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Gossypol stimulates opening of a Ca2+‐ and Na+‐permeable but Ni2+‐ and Co2+‐impermeable pore in bEND.3 endothelial cells
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Cing‐Yu Chen Wen‐Chuan Lin Kar‐Lok Wong Ka‐Shun Cheng Yuk‐Man Leung Shu‐Er Yang 《Clinical and experimental pharmacology & physiology》2018,45(8):788-796
Gossypol, a polyphenolic dialdehyde toxin isolated from cotton seed, has anti‐cancer properties and has recently shown some success in the treatment of glioma. Its effects on brain neurons and blood vessels are poorly understood. In this work we examined the effects of gossypol on cytosolic Ca2+ concentration ([Ca2+]i) of mouse brain bEND.3 endothelial cells. Cell viability tests revealed that after 3 hour and 18 hour exposures, 10 µmol/L gossypol caused 23% and 65% cell death, respectively; 3 µmol/L gossypol caused no and 21% cell death, respectively. [Ca2+]i was raised concentration‐dependently by 1‐10 µmol/L gossypol. We then explored the Ca2+ signalling triggered by 3 µmol/L gossypol, which inflicted minimal toxicity: the Ca2+ signal was composed largely of Ca2+ influx and to a small extent, intracellular Ca2+ release. Such Ca2+ influx was much larger than store‐operated Ca2+ influx triggered by maximal Ca2+ pool depletion. The Ca2+ influx triggered by 3 and 10 µmol/L gossypol caused NO release and cell death, respectively. Gossypol also triggered influx of Mn2+ and Na+, but not Ni2+ and Co2+. Gossypol‐triggered Ca2+ signal was inhibited only by 14% and 37% by 100 µmol/L La3+ and 10 µmol/L nimodipine, respectively; and not suppressed at all by 5 mmol/L Ni2+. Gossypol‐triggered Ca2+ signal was suppressed by 78% by 30 µmol/L ruthenium red, suggesting gossypol may act on TRPV channels. Our results suggest gossypol triggered opening of a non‐selective cation pore, possibly a member of the TRPV family. 相似文献
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Neeraj Shah Min Qian Marco R. Di Tullio Susan Graham Douglas L. Mann Ralph L. Sacco Gregory Y. H. Lip Arthur J. Labovitz Piotr Ponikowski Dirk J. Lok Stefan D. Anker John R. Teerlink John L. P. Thompson Shunichi Homma Ronald S. Freudenberger the WARCEF Investigators 《European journal of clinical investigation》2019,49(6):e13092
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Jugran Arun K. Joshi Ravindra K. Bhatt Indra D. Rawal Ranbeer S. Palni Lok Man S. 《Proceedings of the National Academy of Sciences, India. Section B.》2019,89(1):371-378
Proceedings of the National Academy of Sciences, India Section B: Biological Sciences - In light of the recent evidences that pollinators have a significant implication for maintenance of... 相似文献
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Shaohong Peng Pei Guo Xiao Lin Ying An Kong Hung Sze Matthew Ho Yan Lau Zhefan Stephen Chen Qianwen Wang Wen Li Jacquelyne Ka-Li Sun Sum Yi Ma Ting-Fung Chan Kwok-Fai Lau Jacky Chi Ki Ngo Kin Ming Kwan Chun-Ho Wong Sik Lok Lam Steven C. Zimmerman Tiziano Tuccinardi Zhong Zuo Ho Yu Au-Yeung Hei-Man Chow Ho Yin Edwin Chan 《Proceedings of the National Academy of Sciences of the United States of America》2021,118(19)
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Wai CT Fontana RJ Polson J Hussain M Shakil AO Han SH Davern TJ Lee WM Lok AS;US Acute Liver Failure Study Group 《Journal of viral hepatitis》2005,12(2):192-198
The role of hepatitis B virus (HBV) genotypes in the outcome of acute HBV infection is unclear. In this study, we aimed to evaluate the clinical and virological features of patients with hepatitis B-related acute liver failure (HBV-ALF) in the US. Clinical and laboratory features of consecutive patients with HBV-ALF from the US ALF Study Group were analysed. Prevalence of HBV genotypes, precore stop (G1896A) and core promoter dual (T1762A, A1764T) variants among patients with HBV-ALF were compared with a cohort of 530 patients with chronic HBV infection. Thirty-four HBV-ALF patients were studied: mean age 41 years, 56% men, 25 had detectable HBV-DNA. HBV genotypes A, B, C and D were found in 36, 24, 8 and 32% patients, respectively. Precore stop and core promoter dual variants were detected in 32 and 44% of patients, respectively. Twenty-three (68%) patients survived: 14 after liver transplant, nine without transplant. Older age was the only independent factor associated with poor outcome. Compared with patients with chronic HBV infection, patients with ALF were more likely to be non-Asians (88% vs 44%, P = 0.005) and to have genotype D (32% vs 10%, P < 0.01). A higher prevalence of HBV genotype D persisted even after matching for race and HBeAg status (32% vs 16%, P = 0.007). We concluded that HBV genotype D was more frequently found in patients with HBV-ALF than those with chronic HBV infection in the US. Further studies are needed to determine if HBV genotypes play a role in the outcome of acute HBV infection. 相似文献