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Ischemia-reperfusion injury:molecular mechanisms and therapeutic targets

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signal Transduction and Targeted Therapy 2024年第2期9卷 558-596页

作者： Meng Zhang Qian Liu Hui Meng Hongxia Duan Xin Liu Jian Wu Fei Gao shijun Wang Rubin Tan Jinxiang Yuan The Collaborative Innovation Center Jining Medical UniversityJiningShandong 272067China Clinical medical College Jining Medical UniversityJiningShandong 272067China second Clinical medical College Jining Medical UniversityJiningShandong 272067China shanghai Institute of Cardiovascular Diseases Zhongshan Hospital and Institutes of Biomedical SciencesFudan UniversityShanghaiChina Institute of Zoology Chinese Academy of SciencesBeijingChina Department of Physiology Basic medical schoolXuzhou Medical UniversityXuzhou 221004China

Ischemia-reperfusion(I/R)injury paradoxically occurs during reperfusion following ischemia,exacerbating the initial tissue *** limited understanding of the intricate mechanisms underlying I/R injury hinders the development of effective therapeutic *** Wnt signaling pathway exhibits extensive crosstalk with various other pathways,forming a network system of signaling pathways involved in I/R *** review article elucidates the underlying mechanisms involved in Wnt signaling,as well as the complex interplay between Wnt and other pathways,including Notch,phosphatidylinositol 3-kinase/protein kinase B,transforming growth factor-β,nuclear factor kappa,bone morphogenetic protein,N-methyl-D-aspartic acid receptor-Ca2+-Activin A,Hippo-Yes-associated protein,toll-like receptor 4/toll-interleukine-1 receptor domain-containing adapter-inducing interferon-β,and hepatocyte growth factor/mesenchymal-epithelial transition *** particular,we delve into their respective contributions to key pathological processes,including apoptosis,the inflammatory response,oxidative stress,extracellular matrix remodeling,angiogenesis,cell hypertrophy,fibrosis,ferroptosis,neurogenesis,and blood-brain barrier damage during I/R *** comprehensive analysis of the mechanisms involved in Wnt signaling during I/R reveals that activation of the canonical Wnt pathway promotes organ recovery,while activation of the non-canonical Wnt pathways exacerbates ***,we explore novel therapeutic approaches based on these mechanistic findings,incorporating evidence from animal experiments,current standards,and clinical *** objective of this review is to provide deeper insights into the roles of Wnt and its crosstalk signaling pathways in I/R-mediated processes and organ dysfunction,to facilitate the development of innovative therapeutic agents for I/R injury.

关键词： therapeutic reperfusion damage

Insights into therapeutic peptides in the cancerimmunity cycle:Update and challenges

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Acta Pharmaceutica sinica B 2024年第9期14卷 3818-3833页

作者： Xiaokun Zhang Ye Wu Jiayi Lin shengxin Lu Xinchen Lu Aoyu Cheng Hongzhuan Chen Weidong Zhang Xin Luan shanghai Frontiers science Center for Chinese Medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine Research and Shuguang HospitalShanghai University of Traditional Chinese MedicineShanghai 201203China Institute of Medicinal Plant Development Chinese Academy of Medical Science&Peking Union Medical CollegeBeijing 100193China school of Pharmacy Second Military Medical UniversityShanghai 200433China Department of Pharmacology School of PharmacyFudan UniversityShanghai 201203China

Immunotherapies hold immense potential for achieving durable potency and long-term survival opportunities in cancer *** vital biological mediators,peptides with high tissue penetration and superior selectivity offer significant promise for enhancing cancer immunotherapies(CITs).However,physicochemical peptide features such as conformation and stability pose challenges to their on-target *** review provides a comprehensive overview of recent advancements in therapeutic peptides targeting key steps of the cancer-immunity cycle(CIC),including tumor antigen presentation,immune cell regulation,and immune checkpoint *** attention is given to the opportunities and challenges associated with these peptides in boosting CIC within the context of clinical ***,possible future developments in this field are also discussed to provide insights into emerging CITs with robust efficacy and safety profiles.

关键词： Cancer-immunity cycle Oncolytic peptide Peptide neoantigen vaccine Peptide mimotope Immune checkpoint blockade Cancer immunotherapy synthetic long peptide vaccine Peptide-major histocompatibility complex

Global burden of vision loss attributable to household air pollution from 1990 to 2019:A trend analysis and 10-year prediction

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Chinese medical Journal 2024年第10期137卷 1231-1233页

作者： Cong Li Zuoqian Jing Jianbo shen shunming Liu Lei Liu Xiaohong Yang Honghua Yu Department of Ophthalmology Guangdong Eye InstituteGuangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences)Southern Medical UniversityGuangzhouGuangdong 510080China school of Medicine south china University of Technology Guangzhou 510006China Department of Ophthalmology The First Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Neurosurgery Jincheng People’s HospitalJinchengShanxi 048026China Guangdong Provincial Key Laboratory of Artificial Intelligence in medical Image Analysis and Application Guangzhou 510080China

To the Editor:Blindness and vision loss(BVL)constitute a growing concern affecting an ever-expanding global population.[1]Globally,approximately 40%of the population relies on burning solid fuels for both cooking and *** air pollution(HAP)predominantly arises from the incomplete combustion of solid fuels used for ***,the adverse effects of HAP on eye health in human have ascended as a salient concern for environmental,ophthalmic,and public health.[2]Gaining a comprehensive understanding of the burden and temporal trends of BVL due to HAP is the essential basis for health program planning.

关键词： pollution cooking prediction

Ferroptosis:Iron-mediated cell death linked to disease pathogenesis

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Journal of Biomedical Research 2024年第5期38卷 413-435页

作者： Xiangyu Zhang Yingchao Hu Bingwei Wang shuo Yang Department of Immunology State Key Laboratory of Reproductive MedicineJiangsu Key Lab of Cancer BiomarkersPrevention and TreatmentCollaborative Innovation Center for Personalized Cancer MedicineGusu Schoolthe Affiliated Wuxi People's Hospital of Nanjing Medical UniversityWuxi People's HospitalWuxi Medical CenterNanjing Medical UniversityNanjingJiangsu 211166China Department of Pharmacology Nanjing University of Chinese MedicineNanjingJiangsu 210023China

Ferroptosis is a pattern of iron-mediated regulatory cell death characterized by oxidative *** molecular regulatory mechanisms are related to iron metabolism,lipid peroxidation,and glutathione ***,some immunological signaling pathways,such as the cyclic GMP-AMP synthase-stimulator of the interferon gene axis,the Janus kinase-signal transducer and activator of transcription 1 axis,and the transforming growth factor beta 1-smad3 axis,may also participate in the regulation of *** have shown that ferroptosis is significantly associated with many diseases such as cancer,neurodegenerative diseases,inflammatory diseases,and autoimmune *** the pivotal role of ferroptosis-regulating signaling in the pathogenesis of diverse diseases,the development of ferroptosis inducers or inhibitors may have significant clinical potential for the treatment of aforementioned conditions.

关键词： ferroptosis lipid peroxidation molecular regulatory mechanisms ferroptosis-related diseases ferroptosis inducers ferroptosis inhibitors

Toosendanin: upgrade of an old agent in cancer treatment

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Chinese Journal of Natural Medicines 2024年第10期22卷 887-899页

作者： LI shuwei XIONG Qingyi sHEN Yiwen LIN Jiayi ZHANG Lijun WU Ye JIN Jinmei LUAN Xin shanghai Frontiers science Center for Chinese Medicine Chemical Biology Institute of Interdisciplinary Integrative Medicine Research and shuguang Hospital shanghai University of Traditional Chinese Medicine

Toosendanin(TsN), a tetracyclic triterpenoid derived from Melia toosendan and M. azedarach, demonstrates broad application prospects in cancer treatment. Although previously employed as a pesticide, recent studies have revealed its potential therapeutic value in treating various types of cancer. TsN exerts an anticancer effect via mechanisms including proliferation inhibition, apoptosis induction, migration suppression, and angiogenesis inhibition. However, TsN's toxicity, particularly its hepatotoxicity, significantly limits its therapeutic application. This review explored the dual nature of TsN, evaluating both its anticancer potential and toxicological risks, emphasizing the importance of balancing these aspects in therapeutic applications. Furthermore, we investigated the incorporation of TsN into novel therapeutic strategies, such as Proteolysis-targeting chimeras(PROTAC) technology and nanotechnology-based drug delivery systems(DDs), which enhance treatment efficacy while mitigating toxicity in normal tissues.

关键词： Cancer therapy Hepatotoxicity Nano-delivery systems PROTAC Toosendanin

Neuroprotective effects of ZL006 in Aβ1–42-treated neuronal cells

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Neural Regeneration Research 2020年第12期15卷 2296-2305页

作者： Wen-Yuan Tao Lin-Jie Yu su Jiang Xiang Cao Jian Chen Xin-Yu Bao Fei Li Yun Xu Xiao-Lei Zhu Department of Neurology Drum Tower HospitalMedical School of Nanjing UniversityNanjingJiangsu ProvinceChina The state Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjingJiangsu ProvinceChina jiangsu Key Laboratory for Molecular Medicine NanjingJiangsu ProvinceChina Taizhou People’s Hospital TaizhouJiangsu ProvinceChina Department of Medicinal Chemistry School of PharmacyNanjing Medical UniversityNanjingJiangsu ProvinceChina

Amyloid beta(Aβ)-induced neurotoxicity and oxidative stress plays an important role in the pathogenesis of Alzheimer’s disease(AD).ZL006 is shown to reduce over-produced nitric oxide and oxidative stress in ischemic stroke by interrupting the interaction of neuronal nitric oxide synthase and postsynaptic density protein ***,few studies are reported on the role of ZL006 in *** investigate whether ZL006 exerted neuroprotective effects in AD,we used Aβ1–42 to treat primary cortical neurons and N2a neuroblastoma cells as an in vitro model of *** neurons were incubated with ZL006 or dimethyl sulfoxide for 2 hours and treated with Aβ1–42 or NH3·H2O for another 24 *** results of cell counting Kit-8(CCK-8)assay and calcein-acetoxymethylester/propidium iodide staining showed that ZL006 pretreatment rescued the neuronal death induced by Aβ1–*** and western blot assay were used to detect oxidative stress and apoptosis-related proteins in each group of *** showed that ZL006 pretreatment decreased neuronal apoptosis and oxidative stress induced by Aβ1–*** results of CCK8 assay showed that inhibition of Akt or NF-E2-related factor 2(Nrf2)in cortical neurons abolished the protective effects of ***,similar results were also observed in N2a neuroblastoma ***006 inhibited N2a cell death and oxidative stress induced by Aβ1–42,while inhibition of Akt or Nrf2 abolished the protective effect of *** results demonstrated that ZL006 reduced Aβ1–42-induced neuronal damage and oxidative stress,and the mechanisms might be associated with the activation of Akt/Nrf2/heme oxygenase-1 signaling pathways.

关键词： Akt Alzheimer’s disease amyloid-beta apoptosis heme oxygenase-1 neurotoxicity Nrf2 oxidative stress treatment ZL006

MET inhibitor tepotinib antagonizes multidrug resistance mediated by ABCG2 transporter:In vitro and in vivo study

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Acta Pharmaceutica sinica B 2022年第5期12卷 2609-2618页

作者： Zhuo-Xun Wu Qiu-Xu Teng Yuqi Yang Nikita Acharekar Jing-Quan Wang Min He sabesan Yoganathan Jun Lin Jian Wang Zhe-sheng Chen Department of Pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNY 11439USA Department of Anesthesiology Stony Brook University Health Sciences CenterStony BrookNY 11794USA Department of Radiotherapy the Afﬁliated Jiangyin People’s Hospital of Nantong UniversityJiangyin 214400China

Overexpression of ABCG2 transporter in cancer cells has been linked to the development of multidrug resistance(MDR), an obstacle to cancer therapy. Our recent study uncovered that the MET inhibitor,tepotinib, is a potent reversal agent for ABCB1-mediated MDR. In the present study, we reported for the first time that the MET inhibitor tepotinib can also reverse ABCG2-mediated MDR in vitro and in vivo by directly binding to the drug-binding site of ABCG2 and reversibly inhibiting ABCG2 drug efflux activity, therefore enhancing the cytotoxicity of substrate drugs in drug-resistant cancer cells. Furthermore, the ABCB1/ABCG2 double-transfected cell model and ABCG2 gene knockout cell model demonstrated that tepotinib specifically inhibits the two MDR transporters. In mice bearing drug-resistant tumors, tepotinib increased the intratumoral accumulation of ABCG2 substrate drug topotecan and enhanced its antitumor effect. Therefore, our study provides a new potential of repositioning tepotinib as an ABCG2 inhibitor and combining tepotinib with substrate drugs to antagonize ABCG2-mediated MDR.

关键词： MET inhibitor Tepotinib Multidrug resistance ABCG2 transporter Reversal agent Combination treatment Chemotherapy In vivo study

Improving bifunctional catalytic activity of biochar via in-situ growth of nickel-iron hydroxide as cathodic catalyst for zinc-air batteries

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Biochar 2023年第1期5卷 1045-1056页

作者： Pengxiang Zhang Kang sun Yanyan Liu Benji Zhou shuqi Li Jingjing Zhou Ao Wang Lixia Xie Baojun Li Jianchun Jiang College of science Henan Agricultural UniversityZhengzhou 450002China College of Chemistry Zhengzhou UniversityZhengzhou 450001China Institute of Chemical Industry of Forest Products Chinese Academy of Forestry(CAF)Nanjing 210042China

Expanding the application scenarios of wood-derived biochar guided by the conversion of traditional energy to new energy shows great promise as a *** thrilling energy conversion apparatus,zinc-air batteries(ZABs)require cathode catalysts with high oxygen reduction reaction(ORR)and oxygen evolution reaction(OER)activities and ***,two-dimensional nickel-iron hydroxide nanosheets were creatively assembled in N-doped wood-derived biochar(NiFe-LDH@NC)by an in-situ growth *** categorized porous organization in wood-derived biochar facilitates the rapid seepage of electrolytes and rapid diffusion of reaction *** unique interfacial structure of biochar and NiFe-LDH accelerates electron transfer during oxygen electrocatalysis,and endows NiFe-LDH@NC with first-class catalytic activity and durability for ORR and *** ZAB derived from NiFe-LDH@NC showed elevated discharge productivity and cycle endurance,making it promising for viable *** work provided a convenient way for the conversion of wood-derived biochar to high-value added electrocatalysts.

关键词： Wood-derived biochar Oxygen reduction reaction Oxygen evolution reaction Zinc-air batteries

Learning curve of totally thoracoscopic pulmonarysegmentectomy

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Frontiers of Medicine 2018年第5期12卷 586-592页

作者： Weibing Wu Jing Xu Wei Wen Yue Yu Xinfeng Xu Quan Zhu Liang Chen Department of Thoracic surgery The First Affiliated Hospital of Nanjing Medical University Nanjing 210029 China

Totally thoracoscopic pulmonary segmentectomy (TTPs) is a feasible and safe technique that requires advanced thoracoscopic skills and knowledge of pulmonary anatomy. However, data describing the learning curve of TTPs have yet to be obtained. In this study, 128 patients who underwent TTPs between september 2010 and December 2013 were retrospectively analyzed to evaluate the learning curve and were divided chronologically into three phases, namely, ascending phase (A), plateau phase (B), and descending phase (C), through cumulative summation (CUsUM) for operative time (OT). Phases A, B, and C comprised 39, 33, and 56 cases, respectively. OT and blood loss decreased significantly from phases A to C (P scopy for target bronchus identification decreased gradually (A, 8/39; B, 4/33; C, 3/56; P = 0.06). No significant differences were observed in demographic factors, conversion, complications, hospital stay, and retrieved lymph nodes among the three phases. surgical outcomes and techniques improved with experience and volume. CUsUMOT indicated that the learning curve of TTPs should be more than 72 cases.

关键词： thoracoscopic segmentectomy learning curve CUsUM