Startseite Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway
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Nrf3 alleviates oxidative stress and promotes the survival of colon cancer cells by activating AKT/BCL-2 signal pathway

  • Bi-Qing Cai , Wan-Meng Chen , Meng-Wei Chen , Ya-Hui Chen und Jian-Cai Tang EMAIL logo
Veröffentlicht/Copyright: 23. November 2023
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Open Life Sciences
Aus der Zeitschrift Open Life Sciences Band 18 Heft 1

Abstract

Oxidative stress is closely linked to tumor initiation and development, conferring a survival advantage to cancer cells. Therefore, understanding cancer cells’ antioxidant molecular mechanisms is crucial to cancer therapy. In this study, we discovered that H2O2-induced oxidative stress increased Nrf3 expression in colon cancer cells. Overexpression of Nrf3 decreased H2O2-mediated cytotoxicity and apoptosis. Furthermore, Nrf3 reduced reactive oxygen species levels and malondialdehyde concentrations after H2O2 treatment. Mechanistically, H2O2-mediated cell apoptosis involves multiple signaling proteins, including Akt, bcl-2, JNK, and p38. An increase in Nrf3 expression in colon cancer cells treated with H2O2 partly reversed Akt/Bcl-2 inhibition, whereas it decreased activation of p38 and JNK. In addition, we found that increasing Nrf3 decreased stress-associated chemical-induced cell death, resulting in drug resistance. According to these results, Nrf3 is critical for drug resistance and oxidant adaptation.

Keywords: Nrf3; oxidative stress; colon cancer; Akt/Bcl-2; cell proliferation; apoptosis

1 Introduction

A colorectal cancer diagnosis is the third most common cancer in the world and the fourth leading cause of cancer-related death, responsible for 9.2% of all deaths [1]. Over the last three decades, there has been a consistent rise [2] in the prevalence of early-onset CRC among individuals under the age of 50. Colorectal cancer [3] is currently treated primarily with surgery, radiotherapy, and chemotherapy. Despite significant progress in treatment modalities and management strategies, survival rates of patients have not improved significantly. Consequently, further investigation of colorectal cancer molecular mechanisms and biological behaviors is essential to develop new therapeutic strategies.

Several factors [4] are responsible for the development of colorectal cancer, such as genetic factors, gene mutations, and abnormal signal pathway activation, Oxidative stress [5] induced DNA damage and protein conformations such as DNA single-strand or double-strand breaks, and protein misfolding, which is regarded as a key factor for the initiation and progression of colorectal cancer. Oxidative stress [6] refers to increased intracellular reactive oxygen species (ROS) levels due to an imbalance between oxidants and antioxidants. The elevated levels of ROS observed in cancer cells compared to normal cells can be attributed, in part, to augmented metabolic activity and impaired mitochondrial function [7]. The role of ROS [8,9] in tumor initiation and development is two sided. Low and intermediate ROS levels promote cancer cell proliferation and survival, whereas excessive ROS induces cancer cell apoptosis. The varying levels of ROS play a crucial role in the formulation of effective anticancer approaches aimed at modulating ROS levels. In response to oxidative stress, cancer cells enhance their antioxidant capacity as a means of adapting, consequently leading to the development of drug resistance [10]. However, several drugs [11,12,13], such as cisplatin, 5-Fu, bleomycin, induce cancer cell death by increasing ROS levels. Thus, understanding the mechanisms underlying oxidative adaptation may be critical for cancer therapy.

Nuclear factor erythroid 2-like-3 (Nrf3) [14] belongs to the cap ‘n’ collar family, together with Nrf1, Nrf2, Bach1, and Bach2, all of which have a similar domain. Several reports [15,16,17] have shown that Nrf2 plays a critical role in tumor initiation and development. Both Nrf3 and Nrf2 [18] exhibit identical characteristics to the Neh1L, Neh3L, Neh5L, and Neh6L sequences found in the source’s structural sequence. Additionally, Nrf2 possesses homologous regions known as Neh2 and Neh4. The N-terminal region of Nrf3 is 150 amino acids longer than that of Nrf2, and this sequence includes an endoplasmic reticulum anchoring signal, resulting in distinct subcellular localization compared to Nrf2. However, Nrf3’s role in cancer remains elusive, partly because Nrf3-deficient mice exhibit no evident abnormalities [14]. Recently, reports [19,20,21] have displayed that Nrf3 may also be involved in tumor initiation, progression, and oxidative stress. Multiple types of cancer cells exhibit Nrf3 influence proliferation, survival, migration, and chemoresistance of cancers such as breast cancer [22], colon cancer [20,23], and hepatocellular carcinoma [24]. Nrf3 may also combine with the antioxidant response element (ARE) to promote antioxidant gene expression. Therefore, further exploration of the function of Nrf3 in oxidative stress may be significant for cancer therapy.

In the study, the role of Nrf3 in H2O2-induced oxidative stress colon cancer cells was investigated. As a result of H2O2, Nrf3 expression increased in a dose-dependent manner. Over-expression of Nrf3 upregulated colon cancer cell survival and decreased apoptosis under H2O2-induced oxidative stress. Furthermore, Nrf3 promoted the activation of Akt and Bcl-2, attenuating the activity of p38 and JNK. Interestingly, Nrf3 decreased 5-Fu inducing cell death. Based on these results, Nrf3 may play a crucial role in oxidant adaptation and provide a novel target for treating colon cancer.

2 Materials and methods

2.1 Cell culture and reagents

HCT116, HT29, and SW620 cells were purchased from CellBio Company (Shanghai, China) and cultured with RPMI‑1640 medium (Gibco; Thermo Fisher Scientific, Inc.), supplemented with 10% fetal bovine serum (FBS; cat. no. C04001-500; viva cell; Germany), in 5% CO2 at 37°C. Experiments employ cells that have undergone a maximum of five passages. The Cell Counting Kit-8 (CCK-8) was purchased from Beyotime (catalog number: C0038, Shanghai, China). The Cell Apoptosis Kit (catalog number: AD10-10, Kyushu, Japan) was purchased from Dojindo.

2.2 Chemicals and treatment

H2O2 (30%) was purchased from Sigma (catalog number: 7722-84-1), and 5-Fu was provided by the Selleck Company (catalog number: S1209). H2O2 (30%) was diluted with DMEM to final concentrations (200, 400, 600 μM), and 5-Fu was dissolved in DMSO to 100 mM stock solution. The compound 5-FU was subjected to dilution at various concentrations (1.5, 3, 6, 12, 24 μM) to administer treatment to cells over a duration of 12 h.

2.3 Construction of colon cancer cell line for stable Nrf3 overexpression and knock-down

The recombinant lentivirus for the overexpression of Nrf3 was purchased from Santa Cruz Biotechnology (catalog number: sc-404543-LAC). Two shRNA target sequences for Nrf3 were designed and inserted into the pLKO.1 vector. Recombinant lentiviruses were generated through co-transfecting shRNA plasmids. The Nrf3 shRNA interference target sequences were in accordance with our previous study [25].

A quantity of 2 × 105 HCT116 cells were initially placed in each well and allowed to grow until reaching 40% confluency. Alongside the complete medium, lentiviral particles were introduced at a final concentration of polybrene (5 µM). Following thorough mixing, the original medium was substituted, and infection was permitted for a duration of 24 h. Subsequently, the medium was replaced once more, and puromycin hydrochloride was introduced to facilitate screening for a period of 48 h. The impact of Nrf3 overexpression and knockdown was assessed through the utilization of western blotting.

2.4 CCK-8 assay

HCT116 and HCT116/Nrf3 cells were seeded into 96-well plates and cultured overnight. H2O2 (0, 200, 400, and 600 μM) and 5-FU (0, 15, 3, 6, 12, and 24 μM) were, respectively, applied to HCT116 and HCT116/Nrf3 cells for 12 h. A CCK-8 test was used to determine the viability of cells according to the manufacturer’s instructions.

2.5 Flow cytometry

HCT116 and HCT116/Nrf3 cells were seeded in 6-well plates at 4 × 105 cells/well. The cells were treated with different concentrations of H2O2 (0, 200, 400, and 600 μM) for 12 h. Cell apoptosis was determined using flow cytometry, according to the manufacturer’s instructions. Briefly, HCT116 or HCT116/Nrf3 cells were harvested by trypsin without EDTA. The cells were then resuspended in a binding buffer, which consisted of 2.5 µL AnnexinV FITC and 2.5 µL PI, and incubated for 30 min in the absence of light. The percentage of apoptotic cells was determined using a Beckman Flow Cytometer (Beckman Coulter, Inc.) employing a count model, and the data were analyzed using FlowJo software (Version 10.0; FlowJo LLC).

2.6 The determination of ROS levels and malondialdehyde (MDA) concentrations

Cells were seeded into six-well plates at a density of 5 × 105 cells/well. Subsequently, the cells were exposed to varying concentrations of H2O2 (200, 400, and 600 μM) for a duration of 12 h. The production of ROS in colon cancer cells was evaluated using 2′,7′-dichlorofluorescein diacetate (DCFH-DA; Beyotime, Shanghai, China, catalog number: S0033M). DCFH-DA was diluted with a serum-free medium at a ratio of 1:1,000, resulting in a final concentration of 10 μmol/L. The cell culture medium was then replaced with DCFH-DA solution, and the cells were incubated at 37°C for 20 min. Following incubation, the cells were washed three times with a serum-free medium. Flow cytometry (BD LS) was employed to analyze the levels of ROS.

Intracellular lipid peroxidation was assessed through the quantification of MDA concentration using a Lipid Peroxidation MDA Assay Kit (Jiancheng, Nanjing, China, catalog number: A003-1-2). Cells were subjected to various concentrations of H2O2 (200, 400, and 600 μM) for a duration of 12 h. Subsequently, a specific quantity of cells was collected and the lysate was incubated at 4°C for 2 h, followed by centrifugation at 12,000 rpm for 10 min to obtain the supernatant for subsequent analysis. Next, 0.2 mL of MDA detection working solution was added, and the mixture was thoroughly mixed before being heated to 100°C or boiled in a water bath for 15 min. The absorbance was then measured at 532 nm with a microplate reader. After the MDA content in the sample solution was calculated, it was normalized to the MDA content in the parental cell sample as the protein content per unit weight.

2.7 Western blotting

A six-well plate was plated with colon cancer cells and treated with H2O2. Then, the cells were collected, and total proteins were extracted by RIPA lysis buffer (Beyotime Institute of Biotechnology) and concentration was measured by BCA kit (Beyotime Institute of Biotechnology). For electrophoresis, 20 µg of protein samples were loaded in each lane and were separated using 10% SDS-PAGE gels. Then, the proteins in the gels were transferred onto PVDF membranes, which were then incubated in a blocking buffer (3% bovine serum albumin; Beijing Solarbio Science & Technology Co., Ltd.) for 1 h at room temperature. Next, membranes were blocked with primary antibodies at 4°C overnight, including anti-Nrf3 (cat. no. PA5-102015; 1:1,000; Thermo Fisher Scientific, Inc.), anti-phospho-Akt (S473) (cat. no. 4060; 1:1,000; Cell Signaling Technology, Inc.), anti-Akt (cat. no. 9272; 1:1,000; Cell Signaling Technology, Inc.), anti-Bcl-2 (cat. no. 4223S; 1:1,000; Cell Signaling Technology, Inc.), anti-P38 (cat. no. 14451; 1:1,000; Cell Signaling Technology, Inc.), anti-phospho-P38 (cat. no. 4511; 1:1,000; Cell Signaling Technology, Inc.), anti-JNK (cat. no. 9252; 1:1,000; Cell Signaling Technology, Inc.), anti-phospho-JNK (cat. no. 4668; 1:1,000; Cell Signaling Technology, Inc.), and anti-GAPDH (cat. no. AB0036; 1:5,000; Abways Technology) antibodies. The following day, the membranes were incubated with the relevant secondary antibody. Between and after incubation with the antibodies, membranes were washed with TBST. Signals were visualized using Immobilon ECL Ultra Western HRP (cat. no. WBULS0100, MilliporeSigma). The results were analyzed using a ChemiDoc XRS + Gel Imaging System (Bio-Rad Laboratories, Inc)

2.8 Statistical analysis

All data are presented as mean ± standard deviation. Comparisons between the two groups were made using Student’s t-tests. Three or more groups were compared using a one-way analysis of variance with Tukey’s post hoc test. Differences were considered statistically significant at P < 0.05. All experiments were repeated three times.

3 Results

3.1 H2O2-mediated oxidative stress increased the expression of Nrf3 in colon cancer cells

In the initial set of experiments, we examined the effect of Nrf3 expression induced by H2O2 in colon cancer cells. To address this, the cells were cultured in 6-well plates with a density of 5 × 105 cells/well and subsequently exposed to different concentrations of H2O2: 200, 400, and 600 μM. Following a 12-h incubation period at 37°C, the cells were collected and their total protein content was extracted. The expression of Nrf3 was assessed using Western blot analysis. The findings revealed a dose-dependent elevation in Nrf3 levels in HCT116, HT29, and SW620 cells upon exposure to H2O2 (Figure 1a–d). Notably, the most substantial increase in Nrf3 expression was observed in HCT116 cells treated with 400 μM H2O2. All experiments were repeated three times.

Figure 1 H2O2 upregulates Nrf3 expression. Colon cancer cells were subjected to various concentrations of H2O2 for a duration of 12 h. Following this, protein extraction was performed and Nrf3 expression was detected using Western blot analysis. (a) The expression of Nrf3 in HCT116 cells after H2O2 treatment. (b) The expression of Nrf3 in SW620 cells after H2O2 treatment. (c) The expression of Nrf3 in HT29 cells following H2O2 treatment. (d) The relative quantification of Nrf3 expression (**p < 0.01). The results indicate that H2O2 upregulates Nrf3 expression. All experiments were conducted in triplicate.
Figure 1

H2O2 upregulates Nrf3 expression. Colon cancer cells were subjected to various concentrations of H2O2 for a duration of 12 h. Following this, protein extraction was performed and Nrf3 expression was detected using Western blot analysis. (a) The expression of Nrf3 in HCT116 cells after H2O2 treatment. (b) The expression of Nrf3 in SW620 cells after H2O2 treatment. (c) The expression of Nrf3 in HT29 cells following H2O2 treatment. (d) The relative quantification of Nrf3 expression (**p < 0.01). The results indicate that H2O2 upregulates Nrf3 expression. All experiments were conducted in triplicate.

3.2 Over-expression Nrf3 decreased H2O2-induced cell death

To explore the effect of Nrf3 in H2O2-induced cell death, we constructed cells over-expressing Nrf3 (HCT116/Nrf3)and cells with knocked down Nrf3 (HCT116/ShNrf3-1 and HCT116/ShNrf3-2). The effect of over-expression and knock-down Nrf3 was determined using Western blotting (Figure 2a and b). Cells were treated with different concentrations of H2O2 (0, 200, 400, and 600 μM) for 12 h. CCK-8 was used to determine cell viability. Compared with HCT116 cells, the inhibition rate for HCT116/Nrf3 cells was evidently decreased after H2O2 treatment (Figure 2c). Knock-down of Nrf3 had the opposite effect (Figure 2d). Cell apoptosis was determined using flow cytometry as described in Section 2.5. The results showed that over-expression of Nrf3 reduced cell apoptosis, and Nrf3 knock-down had the opposite results (Figure 2e). These data displayed that Nrf3 over-expression reduces the cytotoxicity of H2O2-mediated oxidative stress, indicating that Nrf3 promotes cell survival under oxidative stress.

Figure 2 Nrf3 decreases H2O2-induced cell death. Specifically, the study investigates the effects of overexpressing Nrf3 in HCT116 cells (a) and knocking down Nrf3 in HCT116 cells (b). The results indicate that overexpression of Nrf3 reduces the inhibition rate of colon cancer cells following H2O2 treatment (c), while knockdown of Nrf3 increases the inhibition rate of colon cancer cells (d). Furthermore, the study examines the influence of Nrf3 on cell apoptosis under varying concentrations of H2O2 (e).
Figure 2

Nrf3 decreases H2O2-induced cell death. Specifically, the study investigates the effects of overexpressing Nrf3 in HCT116 cells (a) and knocking down Nrf3 in HCT116 cells (b). The results indicate that overexpression of Nrf3 reduces the inhibition rate of colon cancer cells following H2O2 treatment (c), while knockdown of Nrf3 increases the inhibition rate of colon cancer cells (d). Furthermore, the study examines the influence of Nrf3 on cell apoptosis under varying concentrations of H2O2 (e).

3.3 Nrf3 decreased the intracellular ROS and MDA under H2O2-induced oxidative stress in HCT116

To investigate the possible mechanisms by which Nrf3 reduces H2O2-induced cytotoxicity, we determined the concentration of ROS and MDA after H2O2 treatment as described in Section 2.6.

In comparison to HCT116 cells, the concentration of ROS in HCT116/Nrf3 cells exhibited a decrease subsequent to treatment with varying concentrations of H2O2 (0, 200, 400, and 600 μM) as depicted in Figure 3a–c. Additionally, the levels of MDA were assessed, revealing that Nrf3 diminished the intracellular MDA concentration following H2O2 treatment, as shown in Figure 3d. These findings suggest that Nrf3 potentially counteracts ROS to reinstate the cellular redox equilibrium and facilitate the survival of cancer cells.

Figure 3 The impact of Nrf3 on the reduction of ROS and MDA levels. (a) The typical images of flow cytometry, (b) the representative fluorescence graphs, (c) the proportion of docosahexaenoic acid following different concentrations of hydrogen peroxide (H2O2), and (d) the concentration of MDA.
Figure 3

The impact of Nrf3 on the reduction of ROS and MDA levels. (a) The typical images of flow cytometry, (b) the representative fluorescence graphs, (c) the proportion of docosahexaenoic acid following different concentrations of hydrogen peroxide (H2O2), and (d) the concentration of MDA.

3.4 H2O2-mediated oxidative stress involves multiple signal pathways in colon cancer cells

Oxidative stress-mediated cell apoptosis may involve multiple signaling pathways, including pro-survival or pro-death signals. In our experiments, the known molecules were selected to explore the possible mechanisms of Nrf3-decreased cytotoxicity of H2O2, which included Akt, Bcl-2, P38, and JNK. These molecules are critical for maintaining cell survival (Akt and Bcl-2) and promoting cell apoptosis (JNK and p38) in the oxidative stress of cancer cells.

The cells were placed into six-well dishes with a density of 5 × 105 cells/well. Afterward, the cells were subjected to different levels of H2O2 (200, 400, and 600 μM) for 12 h. The related molecules were determined by Western blot. The data showed that the expression of p-Akt and Bcl-2 was reduced by treatment with 200 and 400 μM H2O2 but not by 100 μM H2O2 in HCT116 and SW620 cells. Phosphorylation levels of JNK and P38 were significantly boosted by H2O2 treatment at 200 and 400 μM but not 100 μM in both cell lines (Figure 4a–d). These results displayed that high levels of H2O2 (400 μM) suppressed pro-survival signals (Akt and Bcl-2) while enhancing pro-apoptosis signals (JNK and p38).

Figure 4 The involvement of multiple cell signals in H2O2-mediated oxidative stress. HCT116 and SW620 cell lines were subjected to various concentrations of H2O2 for a duration of 12 h, and subsequent protein extraction was performed to assess alterations in cell signals. Specifically, the expression levels of Akt, p-Akt, Bcl-2, JNK, p-JNK, P38, and p-P38 were evaluated in HCT116 cells (a and b), as well as in SW620 cells (c and d), following exposure to different concentrations of H2O2.
Figure 4

The involvement of multiple cell signals in H2O2-mediated oxidative stress. HCT116 and SW620 cell lines were subjected to various concentrations of H2O2 for a duration of 12 h, and subsequent protein extraction was performed to assess alterations in cell signals. Specifically, the expression levels of Akt, p-Akt, Bcl-2, JNK, p-JNK, P38, and p-P38 were evaluated in HCT116 cells (a and b), as well as in SW620 cells (c and d), following exposure to different concentrations of H2O2.

3.5 Over-expression Nrf3 regulates the oxidative signals under H2O2-mediated oxidative stress

Given the observed decrease in H2O2-induced cytotoxicity as a result of Nrf3, our subsequent investigation aimed to ascertain the potential involvement of Nrf3 in the regulation of oxidative signals within colon cancer cells under conditions of H2O2-mediated oxidative stress. The cells were allocated into six-well plates at a density of 5 × 105 cells/well. Subsequently, the cells were exposed to varying concentrations of H2O2 (200, 400, and 600 μM) for a duration of 12 h. The proteins were extracted and subsequently analyzed for the presence of related molecules using Western blotting.

The findings indicated that the upregulation of Nrf3 resulted in enhanced expression of p-Akt and Bcl-2, while concurrently reducing the expression of p-JNK and p-P38 following a 12 h exposure to elevated concentrations of H2O2 (400 μM) in both HCT116 (Figure 5a and c) and SW620 cells (Figure 5c and d).

Figure 5 The influence of Nrf3 on oxidative signals in HCT116 and SW620 cells following a 12-h treatment with H2O2. (a and b) The influence of Nrf3 on oxidative signals in HCT116 cells under H2O2-induced oxidative stress (at a concentration of 400 μM). (c and d) The influence of Nrf3 on oxidative signals in SW620 cells under H2O2-induced oxidative stress (at a concentration of 400 μM).
Figure 5

The influence of Nrf3 on oxidative signals in HCT116 and SW620 cells following a 12-h treatment with H2O2. (a and b) The influence of Nrf3 on oxidative signals in HCT116 cells under H2O2-induced oxidative stress (at a concentration of 400 μM). (c and d) The influence of Nrf3 on oxidative signals in SW620 cells under H2O2-induced oxidative stress (at a concentration of 400 μM).

3.6 Nrf3 decreased 5-FU-induced colon cancer cell death

Oxidative stress plays a crucial role in the initiation and progression of tumors, and it also serves as a significant mechanism for cancer treatment, including radiotherapy and certain chemical drugs (5-Fu and cisplatin). Given that Nrf3 enhances cell survival during oxidative stress induced by H2O2, we aimed to investigate whether Nrf3 reduces the susceptibility of cancer cells to these drugs. Consequently, we focused on further studying the effects of 5-Fu.

Cells were cultured and exposed to varying concentrations of 5-Fu for a duration of 24 h. Subsequently, cell viability was assessed using CCK-8, while apoptosis was measured using flow cytometry. The findings indicated that Nrf3 exhibited a positive impact on cell viability (Figure 6a) and a negative effect on apoptosis (Figure 6b and c).

Figure 6 Nrf3 decreased 5-FU-induced death in HCT116 cells. The cells were exposed to varying concentrations of 5-FU for a duration of 24 h. (a) Nrf3 exhibited a reduction in the inhibitory effects caused by 5-FU treatment. (b) The representative flow cytometry graph depicting cellular apoptosis. (c) Quantification of the apoptosis rate in the cells.
Figure 6

Nrf3 decreased 5-FU-induced death in HCT116 cells. The cells were exposed to varying concentrations of 5-FU for a duration of 24 h. (a) Nrf3 exhibited a reduction in the inhibitory effects caused by 5-FU treatment. (b) The representative flow cytometry graph depicting cellular apoptosis. (c) Quantification of the apoptosis rate in the cells.

4 Discussion

In the present study, Nrf3 has been demonstrated to play a crucial role in the survival of colon cancer cells under oxidative stress through the activation of the Akt/bcl-2 signaling pathway. Initially, it was observed that Nrf3 expression was noticeably increased following treatment with H2O2. Furthermore, the overexpression of Nrf3 was found to significantly enhance cell viability and reduce cell apoptosis in vitro, whereas the knockdown of Nrf3 yielded contrasting outcomes. Additionally, Nrf3 was found to decrease the levels of ROS and MDA after H2O2 treatment. The potential mechanisms underlying Nrf3’s promotion of colon cancer cell survival may be associated with the Akt/Bcl-2 pathway. Ultimately, our investigation revealed that the augmentation of Nrf3 led to a reduction in the occurrence of stress-related chemical-induced (5-Fu) cellular demise, consequently leading to the development of resistance towards the administered drug.

Accumulating evidence displayed that an increase in Nrf3 is observed in colon cancer [20], prostate cancer [26], and hepatocarcinoma [25]. However, the mechanism underlying Nrf3 upregulation remains elusive. Considering that oxidative stress can lead to carcinogenesis, we examined whether Nrf3 expression is affected by a redox imbalance. Our results revealed that Nrf3 expression increased after H2O2-induced oxidative stress in colon cancer cells (Figure 1a–d). Furthermore, we found that over-expression of Nrf3 in colon cancer cells promoted cell proliferation and survival (Figure 2a) and decreased cell apoptosis (Figure 2c) with H2O2 treatment. In addition, our results showed that Nrf3 decreased ROS and MDA levels after H2O2-induced oxidative stress in colon cancer cells (Figure 3a–d). According to these data, Nrf3 expression may be correlated with oxidative stress levels.

Multiple signaling pathways [24,27] control oxidative stress-induced cell death, including signals that promote cell survival (e.g., Akt, bcl-2, NF-κB, and ERK) and signals that induce cell death (e.g., p38 and JNK). To investigate the potential mechanisms underlying the decrease in cytotoxicity of oxidative stress caused by Nrf3, we initially examined several cell signals (Akt, Bcl-2, p38, and JNK) that have been reported to play a significant role in oxidative stress in cancer. We observed that high levels of H2O2-mediated oxidative stress (200 and 400 μM) reduced the activity of the Akt/bcl-2 pathway and increased the expression of p-P38 and p-JNK in colon cancer cells, but there is no influence on these signals at the low level of H2O2 (100 μM) (Figure 4). The inhibition of phosphorylated Akt has been shown to have an inhibitory effect on various downstream pro-survival signals and antioxidant enzymes, including NF-κB and ARE pathways. Therefore, the increased activity of Akt/bcl-2 in colon cancer cells may play a crucial role in promoting cell survival under conditions of high oxidative stress. Additionally, JNK and p38, which are often activated through similar signaling pathways, can activate several pro-death pathways, such as the subsequent activation of Bid or the release of cytochrome c and AIF.

What are the underlying mechanisms responsible for the participation of Nrf3 in reducing the cytotoxic effects of H2O2-induced oxidative stress? Nrf3 [28–30] also plays a role in the signaling pathways involved in the progression of cancer. For instance, Nrf3 [31] promotes the proliferation of human hepatocellular carcinoma (HepG2) cells through the Wnt/β-catenin pathway. Therefore, it is crucial to investigate the impact of Nrf3 on oxidative signaling to elucidate the mechanisms by which Nrf3 inhibits cell death induced by H2O2. Our findings demonstrate that upregulating Nrf3 expression mitigates the inhibition of Akt/bcl-2 by H2O2 in colon cancer (Figure 5). Despite the absence of discernible effects of Nrf3 on p38 and JNK, it is noteworthy that Nrf3 overexpression significantly impeded the expression of p-P38 and p-JNK during high levels of H2O2-induced cellular demise (Figure 5). Our findings imply that the reduction in H2O2-induced cytotoxicity by Nrf3 is associated with the activation of Akt/Bcl-2 and the inhibition of p38/JNK.

The aforementioned findings suggest a strong association between the upregulation of Nrf3 expression in colon cancer cells and oxidative stress. This protein plays a crucial role in enhancing pro-survival signals (Akt and Bcl-2) while dampening pro-death signals (JNK and p38) during oxidative stress, ultimately resulting in a reduction in the cytotoxic effects of H2O2-induced oxidative stress. While this study does not rule out the possibility of other mechanisms contributing to the Nrf3-mediated inhibition of H2O2 cytotoxicity, it does offer potential implications for mitigating oxidative adaptation and increasing the sensitivity of cancer cells to stress-associated chemicals [10,32], such as 5-FU, cisplatin, and bortezomib. Consequently, 5-FU was chosen to validate this hypothesis. Our findings demonstrate that the upregulation of Nrf3 expression in colon cancer cells significantly diminishes the efficacy of 5-FU in inducing cell death (Figure 6). This research elucidates the novel role of Nrf3 as an inhibitor of H2O2-induced cytotoxicity, thereby offering potential avenues for investigating a novel strategy to overcome resistance in colon cancer cells to therapeutic interventions.

  1. Funding information: This work was supported by the Strategic Cooperation Research Project of Nan Chong (20SXCXTD004) and the major emphasis project of the North Sichuan Medical College (CBY22-ZDA02).

  2. Author contributions: All the authors participated in the planning and execution of the experiments, data analysis, and preparation of the manuscript. BQC conceptualized, planned, and conducted experiments; JCT compiled the manuscript and provided funding; WMC partly performed the experiments; and MWC and YHC analyzed the study data.

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

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

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Received: 2023-06-10
Revised: 2023-10-24
Accepted: 2023-11-02
Published Online: 2023-11-23

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

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

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  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-2022-0790
Schlagwörter für diesen Artikel
Nrf3; oxidative stress; colon cancer; Akt/Bcl-2; cell proliferation; apoptosis
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Artikel in diesem Heft

  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”
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Heruntergeladen am 6.9.2025 von https://www.degruyterbrill.com/document/doi/10.1515/biol-2022-0790/html?lang=de
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