence and mechanistic action of sperm DNA fragmentation index on the outcomes of assisted reproduction technology
  63. Novel compound heterozygous mutations in TELO2 in an infant with You-Hoover-Fong syndrome: A case report and literature review
  64. ctDNA as a prognostic biomarker in resectable CLM: Systematic review and meta-analysis
  65. Diagnosis of primary amoebic meningoencephalitis by metagenomic next-generation sequencing: A case report
  66. Phylogenetic analysis of promoter regions of human Dolichol kinase (DOLK) and orthologous genes using bioinformatics tools
  67. Collagen changes in rabbit conjunctiva after conjunctival crosslinking
  68. Effects of NM23 transfection of human gastric carcinoma cells in mice
  69. Oral nifedipine and phytosterol, intravenous nicardipine, and oral nifedipine only: Three-arm, retrospective, cohort study for management of severe preeclampsia
  70. Case report of hepatic retiform hemangioendothelioma: A rare tumor treated with ultrasound-guided microwave ablation
  71. Curcumin induces apoptosis in human hepatocellular carcinoma cells by decreasing the expression of STAT3/VEGF/HIF-1α signaling
  72. Rare presentation of double-clonal Waldenström macroglobulinemia with pulmonary embolism: A case report
  73. Giant duplication of the transverse colon in an adult: A case report and literature review
  74. Ectopic thyroid tissue in the breast: A case report
  75. SDR16C5 promotes proliferation and migration and inhibits apoptosis in pancreatic cancer
  76. Vaginal metastasis from breast cancer: A case report
  77. Screening of the best time window for MSC transplantation to treat acute myocardial infarction with SDF-1α antibody-loaded targeted ultrasonic microbubbles: An in vivo study in miniswine
  78. Inhibition of TAZ impairs the migration ability of melanoma cells
  79. Molecular complexity analysis of the diagnosis of Gitelman syndrome in China
  80. Effects of maternal calcium and protein intake on the development and bone metabolism of offspring mice
  81. Identification of winter wheat pests and diseases based on improved convolutional neural network
  82. Ultra-multiplex PCR technique to guide treatment of Aspergillus-infected aortic valve prostheses
  83. Virtual high-throughput screening: Potential inhibitors targeting aminopeptidase N (CD13) and PIKfyve for SARS-CoV-2
  84. Immune checkpoint inhibitors in cancer patients with COVID-19
  85. Utility of methylene blue mixed with autologous blood in preoperative localization of pulmonary nodules and masses
  86. Integrated analysis of the microbiome and transcriptome in stomach adenocarcinoma
  87. Berberine suppressed sarcopenia insulin resistance through SIRT1-mediated mitophagy
  88. DUSP2 inhibits the progression of lupus nephritis in mice by regulating the STAT3 pathway
  89. Lung abscess by Fusobacterium nucleatum and Streptococcus spp. co-infection by mNGS: A case series
  90. Genetic alterations of KRAS and TP53 in intrahepatic cholangiocarcinoma associated with poor prognosis
  91. Granulomatous polyangiitis involving the fourth ventricle: Report of a rare case and a literature review
  92. Studying infant mortality: A demographic analysis based on data mining models
  93. Metaplastic breast carcinoma with osseous differentiation: A report of a rare case and literature review
  94. Protein Z modulates the metastasis of lung adenocarcinoma cells
  95. Inhibition of pyroptosis and apoptosis by capsaicin protects against LPS-induced acute kidney injury through TRPV1/UCP2 axis in vitro
  96. TAK-242, a toll-like receptor 4 antagonist, against brain injury by alleviates autophagy and inflammation in rats
  97. Primary mediastinum Ewing’s sarcoma with pleural effusion: A case report and literature review
  98. Association of ADRB2 gene polymorphisms and intestinal microbiota in Chinese Han adolescents
  99. Tanshinone IIA alleviates chondrocyte apoptosis and extracellular matrix degeneration by inhibiting ferroptosis
  100. Study on the cytokines related to SARS-Cov-2 in testicular cells and the interaction network between cells based on scRNA-seq data
  101. Effect of periostin on bone metabolic and autophagy factors during tooth eruption in mice
  102. HP1 induces ferroptosis of renal tubular epithelial cells through NRF2 pathway in diabetic nephropathy
  103. Intravaginal estrogen management in postmenopausal patients with vaginal squamous intraepithelial lesions along with CO2 laser ablation: A retrospective study
  104. Hepatocellular carcinoma cell differentiation trajectory predicts immunotherapy, potential therapeutic drugs, and prognosis of patients
  105. Effects of physical exercise on biomarkers of oxidative stress in healthy subjects: A meta-analysis of randomized controlled trials
  106. Identification of lysosome-related genes in connection with prognosis and immune cell infiltration for drug candidates in head and neck cancer
  107. Development of an instrument-free and low-cost ELISA dot-blot test to detect antibodies against SARS-CoV-2
  108. Research progress on gas signal molecular therapy for Parkinson’s disease
  109. Adiponectin inhibits TGF-β1-induced skin fibroblast proliferation and phenotype transformation via the p38 MAPK signaling pathway
  110. The G protein-coupled receptor-related gene signatures for predicting prognosis and immunotherapy response in bladder urothelial carcinoma
  111. α-Fetoprotein contributes to the malignant biological properties of AFP-producing gastric cancer
  112. CXCL12/CXCR4/CXCR7 axis in placenta tissues of patients with placenta previa
  113. Association between thyroid stimulating hormone levels and papillary thyroid cancer risk: A meta-analysis
  114. Significance of sTREM-1 and sST2 combined diagnosis for sepsis detection and prognosis prediction
  115. Diagnostic value of serum neuroactive substances in the acute exacerbation of chronic obstructive pulmonary disease complicated with depression
  116. Research progress of AMP-activated protein kinase and cardiac aging
  117. TRIM29 knockdown prevented the colon cancer progression through decreasing the ubiquitination levels of KRT5
  118. Cross-talk between gut microbiota and liver steatosis: Complications and therapeutic target
  119. Metastasis from small cell lung cancer to ovary: A case report
  120. The early diagnosis and pathogenic mechanisms of sepsis-related acute kidney injury
  121. The effect of NK cell therapy on sepsis secondary to lung cancer: A case report
  122. Erianin alleviates collagen-induced arthritis in mice by inhibiting Th17 cell differentiation
  123. Loss of ACOX1 in clear cell renal cell carcinoma and its correlation with clinical features
  124. Signalling pathways in the osteogenic differentiation of periodontal ligament stem cells
  125. Crosstalk between lactic acid and immune regulation and its value in the diagnosis and treatment of liver failure
  126. Clinicopathological features and differential diagnosis of gastric pleomorphic giant cell carcinoma
  127. Traumatic brain injury and rTMS-ERPs: Case report and literature review
  128. Extracellular fibrin promotes non-small cell lung cancer progression through integrin β1/PTEN/AKT signaling
  129. Knockdown of DLK4 inhibits non-small cell lung cancer tumor growth by downregulating CKS2
  130. The co-expression pattern of VEGFR-2 with indicators related to proliferation, apoptosis, and differentiation of anagen hair follicles
  131. Inflammation-related signaling pathways in tendinopathy
  132. CD4+ T cell count in HIV/TB co-infection and co-occurrence with HL: Case report and literature review
  133. Clinical analysis of severe Chlamydia psittaci pneumonia: Case series study
  134. Bioinformatics analysis to identify potential biomarkers for the pulmonary artery hypertension associated with the basement membrane
  135. Influence of MTHFR polymorphism, alone or in combination with smoking and alcohol consumption, on cancer susceptibility
  136. Catharanthus roseus (L.) G. Don counteracts the ampicillin resistance in multiple antibiotic-resistant Staphylococcus aureus by downregulation of PBP2a synthesis
  137. Combination of a bronchogenic cyst in the thoracic spinal canal with chronic myelocytic leukemia
  138. Bacterial lipoprotein plays an important role in the macrophage autophagy and apoptosis induced by Salmonella typhimurium and Staphylococcus aureus
  139. TCL1A+ B cells predict prognosis in triple-negative breast cancer through integrative analysis of single-cell and bulk transcriptomic data
  140. Ezrin promotes esophageal squamous cell carcinoma progression via the Hippo signaling pathway
  141. Ferroptosis: A potential target of macrophages in plaque vulnerability
  142. Predicting pediatric Crohn's disease based on six mRNA-constructed risk signature using comprehensive bioinformatic approaches
  143. Applications of genetic code expansion and photosensitive UAAs in studying membrane proteins
  144. HK2 contributes to the proliferation, migration, and invasion of diffuse large B-cell lymphoma cells by enhancing the ERK1/2 signaling pathway
  145. IL-17 in osteoarthritis: A narrative review
  146. Circadian cycle and neuroinflammation
  147. Probiotic management and inflammatory factors as a novel treatment in cirrhosis: A systematic review and meta-analysis
  148. Hemorrhagic meningioma with pulmonary metastasis: Case report and literature review
  149. SPOP regulates the expression profiles and alternative splicing events in human hepatocytes
  150. Knockdown of SETD5 inhibited glycolysis and tumor growth in gastric cancer cells by down-regulating Akt signaling pathway
  151. PTX3 promotes IVIG resistance-induced endothelial injury in Kawasaki disease by regulating the NF-κB pathway
  152. Pancreatic ectopic thyroid tissue: A case report and analysis of literature
  153. The prognostic impact of body mass index on female breast cancer patients in underdeveloped regions of northern China differs by menopause status and tumor molecular subtype
  154. Report on a case of liver-originating malignant melanoma of unknown primary
  155. Case report: Herbal treatment of neutropenic enterocolitis after chemotherapy for breast cancer
  156. The fibroblast growth factor–Klotho axis at molecular level
  157. Characterization of amiodarone action on currents in hERG-T618 gain-of-function mutations
  158. A case report of diagnosis and dynamic monitoring of Listeria monocytogenes meningitis with NGS
  159. Effect of autologous platelet-rich plasma on new bone formation and viability of a Marburg bone graft
  160. Small breast epithelial mucin as a useful prognostic marker for breast cancer patients
  161. Continuous non-adherent culture promotes transdifferentiation of human adipose-derived stem cells into retinal lineage
  162. Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
  163. Favorable response to surufatinib in a patient with necrolytic migratory erythema: A case report
  164. Case report of atypical undernutrition of hypoproteinemia type
  165. Down-regulation of COL1A1 inhibits tumor-associated fibroblast activation and mediates matrix remodeling in the tumor microenvironment of breast cancer
  166. Sarcoma protein kinase inhibition alleviates liver fibrosis by promoting hepatic stellate cells ferroptosis
  167. Research progress of serum eosinophil in chronic obstructive pulmonary disease and asthma
  168. Clinicopathological characteristics of co-existing or mixed colorectal cancer and neuroendocrine tumor: Report of five cases
  169. Role of menopausal hormone therapy in the prevention of postmenopausal osteoporosis
  170. Precisional detection of lymph node metastasis using tFCM in colorectal cancer
  171. Advances in diagnosis and treatment of perimenopausal syndrome
  172. A study of forensic genetics: ITO index distribution and kinship judgment between two individuals
  173. Acute lupus pneumonitis resembling miliary tuberculosis: A case-based review
  174. Plasma levels of CD36 and glutathione as biomarkers for ruptured intracranial aneurysm
  175. Fractalkine modulates pulmonary angiogenesis and tube formation by modulating CX3CR1 and growth factors in PVECs
  176. Novel risk prediction models for deep vein thrombosis after thoracotomy and thoracoscopic lung cancer resections, involving coagulation and immune function
  177. Exploring the diagnostic markers of essential tremor: A study based on machine learning algorithms
  178. Evaluation of effects of small-incision approach treatment on proximal tibia fracture by deep learning algorithm-based magnetic resonance imaging
  179. An online diagnosis method for cancer lesions based on intelligent imaging analysis
  180. Medical imaging in rheumatoid arthritis: A review on deep learning approach
  181. Predictive analytics in smart healthcare for child mortality prediction using a machine learning approach
  182. Utility of neutrophil–lymphocyte ratio and platelet–lymphocyte ratio in predicting acute-on-chronic liver failure survival
  183. A biomedical decision support system for meta-analysis of bilateral upper-limb training in stroke patients with hemiplegia
  184. TNF-α and IL-8 levels are positively correlated with hypobaric hypoxic pulmonary hypertension and pulmonary vascular remodeling in rats
  185. Stochastic gradient descent optimisation for convolutional neural network for medical image segmentation
  186. Comparison of the prognostic value of four different critical illness scores in patients with sepsis-induced coagulopathy
  187. Application and teaching of computer molecular simulation embedded technology and artificial intelligence in drug research and development
  188. Hepatobiliary surgery based on intelligent image segmentation technology
  189. Value of brain injury-related indicators based on neural network in the diagnosis of neonatal hypoxic-ischemic encephalopathy
  190. Analysis of early diagnosis methods for asymmetric dementia in brain MR images based on genetic medical technology
  191. Early diagnosis for the onset of peri-implantitis based on artificial neural network
  192. Clinical significance of the detection of serum IgG4 and IgG4/IgG ratio in patients with thyroid-associated ophthalmopathy
  193. Forecast of pain degree of lumbar disc herniation based on back propagation neural network
  194. SPA-UNet: A liver tumor segmentation network based on fused multi-scale features
  195. Systematic evaluation of clinical efficacy of CYP1B1 gene polymorphism in EGFR mutant non-small cell lung cancer observed by medical image
  196. Rehabilitation effect of intelligent rehabilitation training system on hemiplegic limb spasms after stroke
  197. A novel approach for minimising anti-aliasing effects in EEG data acquisition
  198. ErbB4 promotes M2 activation of macrophages in idiopathic pulmonary fibrosis
  199. Clinical role of CYP1B1 gene polymorphism in prediction of postoperative chemotherapy efficacy in NSCLC based on individualized health model
  200. Lung nodule segmentation via semi-residual multi-resolution neural networks
  201. Evaluation of brain nerve function in ICU patients with Delirium by deep learning algorithm-based resting state MRI
  202. A data mining technique for detecting malignant mesothelioma cancer using multiple regression analysis
  203. Markov model combined with MR diffusion tensor imaging for predicting the onset of Alzheimer’s disease
  204. Effectiveness of the treatment of depression associated with cancer and neuroimaging changes in depression-related brain regions in patients treated with the mediator-deuterium acupuncture method
  205. Molecular mechanism of colorectal cancer and screening of molecular markers based on bioinformatics analysis
  206. Monitoring and evaluation of anesthesia depth status data based on neuroscience
  207. Exploring the conformational dynamics and thermodynamics of EGFR S768I and G719X + S768I mutations in non-small cell lung cancer: An in silico approaches
  208. Optimised feature selection-driven convolutional neural network using gray level co-occurrence matrix for detection of cervical cancer
  209. Incidence of different pressure patterns of spinal cerebellar ataxia and analysis of imaging and genetic diagnosis
  210. Pathogenic bacteria and treatment resistance in older cardiovascular disease patients with lung infection and risk prediction model
  211. Adoption value of support vector machine algorithm-based computed tomography imaging in the diagnosis of secondary pulmonary fungal infections in patients with malignant hematological disorders
  212. From slides to insights: Harnessing deep learning for prognostic survival prediction in human colorectal cancer histology
  213. Ecology and Environmental Science
  214. Monitoring of hourly carbon dioxide concentration under different land use types in arid ecosystem
  215. Comparing the differences of prokaryotic microbial community between pit walls and bottom from Chinese liquor revealed by 16S rRNA gene sequencing
  216. Effects of cadmium stress on fruits germination and growth of two herbage species
  217. Bamboo charcoal affects soil properties and bacterial community in tea plantations
  218. Optimization of biogas potential using kinetic models, response surface methodology, and instrumental evidence for biodegradation of tannery fleshings during anaerobic digestion
  219. Understory vegetation diversity patterns of Platycladus orientalis and Pinus elliottii communities in Central and Southern China
  220. Studies on macrofungi diversity and discovery of new species of Abortiporus from Baotianman World Biosphere Reserve
  221. Food Science
  222. Effect of berrycactus fruit (Myrtillocactus geometrizans) on glutamate, glutamine, and GABA levels in the frontal cortex of rats fed with a high-fat diet
  223. Guesstimate of thymoquinone diversity in Nigella sativa L. genotypes and elite varieties collected from Indian states using HPTLC technique
  224. Analysis of bacterial community structure of Fuzhuan tea with different processing techniques
  225. Untargeted metabolomics reveals sour jujube kernel benefiting the nutritional value and flavor of Morchella esculenta
  226. Mycobiota in Slovak wine grapes: A case study from the small Carpathians wine region
  227. Elemental analysis of Fadogia ancylantha leaves used as a nutraceutical in Mashonaland West Province, Zimbabwe
  228. Microbiological transglutaminase: Biotechnological application in the food industry
  229. Influence of solvent-free extraction of fish oil from catfish (Clarias magur) heads using a Taguchi orthogonal array design: A qualitative and quantitative approach
  230. Chromatographic analysis of the chemical composition and anticancer activities of Curcuma longa extract cultivated in Palestine
  231. The potential for the use of leghemoglobin and plant ferritin as sources of iron
  232. Investigating the association between dietary patterns and glycemic control among children and adolescents with T1DM
  233. Bioengineering and Biotechnology
  234. Biocompatibility and osteointegration capability of β-TCP manufactured by stereolithography 3D printing: In vitro study
  235. Clinical characteristics and the prognosis of diabetic foot in Tibet: A single center, retrospective study
  236. Agriculture
  237. Biofertilizer and NPSB fertilizer application effects on nodulation and productivity of common bean (Phaseolus vulgaris L.) at Sodo Zuria, Southern Ethiopia
  238. On correlation between canopy vegetation and growth indexes of maize varieties with different nitrogen efficiencies
  239. Exopolysaccharides from Pseudomonas tolaasii inhibit the growth of Pleurotus ostreatus mycelia
  240. A transcriptomic evaluation of the mechanism of programmed cell death of the replaceable bud in Chinese chestnut
  241. Melatonin enhances salt tolerance in sorghum by modulating photosynthetic performance, osmoregulation, antioxidant defense, and ion homeostasis
  242. Effects of plant density on alfalfa (Medicago sativa L.) seed yield in western Heilongjiang areas
  243. Identification of rice leaf diseases and deficiency disorders using a novel DeepBatch technique
  244. Artificial intelligence and internet of things oriented sustainable precision farming: Towards modern agriculture
  245. Animal Sciences
  246. Effect of ketogenic diet on exercise tolerance and transcriptome of gastrocnemius in mice
  247. Combined analysis of mRNA–miRNA from testis tissue in Tibetan sheep with different FecB genotypes
  248. Isolation, identification, and drug resistance of a partially isolated bacterium from the gill of Siniperca chuatsi
  249. Tracking behavioral changes of confined sows from the first mating to the third parity
  250. The sequencing of the key genes and end products in the TLR4 signaling pathway from the kidney of Rana dybowskii exposed to Aeromonas hydrophila
  251. Development of a new candidate vaccine against piglet diarrhea caused by Escherichia coli
  252. Plant Sciences
  253. Crown and diameter structure of pure Pinus massoniana Lamb. forest in Hunan province, China
  254. Genetic evaluation and germplasm identification analysis on ITS2, trnL-F, and psbA-trnH of alfalfa varieties germplasm resources
  255. Tissue culture and rapid propagation technology for Gentiana rhodantha
  256. Effects of cadmium on the synthesis of active ingredients in Salvia miltiorrhiza
  257. Cloning and expression analysis of VrNAC13 gene in mung bean
  258. Chlorate-induced molecular floral transition revealed by transcriptomes
  259. Effects of warming and drought on growth and development of soybean in Hailun region
  260. Effects of different light conditions on transient expression and biomass in Nicotiana benthamiana leaves
  261. Comparative analysis of the rhizosphere microbiome and medicinally active ingredients of Atractylodes lancea from different geographical origins
  262. Distinguish Dianthus species or varieties based on chloroplast genomes
  263. Comparative transcriptomes reveal molecular mechanisms of apple blossoms of different tolerance genotypes to chilling injury
  264. Study on fresh processing key technology and quality influence of Cut Ophiopogonis Radix based on multi-index evaluation
  265. An advanced approach for fig leaf disease detection and classification: Leveraging image processing and enhanced support vector machine methodology
  266. Erratum
  267. Erratum to “Protein Z modulates the metastasis of lung adenocarcinoma cells”
  268. Erratum to “BRCA1 subcellular localization regulated by PI3K signaling pathway in triple-negative breast cancer MDA-MB-231 cells and hormone-sensitive T47D cells”
  269. Retraction
  270. Retraction to “Protocatechuic acid attenuates cerebral aneurysm formation and progression by inhibiting TNF-alpha/Nrf-2/NF-kB-mediated inflammatory mechanisms in experimental rats”
Sign up now to receive a 20% welcome discount
Institutional Access
How does access work?
Have an idea on how to improve our website?
Please write us.
© 2025 De Gruyter Brill
Downloaded on 6.9.2025 from https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0551/html
Scroll to top button