ENVIRONMENT INTERNATIONAL
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2024
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IF 10.3
Bingli Zhang,Yizhou Zhong,Jiaxin Du,Rongyi Ye,Bingchi Fan,Yanhong Deng,Ruobing Bai,Yu Feng,Xiaohong Yang,Yuji Huang,Boxuan Liang,Jiewei Zheng,Weifeng Rong,Xingfen Yang,Zhenlie Huang
1,2-Dichloroethane (1,2-DCE) is a prevalent environmental contaminant, and our study revealed its induction of testicular toxicity in mice upon subacute exposure. Melatonin, a prominent secretory product of the pineal gland, has been shown to offer protection against pyroptosis in male reproductive toxicity. However, the exact mechanism underlying 1,2-DCE-induced testicular toxicity and the comprehensive extent of melatonin's protective effects in this regard remain largely unexplored. Therefore, we sequenced testis piRNAs in mice exposed to environmentally relevant concentrations of 1,2-DCE by 28-day dynamic inhalation, and investigated the role of key piRNAs using GC-2 spd cells. Our results showed that 1,2-DCE induced mouse testicular damage and GC-2 spd cell pyroptosis. 1,2-DCE upregulated the expression of pyroptosis-correlated proteins in both mouse testes and GC-2 spd cells. 1,2-DCE exposure caused pore formation on cellular membranes and lactate dehydrogenase leakage in GC-2 spd cells. Additionally, we identified three upregulated piRNAs in 1,2-DCE-exposed mouse testes, among which piR-mmu-1019957 induced pyroptosis in GC-2 spd cells, and its inhibition alleviated 1,2-DCE-induced pyroptosis. PiR-mmu-1019957 mimic and 1,2-DCE treatment activated the expression of interferon regulatory factor 7 (IRF7) in GC-2 spd cells. IRF7 knockdown reversed 1,2-DCE-induced cellular pyroptosis, and overexpression of piR-mmu-1019957 did not promote pyroptosis when IRF7 was inhibited. Notably, melatonin reversed 1,2-DCE-caused testicular toxicity, cellular pyroptosis, and upregulated piR-mmu-1019957 and IRF7. Collectively, our findings indicated that melatonin mitigates this effect, suggesting its potential as a therapeutic intervention against 1,2-DCE-induced male reproductive toxicity in clinical practice.
研究领域:
环境毒理学
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生殖生物学
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分子生物学
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药理学
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DOI
PubMed
高影响因子
International Heart Journal
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2024
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IF 1.2
Xiaoyu Shen,Jiamei Zhang,Zhou Zhou,Ruiqun Yu
Cardiomyocyte lipotoxicity and ferroptosis are the key to the development of diabetic cardiomyopathy (DCM). Perilipin 5 (PLIN5) is perceived as a significant target of DCM. This study aimed to focus on the role and mechanism of PLIN5 on lipotoxicity and ferroptosis in DCM.Following transfection, mouse cardiomyocytes HL-1 were induced by 0.1 mM palmitic acid (PA) to set up lipotoxic cardiomyocyte models. The cell viability and lipid accumulation were evaluated by cell counting kit-8 assay and Oil red O staining, respectively. Ferrous ion (Fe2+), glutathione (GSH), malondialdehyde (MDA), and reactive oxygen species (ROS) levels were determined to verify the effects of PLIN5 or Pirin (PIR) on ferroptosis. Quantitative real-time reverse transcription polymerase chain reaction or Western blot was performed for quantitative analysis.PLIN5 overexpression promoted the viability, GSH level, and expression of GPX4/PIR/intracellular P65, yet suppressed lipid accumulation, level of Fe2+/MDA/ROS, and expression of interleukin (IL) -1β/IL-18/intranuclear P65 in PA-stimulated HL-1 cells. PIR silencing counteracted the roles of PLIN5 overexpression in PA-stimulated HL-1 cells.PLIN5 suppresses lipotoxicity and ferroptosis in cardiomyocyte via modulating PIR/NF-κB axis, hinting its potential as a therapeutic target in DCM.
研究领域:
心脏病学
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细胞生物学
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分子生物学
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糖尿病
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病理学
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产品关联
DOI
PubMed
高影响因子
MEDICAL SCIENCE MONITOR
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2018
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IF 1.894
Xuechan Tang,Xiaoli Xie,Xin Wang,Yan Wang,Xiaoyu Jiang,Huiqing Jiang
Background Piwi-interacting RNA (piRNA) is the largest class of small non-coding RNA, which has also been identified in somatic tissues, and aberrant expression of piRNAs in tumor tissues may be implicated in carcinogenesis. piR-823 is increased in liver cirrhosis and hepatocellular carcinoma (HCC). However, there is no report on the function of piR-823 in hepatic stellate cells (HSCs) activation during hepatic fibrosis. The present study investigated the role of piR-823 in HSC activation. Matreial/Methods Liver fibrosis was induced in mice by carbon tetrachloride (CCL 4 ) injection and bile duct ligation (BDL). The primary HSCs were isolated from mice and cultured. The expression of piR-823 was measured by real-time PCR. The effect of piR-823 on HSCs was evaluated by either sense sequence or antisense sequence of piR-823 carried by liposome. Proteins binding to piR-823 were assayed by RNA pull-down technique and liquid chromatography-mass spectrometry (LC-MS). Results Our data for the first time show that piR-823 is significantly upregulated in activated HSCs. Overexpression of piR-823 promoted HSC proliferation, α-SMA and COL1a1 production, whereas inhibition of piR-823 suppressed the activity of HSCs. Interestingly, the combination of piR-823 and EIF3B promoted TGF-β1 expression. Conclusions Our data illustrate a novel mechanism of piR-823 in HSC activities. The combination of piR-823 and EIF3B increased TGF-β1 expression, which activates HSCs in liver fibrosis. piR-823 may be a new target in the treatment of liver fibrosis.
研究领域:
分子生物学
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肝病学
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细胞生物学
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基因组学
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DOI
PubMed
高影响因子
CHEMICAL ENGINEERING JOURNAL
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2026
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IF 12.5
Tingting Yu,Peng Song,Ruixue Wang,Ziwen Chen,Liang Zhao,Ming Wang,Jianying Wang,Tao Mei,Xianbao Wang,Jinhua Li
Colorectal cancer (CRC) is one of the malignant tumors with high morbidity and mortality rates worldwide. Conventional screening methods, such as endoscopy and fecal testing, are invasive and have low compliance, highlighting the urgent need for efficient, non-invasive diagnostics. Circulating small RNAs, including the sequence annotated as PIWI-interacting RNA-54265 (piR-54265), have been reported to be closely associated with CRC and represent promising serum biomarkers in liquid biopsy research. This study aims to develop an ultrasensitive, label-free solution-gated graphene transistor (SGGT) based biosensor to detect piR-54265 in serum samples, addressing limitations of current CRC biomarker detection. The Polyadenine 15 -thymine 5 (PolyA 15 T 5 -DNA) probe was designed with an L-shaped configuration, constructing a sensing interface. This configuration is proposed to facilitate a favorable probe conformation for nucleic acid recognition at the gate interface, thereby contributing to the overall sensing performance of the biosensor. The biosensor achieves a remarkable limit of detection (LOD) of 8.56 × 10 −19 M, with a linear detection range from 1 aM to 10 nM, and excellent selectivity for piR-54265. Clinical serum samples analyzed under diluted conditions demonstrate clear differentiation between CRC patients and non-cancer controls, with receiver operating characteristic (ROC) analysis further confirming its exceptional diagnostic performance and achieving an area under the curve (AUC) of 1.0. These results establish a SGGT-based sensing platform for CRC-associated RNA detection and highlight its potential for non-invasive biomarker detection and future diagnostic applications.
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产品关联
DOI
高影响因子
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