Home Medicine Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
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Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy

  • Kai-yan Wu , Fei Deng , Xin-yu Mao , Dan Zhou EMAIL logo and Wei-gan Shen EMAIL logo
Published/Copyright: October 9, 2023
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Open Medicine
From the journal Open Medicine Volume 18 Issue 1

Abstract

Accumulating evidence shows that Schwann cells’ (SCs) death caused by high glucose (HG) is involved in the pathological process of diabetic peripheral neuropathy (DPN). Ferroptosis is a novel form of regulatory cell death driven by iron-dependent lipid peroxidation. However, it is not clear whether ferroptosis is involved in the death process of SCs induced by HG. The expression of ferroptosis-related indicators in the serum of DPN patients was detected by ELISA. Subsequently, using cell counting kit‑8, western blot, real-time PCR, and Ki-67 staining, we investigated the effects of HG on the ferroptosis of SCs and initially explored the underlying mechanism. The results showed that the serum levels of glutathione peroxidase 4 (GPX4) and glutathione in patients with DPN decreased, while malondialdehyde levels increased significantly. Then, we observed that erastin and HG induced ferroptosis in SCs, resulting in the decrease in cell activity and the expression level of GPX4 and SLC7A11, which could be effectively reversed by the ferroptosis inhibitor Fer-1. Mechanistically, HG induced ferroptosis in SCs by inhibiting the NRF2 signaling pathway. Our results showed that ferroptosis was involved in the death process of SCs induced by HG. Inhibition of ferroptosis in SCs might create a new avenue for the treatment of DPN.

keywords: ferroptosis; diabetic peripheral neuropathy; Schwann cell; NRF2 signaling pathway

1 Introduction

Diabetic peripheral neuropathy (DPN), one of the most common chronic complications of diabetes, affects up to 50% of diabetic patients [1]. Nowadays, clinical treatment for DPN mainly focuses on strict hypoglycemic therapy and pain management, while a restricted number of patients benefit from it, which means more culprits besides hyperglycemia may participate in the process of DPN [2]. Accumulating evidence indicates that the death of Schwann cells (SCs) induced by hyperglycemia is involved in the pathogenesis of DPN, including oxidative stress, inflammatory response, autophagy dysfunction, ERS, and other pathological processes [3]. In particular, during DPN, the death of SCs will lead to myelin destruction, demyelination, axonal conduction abnormalities, and impaired neuronal regeneration, thus accelerating the progress of DPN [4]. Therefore, understanding the death mechanism of SCs under hyperglycemia may be an important entry point for the treatment of DPN.

Programmed cell death is strictly regulated by complex intracellular and extracellular signals, which is very important for diverse various biological processes, including mammalian development, homeostasis, and disease [5]. Ferroptosis is a novel form of programmed cell death, which is different from the traditional cognitive cell death modes [6]. The key mediators of ferroptosis are glutathione peroxidase 4 (GPX4) and SLC7A11, a functional subunit of cystine/glutamate reverse transport system Xc−. Low levels of SLC7A11 and GPX4 inactivation reduce glutathione (GSH) synthesis and lipid peroxide degradation, respectively. Both of these changes cause the accumulation of lipid peroxides, which in turn leads to the occurrence of cell ferroptosis [7,8,9]. Recent studies revealed that HG can induce ferroptosis in osteoblasts via increased intracellular ROS and the accumulation of lipid oxides and GSH depletion in diabetic osteoporosis [10]. During DPN, the enhancement of oxidative stress and reactive oxygen species (ROS) are dominant features that lead to SCs’ death, while ferroptosis is a cell death mode closely related to ROS [11,12,13]. Therefore, we speculate that ferroptosis may be involved in the death of SCs induced by HG.

In this study, the aim was to explore the role of ferroptosis in HG-induced SCs’ death. To test our hypothesis, we used HG-stimulated cultured SCs in vitro. Furthermore, we sought to determine the possible associated mechanism.

2 Materials and methods

2.1 Baseline data

From January 2021 to August 2021, DPN patients (n = 65) who underwent treatment and healthy volunteers (n = 23) who underwent physical examination in the Jintan Hospital affiliated to Jiangsu University were recruited for our research. Healthy volunteers were selected as a control group. Clinical data were recorded for all participants including gender, age, and diabetes mellitus (DM) duration. Inclusion criteria for DPN were as follows: (1) met the diagnostic criteria for DM and (2) the symptoms of DPN met the diagnostic criteria in the Chinese Guidelines for the Prevention and Treatment of Type 2 DM (2020 edition) [14]. Exclusion criteria were as follows: (1) patients with other forms of neuropathy, including neuropathy caused by drugs, cervical and lumbar spine lesions, Guillain–Barré syndrome, and other causes; (2) those with gestational diabetes; (3) those with tumor; (4) those with serious diseases of other organ systems in combination; and (5) those with mental disorders, hearing impairment, and cognitive dysfunction. This study was approved by the Ethics Review Committee of Jintan Hospital affiliated to Jiangsu University (no. LS2021009). All participants were informed of the study details and provided informed consent.

2.2 Detection of biochemical parameters

Whole blood was collected from the elbow vein of the participants who fasted overnight using a vacuum blood collection tube with anticoagulant or without anticoagulant. The whole blood containing anticoagulant was used to detect hemoglobin A1c (HbA1c) using a Lifotronic H9 (Lifotronic Technology Co., Ltd, Shenzhen, China). When whole blood without anticoagulants coagulated, the serum was separated by centrifugation at 3,000 rpm for 5 min. Serum levels of glucose were estimated using a LABOSPECT 008AS Automatic Chemical Analyzer (Hitachi, Tokyo, Japan). Human ELISA kit (Bios-wamp, Wuhan, China) was used to quantify serum levels of GPX4, GSH, and malondialdehyde (MDA) in patients with DPN and volunteers. All analysis steps were performed according to the manufacturer’s instructions.

2.3 Vibration perception threshold measurement

Vibration perception threshold (VPT) was assessed using a Sensiometer A100 (Laxons Technology Co., Ltd, Beijing, China). The patient was informed and familiar with the vibration sensation, and then, the professional performed the operation according to the manufacturer’s instructions. Each foot of the patient was repeated for 3 times, and the average VPT of both feet was recorded. In addition, according to the test value, the risk of diabetic foot is predicted. 0–10, 10–15, 15–25, and more than 25 V are considered normal, light risk, middle risk and severe risk, respectively.

2.4 Cell culture and treatment

SC line RSC96 was purchased from the cell bank of the China Academy of Sciences (Shanghai, China). The cell line was cultured in DMEM (Gibco, Grand Island, USA) supplemented with 10% fetal bovine serum (Gibco) and 1% pen/strep (Gibco), and incubated at 5% CO2 and 37°C.

To establish an HG cell model RSC96 was treated with DMEM containing 100 mM glucose for 48 h as previously described [15]. Cells were cultured to logarithmic phase and grouped as follows: normal control group (DMEM containing 25 mM glucose), high-glucose group (DMEM containing 100 mM glucose), Erastin (Selleckchem, Houston, USA) group (DMEM containing 25 mM glucose and 2 μM Erastin), and the ferroptosis inhibitor ferrostatin-1 (Fer-1) (Selleckchem) group (DMEM containing 100 mM glucose and 10 μM Fer-1). Erastin, as an inducer of cell ferroptosis, was used as a positive control.

2.5 Cell viability assay

Cell viability was analyzed using the cell counting kit-8 (CCK-8) (Biosharp, Beijing, China). RSC96 cells under different treatment conditions were seeded in 96-well plates (5  ×  103 cells per well) and cultured for 48 h. Then, 10 μL of CCK-8 solution was added to RSC96 cells for incubation for 1.5 h. The absorbance of the cells in each well at 450 nm was measured on a microplate reader (Multiskan FC, Thermoscientific, Waltham, USA).

2.6 Cell transfection

NRF2 gene expression was knocked down by transfecting RSC96 cells with siRNA-NRF2 or siRNA control (GenePharma Co., Ltd., Shanghai, China). Transient siRNA transfection was performed using Lipofectamine 2000 (Invitrogen, Carlsbad, CA, USA), according to the manufacturer’s instructions. After 24 h of transfection, SCs were treated with HG and Fer-1. The transfection efficiency was verified by real-time PCR and western blotting.

2.7 Immunofluorescence staining

Briefly, RSC96 cells under different treatment conditions were fixed with 4% paraformaldehyde at 4°C for 30 min. Subsequently, paraformaldehyde was removed and cells were permeabilized with 0.5% Triton X-100 and blocked with 5% BSA in PBS. Then, the cells were incubated with Ki-67 rabbit monoclonal antibody (1:200 dilution, Servicebio, Wuhan, China) at 4°C overnight, followed by washing and incubation with Cy3-conjugated secondary antibody (1:200 dilution, Servicebio) at 37 °C for 1 h. The cells were stained with DAPI nuclear stain (5 μg/mL) for 5–10 min. The images were taken using a CK-X53 fluorescent microscope (Olympus, Tokyo, Japan).

2.8 Western blotting

Western blot analysis was performed as previously described [16]. Briefly, the collected cells were lysed with RIPA to extract protein. Afterwards, the samples were transferred to nitrocellulose filter membranes and 5% skim milk powder solution, and then, the primary antibody (GPX4, SLC7A11, NQO1, HO-1, 1:1,000 dilution, Abcam, Cambridge, USA; NRF2, 1:1,000 dilution, Beyotime, China) was incubated at 4°C overnight. The membranes were then washed and incubated with the secondary antibody. β-Actin (1:2,000 dilution, CST, Danvers, USA) was used as an internal control.

2.9 RNA isolation and quantitative real-time PCR

Total RNA was extracted from cells. cDNA was synthesized using All-in-One™ First-Strand cDNA Synthesis Kit (Genecopoeia, Germantown, USA) according to the manufacturer’s protocols. qRT-PCR analysis was performed with All-in-One™ qPCR Mix (Genecopoeia). The primers were purchased from Genecopoeia. Real-time PCR was performed using a Quant Gene 9600 system (Bioer, Hangzhou, China). The relative expression of mRNA was evaluated by the 2−ΔΔCt method and normalized to GAPDH.

2.10 Statistical analysis

Statistical analyses were performed using the GraphPad Prism software (Version 5.0, GraphPad, San Diego, CA, USA). Data were presented as mean ± standard error of the mean. The groups were compared using the Student’s t test and one-way analysis of variance. Results were considered statistically significant for P values less than 0.05.

3 Results

3.1 Characteristics of baseline data

The baseline characteristics of the DPN group and the control group are shown in Table 1. The age of the DPN and control groups was 62.25 ± 11.48 (median age 59 (34–85)) and 26.30 ± 13.90 (median age 21 (15–75) years, respectively. The mean DM duration of the DPN group was 9.60 ± 6.49 years. When comparing the control group, GLU and HbA1c in the DPN group tended to have higher levels.

Table 1

Clinical characteristics

Characteristics Control group (n = 23) DPN group (n = 65)
Gender, n (%)
 Male 17 (73.91) 40 (61.54)
 Female 6 (26.09) 25 (38.46)
Age (years) 26.30 ± 13.90 62.25 ± 11.48
GLU (mmol/L) 4.95 ± 0.34 9.37 ± 3.39
HbA1c (%) 4.90 ± 0.20 9.47 ± 2.16

GLU, glucose; HbA1C, hemoglobin A1c.

3.2 The level of ferroptosis elevated in DPN patients

We first measured the indicators directly related to ferroptosis in the serum of DPN patients and healthy volunteers. The results showed that GPX4 and GSH were decreased significantly, and lipid peroxide MDA was markedly increased in the serum of patients with DPN compared with those in the serum of healthy volunteers, (Figure 1a–c). Given that the detection results of VPT can not only be used to diagnose DPN, but also predict the risk of diabetic foot, we further evaluated the differences in these related indicators of ferroptosis under different risk stratification. The data showed that GSH, GPX4 and MDA in different risk stratification were statistically significant compared with the control group, but there was no statistical difference between risk stratification groups (Figure 1d–f). These results suggest that the level of ferroptosis is increased in the serum of DPN patients, which is not directly related to the degree of risk of diabetic foot predicted by VPT.

Figure 1 The level of ferroptosis elevated in DPN patients. (a–c) ELISA was used to detect the serum level of ferroptosis-related index, including GPX4, GSH, and MDA. (d–f) Expression level of GPX4, GSH, and MDA in different risk stratification. ***P < 0.001.
Figure 1

The level of ferroptosis elevated in DPN patients. (a–c) ELISA was used to detect the serum level of ferroptosis-related index, including GPX4, GSH, and MDA. (d–f) Expression level of GPX4, GSH, and MDA in different risk stratification. ***P < 0.001.

3.3 HG induced the ferroptosis of SCs

We constructed an in vitro model of SCs induced by HG. Consistent with previously reported [15], HG effectively inhibited the proliferation activity of SCs (Figure 2a). To determine whether the decrease of the proliferation activity of SCs induced by HG was due to ferroptosis. Erastin, a classic activator of ferroptosis, was used to treat SCs. We found that the trend of erastin inhibiting SCs’ proliferation activity was similar to that induced by HG, while Fer-1 (a specific inhibitor of ferroptosis) reversed the effect of HG-induced decrease in the proliferation activity of SCs (Figure 2a). Importantly, treatment of HG-induced SCs with Fer-1 significantly increased the expression of GPX4 and SLC7A11, which resisted the key regulatory components of cell ferroptosis (Figure 2b and Figure S1). Moreover, qRT-PCR analysis showed that the level of GPX4 in SCs exposed to erastin and glucose decreased; whereas Fer-1 increased the level of GPX4 in HG-treated SCs (Figure 2c). Taken together, these results suggest that HG could induce ferroptosis in SCs.

Figure 2 High glucose-induced ferroptosis in SCs. SCs were cultured and treated with eratin and fer-1 combined with high glucose. (a) CCK-8 assay was performed to estimate the cell proliferation viability of SCs. (b) The Ferroptosis-related protein levels of GPX4 and SLC7A11 were determined by western blotting. (c) Real-time PCR analysis of the expression of GPX4. **P < 0.001, ***P < 0.0001.
Figure 2

High glucose-induced ferroptosis in SCs. SCs were cultured and treated with eratin and fer-1 combined with high glucose. (a) CCK-8 assay was performed to estimate the cell proliferation viability of SCs. (b) The Ferroptosis-related protein levels of GPX4 and SLC7A11 were determined by western blotting. (c) Real-time PCR analysis of the expression of GPX4. **P < 0.001, ***P < 0.0001.

3.4 HG-induced ferroptosis in SCs by inhibiting NRF2 signaling pathway

The typical characteristic of ferroptosis is the overproduction of lipid ROS. However, Previous research has established that HG can induce SCs’ oxidative stress, that is, ROS production increase and antioxidant protein decrease [17]. NRF2 signaling pathway is the direct downstream pathway of ROS, which regulates the transcription of ARE-dependent genes to balance the oxidation medium and maintain the redox homeostasis of cells [18]. The levels of NRF2, NQO1, and HO-1 were inhibited during HG or erastin-induced ferroptosis, as shown by western blotting. However, these proteins’ expression was significantly increased by treatment with Fer-1 (Figure 3a and Figure S2), suggesting that the NRF2 signaling pathway is involved in the process of ferroptosis in SCs induced by HG. To further determine the role of the NRF2 pathway in HG-induced ferroptosis, SCs were transiently transfected with NRF2-siRNA or NC-siRNA, which led to a decrease in NRF2 expression in the SCs Figure 3b and c and Figure S3. Due to NRF2-siRNA1 having the best knock-down efficiency, we chose it for SCs’ transfection and then stimulated with HG. As shown in Figure 3d and e, HG significantly inhibited the proliferation of SCs transfected with NRF2-siRNA, but this detrimental effect could be strongly reversed by Fer-1. The beneficial effect of Fer-1 may be achieved by improving the expression of NRF2 (Figure 3f). Additionally, HG-treated SCs with NRF2-siRNA transfected aggravated the down-regulation of GPX4 and SLCA711 compared with the HG group, whereas this was alleviated in the Fer-1 treatment group Figure 3g and Figure S4, suggesting that the mechanism of HG-induced ferroptosis in SCs may be through inhibiting NRF2 signal pathway.

Figure 3 High glucose-induced ferroptosis via inhibiting NRF2 signaling pathway. (a) The protein levels of NRF2, NQO1, and HO-1 were determined using western blot assays. (b) Expression of NRF2 level in SCs with NRF2 knock-down was assessed by real-time PCR and Western blot (c). (d and e) Representative images and quantification data of Ki67 staining. Scale bar: 50 μm. (f) Real-time PCR analysis of NRF2 expression in SCs after treatments. (g) GPX4 and SLC7A11 protein levels were determined by western blot in each group. *P < 0.05, **P < 0.001.
Figure 3

High glucose-induced ferroptosis via inhibiting NRF2 signaling pathway. (a) The protein levels of NRF2, NQO1, and HO-1 were determined using western blot assays. (b) Expression of NRF2 level in SCs with NRF2 knock-down was assessed by real-time PCR and Western blot (c). (d and e) Representative images and quantification data of Ki67 staining. Scale bar: 50 μm. (f) Real-time PCR analysis of NRF2 expression in SCs after treatments. (g) GPX4 and SLC7A11 protein levels were determined by western blot in each group. *P < 0.05, **P < 0.001.

4 Discussion

DPN, as the most common complication of diabetes, is characterized by the impaired nerve fibers undergoing segmental demyelination [1,19]. As supporting cells in the peripheral nervous system, the death of SCs under hyperglycemia has been considered the underlying cause of demyelination [20,21]. Therefore, understanding the death of SCs may help to reveal their mechanism in the associated loss of the myelin sheath in DPN. However, most previous studies on SCs’ death under diabetic conditions mainly focused on apoptotic cell death [17,22,23]. In recent years, some emerging cell death modes, including necroptosis [24], pyroptosis [25], and autophagy [26], have made contributions to the cognition of SCs death. In this study, we further demonstrated that ferroptosis involves in SCs’ death in DPN.

Previous studies have shown that demyelination is a significant feature of DPN pathological changes [27]. In the peripheral nervous system, axon demyelination is closely related to the abnormality of SCs, because the formation of myelin sheath depends on the development and maturity of SC to wrap the axon [28]. In addition, SCs can provide abundant neurotrophic factors and oxygen support for axons [28]. Under the condition of hyperglycemia, the production of ROS is higher than that of the formation of antioxidants, which will lead to the imbalance of redox homeostasis. The imbalance of redox homeostasis elicits the peroxidation of protein, lipid, and nucleic acid and further triggers the over-activation of oxidative stress, resulting in metabolic dysfunction and death of SCs [17]. Consistent with this, our results showed that antioxidants GPX4 and GSH were significantly reduced in the serum of DPN patients, while MDA, an indicator closely related to lipid peroxidation, was significantly increased. Lipid peroxidation is considered to induce ferroptosis, a new type of programmed cell death, which is characterized by the increase in iron content in cells and the increase in ROS production caused by GSH depletion, leading to lipid peroxidation and eventually cell death [7,29,30]. This implies that the increase in ROS concentration in SCs may induce ferroptosis, leading to myelin damage, even demyelination. In this study, we observed that the decrease in SCs’ viability induced by HG exhibited the similar effects to erastin, while Fer-1 could reverse this harmful effect. Moreover, Fer-1 also increased the expression of GPX4 and SLC7A11 in SCs induced by HG. These results confirmed the occurrence of ferroptosis in SCs induced by HG which may help us understand the mechanism of axonal demyelination in DPN. A recent study is similar to our results, that is, human herpesvirus 7 mediates the increase of ROS production by up-regulating Cox4i2, which results in SCs ferroptosis and the myelin sheath damage of facial nerve, while inhibiting the ferroptosis can promote the maturity of SCs and allow the nerve to form a more morphological myelin sheath [31,32]. Therefore, we speculate that reversing the ferroptosis of SCs may contribute to myelin regeneration during DPN.NRF2, a well-known transcription factor, has been identified as the main regulator of the defensive response to oxidative stress [33]. During oxidative stress, NRF2 dissociates from the heterodimer of Keap1 in the cytosol, allowing NRF2 to translocate to the nucleus, where NRF2 interacts with ARE to induce the expression of the downstream antioxidant gene (including HO-1, NQO1, etc.) to maintain oxidative stress homeostasis in the cell [18,34]. In fact, HG can induce the excessive production of ROS in cells, which leads to peroxidation and the collapse of NRF2 antioxidant system [35,36]. It is worth noting that many protein enzymes responsible for preventing lipid peroxidation and causing ferroptosis are NRF2 target genes [18,37]. It is reminiscent that HG by inhibiting the NRF2 signaling pathway may initiate the cellular suicide procedure, especially ferroptosis. Therefore, we put forward a reasonable hypothesis that HG-induced ferroptosis in SCs may be achieved by inhibiting the NRF2 signaling pathway. As predicted, HG-treated SCs exhibited decreased NRF2 as well as its downstream targets including HO-1 and NQO1. Moreover, when NRF2 was knocked down, HG aggravated the inhibition effect of SCs proliferation and decreased the expression of GPX4 and SLC7A11 in SCs, whereas Fer-1 alleviated these outcomes. Overall, these findings reveal that HG induced ferroptosis in SCs by inhibiting NRF2 pathway.

There are still some limitations of this study which are as follows: (1) only the indicators directly related to ferroptosis in the serum of DPN patients and healthy volunteers were detected in this experiment, and the serum of diabetic patients needs to be detected and further evaluated. (2) In vivo experiments have not been carried out, and animal experiments need to be further verified to enrich our findings.

5 Conclusion

In summary, the results of the present study provide evidence that HG induced ferroptosis in SCs by inhibiting the NRF2 pathway. From the perspective of ferroptosis, we describe a new mechanism of SCs death during DPN (Figure 4). More importantly and practically, targeting SCs ferroptosis may be a promising treatment strategy for DPN.

Figure 4 A schematic diagram of proposed molecular mechanisms of ferroptosis induced by high glucose in SCs. HG may induce ferroptosis in SCs by inhibiting NRF2 pathway and downstream ferroptosis-related proteins (SLC7A11, GSH, and GPX4).
Figure 4

A schematic diagram of proposed molecular mechanisms of ferroptosis induced by high glucose in SCs. HG may induce ferroptosis in SCs by inhibiting NRF2 pathway and downstream ferroptosis-related proteins (SLC7A11, GSH, and GPX4).

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  1. Funding information: This work was supported by the grants from the Science and Technology Plan Project of Changzhou (CJ20210009) to Dan Zhou.

  2. Author contributions: WGS and DZ contributed to the conception and design of the experiments. KYW, FD, and XYM performed the experiments. DZ collected/analyzed the data. DZ contributed reagents/materials/analysis tools. WGS and DZ wrote the paper. All authors have given final approval to the article.

  3. Conflict of interest: The authors declare that they have no competing interest.

  4. Data availability statement: The data that support the findings of this study are available from the corresponding author upon reasonable request.

References

[1] Barrell K, Smith AG. Peripheral neuropathy. Med Clin North Am. 2019;103(2):383–97.10.1016/j.mcna.2018.10.006Search in Google Scholar PubMed

[2] Stino AM, Rumora AE, Kim B, Feldman EL. Evolving concepts on the role of dyslipidemia, bioenergetics, and inflammation in the pathogenesis and treatment of diabetic peripheral neuropathy. J Peripher Nerv Syst. 2020;25(2):76–84.10.1111/jns.12387Search in Google Scholar PubMed PubMed Central

[3] Li J, Guan R, Pan L. Mechanism of Schwann cells in diabetic peripheral neuropathy: A review. Medicine (Baltimore). 2023;102(1):e32653.10.1097/MD.0000000000032653Search in Google Scholar PubMed PubMed Central

[4] Goncalves NP, Vaegter CB, Andersen H, Ostergaard L, Calcutt NA, Jensen TS. Schwann cell interactions with axons and microvessels in diabetic neuropathy. Nat Rev Neurol. 2017;13(3):135–47.10.1038/nrneurol.2016.201Search in Google Scholar PubMed PubMed Central

[5] Moujalled D, Strasser A, Liddell JR. Molecular mechanisms of cell death in neurological diseases. Cell Death Differ. 2021;28(7):2029–44.10.1038/s41418-021-00814-ySearch in Google Scholar PubMed PubMed Central

[6] Stockwell BR, Friedmann Angeli JP, Bayir H, Bush AI, Conrad M, Dixon SJ, et al. Ferroptosis: A regulated cell death nexus linking metabolism, redox biology, and disease. Cell. 2017;171(2):273–85.10.1016/j.cell.2017.09.021Search in Google Scholar PubMed PubMed Central

[7] Xie Y, Hou W, Song X, Yu Y, Huang J, Sun X, et al. Ferroptosis: Process and function. Cell Death Differ. 2016;23(3):369–79.10.1038/cdd.2015.158Search in Google Scholar PubMed PubMed Central

[8] Yang WS, Stockwell BR. Ferroptosis: Death by lipid peroxidation. Trends Cell Biol. 2016;26(3):165–76.10.1016/j.tcb.2015.10.014Search in Google Scholar PubMed PubMed Central

[9] Ursini F, Maiorino M. Lipid peroxidation and ferroptosis: The role of GSH and GPx4. Free Radic Biol Med. 2020;152:175–85.10.1016/j.freeradbiomed.2020.02.027Search in Google Scholar PubMed

[10] Ma H, Wang X, Zhang W, Li H, Zhao W, Sun J, et al. Melatonin suppresses ferroptosis induced by high glucose via activation of the Nrf2/HO-1 signaling pathway in type 2 diabetic osteoporosis. Oxid Med Cell Longev. 2020;2020:9067610.10.1155/2020/9067610Search in Google Scholar PubMed PubMed Central

[11] Pop-Busui R, Sima A, Stevens M. Diabetic neuropathy and oxidative stress. Diabetes Metab Res Rev. 2006;22(4):257–73.10.1002/dmrr.625Search in Google Scholar PubMed

[12] Vincent AM, Brownlee M, Russell JW. Oxidative stress and programmed cell death in diabetic neuropathy. Ann N Y Acad Sci. 2002;959:368–83.10.1111/j.1749-6632.2002.tb02108.xSearch in Google Scholar PubMed

[13] Cao JY, Dixon SJ. Mechanisms of ferroptosis. Cell Mol Life Sci. 2016;73(11–12):2195–209.10.1007/s00018-016-2194-1Search in Google Scholar PubMed PubMed Central

[14] Society C. Guideline for the prevention and treatment of type 2 diabetes mellitus in China (2020 edition). Chin J Diabetes Mellitus. 2021;13(4):315–409.Search in Google Scholar

[15] Xu DD, Li WT, Jiang D, Wu HG, Ren MS, Chen MQ, et al. 3-N-Butylphthalide mitigates high glucose-induced injury to Schwann cells: Association with nitrosation and apoptosis. Neural Regen Res. 2019;14(3):513–8.10.4103/1673-5374.245590Search in Google Scholar PubMed PubMed Central

[16] Ma Y, Dong L, Zhou D, Li L, Zhang W, Zhen Y, et al. Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats. J Cell Mol Med. 2019;23(4):2822–35.10.1111/jcmm.14190Search in Google Scholar PubMed PubMed Central

[17] Li R, Wang B, Wu C, Li D, Wu Y, Ye L, et al. Acidic fibroblast growth factor attenuates type 2 diabetes-induced demyelination via suppressing oxidative stress damage. Cell Death Dis. 2021;12(1):107.10.1038/s41419-021-03407-2Search in Google Scholar PubMed PubMed Central

[18] Dodson M, Castro-Portuguez R, Zhang DD. NRF2 plays a critical role in mitigating lipid peroxidation and ferroptosis. Redox Biol. 2019;23:101107.10.1016/j.redox.2019.101107Search in Google Scholar PubMed PubMed Central

[19] Malik RA. Pathology of human diabetic neuropathy. Handb Clin Neurol. 2014;126:249–59.10.1016/B978-0-444-53480-4.00016-3Search in Google Scholar PubMed

[20] Mizisin AP, Shelton GD, Wagner S, Rusbridge C, Powell HC. Myelin splitting, Schwann cell injury and demyelination in feline diabetic neuropathy. Acta Neuropathol. 1998;95(2):171–4.10.1007/s004010050783Search in Google Scholar PubMed

[21] Naruse K. Schwann cells as crucial players in diabetic neuropathy. Adv Exp Med Biol. 2019;1190:345–56.10.1007/978-981-32-9636-7_22Search in Google Scholar PubMed

[22] Liu YP, Shao SJ, Guo HD. Schwann cells apoptosis is induced by high glucose in diabetic peripheral neuropathy. Life Sci. 2020;248:117459.10.1016/j.lfs.2020.117459Search in Google Scholar

[23] Zhang D, Chang S, Li X, Shi H, Jing B, Chen Z, et al. Therapeutic effect of paeoniflorin on chronic constriction injury of the sciatic nerve via the inhibition of Schwann cell apoptosis. Phytother Res. 2022;36(6):2572–82.10.1002/ptr.7472Search in Google Scholar

[24] Belavgeni A, Maremonti F, Stadtmuller M, Bornstein SR, Linkermann A. Schwann cell necroptosis in diabetic neuropathy. Proc Natl Acad Sci U S A. 2022;119(17):e2204049119.10.1073/pnas.2204049119Search in Google Scholar

[25] Cheng YC, Chu LW, Chen JY, Hsieh SL, Chang YC, Dai ZK, et al. Loganin attenuates high glucose-induced schwann cells pyroptosis by inhibiting ROS generation and NLRP3 inflammasome activation. Cells. 2020;9(9):1948.10.3390/cells9091948Search in Google Scholar

[26] Choi SJ, Kim S, Lee WS, Kim DW, Kim CS, Oh SH. Autophagy dysfunction in a diabetic peripheral neuropathy model. Plast Reconstr Surg. 2023;151(2):355–64.10.1097/PRS.0000000000009844Search in Google Scholar

[27] Jaffey PB, Gelman BB. Increased vulnerability to demyelination in streptozotocin diabetic rats. J Comp Neurol. 1996;373(1):55–61.10.1002/(SICI)1096-9861(19960909)373:1<55::AID-CNE5>3.0.CO;2-CSearch in Google Scholar

[28] Jessen KR, Mirsky R. The origin and development of glial cells in peripheral nerves. Nat Rev Neurosci. 2005;6(9):671–82.10.1038/nrn1746Search in Google Scholar

[29] Dixon SJ, Lemberg KM, Lamprecht MR, Skouta R, Zaitsev EM, Gleason CE, et al. Ferroptosis: An iron-dependent form of nonapoptotic cell death. Cell. 2012;149(5):1060–72.10.1016/j.cell.2012.03.042Search in Google Scholar

[30] Ren JX, Sun X, Yan XL, Guo ZN, Yang Y. Ferroptosis in neurological diseases. Front Cell Neurosci. 2020;14:218.10.3389/fncel.2020.00218Search in Google Scholar

[31] Chang B, Guan H, Wang X, Chen Z, Zhu W, Wei X, et al. Cox4i2 triggers an increase in reactive oxygen species, leading to ferroptosis and apoptosis in HHV7 infected Schwann cells. Front Mol Biosci. 2021;8:660072.10.3389/fmolb.2021.660072Search in Google Scholar

[32] Gao D, Huang Y, Sun X, Yang J, Chen J, He J. Overexpression of c-Jun inhibits erastin-induced ferroptosis in Schwann cells and promotes repair of facial nerve function. J Cell Mol Med. 2022;26(8):2191–204.10.1111/jcmm.17241Search in Google Scholar PubMed PubMed Central

[33] Tonelli C, Chio IIC, Tuveson DA. Transcriptional regulation by Nrf2. Antioxid Redox Signal. 2018;29(17):1727–45.10.1089/ars.2017.7342Search in Google Scholar PubMed PubMed Central

[34] Pasupuleti VR, Arigela CS, Gan SH, Salam SKN, Krishnan KT, Rahman NA, et al. A review on oxidative stress, diabetic complications, and the roles of honey polyphenols. Oxid Med Cell Longev. 2020;2020:8878172.10.1155/2020/8878172Search in Google Scholar PubMed PubMed Central

[35] Kumar A, Mittal R. Nrf2: A potential therapeutic target for diabetic neuropathy. Inflammopharmacology. 2017;25(4):393–402.10.1007/s10787-017-0339-ySearch in Google Scholar PubMed

[36] Gupta A, Behl T, Sehgal A, Bhatia S, Jaglan D, Bungau S. Therapeutic potential of Nrf-2 pathway in the treatment of diabetic neuropathy and nephropathy. Mol Biol Rep. 2021;48(3):2761–74.10.1007/s11033-021-06257-5Search in Google Scholar PubMed

[37] Shakya A, McKee NW, Dodson M, Chapman E, Zhang DD. Anti-ferroptotic effects of Nrf2: Beyond the antioxidant response. Mol Cell. 2023;46(3):165–75.10.14348/molcells.2023.0005Search in Google Scholar PubMed PubMed Central

Received: 2023-04-27
Revised: 2023-08-16
Accepted: 2023-09-01
Published Online: 2023-10-09

© 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. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
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  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
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  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
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  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
https://doi.org/10.1515/med-2023-0809
Keywords for this article
ferroptosis; diabetic peripheral neuropathy; Schwann cell; NRF2 signaling pathway
Creative Commons
BY 4.0

Articles in the same Issue

  1. Research Articles
  2. Exosomes derived from mesenchymal stem cells overexpressing miR-210 inhibits neuronal inflammation and contribute to neurite outgrowth through modulating microglia polarization
  3. Current situation of acute ST-segment elevation myocardial infarction in a county hospital chest pain center during an epidemic of novel coronavirus pneumonia
  4. circ-IARS depletion inhibits the progression of non-small-cell lung cancer by circ-IARS/miR-1252-5p/HDGF ceRNA pathway
  5. circRNA ITGA7 restrains growth and enhances radiosensitivity by up-regulating SMAD4 in colorectal carcinoma
  6. WDR79 promotes aerobic glycolysis of pancreatic ductal adenocarcinoma (PDAC) by the suppression of SIRT4
  7. Up-regulation of collagen type V alpha 2 (COL5A2) promotes malignant phenotypes in gastric cancer cell via inducing epithelial–mesenchymal transition (EMT)
  8. Inhibition of TERC inhibits neural apoptosis and inflammation in spinal cord injury through Akt activation and p-38 inhibition via the miR-34a-5p/XBP-1 axis
  9. 3D-printed polyether-ether-ketone/n-TiO2 composite enhances the cytocompatibility and osteogenic differentiation of MC3T3-E1 cells by downregulating miR-154-5p
  10. Propofol-mediated circ_0000735 downregulation restrains tumor growth by decreasing integrin-β1 expression in non-small cell lung cancer
  11. PVT1/miR-16/CCND1 axis regulates gastric cancer progression
  12. Silencing of circ_002136 sensitizes gastric cancer to paclitaxel by targeting the miR-16-5p/HMGA1 axis
  13. Short-term outcomes after simultaneous gastrectomy plus cholecystectomy in gastric cancer: A pooling up analysis
  14. SCARA5 inhibits oral squamous cell carcinoma via inactivating the STAT3 and PI3K/AKT signaling pathways
  15. Molecular mechanism by which the Notch signaling pathway regulates autophagy in a rat model of pulmonary fibrosis in pigeon breeder’s lung
  16. lncRNA TPT1-AS1 promotes cell migration and invasion in esophageal squamous-cell carcinomas by regulating the miR-26a/HMGA1 axis
  17. SIRT1/APE1 promotes the viability of gastric cancer cells by inhibiting p53 to suppress ferroptosis
  18. Glycoprotein non-metastatic melanoma B interacts with epidermal growth factor receptor to regulate neural stem cell survival and differentiation
  19. Treatments for brain metastases from EGFR/ALK-negative/unselected NSCLC: A network meta-analysis
  20. Association of osteoporosis and skeletal muscle loss with serum type I collagen carboxyl-terminal peptide β glypeptide: A cross-sectional study in elder Chinese population
  21. circ_0000376 knockdown suppresses non-small cell lung cancer cell tumor properties by the miR-545-3p/PDPK1 pathway
  22. Delivery in a vertical birth chair supported by freedom of movement during labor: A randomized control trial
  23. UBE2J1 knockdown promotes cell apoptosis in endometrial cancer via regulating PI3K/AKT and MDM2/p53 signaling
  24. Metabolic resuscitation therapy in critically ill patients with sepsis and septic shock: A pilot prospective randomized controlled trial
  25. Lycopene ameliorates locomotor activity and urinary frequency induced by pelvic venous congestion in rats
  26. UHRF1-induced connexin26 methylation is involved in hearing damage triggered by intermittent hypoxia in neonatal rats
  27. LINC00511 promotes melanoma progression by targeting miR-610/NUCB2
  28. Ultra-high-performance liquid chromatography-tandem mass spectrometry analysis of serum metabolomic characteristics in people with different vitamin D levels
  29. Role of Jumonji domain-containing protein D3 and its inhibitor GSK-J4 in Hashimoto’s thyroiditis
  30. circ_0014736 induces GPR4 to regulate the biological behaviors of human placental trophoblast cells through miR-942-5p in preeclampsia
  31. Monitoring of sirolimus in the whole blood samples from pediatric patients with lymphatic anomalies
  32. Effects of osteogenic growth peptide C-terminal pentapeptide and its analogue on bone remodeling in an osteoporosis rat model
  33. A novel autophagy-related long non-coding RNAs signature predicting progression-free interval and I-131 therapy benefits in papillary thyroid carcinoma
  34. WGCNA-based identification of potential targets and pathways in response to treatment in locally advanced breast cancer patients
  35. Radiomics model using preoperative computed tomography angiography images to differentiate new from old emboli of acute lower limb arterial embolism
  36. Dysregulated lncRNAs are involved in the progress of myocardial infarction by constructing regulatory networks
  37. Single-arm trial to evaluate the efficacy and safety of baclofen in treatment of intractable hiccup caused by malignant tumor chemotherapy
  38. Genetic polymorphisms of MRPS30-DT and NINJ2 may influence lung cancer risk
  39. Efficacy of immune checkpoint inhibitors in patients with KRAS-mutant advanced non-small cell lung cancer: A retrospective analysis
  40. Pyroptosis-based risk score predicts prognosis and drug sensitivity in lung adenocarcinoma
  41. Upregulation of lncRNA LANCL1-AS1 inhibits the progression of non-small-cell lung cancer via the miR-3680-3p/GMFG axis
  42. CircRANBP17 modulated KDM1A to regulate neuroblastoma progression by sponging miR-27b-3p
  43. Exosomal miR-93-5p regulated the progression of osteoarthritis by targeting ADAMTS9
  44. Downregulation of RBM17 enhances cisplatin sensitivity and inhibits cell invasion in human hypopharyngeal cancer cells
  45. HDAC5-mediated PRAME regulates the proliferation, migration, invasion, and EMT of laryngeal squamous cell carcinoma via the PI3K/AKT/mTOR signaling pathway
  46. The association between sleep duration, quality, and nonalcoholic fatty liver disease: A cross-sectional study
  47. Myostatin silencing inhibits podocyte apoptosis in membranous nephropathy through Smad3/PKA/NOX4 signaling pathway
  48. A novel long noncoding RNA AC125257.1 facilitates colorectal cancer progression by targeting miR-133a-3p/CASC5 axis
  49. Impact of omicron wave and associated control measures in Shanghai on health management and psychosocial well-being of patients with chronic conditions
  50. Clinicopathological characteristics and prognosis of young patients aged ≤45 years old with non-small cell lung cancer
  51. TMT-based comprehensive proteomic profiling identifies serum prognostic signatures of acute myeloid leukemia
  52. The dose limits of teeth protection for patients with nasopharyngeal carcinoma undergoing radiotherapy based on the early oral health-related quality of life
  53. miR-30b-5p targeting GRIN2A inhibits hippocampal damage in epilepsy
  54. Long non-coding RNA AL137789.1 promoted malignant biological behaviors and immune escape of pancreatic carcinoma cells
  55. IRF6 and FGF1 polymorphisms in non-syndromic cleft lip with or without cleft palate in the Polish population
  56. Comprehensive analysis of the role of SFXN family in breast cancer
  57. Efficacy of bronchoscopic intratumoral injection of endostar and cisplatin in lung squamous cell carcinoma patients underwent conventional chemoradiotherapy
  58. Silencing of long noncoding RNA MIAT inhibits the viability and proliferation of breast cancer cells by promoting miR-378a-5p expression
  59. AG1024, an IGF-1 receptor inhibitor, ameliorates renal injury in rats with diabetic nephropathy via the SOCS/JAK2/STAT pathway
  60. Downregulation of KIAA1199 alleviated the activation, proliferation, and migration of hepatic stellate cells by the inhibition of epithelial–mesenchymal transition
  61. Exendin-4 regulates the MAPK and WNT signaling pathways to alleviate the osteogenic inhibition of periodontal ligament stem cells in a high glucose environment
  62. Inhibition of glycolysis represses the growth and alleviates the endoplasmic reticulum stress of breast cancer cells by regulating TMTC3
  63. The function of lncRNA EMX2OS/miR-653-5p and its regulatory mechanism in lung adenocarcinoma
  64. Tectorigenin alleviates the apoptosis and inflammation in spinal cord injury cell model through inhibiting insulin-like growth factor-binding protein 6
  65. Ultrasound examination supporting CT or MRI in the evaluation of cervical lymphadenopathy in patients with irradiation-treated head and neck cancer
  66. F-box and WD repeat domain containing 7 inhibits the activation of hepatic stellate cells by degrading delta-like ligand 1 to block Notch signaling pathway
  67. Knockdown of circ_0005615 enhances the radiosensitivity of colorectal cancer by regulating the miR-665/NOTCH1 axis
  68. Long noncoding RNA Mhrt alleviates angiotensin II-induced cardiac hypertrophy phenotypes by mediating the miR-765/Wnt family member 7B pathway
  69. Effect of miR-499-5p/SOX6 axis on atrial fibrosis in rats with atrial fibrillation
  70. Cholesterol induces inflammation and reduces glucose utilization
  71. circ_0004904 regulates the trophoblast cell in preeclampsia via miR-19b-3p/ARRDC3 axis
  72. NECAB3 promotes the migration and invasion of liver cancer cells through HIF-1α/RIT1 signaling pathway
  73. The poor performance of cardiovascular risk scores in identifying patients with idiopathic inflammatory myopathies at high cardiovascular risk
  74. miR-2053 inhibits the growth of ovarian cancer cells by downregulating SOX4
  75. Nucleophosmin 1 associating with engulfment and cell motility protein 1 regulates hepatocellular carcinoma cell chemotaxis and metastasis
  76. α-Hederin regulates macrophage polarization to relieve sepsis-induced lung and liver injuries in mice
  77. Changes of microbiota level in urinary tract infections: A meta-analysis
  78. Identification of key enzalutamide-resistance-related genes in castration-resistant prostate cancer and verification of RAD51 functions
  79. Falls during oxaliplatin-based chemotherapy for gastrointestinal malignancies – (lessons learned from) a prospective study
  80. Outcomes of low-risk birth care during the Covid-19 pandemic: A cohort study from a tertiary care center in Lithuania
  81. Vitamin D protects intestines from liver cirrhosis-induced inflammation and oxidative stress by inhibiting the TLR4/MyD88/NF-κB signaling pathway
  82. Integrated transcriptome analysis identifies APPL1/RPS6KB2/GALK1 as immune-related metastasis factors in breast cancer
  83. Genomic analysis of immunogenic cell death-related subtypes for predicting prognosis and immunotherapy outcomes in glioblastoma multiforme
  84. Circular RNA Circ_0038467 promotes the maturation of miRNA-203 to increase lipopolysaccharide-induced apoptosis of chondrocytes
  85. An economic evaluation of fine-needle cytology as the primary diagnostic tool in the diagnosis of lymphadenopathy
  86. Midazolam impedes lung carcinoma cell proliferation and migration via EGFR/MEK/ERK signaling pathway
  87. Network pharmacology combined with molecular docking and experimental validation to reveal the pharmacological mechanism of naringin against renal fibrosis
  88. PTPN12 down-regulated by miR-146b-3p gene affects the malignant progression of laryngeal squamous cell carcinoma
  89. miR-141-3p accelerates ovarian cancer progression and promotes M2-like macrophage polarization by targeting the Keap1-Nrf2 pathway
  90. lncRNA OIP5-AS1 attenuates the osteoarthritis progression in IL-1β-stimulated chondrocytes
  91. Overexpression of LINC00607 inhibits cell growth and aggressiveness by regulating the miR-1289/EFNA5 axis in non-small-cell lung cancer
  92. Subjective well-being in informal caregivers during the COVID-19 pandemic
  93. Nrf2 protects against myocardial ischemia-reperfusion injury in diabetic rats by inhibiting Drp1-mediated mitochondrial fission
  94. Unfolded protein response inhibits KAT2B/MLKL-mediated necroptosis of hepatocytes by promoting BMI1 level to ubiquitinate KAT2B
  95. Bladder cancer screening: The new selection and prediction model
  96. circNFATC3 facilitated the progression of oral squamous cell carcinoma via the miR-520h/LDHA axis
  97. Prone position effect in intensive care patients with SARS-COV-2 pneumonia
  98. Clinical observation on the efficacy of Tongdu Tuina manipulation in the treatment of primary enuresis in children
  99. Dihydroartemisinin ameliorates cerebral I/R injury in rats via regulating VWF and autophagy-mediated SIRT1/FOXO1 pathway
  100. Knockdown of circ_0113656 assuages oxidized low-density lipoprotein-induced vascular smooth muscle cell injury through the miR-188-3p/IGF2 pathway
  101. Low Ang-(1–7) and high des-Arg9 bradykinin serum levels are correlated with cardiovascular risk factors in patients with COVID-19
  102. Effect of maternal age and body mass index on induction of labor with oral misoprostol for premature rupture of membrane at term: A retrospective cross-sectional study
  103. Potential protective effects of Huanglian Jiedu Decoction against COVID-19-associated acute kidney injury: A network-based pharmacological and molecular docking study
  104. Clinical significance of serum MBD3 detection in girls with central precocious puberty
  105. Clinical features of varicella-zoster virus caused neurological diseases detected by metagenomic next-generation sequencing
  106. Collagen treatment of complex anorectal fistula: 3 years follow-up
  107. LncRNA CASC15 inhibition relieves renal fibrosis in diabetic nephropathy through down-regulating SP-A by sponging to miR-424
  108. Efficacy analysis of empirical bismuth quadruple therapy, high-dose dual therapy, and resistance gene-based triple therapy as a first-line Helicobacter pylori eradication regimen – An open-label, randomized trial
  109. SMOC2 plays a role in heart failure via regulating TGF-β1/Smad3 pathway-mediated autophagy
  110. A prospective cohort study of the impact of chronic disease on fall injuries in middle-aged and older adults
  111. circRNA THBS1 silencing inhibits the malignant biological behavior of cervical cancer cells via the regulation of miR-543/HMGB2 axis
  112. hsa_circ_0000285 sponging miR-582-3p promotes neuroblastoma progression by regulating the Wnt/β-catenin signaling pathway
  113. Long non-coding RNA GNAS-AS1 knockdown inhibits proliferation and epithelial–mesenchymal transition of lung adenocarcinoma cells via the microRNA-433-3p/Rab3A axis
  114. lncRNA UCA1 regulates miR-132/Lrrfip1 axis to promote vascular smooth muscle cell proliferation
  115. Twenty-four-color full spectrum flow cytometry panel for minimal residual disease detection in acute myeloid leukemia
  116. Hsa-miR-223-3p participates in the process of anthracycline-induced cardiomyocyte damage by regulating NFIA gene
  117. Anti-inflammatory effect of ApoE23 on Salmonella typhimurium-induced sepsis in mice
  118. Analysis of somatic mutations and key driving factors of cervical cancer progression
  119. Hsa_circ_0028007 regulates the progression of nasopharyngeal carcinoma through the miR-1179/SQLE axis
  120. Variations in sexual function after laparoendoscopic single-site hysterectomy in women with benign gynecologic diseases
  121. Effects of pharmacological delay with roxadustat on multi-territory perforator flap survival in rats
  122. Analysis of heroin effects on calcium channels in rat cardiomyocytes based on transcriptomics and metabolomics
  123. Risk factors of recurrent bacterial vaginosis among women of reproductive age: A cross-sectional study
  124. Alkbh5 plays indispensable roles in maintaining self-renewal of hematopoietic stem cells
  125. Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients
  126. Correlation between microvessel maturity and ISUP grades assessed using contrast-enhanced transrectal ultrasonography in prostate cancer
  127. The protective effect of caffeic acid phenethyl ester in the nephrotoxicity induced by α-cypermethrin
  128. Norepinephrine alleviates cyclosporin A-induced nephrotoxicity by enhancing the expression of SFRP1
  129. Effect of RUNX1/FOXP3 axis on apoptosis of T and B lymphocytes and immunosuppression in sepsis
  130. The function of Foxp1 represses β-adrenergic receptor transcription in the occurrence and development of bladder cancer through STAT3 activity
  131. Risk model and validation of carbapenem-resistant Klebsiella pneumoniae infection in patients with cerebrovascular disease in the ICU
  132. Calycosin protects against chronic prostatitis in rats via inhibition of the p38MAPK/NF-κB pathway
  133. Pan-cancer analysis of the PDE4DIP gene with potential prognostic and immunotherapeutic values in multiple cancers including acute myeloid leukemia
  134. The safety and immunogenicity to inactivated COVID-19 vaccine in patients with hyperlipemia
  135. Circ-UBR4 regulates the proliferation, migration, inflammation, and apoptosis in ox-LDL-induced vascular smooth muscle cells via miR-515-5p/IGF2 axis
  136. Clinical characteristics of current COVID-19 rehabilitation outpatients in China
  137. Luteolin alleviates ulcerative colitis in rats via regulating immune response, oxidative stress, and metabolic profiling
  138. miR-199a-5p inhibits aortic valve calcification by targeting ATF6 and GRP78 in valve interstitial cells
  139. The application of iliac fascia space block combined with esketamine intravenous general anesthesia in PFNA surgery of the elderly: A prospective, single-center, controlled trial
  140. Elevated blood acetoacetate levels reduce major adverse cardiac and cerebrovascular events risk in acute myocardial infarction
  141. The effects of progesterone on the healing of obstetric anal sphincter damage in female rats
  142. Identification of cuproptosis-related genes for predicting the development of prostate cancer
  143. Lumican silencing ameliorates β-glycerophosphate-mediated vascular smooth muscle cell calcification by attenuating the inhibition of APOB on KIF2C activity
  144. Targeting PTBP1 blocks glutamine metabolism to improve the cisplatin sensitivity of hepatocarcinoma cells through modulating the mRNA stability of glutaminase
  145. A single center prospective study: Influences of different hip flexion angles on the measurement of lumbar spine bone mineral density by dual energy X-ray absorptiometry
  146. Clinical analysis of AN69ST membrane continuous venous hemofiltration in the treatment of severe sepsis
  147. Antibiotics therapy combined with probiotics administered intravaginally for the treatment of bacterial vaginosis: A systematic review and meta-analysis
  148. Construction of a ceRNA network to reveal a vascular invasion associated prognostic model in hepatocellular carcinoma
  149. A pan-cancer analysis of STAT3 expression and genetic alterations in human tumors
  150. A prognostic signature based on seven T-cell-related cell clustering genes in bladder urothelial carcinoma
  151. Pepsin concentration in oral lavage fluid of rabbit reflux model constructed by dilating the lower esophageal sphincter
  152. The antihypertensive felodipine shows synergistic activity with immune checkpoint blockade and inhibits tumor growth via NFAT1 in LUSC
  153. Tanshinone IIA attenuates valvular interstitial cells’ calcification induced by oxidized low density lipoprotein via reducing endoplasmic reticulum stress
  154. AS-IV enhances the antitumor effects of propofol in NSCLC cells by inhibiting autophagy
  155. Establishment of two oxaliplatin-resistant gallbladder cancer cell lines and comprehensive analysis of dysregulated genes
  156. Trial protocol: Feasibility of neuromodulation with connectivity-guided intermittent theta-burst stimulation for improving cognition in multiple sclerosis
  157. LncRNA LINC00592 mediates the promoter methylation of WIF1 to promote the development of bladder cancer
  158. Factors associated with gastrointestinal dysmotility in critically ill patients
  159. Mechanisms by which spinal cord stimulation intervenes in atrial fibrillation: The involvement of the endothelin-1 and nerve growth factor/p75NTR pathways
  160. Analysis of two-gene signatures and related drugs in small-cell lung cancer by bioinformatics
  161. Silencing USP19 alleviates cigarette smoke extract-induced mitochondrial dysfunction in BEAS-2B cells by targeting FUNDC1
  162. Menstrual irregularities associated with COVID-19 vaccines among women in Saudi Arabia: A survey during 2022
  163. Ferroptosis involves in Schwann cell death in diabetic peripheral neuropathy
  164. The effect of AQP4 on tau protein aggregation in neurodegeneration and persistent neuroinflammation after cerebral microinfarcts
  165. Activation of UBEC2 by transcription factor MYBL2 affects DNA damage and promotes gastric cancer progression and cisplatin resistance
  166. Analysis of clinical characteristics in proximal and distal reflux monitoring among patients with gastroesophageal reflux disease
  167. Exosomal circ-0020887 and circ-0009590 as novel biomarkers for the diagnosis and prediction of short-term adverse cardiovascular outcomes in STEMI patients
  168. Upregulated microRNA-429 confers endometrial stromal cell dysfunction by targeting HIF1AN and regulating the HIF1A/VEGF pathway
  169. Bibliometrics and knowledge map analysis of ultrasound-guided regional anesthesia
  170. Knockdown of NUPR1 inhibits angiogenesis in lung cancer through IRE1/XBP1 and PERK/eIF2α/ATF4 signaling pathways
  171. D-dimer trends predict COVID-19 patient’s prognosis: A retrospective chart review study
  172. WTAP affects intracranial aneurysm progression by regulating m6A methylation modification
  173. Using of endoscopic polypectomy in patients with diagnosed malignant colorectal polyp – The cross-sectional clinical study
  174. Anti-S100A4 antibody administration alleviates bronchial epithelial–mesenchymal transition in asthmatic mice
  175. Prognostic evaluation of system immune-inflammatory index and prognostic nutritional index in double expressor diffuse large B-cell lymphoma
  176. Prevalence and antibiogram of bacteria causing urinary tract infection among patients with chronic kidney disease
  177. Reactive oxygen species within the vaginal space: An additional promoter of cervical intraepithelial neoplasia and uterine cervical cancer development?
  178. Identification of disulfidptosis-related genes and immune infiltration in lower-grade glioma
  179. A new technique for uterine-preserving pelvic organ prolapse surgery: Laparoscopic rectus abdominis hysteropexy for uterine prolapse by comparing with traditional techniques
  180. Self-isolation of an Italian long-term care facility during COVID-19 pandemic: A comparison study on care-related infectious episodes
  181. A comparative study on the overlapping effects of clinically applicable therapeutic interventions in patients with central nervous system damage
  182. Low intensity extracorporeal shockwave therapy for chronic pelvic pain syndrome: Long-term follow-up
  183. The diagnostic accuracy of touch imprint cytology for sentinel lymph node metastases of breast cancer: An up-to-date meta-analysis of 4,073 patients
  184. Mortality associated with Sjögren’s syndrome in the United States in the 1999–2020 period: A multiple cause-of-death study
  185. CircMMP11 as a prognostic biomarker mediates miR-361-3p/HMGB1 axis to accelerate malignant progression of hepatocellular carcinoma
  186. Analysis of the clinical characteristics and prognosis of adult de novo acute myeloid leukemia (none APL) with PTPN11 mutations
  187. KMT2A maintains stemness of gastric cancer cells through regulating Wnt/β-catenin signaling-activated transcriptional factor KLF11
  188. Evaluation of placental oxygenation by near-infrared spectroscopy in relation to ultrasound maturation grade in physiological term pregnancies
  189. The role of ultrasonographic findings for PIK3CA-mutated, hormone receptor-positive, human epidermal growth factor receptor-2-negative breast cancer
  190. Construction of immunogenic cell death-related molecular subtypes and prognostic signature in colorectal cancer
  191. Long-term prognostic value of high-sensitivity cardiac troponin-I in patients with idiopathic dilated cardiomyopathy
  192. Establishing a novel Fanconi anemia signaling pathway-associated prognostic model and tumor clustering for pediatric acute myeloid leukemia patients
  193. Integrative bioinformatics analysis reveals STAT2 as a novel biomarker of inflammation-related cardiac dysfunction in atrial fibrillation
  194. Adipose-derived stem cells repair radiation-induced chronic lung injury via inhibiting TGF-β1/Smad 3 signaling pathway
  195. Real-world practice of idiopathic pulmonary fibrosis: Results from a 2000–2016 cohort
  196. lncRNA LENGA sponges miR-378 to promote myocardial fibrosis in atrial fibrillation
  197. Diagnostic value of urinary Tamm-Horsfall protein and 24 h urine osmolality for recurrent calcium oxalate stones of the upper urinary tract: Cross-sectional study
  198. The value of color Doppler ultrasonography combined with serum tumor markers in differential diagnosis of gastric stromal tumor and gastric cancer
  199. The spike protein of SARS-CoV-2 induces inflammation and EMT of lung epithelial cells and fibroblasts through the upregulation of GADD45A
  200. Mycophenolate mofetil versus cyclophosphamide plus in patients with connective tissue disease-associated interstitial lung disease: Efficacy and safety analysis
  201. MiR-1278 targets CALD1 and suppresses the progression of gastric cancer via the MAPK pathway
  202. Metabolomic analysis of serum short-chain fatty acid concentrations in a mouse of MPTP-induced Parkinson’s disease after dietary supplementation with branched-chain amino acids
  203. Cimifugin inhibits adipogenesis and TNF-α-induced insulin resistance in 3T3-L1 cells
  204. Predictors of gastrointestinal complaints in patients on metformin therapy
  205. Prescribing patterns in patients with chronic obstructive pulmonary disease and atrial fibrillation
  206. A retrospective analysis of the effect of latent tuberculosis infection on clinical pregnancy outcomes of in vitro fertilization–fresh embryo transferred in infertile women
  207. Appropriateness and clinical outcomes of short sustained low-efficiency dialysis: A national experience
  208. miR-29 regulates metabolism by inhibiting JNK-1 expression in non-obese patients with type 2 diabetes mellitus and NAFLD
  209. Clinical features and management of lymphoepithelial cyst
  210. Serum VEGF, high-sensitivity CRP, and cystatin-C assist in the diagnosis of type 2 diabetic retinopathy complicated with hyperuricemia
  211. ENPP1 ameliorates vascular calcification via inhibiting the osteogenic transformation of VSMCs and generating PPi
  212. Significance of monitoring the levels of thyroid hormone antibodies and glucose and lipid metabolism antibodies in patients suffer from type 2 diabetes
  213. The causal relationship between immune cells and different kidney diseases: A Mendelian randomization study
  214. Interleukin 33, soluble suppression of tumorigenicity 2, interleukin 27, and galectin 3 as predictors for outcome in patients admitted to intensive care units
  215. Identification of diagnostic immune-related gene biomarkers for predicting heart failure after acute myocardial infarction
  216. Long-term administration of probiotics prevents gastrointestinal mucosal barrier dysfunction in septic mice partly by upregulating the 5-HT degradation pathway
  217. miR-192 inhibits the activation of hepatic stellate cells by targeting Rictor
  218. Diagnostic and prognostic value of MR-pro ADM, procalcitonin, and copeptin in sepsis
  219. Review Articles
  220. Prenatal diagnosis of fetal defects and its implications on the delivery mode
  221. Electromagnetic fields exposure on fetal and childhood abnormalities: Systematic review and meta-analysis
  222. Characteristics of antibiotic resistance mechanisms and genes of Klebsiella pneumoniae
  223. Saddle pulmonary embolism in the setting of COVID-19 infection: A systematic review of case reports and case series
  224. Vitamin C and epigenetics: A short physiological overview
  225. Ebselen: A promising therapy protecting cardiomyocytes from excess iron in iron-overloaded thalassemia patients
  226. Aspirin versus LMWH for VTE prophylaxis after orthopedic surgery
  227. Mechanism of rhubarb in the treatment of hyperlipidemia: A recent review
  228. Surgical management and outcomes of traumatic global brachial plexus injury: A concise review and our center approach
  229. The progress of autoimmune hepatitis research and future challenges
  230. METTL16 in human diseases: What should we do next?
  231. New insights into the prevention of ureteral stents encrustation
  232. VISTA as a prospective immune checkpoint in gynecological malignant tumors: A review of the literature
  233. Case Reports
  234. Mycobacterium xenopi infection of the kidney and lymph nodes: A case report
  235. Genetic mutation of SLC6A20 (c.1072T > C) in a family with nephrolithiasis: A case report
  236. Chronic hepatitis B complicated with secondary hemochromatosis was cured clinically: A case report
  237. Liver abscess complicated with multiple organ invasive infection caused by hematogenous disseminated hypervirulent Klebsiella pneumoniae: A case report
  238. Urokinase-based lock solutions for catheter salvage: A case of an upcoming kidney transplant recipient
  239. Two case reports of maturity-onset diabetes of the young type 3 caused by the hepatocyte nuclear factor 1α gene mutation
  240. Immune checkpoint inhibitor-related pancreatitis: What is known and what is not
  241. Does total hip arthroplasty result in intercostal nerve injury? A case report and literature review
  242. Clinicopathological characteristics and diagnosis of hepatic sinusoidal obstruction syndrome caused by Tusanqi – Case report and literature review
  243. Synchronous triple primary gastrointestinal malignant tumors treated with laparoscopic surgery: A case report
  244. CT-guided percutaneous microwave ablation combined with bone cement injection for the treatment of transverse metastases: A case report
  245. Malignant hyperthermia: Report on a successful rescue of a case with the highest temperature of 44.2°C
  246. Anesthetic management of fetal pulmonary valvuloplasty: A case report
  247. Rapid Communication
  248. Impact of COVID-19 lockdown on glycemic levels during pregnancy: A retrospective analysis
  249. Erratum
  250. Erratum to “Inhibition of miR-21 improves pulmonary vascular responses in bronchopulmonary dysplasia by targeting the DDAH1/ADMA/NO pathway”
  251. Erratum to: “Fer exacerbates renal fibrosis and can be targeted by miR-29c-3p”
  252. Retraction
  253. Retraction of “Study to compare the effect of casirivimab and imdevimab, remdesivir, and favipiravir on progression and multi-organ function of hospitalized COVID-19 patients”
  254. Retraction of “circ_0062491 alleviates periodontitis via the miR-142-5p/IGF1 axis”
  255. Retraction of “miR-223-3p alleviates TGF-β-induced epithelial-mesenchymal transition and extracellular matrix deposition by targeting SP3 in endometrial epithelial cells”
  256. Retraction of “SLCO4A1-AS1 mediates pancreatic cancer development via miR-4673/KIF21B axis”
  257. Retraction of “circRNA_0001679/miR-338-3p/DUSP16 axis aggravates acute lung injury”
  258. Retraction of “lncRNA ACTA2-AS1 inhibits malignant phenotypes of gastric cancer cells”
  259. Special issue Linking Pathobiological Mechanisms to Clinical Application for cardiovascular diseases
  260. Effect of cardiac rehabilitation therapy on depressed patients with cardiac insufficiency after cardiac surgery
  261. Special issue The evolving saga of RNAs from bench to bedside - Part I
  262. FBLIM1 mRNA is a novel prognostic biomarker and is associated with immune infiltrates in glioma
  263. Special Issue Computational Intelligence Methodologies Meets Recurrent Cancers - Part III
  264. Development of a machine learning-based signature utilizing inflammatory response genes for predicting prognosis and immune microenvironment in ovarian cancer
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