DNA AND CELL BIOLOGY
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2025
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IF 2.6
Lijiang Zhao,Xueqing Wu,Qiang Li,Yan Shen,Sheng Zeng,Jinbao Wang,Qian Liu
Bisphenol A (BPA) is the most common endocrine disruptor that has toxicity to the reproductive system and male infertility. However, the underlying mechanisms of BPA’s toxicity to Sertoli cells remain poorly understood. Cellular communication network factor 5 (CCN5) is reported to regulate cell proliferation, apoptosis, and differentiation. Our study demonstrated a significant elevation of CCN5 expression in the testis of nonobstructive azoospermia patients and TM4 Sertoli cells exposed to BPA. Knockdown of CCN5 reduced apoptotic cells after BPA treatment, as determined by flow cytometry and terminal deoxynucleotidyl transferase dUTP nick end labeling assays. Cells exposed to BPA showed increased expressions of Bax and cleaved poly(ADP-ribose) polymerase, decreased expression of Bcl-2, as well as elevated activities of caspase-3 and caspase-9 in BPA-induced TM4 cells, which were reversed by CCN5 inhibition. Loss of CCN5 declined phosphorylation of protein kinase R-like endoplasmic reticulum kinase and eukaryotic translation initiation factor 2A and decreased activating transcription factor 4 and C/EBP-homologous protein in BPA-treated cells. Furthermore, silencing CCN5 blocked BPA-induced phosphorylation of p38 and c-Jun N-terminal kinase (JNK). Administration of anisomycin, a mitogen-activated protein kinase (MAPK) activator, reversed the effects of CCN5 knockdown on BPA-induced endoplasmic reticulum (ER) stress and apoptosis. Taken together, CCN5 promotes apoptosis and ER stress in Sertoli cells exposed to BPA by activating the p38/JNK MAPK signaling pathway.
研究领域:
生殖生物学
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毒理学
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分子生物学
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PubMed
高影响因子
Chemical Biology & Drug Design
·
2023
·Vol. 103
·期 1
·e14408
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IF 3
Xiao-Wen Nie,Ali Adnan Nasim,Xiao-Jun Yao,Xing-Xing Fan
The emergency of tyrosine kinase inhibitors has remarkably enhanced the clinical outcomes of cancer therapy, especially the use of EGFR inhibitors for non-small cell lung cancer (NSCLC). However, acquired resistance is inevitable after 8–12 months treatment. New agents or treatments are urgently required to resolve this problem. In this study, we identified that compound ZYZ384 can selectively inhibit the growth of gefitinib-resistant (G-R) lung cancer cells, without affecting that of normal lung epithelial cells. ZYZ384 induced G2 arrest in G-R NSCLC cells, decreasing the expression of Cyclin B1 and increasing the expression of P21. Meanwhile, ZYZ384 also induced apoptosis in NSCLC cells and correspondingly increased the expression of cleaved Caspase 3, 8, and 9 proteins. The expression of p-JNK, p-P38, and p-ERK were also increased in H1975 NSCLC cells treated with ZYZ384. Finally, we observed that the JNK inhibitor effectively reversed the pro-apoptotic effect of ZYZ384. In conclusion, ZYZ384 is a potential therapeutic agent to inhibit the growth of NSCLCs with EGFR mutations through activating JNK, which will help the development of related anticancer drugs.
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高影响因子
POULTRY SCIENCE
·
2022
·
IF 4.014
Yusong Miao,Dong Niu,Ze Wang,Jian Wang,Zhiyong Wu,Jiaxin Bao,Xiaodi Jin,Rui Li,Muhammad Ishfaq,Jichang Li
ABSTRACT Mycoplasma gallisepticum ( MG ) is an avian pathogen that commonly causes respiratory diseases in poultry. Methylsulfonylmethane ( MSM ) is a sulfur-containing natural compound that could alleviate inflammatory injury through its excellent anti-inflammatory and antioxidant properties. However, it is still unclear whether MSM prevents MG infection. The purpose of this study is to determine whether MSM has mitigative effects on MG-induced inflammatory injury in chicken and chicken like macrophages ( HD11 cells ). In this research, White Leghorn chickens and HD11 cells were used to build the MG-infection model. Besides, the protective effects of MSM against MG infection were evaluated by detecting MG colonization, histopathological changes, oxidative stress and inflammatory injury of trachea, and HD11 cells. The results revealed that MG infection induced inflammatory injury and oxidative stress in trachea and HD11 cells. However, MSM treatment significantly ameliorated oxidative stress, partially alleviated the abnormal morphological changes and reduced MG colonization under MG infection. Moreover, MSM reduced the mRNA expression of proinflammatory cytokines-related genes and decreased the number of death cells under MG infection. Importantly, the protective effects of MSM were associated with suppression of nuclear factor-kappa B ( NF-κB ) and extracellular signal-related kinases (ERK) /Jun amino terminal kinases (JNK) -mitogen-activated protein kinases ( MAPK ) pathway in trachea and HD11 cells. These results proved that MSM has protective effects on MG-induced inflammation in chicken, and supplied a better strategy for the protective intervention of this disease.
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高影响因子
Nutrients
·
2024
·Vol. 16
·期 4
·514
·
IF 4.8
Xiao Wang,Yongjie Liang,Bohan Zhang,Lixin He,Wenxuan Li,Wenwen Zhang,Chengzong Li,Lihong Luo,Talha Umar,Huili Feng,Changwei Qiu
2’-Hydroxychalcone is a hydroxyl derivative of chalcones, which are biosynthetic precursors of flavonoids and rich in the human diet. The anticancer activity of 2’-hydroxychalcone has been reported in several cancers but remains to be investigated in breast cancer. In the current study, 2’-hydroxychalcone showed significant cytotoxicity against breast cancer cell lines MCF-7 and CMT-1211. It could inhibit breast cancer cell proliferation, migration, and invasion in vitro and suppress tumor growth and metastasis in vivo. Mechanistic investigation revealed that the NF-κB pathway was significantly inhibited by 2’-hydroxychalcone treatment accompanied by an excessive intracellular accumulation of reactive oxygen species, induction of endoplasmic reticulum stress, and activation of JNK/MAPK. In addition, 2’-hydroxychalcone elevated the autophagic levels in breast cancer cells equipped with increasing numbers of autophagy vesicles and complete autophagic flux. Finally, autophagy-dependent apoptosis was observed in 2’-hydroxychalcone-induced cell death. In conclusion, 2’-hydroxychalcone enhances the autophagic levels and induces apoptosis in breast cancer cells, which could be contributed to the inhibition of the pro-survival NF-κB signaling, indicating a promising potential for 2’-hydroxychalcone in future anticancer drug development.
研究领域:
肿瘤学
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药理学
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细胞生物学
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分子生物学
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PubMed
高影响因子
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