Frontiers in Medicine
·
2024
·
IF 3.1
Liu Yan,Ge Ri-Li,Shan Zhen-Zhen,Wang Yan-Jun,Yang Yan-Yan,Sun Xue,Luo Peng-Li
Podocytopathies encompass kidney diseases where direct or indirect podocyte injury leads to proteinuria or nephrotic syndrome. Although Semaphorin3A (Sema3A) is expressed in podocytes and tubular cells in adult mammalian kidneys and has a common effect on the progression of podocyte injury, its mechanism remains unclear. Previous studies have shown increased Sema3A expression in various glomerulopathies, indicating a gap in understanding its role. In this study, analysis of human data revealed a positive correlation between the levels of urinary Sema3A and Podocalyxin (PCX), suggesting a close relationship between Sema3A and podocyte loss. Furthermore, the impact of Adriamycin on podocytes was investigated. Adriamycin induced podocyte migration and apoptosis, along with an increase in Sema3A expression, all of which were ameliorated by the inhibition of Sema3A. Importantly, TRPC5 was found to increase the overexpression of Sema3A in podocytes. A TRPC5 inhibitor, AC1903, alleviated podocyte migration and apoptosis, inhibiting the formation of lamellar pseudopodia in the podocyte cytoskeleton by lowering the expression of Rac1. Furthermore, AC1903 relieved massive albuminuria and foot process effacement in the kidneys of Adriamycin-treated mice in vivo. In conclusion, our findings suggest that Sema3A may impact the cytoskeletal stability of podocytes through TRPC5 ion channels, mediated by Rac1, ultimately leading to foot process effacement. Notably, AC1903 demonstrates the potential to reverse Adriamycin-induced foot process fusion and urine protein. These results contribute to a deeper understanding of the mechanisms involved in podocytopathies and highlight the therapeutic potential of targeting the Sema3A-TRPC5 pathway.
研究领域:
肾脏病学
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分子生物学
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DOI
PubMed
高影响因子
Biomed Research International
·
2020
·
IF 2.276
Jiyu Chen,Zhenzhen Bao,Yanli Huang,Zhenglong Wang,Yucheng Zhao
Quantitative real-time PCR (qPCR) has become a widely used approach to analyze the expression level of selected genes. However, owing to variations in cell types and drug treatments, a suitable reference gene should be selected according to special experimental design. In this study, we investigated the expression level of ten candidate reference genes in hepatoma carcinoma cell (HepG2) and human hepatocyte cell line (L02) treated with ethanol (EtOH), hydrogen peroxide (H2O2), acetaminophen (APAP), and carbon tetrachloride (CCl4), respectively. To analyze raw cycle threshold values (Cp values) from qPCR run, three reference gene validation programs, including Bestkeeper, geNorm, and NormFinder, were used to evaluate the stability of ten candidate reference genes. The results showed that TATA-box binding protein (TBP) and tubulin beta 2a (TUBB2a) presented the highest stability for normalization under different treatments and were regarded as the most suitable reference genes of HepG2 and L02. In addition, this study not only identified the most stable reference genes of each treatment, but also suggested that β-actin (ACTB), glyceraldehade-3-phosphate dehydrogenase (GAPDH), tyrosine 3-monooxygenase/tryptophan 5-monooxygenase activation protein zeta (YWHAZ), and beta-2 microglobulin (B2M) were the least stable reference genes in HepG2 and L02. This work was the first report to systematically explore the stability of reference genes in injured models of HepG2 and L02.
研究领域:
分子生物学
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遗传学
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产品关联
DOI
PubMed
高影响因子
Heliyon
·
2024
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IF 3.4
Bin Hu,Gongwen Du
Osteoarthritis (OA) is an age-related joint disease characterized by progressive heterogeneous changes in articular cartilage and subchondral bone. Osteoclast stimulating factor 1 (OSTF1) is a small intracellular protein involved in bone formation and bone resorption. However, to our best knowledge, its role in OA is still unclear. In this study, an OA rat model was established by anterior cruciate ligament transection (ALCT). OSTF1 was increased in the cartilage tissues of OA patients and OA rats. Next, the role of OSTF1 in interleukin-1β (IL-1β)-induced chondrocyte apoptosis, inflammation and extracellular matrix degradation was explored through loss of function assays. Strikingly, OSTF1 knockdown relieved IL-1β-induced chondrocyte apoptosis, with decreased cleaved caspase-3 and cleaved PARP levels. Besides, OSTF1 knockdown restrained IL-1β-induced inflammation and degradation of extracellular matrix of chondrocytes. Subsequently, the molecular mechanism of OSTF1 was explored. Transcriptomic analysis revealed the potential gene network map regulated by OSTF1 knockdown. Some differentially expressed genes (DEGs) were involved in regulating the NF-κB signaling pathway. Furthermore, our results demonstrated that OSTF1 knockdown inhibited IL-1β-activated the NF-κB signaling pathway. Ultimately, we analyzed the potential gene network map regulated by OSTF1 and its downstream NF-κB. Bioinformatics analysis showed that 18 DEGs in OSTF1-silenced chondrocytes overlapped with the NF-κB downstream targets. Collectively, our findings indicate that OSTF1 knockdown mitigates IL-1β-induced chondrocyte injury via inhibiting the NF-κB signaling pathway.
研究领域:
医学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES
·
2025
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IF 2.8
Aiping Li,Xiaoyu Zhang,Zheng Ju,Tingting Luo,Ting Cui,Xuemei Qin,Guangzhen Liu
To elucidate the molecular mechanisms of the MIX (combined in proportion to the content in Astragali Radix (AR), named the MIX) repairing podocyte damage to ameliorate nephropathy. MTT assay and western blot analysis were used to evaluate the protective effects of MIX on MPC5 cells induced by Adriamycin (ADR). Screening of potential pharmacodynamic markers, relevant drugs and disease targets were conducted by using metabolomics combined with bioinformatics, and the most relevant metabolic pathways were identified by analyzing shared target and KEGG pathways. The key mechanism was subsequently validated by cell adhesion assays, western blot assays, and immunofluorescence staining. The results showed that the MIX has the capacity to repair adriamycin-induced damage in MPC5 cells, as evidenced by enhanced cell viability and synaptopodin expression. Additionally, the MIX shows promise in potentially reinstating the podocyte adhesion through the modulation of the expression of podocyte adhesion-related proteins linked to nucleotide metabolites. The MIX has the potential to beneficially affect podocyte injury by modulating the cell adhesion pathway, contributing to one of the pharmacodynamic mechanisms of AR treatment of nephrotic syndrome. This has implications for the development and utilization of AR resources and achievement the social benefit of empowering rural revitalization.
研究领域:
药理学
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代谢组学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
ANALYST
·
2020
·Vol. 146
·期 2
·620-627
·
IF 3.978
Gaoqing Fu,Guoxing Yin,Tingting Niu,Wei Wu,Hui Han,Haimin Chen,Peng Yin
A sensitive fluorescent probe (E)-4-(3-(benzo[d]thiazol-2-yl)-4-hydroxy-5-methylstyryl)-1-methylpyridin-1-ium iodide (HBTMP) for the monitoring of pH in mitochondria was rationally exploited. This novel probe exhibited remarkable pH-dependent behavior in the linear range of 5.5–8.0, along with a pKa value of 6.829 ± 0.02627. A large Stokes shift of 205 nm was obtained. This fluorescent probe demonstrated good biocompatibility and high sensitivity for detecting the dynamic changes in mitochondrial pH in living cells and zebrafish. The results of the CCCP (m-chlorophenyl hydrazone) treatment experiment indicated that the probe can effectively monitor changes in mitochondrial pH caused by cell damage.
研究领域:
生物化学
·
细胞生物学
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分析化学
✓ 已验证
DOI
PubMed
高影响因子
Molecular & Cellular Toxicology
·
2021
·Vol. 17
·期 2
·161-168
·
IF 1.08
Chang Yicong,He Jingshan,Ma Bingke,Ishfaq Muhammad,Wang Jiaqi,Zhang Ruichen,Yuan Liang,Liu Jiarui,Li Changwen,Liu Fangping
Background Glutathione S-transferase A1 (GSTA1) is a detoxification enzyme and a sensitive marker for hepatotoxicity. We investigated the effects of JNK inhibition on different degrees of Acetaminophen (APAP)-induced hepatocyte injury and GSTA1 expression. Objective This study aimed to investigate the role of JNK signaling pathway in APAP-induced different degrees of hepatocyte injury and its correlation with GSTA1 by inhibiting the phosphorylation of JNK by SP600125. Results 6 and 8 mM APAP induced different degrees of hepatocyte injury and apoptosis, both activated JNK signaling pathway. In contrast, JNK inhibitor significantly reduced activation of JNK and c-JUN on exposure to APAP. Meanwhile, the levels of hepatocyte injury, oxidative stress, and apoptosis obviously decreased. Importantly, GSTA1 expression was significantly increased by JNK inhibition. Conclusions JNK inhibition attenuates APAP-induced hepatocyte injury and oxidative stress and increases GSTA1 expression. Furthermore, GSTA1 may be involved in this signaling pathway for detoxification.
研究领域:
药理学
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毒理学
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肝脏病学
✓ 已验证
产品关联
DOI
高影响因子
International Journal of Endocrinology
·
2025
·Vol. 2025
·期 1
·4473803
·
IF 2.3
Song Xue,Wei Fan,Qingping Li,Hong Huang,Yibo Tang,Min Wu
Background: This study aimed to investigate the potential mechanisms of puerarin in alleviating diabetic nephropathy (DKD) in mice. Method: The DKD model was induced by multiple low-dose injections of streptozotocin (STZ) and a high-sugar and high-fat diet in male C57BL/6J mice. After confirming the onset of DKD, mice were given irbesartan, distilled water, or different concentrations of puerarin (40 and 80 mg/kg/d) by gavage for 8 weeks. HE staining and PAS staining were adopted to assess the pathological changes in the kidney tissues. Meanwhile, the levels of superoxide dismutase, catalase, creatinine, and cystatin C in the serum and the urine albumin and creatinine were measured, and the renal indices as well as the urinary albumin-to-creatinine ratio (UACR) were calculated. The changes of podocin and protein expression levels associated with AMPK/Nrf2 signaling pathway were evaluated by western blot. Results: Puerarin significantly reduced the level of fasting blood glucose, renal index, glomerular mesangial expansion index, renal function, and oxidative stress induced by STZ ( p < 0.05). The pathological injuries in kidney tissues were also alleviated. Furthermore, we demonstrated that the expression level of podocin and protein related to the AMPK/Nrf2 signaling pathway was also decreased significantly by the treatment of puerarin. At the same time, the efficacy of puerarin in the treatment of DKD was better than that of irbesartan, and the treatment effect of the high-dose group (80 mg/kg/d) was also significantly better than that of the low-dose group (40 mg/kg/d). Conclusion: Puerarin could attenuate the severity of DKD and protect the podocyte in mice in a dose-dependent way. Also, it might be performed by regulating the AMPK/Nrf2 pathway. These findings may provide a theoretical basis for updating the clinical management of DKD.
研究领域:
医学
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药理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
JOURNAL OF NANOBIOTECHNOLOGY
·
2023
·Vol. 21
·期 1
·1-17
·
IF 10.2
Liu Lili,Chang Meiqi,Yang Rong,Ding Li,Chen Yu,Kang Yulin
Background Primary nephrotic syndrome (PNS) is characterized by edema, heavy proteinuria, hypoalbuminemia and hyperlipidemia. Moreover, podocyte injury is the key pathological change of PNS. Even though the pathophysiological etiology of PNS has not been fully understood, the production of excessive reactive oxygen species (ROS) plays an important role in the development and progression of the disease. Glucocorticoids are the first-line medications for patients with PNS, but their clinical use is hampered by dose-dependent side effects. Herein, we accelerated the rate of conversion from Ce 4+ to Ce 3+ by doping Zr 4+ in ceria-zirconia nanomedicines to treat the PNS rat model by removal of ROS. Results The engineered Ce 0.7 Zr 0.3 O 2 (7CZ) nanomedicines significantly improved the ROS scavenging ability of podocytes at a very low dose, enabling effective inhibition of podocyte apoptosis and actin cytoskeleton depolymerization induced by adriamycin (ADR). Accordingly, podocyte injury was effectively alleviated in rat models of ADR-induced nephrotic syndrome, as confirmed by serum tests and renal tissue staining. Moreover, the mRNA sequencing assay revealed the protective molecular signaling pathways of 7CZ nanomedicines in podocytes. Conclusion 7CZ nanomedicines were highly effective in protecting against ADR-induced podocyte injury in vitro and in vivo at a very low concentration. Graphical Abstract
研究领域:
纳米医学
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肾病学
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分子生物学
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产品关联
DOI
PubMed
高影响因子
SCIENCE OF THE TOTAL ENVIRONMENT
·
2019
·
IF 5.589
Feilong Dong,Qiufeng Lin,Jing Deng,Tuqiao Zhang,Cong Li,Xuedong Zai
The frequent occurrence of algal blooms in surface water has attracted more and more attention, which caused many water quality problems, including disinfection byproducts (DBPs). Algal organic matter (AOM) including intracellular organic matter (IOM) and extracellular organic matter (EOM), was a well-known precursor to DBPs formation in drinking water. This study evaluated the effect of ultraviolet (UV) irradiation on the cell integrity, IOM release and DBPs formation during subsequent chlorination of Chlorella sp. Results showed the damage rates of algal cells increased to 40.1% after the high UV irradiation of 528 mJ/cm 2 , which contributed to the release of IOM. In addition, UV irradiation was effective in reducing the formation of haloacetic acids (HAAs) both in AOM and IOM, but promoted the formation of nitrogenous DBPs (N-DBPs) from AOM in subsequent chlorination. Furthermore, neutral pH exerted a positive effect on the formation of DBPs. UV irradiation decreased the bromine substitution factor (BSF) value of AOM at a high bromide level. The BSF values increased with increasing of the concentration of bromide. Moreover, more amino acids and low molecular weight precursors were produced after UV irradiation in filtered supernatant, which contributed to the formation of N-DBPs with algal chlorination. Overall, this information demonstrated pre-oxidation of UV irradiation could be used to treat the algal-rich drinking water.
研究领域:
环境科学
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水处理工程
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产品关联
DOI
PubMed
高影响因子
JOURNAL OF APPLIED TOXICOLOGY
·
2019
·Vol. 39
·期 12
·1640-1650
·
IF 3.065
Yicong Chang,Feng Wang,Yang Yang,Yuanyuan Zhang,Ishfaq Muhammad,Rui Li,Changwen Li,Ying Li,Chenxi Shi,Xin Ma,Beili Hao,Fangping Liu
Acetaminophen (APAP) is an antipyretic and analgesic, which is commonly associated with drug-induced hepatic injury. C2-ceramide plays a key role in mediating cell life activities, and oltipraz was extensively studied as a cancer chemopreventive agent. Glutathione S -transferase A1 (GSTA1) acts as a vital liver detoxification enzyme. Hepatocyte nuclear factor 1 (HNF-1) regulates various cellular signaling pathways. In this study, we investigated the effects of C2-ceramide and oltipraz on APAP-induced hepatocyte injury and the changes of HNF-1 and GSTA1. Results showed that C2-ceramide (6 μmol/L) exacerbated APAP-induced hepatocyte injury and caused a significant decrease ( P < .01) in HNF-1 and GSTA1 expressions. Meanwhile, GSTA1 content in supernatant was significantly increased ( P < .01). In contrast, oltipraz (8 μmol/L) reduced the injury and significantly elevated ( P < .01) HNF-1 and GSTA1 expressions while GSTA1 content in supernatant was significantly decreased ( P < .01). In conclusion, these findings revealed that C2-ceramide inhibited HNF-1 and GSTA1 expression and exacerbated hepatocyte injury, while oltipraz treatment results in the reduction of hepatocyte injury, and promoted HNF-1 and GSTA1 expression. Additionally, the changes in HNF-1 and GSTA1 were related to APAP-induced hepatocyte injury. These results were useful to investigate the mechanism of an antipyretic and analgesic drug combination.
研究领域:
药理学
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毒理学
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分子生物学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
Food Bioscience
·
2023
·
IF 5.2
Hengju Ge,Jiaxin Li,Yang Xu,Jiahong Xie,Naymul Karim,Fujie Yan,Jianling Mo,Wei Chen
Fructus Gardeniae (FG) is the dried ripe fruit of Gardenia jasminoides Ellis, having beneficial effects for human health. In this study, we discovered that the most relevant pathway influenced by Fructus Gardeniae extract (FGE) is lipid metabolism according to the analysis of network pharmacology. Furthermore, the protective effect of FGE against palmitic acid-induced lipotoxicity was investigated. In L02 cells, FGE significantly promoted cellular proliferation after being treated with palmitic acid , and reduced the accumulation of lipid droplets and triglyceride level . Palmitic acid led to an increase of ROS content, which was reduced by FGE. Additionally, FGE could facilitate Nrf2 localized to nuclear and followed by activating its downstream targets. ML385 (a Nrf2 inhibitor) treatment further proved that FGE attenuated lipotoxicity through regulating Nrf2/ARE pathway. Consequently, we demonstrated for the first time FGE could be regarded as potential functional food materials for hepatic protection.
研究领域:
药理学
·
肝脏病学
✓ 已验证
产品关联
DOI
高影响因子
ENVIRONMENTAL TOXICOLOGY AND PHARMACOLOGY
·
2017
·
IF 2.313
Hui Zhang,Xiaoxing Wu,Khalid Mehmood,Zhenyu Chang,Kun Li,Xiong Jiang,Fazul Nabi,Muhammad Ijaz,Mujeeb Ur Rehman,Muhammad Tariq Javed,Donghai Zhou
The nano copper has been widely used in modern clinical medicine practice. However, it has been noticed that nano copper particles induce cell injury and toxicity. The present study was designed to determine the effect of nano copper particles on cell injury of intestinal epithelial cells (IECs) in piglets. The IECs were treated with different doses of nano copper (5, 10, 20 and 40 μg/ml) for 24–48 h to observe cell injury and toxicity. Cell injury was measured based on morphological and other changes including oxidative stress and genes expression. The oxidative stress markers were assayed by differential expression levels of SOD, MDA and Metallothionein (MT) in addition to CTR1, SOD1, COX17, MT and ATOX1 genes expression. Cellular morphology showed an increasing growth of cells without nano copper treatment and nano copper showed significant damage to IECs with higher dose as compared to low dose. Higher doses of copper nanoparticles (10, 20 and 40 μg/ml) have membrane damaging effect on the intestinal epithelial cells, whereas MDA contents and MT value were significantly increased, and SOD activity was decreased with the increase in concentration of nanoparticles. Nano copper up-regulated the CTR1 and SOD1 genes and down-regulated the relative expression of COX17, MT and ATOX1 genes significantly in a dose-dependent manner. The findings of the current study provide important insights that nano copper plays an important role in intestinal epithelial cell injury and oxidative stress.
研究领域:
毒理学
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分子生物学
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兽医学
✓ 已验证
产品关联
DOI
PubMed
高影响因子
危险品化学品经营许可证（带存储）