COMPARATIVE BIOCHEMISTRY AND PHYSIOLOGY C-TOXICOLOGY & PHARMACOLOGY
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2024
·
IF 3.9
Ying Sun,Xiaohui Jin,Zuwang Yang,Zunhan Hu,Qiulu Li,Jingquan Dong,Mian Fu
Difenoconazole (DFZ) is a widely used triazole fungicide in agricultural production. However, the presence of DFZ residue in the environment poses a significant risk to non-target organisms. Ferulic acid (FA) is a phenolic compound known for its antioxidant and anti-inflammatory properties. This study aims to investigate the hepatic damage caused by DFZ in carp and explore the mechanism through which FA alleviates this damage. The findings revealed that FA enhanced the antioxidant capability of the carp's liver and reduced the accumulation of reactive oxygen species (ROS) in the liver tissue. Moreover, FA regulated the transcriptional levels of inflammation-related factors, effectively preventing the inflammatory response triggered by the NF-κB signaling pathway. Additionally, TUNEL results demonstrated that DFZ initiated apoptosis, while dietary supplementation with FA decreased the protein expression levels of Bax and Cytochrome C (Cyt c) and the transcriptional levels of bax , caspase3 , caspase9 , p53 genes. Furthermore, FA increased the protein expression and transcriptional levels of Bcl-2. In conclusion, FA protects against liver injury induced by DFZ exposure in carp by modulating oxidative damage, inflammation, and apoptosis.
研究领域:
环境毒理学
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水生生物学
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL SCIENCE AND POLLUTION RESEARCH
·
2022
·Vol. 30
·期 1
·1060-1071
·
IF 5.19
Zhang Xinyu,Sun Kexin,Wang Xu,Shi Xu,Gong Duqiang
Chlorpyrifos (CPF), an organophosphorus pesticide, is detected commonly in environments, where it is thought to be highly toxic to non-target organisms. However, the mechanism of CYP450s pathway mediated by nuclear receptors on CPF-induced apoptosis and necroptosis at the cellular level and the effect of CPF on the cytotoxicity of the chicken hepatocarcinoma cell line (LMH) has also not been reported in detail. Therefore, this experiment aims to explore whether CPF can improve apoptosis and necroptosis in LMH cells by activating the nuclear receptors/CYP450s axis. LMH cells, the subject of this study, were exposed to 5 μg/mL, 10 μg/mL, and 15 μg/mL doses of CPF. With the increase of CPF concentration, the increase of nuclear receptor level led to the up-regulation of CYP450s activity. With the massive production of ROS, the expression of apoptotic pathway genes (Bax, Caspase9, and Caspase3) enhanced, while Bcl-2 expression dropped sharply. The expression of programmed necroptosis genes (RIPK1, RIPK3, and MLKL) heightened, and Caspase8 reduced considerably. In short, our data suggests that excessive activation of nuclear receptors and CYP450s induced by CPF promotes ROS production, which directs apoptosis and programmed necroptosis in LMH cells. Graphical abstract
研究领域:
毒理学
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细胞生物学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES
·
2024
·Vol. 25
·期 21
·11686
·
IF 4.9
Kangli Wang,Lingchen Tao,Meifei Zhu,Xinyu Yu,Yuanyuan Lu,Bin Yuan,Fuliang Hu
Melittin has previously been found to have a positive effect on colorectal cancer (CRC) treatment, one of the most difficult-to-treat malignancies, but the mechanism by which this effect occurs remains unclear. We evaluated melittin’s pro-apoptotic and anti-metastatic effects on CRC in vitro and in vivo. The results showed that melittin-induced mitochondrial ROS bursts decreased ΔΨm, inhibited Bcl-2 expression, and increased Bax expression in both cells and tumor tissues. This led to increased mitochondrial membrane permeability and the release of pro-apoptotic factors, particularly the high expression of Cytochrome C, initiating the apoptosis program. Additionally, through wound-healing and transwell assays, melittin inhibited the migration and invasion of CRC cells. In vivo, the anti-metastatic effect of melittin was also verified in a lung metastasis mouse model. Western blotting and immunohistochemistry analysis indicated that melittin suppressed the expression of MMPs and regulated the expression of crucial EMT markers and related transcription factors, thereby inhibiting EMT. Furthermore, the melittin disrupts neovascularization, ultimately inhibiting the metastasis of CRC. In conclusion, melittin exerts anti-CRC effects by promoting apoptosis and inhibiting metastasis, providing a theoretical basis for further research on melittin as a targeted therapeutic agent for CRC.
研究领域:
肿瘤学
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分子生物学
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药理学
✓ 已验证
DOI
PubMed
高影响因子
PLoS One
·
2025
·Vol. 20
·期 7
·e0328000
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IF 2.6
Shuaijun Peng,Ruiqin Sun,Hui Liu,Baoying Wang,Yucheng Li
Gastric mucosal injury can lead to significant gastrointestinal disorders, including inflammation, ulcers, and intestinal metaplasia in severe cases. Although bile acids are known contributors to mucosal damage due to their acidity, the role of chenodeoxycholic acid (CDCA), a primary bile acid, in gastric mucosal injury remains unclear. This study investigates the role of CDCA in inducing gastric mucosal injury and its underlying mechanisms, with a focus on apoptosis and FXR activation, to identify potential therapeutic targets. Mice were administered varying doses of CDCA to evaluate changes in body weight, food intake, and gastric mucosal pathology using hematoxylin-eosin (HE) and alcian blue-periodic acid-Schiff (AB-PAS) staining. Expression levels of apoptosis-related genes (BAX, BCL-2) and the intestinal metaplasia marker gene (CDX2) were analyzed via RT-PCR and Western blotting (WB). GES-1 cells were treated with different CDCA concentrations to assess cell viability via the CCK-8 assay. Apoptosis rates were measured using flow cytometry, and FXR inhibitors were applied to examine their impact on CDCA-induced effects. CDCA administration in mice resulted in weight loss, reduced food and water intake, gastric epithelial shedding, and intestinal metaplasia. CDCA exposure upregulated Bax and CDX2 expression, while reducing BCL-2 levels. In vitro, CDCA inhibited GES-1 cell viability and increased apoptosis rates, effects that were reversed by FXR inhibition. CDCA induces gastric mucosal injury through apoptosis and FXR activation. These findings provide insights into the mechanisms of bile acid-mediated mucosal damage and highlight FXR as a potential therapeutic target for gastric mucosal disorders.
研究领域:
胃肠病学
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细胞生物学
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分子生物学
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药理学
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病理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
BIOMEDICINE & PHARMACOTHERAPY
·
2021
·
IF 6.53
Wei-ni Qin,Kai-cheng Zhang,Ting Geng,Fang-fang Cheng,Pei-dong Chen,Wei-feng Yao,Li Zhang,Yu-dan Cao
Euphorbiae pekinensis Radix (EP) is effective in treating various diseases, but it’s toxicity is a major obstacle in use in clinical. Although EP was processed with vinegar to reduce it’s toxicity, the detailed mechanism of toxicity in EP have not been clearly delineated. This study investigate the toxicity attenuation-mechanism of Euphorbiae pekinensis after being processed with vinegar (VEP) and the toxic mechanism of four compounds from EP on zebrafish embryos. The contents of four compounds decreased obviously in VEP. Correspondingly, slower development on embryos can be seen as some symptoms like reduction of heart rate, liver area and gastrointestinal peristalsis after exposed to the compounds. Some obvious pathological signals such as pericardial edema and yolk sac edema were observed. Furthermore, the compounds could increase the contents of MDA and GSH-PX and induce oxidative damage by inhibiting the activity of SOD. Also, four compounds could provoke apoptosis by up-regulating the expression level of p53, MDM2, Bax, Bcl-2 and activating the activity of caspase-3, caspase-9. In conclusion, the four compounds play an important role in the toxicity attenuation effects of VEP, which may be related to the apoptosis induction and oxidative damage. This would contribute to the clinical application and further toxicity-reduction mechanism research.
研究领域:
药理学
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毒理学
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发育生物学
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生物化学
✓ 已验证
DOI
PubMed
高影响因子
JOURNAL OF PHARMACY AND PHARMACOLOGY
·
2021
·Vol. 74
·期 4
·596-604
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IF 3.765
Sun Liyun,Shang Huoli,Wu Yuzhen,Xin Xiujuan
ObjectivesThe combination of gemcitabine (Gem) and hypericin (HY) enhances the apoptosis of Capan-2 cells, providing a promising option for the treatment of pancreatic cancer. Our study further explored the cytotoxic mechanism of HY combined with chemotherapy drugs on pancreatic cancer.MethodsThe proliferation rate of the cells assayed with the MTT method. The ROS (reactive oxygen species) levels of each treatment were evaluated by DCFH-DA oxidisation methods. The activity of glutathione reductase and the levels of reduced glutathione (GSH) and oxidised glutathione (GSSG) were assessed using assay kits. The expression levels of apoptosis-related proteins were analysed by western blotting.Key findingsThe activity of glucose-6-phosphate dehydrogenase (G6PDH), a key enzyme of the pentose phosphate pathway, significantly decreased in Gem + HY groups, however, the ROS level enhanced accompanying with GSH depleting, mitochondrial membrane depolarisation and cytochrome C release. Gem + HY inhibits the expression of Bcl-2 but stimulates Bax level, triggering caspase activation and PARP cleavage and thus promoted apoptosis of Capan-2 cells.ConclusionsWe demonstrated that Gem combined HY-PDT could inhibit the proliferation of Capan-2 cells and induce cell apoptosis. HY-PDT combined with Gem had a great potential on pancreatic cancer treatment clinically.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
CLINICAL AND EXPERIMENTAL PHARMACOLOGY AND PHYSIOLOGY
·
2020
·Vol. 47
·期 6
·1083-1091
·
IF 2.456
Zhu Wang,Qianqian Wang,Tao He,Wen Li,Yan Liu,Yuan Fan,Yanping Wang,Qi Wang,Jie Chen
Carboplatin (CBP) is a widely used targeted anticancer therapeutic drug; however, multi-drug resistance induced by the accumulation of CBP eventually causes diseases progression. The anti-malarial drug artesunate (ART) also exerts anticancer effects in various cancers; however, the combined effect of ART and CBP on non-small cell lung cancer (NSCLC) remains unclear. In the present study, the NSCLC cell line A549 was pretreated with various concentrations of CBP, ART and gemcitabine (GEM). 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assays were conducted to detect cell viability. Cell apoptosis was evaluated by both flow cytometry and TUNEL apoptotic assay. The expression profiles of cell cycle-related proteins and apoptotic proteins were determined by western blot. Cell clone numbers were visualized using crystal violet staining. Here, we found that both CBP and ART suppressed cell viability, and promoted cell apoptosis, and the combined application of ART and CBP at a lower concentration exhibited synergistic effects. Specifically, the combination of ART and CBP at a lower concentration suppressed cell clone numbers, promoted cell cycle arrest at the G 2 /M phase, and induced the expression of the cell cycle and apoptosis-related proteins BAX, p21, p53, and Caspase-3, while decreasing Bcl-2 and Cyclin B1 expression. Based on these results, we concluded that combined application of ART and CBP exerts synergistic anti-tumour effects on NSCLC by enhancing cell apoptosis in a mitochondria-dependent manner.
研究领域:
肿瘤学
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药理学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
ENVIRONMENTAL POLLUTION
·
2019
·
IF 5.714
Da Lv,Yi Gu,Ming Guo,Ping Hou,Yan Li,Ronghui Wu
To better understand the toxicological activities of perfluorooctanoic acid (PFOA), we examined the effects of PFOA on apoptosis and its molecular mechanism in SMMC-7721 hepatoma cells. Cell viability was evaluated by MTT assay and apoptosis was determined by flow cytometry. Western blot and quantitative real-time PCR were used to examine the protein and gene expressions of Bax and Bcl-2. Our results showed that PFOA inhibited SMMC-7721 cell growth and induced apoptosis. PFOA treatment increased Bax expression and increased Bcl-2 expression at both gene and protein levels. Our study demonstrated that PFOA had toxic effects on SMMC-7721 cells, such as inhibiting cell proliferation and inducing apoptosis. Furthermore, we showed that PFOA-mediated induction of apoptosis involved inducing Bax and decreasing Bcl-2 expression as a molecular mechanism of its toxicological effects.
研究领域:
毒理学
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细胞生物学
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癌症研究
✓ 已验证
产品关联
DOI
PubMed
高影响因子
COLLOIDS AND SURFACES B-BIOINTERFACES
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2022
·
IF 5.999
Fang Pan,Yueping Li,Yujie Ding,Songwei Lv,Rongrong You,Roja Hadianamrei,Mhd Anas Tomeh,Xiubo Zhao
Anticancer peptides (ACPs) have attracted increasing attention in cancer therapy due to their unique mechanism of action on cancer cells. The main challenge is to establish the correlation between their physicochemical properties and their selectivity and anticancer effect, leading to a clear design strategy. In this study, a series of new α-helical short peptides (coded At1-At12) with different anticancer activities were systematically designed with different amphiphilicity based on a natural α-helical antimicrobial peptide (AMP) derived from ant. Three of the designed peptides, At7, At10 and At11, showed considerable anticancer activity with low toxicity to normal skin fibroblasts. The high selectivity of the peptides is attributed to their balanced amphiphilicity and cationic nature which favours binding to the outer membrane of negatively charged cancer cells over the neutral membrane of normal mammalian cells . In addition to rapid membrane penetration, the designed peptides also damaged the mitochondria and induced mitochondrial membrane depolarization. Moreover, these peptides were found to induce apoptosis in cancer cells by up-regulating the expression of apoptotic proteins Bax and Caspase-3, down-regulating the apoptotic protein Bcl-2, and activating the Caspase enzyme-linked reaction. The results of this study reveal the potential of these peptides for clinical applications, and provide a guidance for further development of highly selective anticancer medications.
研究领域:
肿瘤学
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药学
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分子生物学
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细胞生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Journal of Cancer
·
2024
·Vol. 15
·期 17
·5594-5604
·
IF 3.3
Cheng Yuanyuan,Gong Shushu,Li Qianqian,Shen Juan,Huang Hongjuan
Objective: To demonstrate the efficacy of photodynamic therapy (PDT) using hematoporphyrin derivative (HPD) nanomedicine in combination with conventional chemotherapy based on gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) magnetic resonance imaging (MRI) for hepatocellular carcinoma (HCC) therapy.Methods: HPD nanomedicine was prepared, and the cytotoxicity of HPD nanomedicine at different concentrations on HCC cells and the half-maximal inhibitory concentration (IC50) were analyzed. Sixty HCC patients who visited our hospital from 2021 to 2023 were retrospectively analyzed. Patient data were analyzed, with 30 cases in control group (CG) receiving conventional chemotherapy for HCC, and 30 cases in observation group (OG) receiving conventional chemotherapy combined with HPD nanomedicine PDT. Gd-DTPA MRI was utilized to monitor the morphological and biological characteristics of the lesions in patients. After treatment completion, the long-term efficacy of patients and the levels of bcl-2 and bax proteins in primary HCC cells were evaluated.Results: The IC50 values of HPD on HepG2 cell proliferation and the cell inhibition rates gradually increased with increasing doses of HPD (50 μM, 25 μM, 12.5 μM, 6.25 μM, 3.13 μM, 1.56 μM, 0.78 μM). HPD exhibited great anti-proliferative effects on HepG2 cells at relatively low concentrations. The differences in expression rates of bcl-2 protein and bax protein between groups were considerable (P<0.05). There were neglectable changes in AST and ALT levels between the two groups before treatment, but they were markedly reduced after treatment versus before treatment (P<0.05), with OG showing considerably lower levels than CG after treatment (P<0.05). Additionally, patients in OG exhibited better survival rates after the course of treatment versus those in CG.Conclusion: This study demonstrates that the combination of conventional chemotherapy based on Gd-DTPA MRI with HPD nanomedicine PDT greatly improves the efficacy of treatment for HCC patients. This combined treatment strategy not only enhances therapeutic outcomes but also alleviates adverse reactions associated with conventional treatment, providing a novel approach for future research in the treatment of HCC.
研究领域:
肿瘤学
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药理学
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医学影像学
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纳米技术
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细胞生物学
✓ 已验证
DOI
PubMed
高影响因子
ANTIVIRAL RESEARCH
·
2016
·
IF 4.909
Xiao-Bo Yu,Xiao-Hui Chen,Fei Ling,Kai Hao,Gao-Xue Wang,Bin Zhu
Moroxydine hydrochloride (Mor) is known to have multi-antiviral activities against DNA and RNA viruses but very little information exists on its pharmacology. The paper was undertaken to explore the antiviral response and antiapoptotic mechanism of Mor against grass carp reovirus (GCRV) in Ctenopharyngodon idella kidney (CIK) cells. The results showed that exposing GCRV-infected cell to 6.3 μg mL −1 of Mor for 96 h avoid ca. 50% apoptosis . Meanwhile, Mor had lower cytotoxicity than ribavirin (Rib) as the value of safe concentration was threefold higher than effective concentration and the compound could ensure sufficient into and out of cells within 4 h when tested at the maximal safe concentration. Mor blocked the GCRV-induced cytopathic effects and eliminated nucleocapsids in CIK cells to keep the normal morphological structure. Moreover, the expressions of viral protein genes were significantly inhibited especially the guanylyl transferase and RNA-dependent RNA polymerase related expression. Furthermore, GCRV caused Bcl-2 down-regulation and Bax mitochondrial translocation was prevented by treatment of CIK cells with Mor. The downstream effector, caspase activity was also significantly inhibited in Mor treated cells. The potential mechanism might be that mitochondrial apoptotic signals were not activated by the intervention of Mor for targeting viral gene expression. Taken together, Mor showed high anti-GCRV activity and had been proved as a secure and promising agent in viral controlling in aquaculture industry.
研究领域:
兽医学
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病毒学
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水产养殖
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药理学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
CELLULAR PHYSIOLOGY AND BIOCHEMISTRY
·
2017
·Vol. 43
·期 4
·1359-1368
·
IF 5.104
Du Lifen,Lei Yongfang,Chen Jinglou,Song Hongping,Wu Xinying
Background/Aims: Cadmium (Cd) is an environmental pollutant with reproductive toxicity. Swertia mileensis is used in Chinese medicine for the treatment of prostatic deficits and named as Qing Ye Dan (QYD). This study was undertaken to investigate the potential protective effects of QYD against Cd-induced prostatic deficits. Method: Rat model of prostatic deficits was induced by 0.2 mg/kg/d CdCl2 subcutaneous injection for 15 days. The prostatic oxidative stress was evaluated by detecting the levels of malondialdehyde, nitric oxide, reduced/ oxidized glutathione, total sulfhydryl groups and enzymatic antioxidant status. The prostatic inflammation was estimated by testing the levels of pro-inflammatory cytokines. The levels of epithelial-mesenchymal transition (EMT) markers E-cadherin, fibronectin, vimentin and α-smooth muscle actin were measured by qPCR analysis. Additionally, the prostatic expressions of transforming growth factor-β1 (TGF-β1), type I TGF-β receptor (TGF-βRI), Smad2, phosphorylation-Smad2 (p-Smad2), Smad3, p-Smad3, Smad7, nuclear related factor-2 (Nrf-2), heme oxygenase-1 (HO-1), B-cell CLL/lymphoma (Bcl)-2 and Bcl-2-associated X protein (Bax) were measured by western blot assay. Results: It was found that QYD ameliorated the Cd-induced prostatic oxidative stress and inflammation, attenuated prostatic EMT, inhibited the TGF-β1/Smad pathway, increased Bcl-2/Bax ratio and enhanced the activity of Nrf-2/HO-1 pathway. Conclusion: These results showed that QYD could ameliorate Cd-induced prostatic deficits via modulating Nrf-2/HO-1 and TGF-β1/Smad pathways
研究领域:
药理学
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毒理学
·
分子生物学
·
生殖医学
✓ 已验证
DOI
PubMed
高影响因子
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