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Selective G6PDH inactivation for Helicobacter pylori eradication with transformed polysulfide

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Science China Life Sciences 2025年

作者： Xiaonan Wang Ning Zhou Xuejiao J.Gao Zijing Zhu Minmin Sun Qian Wang Haolin Cao Xuetong Wu Caiyu Zhou Qingkang Zheng Ye Yuan Yuan Liu Lei Chen Jing Jiang Pengcheng Bu Lizeng Gao CAS Engineering laboratory for Nanozyme Key Laboratory of Biomacromolecules Institute of Biophysics Chinese Academy of Sciences School of Life Sciences University of Chinese Academy of Sciences College of Chemistry and Chemical Engineering Jiangxi Normal University key laboratory of Epigenetic Regulation and intervention Institute of Biophysics Chinese Academy of Sciences Nanozyme laboratory in Zhongyuan School of Basic Medical Sciences Zhengzhou University Nanozyme laboratory in Zhongyuan Henan Academy of Innovations in Medical Science

Alternative treatment for the highly prevalent Helicobacter pylori infection is imperative due to rising antibiotic resistance. We unexpectedly discovered that the anti-H. pylori component in garlic is hydrogen polysulfide（H2S_n, n≥2）, not organic polysulfides. Studies on the mechanism of action（MoA） show that H2S_nspecifically inactivates H. pylori glucose-6-phosphate dehydrogenase（G6PDH） by interfering with electron transfer from glucose-6-phosphate（G6P） to nicotinamide adenine dinucleotide phosphate（NADP+）. However, low H2S_nyield makes garlic derivatives hard to be a reliable donor of H2S_nto treat H. pylori infection. To address this challenge, we established a polysulfide transformation process from garlic organosulfur compounds into Fe3S4that generates H2S_nwith a 25–58 times increase in *** chitosan encapsulation, we designed a gastric-adaptive H2S_nmicroreactor（GAPSR） that eradicates H. pylori with 250 times higher efficiency under gastric conditions. A single GAPSR achieves more rapid H. pylori eradication than combined antibiotics therapy without disturbing the gut microbiota. These findings indicate a distinct MoA transformation mediated by polysulfide as an alternative candidate to treat H. pylori infection.

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γ-catenin alleviates cardiac fibrosis through inhibiting phosphorylation of GSK-3β

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The Journal of Biomedical Research 2020年第1期34卷 27-35页

作者： Xin Tang Jiaxin Tian Liping Xie Yong Ji key laboratory of cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention and Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Cardiac fibrosis is a common pathological change of many cardiovascular diseases. β-catenin has been shown to promote fibrosis. However, the precise role of its homolog γ-catenin in the process of fibrosis remains largely unclear. In this study, we found that the expression of γ-catenin was significantly decreased in angiotensin Ⅱ(Ang Ⅱ)-induced cardiac fibrosis model, contrary to most reports of β-catenin. Overexpression of γ-catenin in cardiac fibroblasts(CFs) significantly inhibited the expression of α-smooth muscle actin(α-SMA), whereas knocking down the expression of γ-catenin with si RNA promoted the occurrence of cardiac ***, γ-catenin could bind to GSK-3β to inhibit the phosphorylation of GSK-3β, therefore preventing cardiac fibrosis. Our study shows that γ-catenin is an important protective factor in cardiac fibrosis, which provides a new potential target for the treatment of cardiac fibrosis.

关键词： γ-catenin cardiac fibrosis GSK-3β

H2S protects against diabetes-accelerated atherosclerosis by preventing the activation of NLRP3 inflammasome

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The Journal of Biomedical Research 2020年第2期34卷 94-102页

作者： Qiao Zheng Lihong Pan Yong Ji key laboratory of cardiovascular and Cerebrovascular Medicine Key Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Hydrogen sulfide(H2S) is an important messenger for its strong anti-inflammatory effects, which may be involved in multiple cardiovascular diseases. In our previous study, we revealed that H2S attenuated diabetesaccelerated atherosclerosis through suppressing oxidative stress. Here we report that GYY4137, a H2S donor,reduced the plaque formation of aortic roots and the levels of both intercellular cell adhesion molecule 1(ICAM1)and vascular cell adhesion molecule 1(VCAM1) in diabetes-accelerated atherosclerotic cells and mouse *** inflammatory factors of TNF-α, IL-1β, IL-6, and MCP1 were also significantly reduced by ***, GYY4137 suppressed the activation of pyrin domain containing protein 3(NLRP3) inflammasome in diabetes-accelerated atherosclerosis conditions. Upon knockdown of NLRP3, the increase of ICAM1 and VCAM1 caused by high glucose and ox LDL could be reversed, indicating that H2S protected the endothelium by inhibiting the activity of NLRP3 inflammasome. In conclusion, our study indicates that GYY4137 effectively protects against the development of diabetes-accelerated atherosclerosis by inhibiting inflammasome activation.

关键词： H2S NLRP3 inflammation diabetes-accelerated atherosclerosis

Factors in?uencing the somatic cell nuclear transfer ef?ciency in pigs

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Frontiers of Agricultural Science and Engineering 2019年第1期6卷 73-80页

作者： Yong JIN Manling ZHANG Xinrong JU Shuang LIANG Qiang XIONG Lihua ZHAO Xiaowei NIE Daorong HOU Qiang LIU Junzheng WANG Chenyu WANG Xiaokang LI Lining ZHANG Xiaorui LIU Ying WANG Haiyuan YANG Yifan DAI Rongfeng LI Jiangsu key laboratory of Xenotransplantation/key laboratory of targeted intervention of cardiovascular disease/Collaborative Innovation Center for cardiovascular disease Translational Medicine Nanjing Medical University

Using a data set from our laboratory, we assessed the effects of several factors on pig cloning ef?ciency. The results demonstrated that cells at high con?uence( > 90%) used as donor cell resulted in higher pregnancy rate, delivery rate and overall cloning ef?ciency(number of live offspring born per reconstructed embryo transferred to recipients) compared with the cells at 60% to79% con?uence and 80% to 89% con?uence. Cells with four, ?ve and six passages compromised the pregnancy and delivery rates compared with ?rst passage cells. The number of blastocysts transferred by somatic cell nuclear transfer(SCNT) did not signi?cantly affect the cloning ef?ciency, but transfer of blastocyst derived from in vitro culture 5 d after SCNT achieved a signi?cantly higher pregnancy rate compared with one to two cell SCNT embryos from overnight culture. The highest pregnancy rate, delivery rate and the largest litter size were obtained when Bama Miniature pig ?broblasts were used as donor cells and Landrace/Yorkshire hybrid gilts were used as recipients. Recipients treated with chemicals for estrus synchronization had higher pregnancy rates compared with untreated recipients. Our data might be helpful for improving SCNT ef?ciency in pigs.

关键词： blastocyst donor cell estrus synchronization pregnancy rate pig cloning somatic cell nuclear transfer

Fucoidan antagonizes diet-induced obesity and inflammation in mice

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The Journal of Biomedical Research 2021年第3期35卷 197-205页

作者： Lei Wang Kun Zhang Xin Ding Yan Wang Hui Bai Qing Yang Jingjing Ben Hanwen Zhang Xiaoyu Li Qi Chen Xudong Zhu key laboratory of targeted intervention of cardiovascular disease Collaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjingJiangsu 211166China

Obesity is an escalating global pandemic posing a serious threat to human *** intervention therapy using weight-reducing drugs,accompanied by lifestyle modification,is a strategy for the treatment of *** the present study,we explored the role of fucoidan,a seaweed compound,on high-fat diet(HFD)-induced obesity in *** found that fucoidan treatment significantly reduced the body fat and caused redistribution of visceral and subcutaneous fat in HFD-fed ***,fucoidan treatment inhibited adipocyte hypertrophy and inflammation in adipose ***,these results suggest that fucoidan may be a promising treatment for obesity and obesity-induced complications.

关键词： obesity adipose tissue fucoidan inflammation

Endoplasmic reticulum stress and autophagy in cerebral ischemia/reperfusion injury:PERK as a potential target for intervention

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Neural Regeneration Research 2025年第5期20卷 1455-1466页

作者： Ju Zheng Yixin Li Ting Zhang Yanlin Fu Peiyan Long Xiao Gao Zhengwei Wang Zhizhong Guan Xiaolan Qi Wei Hong Yan Xiao key laboratory of Endemic and Ethnic diseases Ministry of Education&Key Laboratory of Medical Molecular Biology of Guizhou ProvinceGuizhou Medical UniversityGuiyangGuizhou ProvinceChina Guizhou Center for disease Control and Prevention GuiyangGuizhou ProvinceChina Department of Histology and Embryology Guizhou Medical UniversityGuiyangGuizhou ProvinceChina Collaborative Innovation Center for Prevention and Control of Endemic and Ethnic Regional diseases Co-constructed by the Province and Ministry GuiyangGuizhou ProvinceChina

Several studies have shown that activation of unfolded protein response and endoplasmic reticulum(ER)stress plays a crucial role in severe cerebral ischemia/reperfusion *** occurs within hours after cerebral ischemia,but the relationship between ER stress and autophagy remains *** this study,we established experimental models using oxygen-glucose deprivation/reoxygenation in PC12 cells and primary neurons to simulate cerebral ischemia/reperfusion *** found that prolongation of oxygen-glucose deprivation activated the ER stress pathway protein kinase-like endoplasmic reticulum kinase(PERK)/eukaryotic translation initiation factor 2 subunit alpha(e IF2α)-activating transcription factor 4(ATF4)-C/EBP homologous protein(CHOP),increased neuronal apoptosis,and induced ***,inhibition of ER stress using inhibitors or by si RNA knockdown of the PERK gene significantly attenuated excessive autophagy and neuronal apoptosis,indicating an interaction between autophagy and ER stress and suggesting PERK as an essential target for regulating *** autophagy with chloroquine exacerbated ER stress-induced apoptosis,indicating that normal levels of autophagy play a protective role in neuronal injury following cerebral ischemia/reperfusion *** from this study indicate that cerebral ischemia/reperfusion injury can trigger neuronal ER stress and promote autophagy,and suggest that PERK is a possible target for inhibiting excessive autophagy in cerebral ischemia/reperfusion injury.

关键词： apoptosis ATF4 autophagy C/EBP homologous protein cerebral ischemia/reperfusion injury eIF2α endoplasmic reticulum stress PERK

Significant implications of Bcl-2 in the formation of striatonigral projection neurons in the ischemic striatum

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Neuroscience Bulletin 2012年第6期28卷 667-668页

作者： Dong-Ya Zhu laboratory of Cerebrovascular disease Key Laboratory of Cardiovascular Disease and Molecular InterventionNanjing Medical University

In adult mammals, including humans, the subventricular zone （SVZ） of the lateral ventricles and the subgranular zone of the dentate gyms （DG） show ongoing neurogenesis. Cerebral ischemic insults trigger neurogenesis from neural stem cells or progenitor cells located in the SVZ and DG. Newborn neurons are then functionally recruited into the circuitry of the CA1 region, striatum and DG granule cell layer.

关键词： In Pro Significant implications of Bcl-2 in the formation of striatonigral projection neurons in the ischemic striatum SVZ

Human organoids in basic research and clinical applications

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Signal Transduction and targeted Therapy 2022年第6期7卷 2010-2026页

作者： Xiao-Yan Tang Shanshan Wu Da Wang Chu Chu Yuan Hong Mengdan Tao Hao Hu Min Xu Xing Guo Yan Liu Institute for Stem Cell and Neural Regeneration School of PharmacyState Key Laboratory of Reproductive MedicineKey Laboratory of Targeted Intervention of Cardiovascular DiseaseCollaborative Innovation Center for Cardiovascular Disease Translational MedicineNanjing Medical UniversityNanjingChina Department of Neurobiology School of Basic Medical SciencesNanjing Medical UniversityNanjingChina

Organoids are three-dimensional(3D)miniature structures cultured in vitro produced from either human pluripotent stem cells(hPSCs)or adult stem cells(AdSCs)derived from healthy individuals or patients that recapitulate the cellular heterogeneity,structure,and functions of human *** advent of human 3D organoid systems is now possible to allow remarkably detailed observation of stem cell morphogens,maintenance and differentiation resemble primary tissues,enhancing the potential to study both human physiology and developmental *** they are similar to their original organs and carry human genetic information,organoids derived from patient hold great promise for biomedical research and preclinical drug testing and is currently used for personalized,regenerative medicine,gene repair and transplantation *** recent decades,researchers have succeeded in generating various types of organoids mimicking in vivo ***,we provide an update on current in vitro differentiation technologies of brain,retinal,kidney,liver,lung,gastrointestinal,cardiac,vascularized and multi-lineage organoids,discuss the differences between PSC-and AdSC-derived organoids,summarize the potential applications of stem cell-derived organoids systems in the laboratory and clinic,and outline the current challenges for the application of organoids,which would deepen the understanding of mechanisms of human development and enhance further utility of organoids in basic research and clinical studies.

关键词： organs clinical generating

Protein inhibitor of activated STAT 4(PIAS4) regulates liver fibrosis through modulating SMAD3 activity

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The Journal of Biomedical Research 2016年第6期30卷 496-501页

作者： Huihui Xu Zhiwen Fan Wenfang Tian Yong Xu key laboratory of cardiovascular disease and Molecular intervention Department of PathophysiologyNanjing Medical University

Excessive fibrogenesis disrupts normal liver structure,impairs liver function,and precipitates the development of cirrhosis,an irreversible end-stage liver disease.A host of factors including nutrition surplus contribute to liver fibrosis but the underlying mechanism is not fully *** the present study,we investigated the involvement of protein inhibitor for activated stat 4（PIAS4）in liver fibrosis in a mouse model of non-alcoholic steatohepatitis（NASH）.We report that PIAS4 silencing using short hairpin RNA（shRNA）attenuated high-fat high-carbohydrate（HFHC）diet induced liver fibrosis in *** PCR and Western blotting analyses confirmed that PIAS4 knockdown downregulated a panel of pro-fibrogenic genes including type I and type III collagens,smooth muscle actin,and tissue inhibitors of ***,PIAS4 silencing blocked the recruitment of SMAD3,a potent pro-fibrogenic transcription factor,to the promoter regions of pro-fibrogenic genes and dampened SMAD3 acetylation likely by upregulating SIRT1 *** conclusion,PIAS4 may contribute to liver fibrosis by modulating SIRT1-dependent SMAD3 acetylation.

关键词： liver fibrosis PIAS4 SMAD3 acetylation transcriptional regulation