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Regulatory role of peroxynitrite in advanced glycation end products mediated diabetic cardiovascular complications

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World Journal of Diabetes 2024年第3期15卷 572-574页

作者： Asis Bala Pharmacology and Drug Discovery Research Laboratory Division of Life SciencesInstitute of Advanced Study in Science and TechnologyGuwahati 781035AssamIndia

The Advanced Glycation End Products(AGE)binding with its receptor can increase reactive oxygen species(ROS)generation through specific signaling *** effect of superoxide(O2-)and O2-mediated ROS and reactive nitrogen species depends on their concentration and location of *** oxide(NO)has anti-inflammatory and anticoagulant properties and a vasodilation effect,but NO can be deactivated by reacting with O_(2)^(-).This reaction between NO and O2-produces the potent oxidant ONOO−.Therefore,ONOO-'s regulatory role in AGEs in diabetic cardiovascular complications must considered as a regulator of cardiovascular complications in diabetes.

关键词： Diabetes Cardiovascular complication Advanced glycation end products Reactive oxygen species Reactive nitrogen species Peroxynitrite

Fusobacterium nucleatum-induced imbalance in microbiome-derived butyric acid levels promotes the occurrence and development of colorectal cancer

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World Journal of Gastroenterology 2024年第14期30卷 2018-2037页

作者： Qi-Long Wu Xiao-Ting Fang Xin-Xin Wan Qing-Yong Ding Yan-Jun Zhang Ling Ji Yong-Liang Lou Xiang Li School of Laboratory medicine and life sciences Wenzhou Medical UniversityKey Laboratory of Laboratory MedicineMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesWenzhou 325035Zhejiang ProvinceChina School of Laboratory medicine and life sciences Wenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of General Surgery The First Affiliated Hospital of Wenzhou Medical UniversityWenzhou 325035Zhejiang ProvinceChina School of Laboratory medicine and life sciences Institute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina Department of Health Inspection and Quarantine School of Laboratory Medicine and Life SciencesInstitute of One HealthWenzhou Medical UniversityZhejiang Provincial Key Laboratory of Medical GeneticsMinistry of EducationWenzhou 325035Zhejiang ProvinceChina

BACKGROUND Colorectal cancer(CRC)ranks among the most prevalent malignant tumors *** reports suggest that Fusobacterium nucleatum(***)contributes to the initiation,progression,and prognosis of ***,a short-chain fatty acid derived from the bacterial fermentation of soluble dietary fiber,is known to inhibit various *** study is designed to explore whether *** influences the onset and progression of CRC by impacting the intestinal metabolite butyric *** To investigate the mechanism by which *** affects CRC occurrence and *** Alterations in the gut microbiota of BALB/c mice were observed following the oral administration of ***,DLD-1 and HCT116 cell lines were exposed to sodium butyrate(NaB)and *** in vitro to examine the effects on proliferative proteins and mitochondrial *** Our research indicates that the prevalence of *** in fecal samples from CRC patients is significantly greater than in healthy counterparts,while the prevalence of butyrate-producing bacteria is notably *** mice colonized with ***,the population of butyrate-producing bacteria decreased,resulting in altered levels of butyric acid,a key intestinal metabolite of *** to NaB can impair mitochondrial morphology and diminish mitochondrial membrane potential in DLD-1 and HCT116 CRC ***,this leads to modulated production of adenosine triphosphate and reactive oxygen species,thereby inhibiting cancer cell ***,NaB triggers the adenosine monophosphate-activated protein kinase(AMPK)signaling pathway,blocks the cell cycle in HCT116 and DLD-1 cells,and curtails the proliferation of CRC *** combined presence of *** and NaB attenuated the effects of the *** employing small interfering RNA to suppress AMPK,it was demonstrated that AMPK is essential for NaB’s inhibition of CRC cell *** F.n

关键词： Colorectal cancer Fusobacterium nucleatum Butyric acid Gut microbiota Adenosine monophosphate-activated protein kinase signal pathway

Frontiers and future perspectives of neuroimmunology

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Fundamental Research 2024年第2期4卷 206-217页

作者： Hai Qi Shumin Duan Yanying Xu Hongliang Zhang School of medicine Tsinghua UniversityBeijing 100084China Faculty of medicine and Pharmaceutical sciences Zhejiang UniversityHangzhou 310014China Department of life sciences National Natural Science Foundation of ChinaBeijing 100085China

Neuroimmunology is an interdisciplinary branch of biomedical science that emerges from the intersection of studies on the nervous system and the immune *** complex interplay between the two systems has long been *** efforts directed at the underlying functional interface and associated pathophysiology,however,have garnered attention only in recent *** this narrative review,we highlight significant advances in research on neuroimmune interplay and modulation.A particular focus is on early-and middle-career neuroimmunologists in China and their achievements in frontier areas of"neuroimmune interface","neuro-endocrine-immune network and modulation","neuroimmune interactions in diseases","meningeal lymphatic and glymphatic systems in health and disease",and"tools and methodologies in neuroimmunology research".Key scientific questions and future directions for potential breakthroughs in neuroimmunology research are proposed.

关键词： Neuroimmunology Neuroimmune interplay Neuro-endocrine-immune network Basic research Key scientific questions

Extracellular Disintegration of Viral Proteins as an Innovative Strategy for Developing Broad-Spectrum Antivirals Against Coronavirus

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CCS Chemistry 2024年第2期6卷 487-496页

作者： Ke Sun Zhe Ding Xiaoying Jia Haonan Cheng Yingwen Li Yan Wu Zhuoyu Li Xiaohua Huang Fangxu Pu Entao Li Guiyou Wang Wei Wang Yun Ding Gary Wong Sandra Chiu Jiaming Lan Aiguo Hu Shanghai Key Laboratory of Advanced Polymeric Materials School of Materials Science and EngineeringEast China University of Science and TechnologyShanghai 200237 CAS Key Laboratory of Molecular Virology&Immunology Chinese Academy of SciencesShanghai 200031 University of the Chinese Academy of sciences Beijing 100049 State Key Laboratory of Virology Center for Biosafety Mega-ScienceWuhan Institute of VirologyChinese Academy of SciencesWuhan 430071 division of life sciences and medicine University of Science and Technology of ChinaHefeiAnhui 230027 Department of Clinical Laboratory The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230001

The coronavirus disease 2019(COVID-19)pandemic,caused by severe acute respiratory syndrome coronavirus 2(SARS-CoV-2),has claimedmillions of lives and caused innumerable economic losses ***,state-of-the-art treatments still lag behind the continual emergence of new *** to resolving this issue is developing antivirals to deactivate coronaviruses regardless of their structural ***,we report an innovative antiviral strategy involving extracellular disintegration of viral proteins with hyperanion-grafted enediyne(EDY)*** core EDY generates reactive radical species and causes significant damage to the spike protein of coronavirus,while the hyperanion groups ensure negligible cytotoxicity of the *** EDYs exhibit antiviral activity down to nanomolar concentrations,and the selectivity index of up to 20,000 against four kinds of human coronavirus,including the SARS-CoV-2 Omicron variant,suggesting the high potential of this new strategy in combating the COVID-19 pandemic and a future“disease X.”

关键词： enediyne broad spectrum antiviral protein disintegration coronavirus polyanions

Rotating magnetic field inhibits Aβ protein aggregation and alleviates cognitive impairment in Alzheimer’s disease mice

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Zoological Research 2024年第4期45卷 924-936页

作者： Ruo-Wen Guo Wen-Jing Xie Biao Yu Chao Song Xin-Miao Ji Xin-Yu Wang Mei Zhang Xin Zhang High Magnetic Field Laboratory CAS Key Laboratory of High Magnetic Field and Ion Beam Physical BiologyHefei Institutes of Physical ScienceChinese Academy of SciencesHefeiAnhui 230031China Science Island Branch of Graduate School University of Science and Technology of ChinaHefeiAnhui 230036China Institutes of Physical Science and Information Technology Anhui UniversityHefeiAnhui 230601China School of life sciences Division of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefeiAnhui 230026China

Amyloid beta(Aβ)monomers aggregate to form fibrils and amyloid plaques,which are critical mechanisms in the pathogenesis of Alzheimer’s disease(AD).Given the important role of Aβ1-42 aggregation in plaque formation,leading to brain lesions and cognitive impairment,numerous studies have aimed to reduce Aβaggregation and slow AD *** diphenylalanine(FF)sequence is critical for amyloid aggregation,and magnetic fields can affect peptide alignment due to the diamagnetic anisotropy of aromatic *** this study,we examined the effects of a moderate-intensity rotating magnetic field(RMF)on Aβaggregation and AD *** indicated that the RMF directly inhibited Aβamyloid fibril formation and reduced Aβ-induced cytotoxicity in neural cells in *** the AD mouse model APP/PS1,RMF restored motor abilities to healthy control levels and significantly alleviated cognitive impairments,including exploration and spatial and non-spatial memory *** examinations demonstrated that RMF reduced amyloid plaque accumulation,attenuated microglial activation,and reduced oxidative stress in the APP/PS1 mouse *** findings suggest that RMF holds considerable potential as a non-invasive,high-penetration physical approach for AD treatment.

关键词： lzheimer’s disease Rotating magnetic field Amyloid-β Cognitive function Alzheimer’s disease animal models

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Retinitis pigmentosa and stem cell therapy

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International Journal of Ophthalmology(English edition) 2024年第7期17卷 1363-1369页

作者： Xin-Ya Qi Chen-Hui Mi De-Rui Cao Xie-Qun Chen Peng Zhang School of medicine Department of Life Sciences and MedicineNorthwest UniversityXi’an 710069Shaanxi ProvinceChina The Third Hospital of Xi’an Affiliated Hospital of Northwest UniversityXi’an 710021Shaanxi ProvinceChina

Retinitis pigmentosa(RP)is a group of genetic disorders characterized by progressive degeneration of photoreceptors and retinal pigment epithelium(RPE)*** main clinical manifestations include night blindness and progressive loss of peripheral vision,making it a prevalent debilitating eye disease that significantly impacts patients’quality of *** exhibits significant phenotypic and genetic *** instance,numerous abnormal genes are implicated in RP,resulting in varying clinical presentations,disease progression rates,and pathological characteristics among different ***,gene therapy for RP poses challenges due to these ***,stem cells have garnered considerable attention in the field of RPE therapy since both RPE cells and photoreceptors can be derived from stem *** recent years,a large number of animal experiments and clinical trials based on stem cell transplantation attempts,especially cord blood mesenchymal stem cell(MSC)transplantation and bone marrow-derived MSC transplantation,have confirmed that stem cell therapy can effectively and safely improve the outer retinal function of the RP-affected ***,stem cell therapy also has certain limitations,such as the fact that RP patients may involve multiple types of retinal cytopathia,which brings great challenges to stem cell transplantation therapy,and further research is needed to solve various problems faced by this approach in the *** comprehensive analysis of the etiology and histopathological changes associated with RP,this study substantiates the efficacy and safety of stem cell therapy based on rigorous animal experimentation and clinical trials,while also highlighting the existing limitations that warrant further investigation.

关键词： retinitis pigmentosa photoreceptor stem cell therapy

Osteoarthritis versus psoriasis arthritis: Physiopathology, cellular signaling, and therapeutic strategies

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Genes & Diseases 2024年第3期11卷 232-247页

作者： Salma Nassor Juma Junguang Liao Yuping Huang Rexhina Vlashi Qingwan Wang Bocong Wu Dan Wang Mengrui Wu Guiqian Chen College of life Science and medicine Zhejiang Provincial Key Laboratory of Silkworm Bioreactor and BiomedicineZhejiang Sci-Tech UniversityHangzhouZhejiang 310018China Department of Cell and Developmental Biology College of Life SciencesZhejiang UniversityHangzhouZhejiang 310058China

Osteoarthritis and psoriasis arthritis are two degenerative forms of arthritis that share similar yet also different manifestations at the histological,cellular,and clinical *** have marked them as two entirely distinct *** recent dis-coveries in disease initiation and progression,potential mechanisms,cellular signaling path-ways,and ongoing clinical therapeutics,there are now more opportunities for discovering osteoarthritis *** review summarized the osteoarthritis and psoriasis arthritis signaling pathways,crosstalk between BMP,WNT,TGF-β,VEGF,TLR,and FGF signaling pathways,bio-markers,and anatomical *** bench research,we demonstrated that regen-erative medicine is a promising alternative for treating osteoarthritis by highlighting significant scientific discoveries on entheses,multiple signaling blockers,and novel molecules such as immunoglobulin new antigen receptors targeted for potential drug ***,we offered valuable therapeutic approaches with a multidisciplinary strategy to treat patients with osteoarthritis or psoriasis arthritis in the coming future in the clinic.

关键词： Newantigen receptor Osteoarthritis Physiopathology Psoriasisarthritis Signaling pathway

STING signaling in islet macrophages impairs insulin secretion in obesity

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Science China(life sciences) 2024年第2期67卷 345-359页

作者： Ze Hong Saihua Chen Jing Sun Dan Cheng Hanli Guo Jiahao Mei Xiang Zhang Munire Maimaiti Haiping Hao Peng Cao Haiyang Hu Chen Wang School of Pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Natural medicines Department of Life Science and TechnologyChina Pharmaceutical UniversityNanjing 211198China School of life sciences Westlake UniversityHangzhou 310012China

The innate immune regulator stimulator of interferon genes(STING)mediates self-DNA sensing and leads to the induction of type I interferons and inflammatory cytokines,which promotes the progression of various inflammatory and autoimmune *** immune system plays a critical role in regulating obesity-induced islet dysfunction,whereas the potential effect of STING signaling is not fully ***,we demonstrate that STING is mainly expressed and activated in islet macrophages upon high-fat diet(HFD)***^(-/-)alleviates HFD-induced islet inflammation by inhibiting the expression of pro-inflammatory cytokines and the infiltration of ***,palmitic acid incubation promotes mitochondrial DNA leakage into the cytosol and subsequently activates STING pathway in ***,STING activation in macrophages impairs glucose-stimulated insulin secretion by mediating the engulfment ofβcell insulin secretory *** inhibiting STING activation enhances insulin secretion to control ***,our results reveal a regulatory mechanism in controlling the islet inflammation and insulin secretion in dietinduced obesity and suggest that selective blocking of the STING activation may be a promising strategy for treating type 2 diabetes.

关键词： STING obesity type 2 diabetes insulin macrophages islet

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Immune checkpoint inhibitors:breakthroughs in cancer treatment

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Cancer Biology & medicine 2024年第6期21卷 451-472页

作者： Xueqing Kong Jinyi Zhang Shuwei Chen Xianyang Wang Qing Xi Han Shen Rongxin Zhang Laboratory of Immunology and Inflammation School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China Department of Biology School of Life Sciences and BiopharmaceuticsGuangdong Pharmaceutical UniversityGuangzhou 510006China

Over the past two decades,immunotherapies have increasingly been considered as first-line treatments for most *** such treatment is immune checkpoint blockade(ICB),which has demonstrated promising results against various solid tumors in clinical *** antibodies(mAbs)are currently available as immune checkpoint inhibitors(ICIs).These ICIs target specific immune checkpoints,including cytotoxic T-lymphocyte-associated antigen-4(CTLA-4)and programmed cell death protein 1(PD-1).Clinical trial results strongly support the feasibility of this immunotherapeutic ***,a substantial proportion of patients with cancer develop resistance or tolerance to treatment,owing to tumor immune evasion mechanisms that counteract the host immune ***,substantial research focus has been aimed at identifying additional ICIs or synergistic inhibitory receptors to enhance the effectiveness of anti-PD-1,anti-programmed cell death ligand 1(anti-PD-L1),and anti-CTLA-4 ***,several immune checkpoint molecular targets have been identified,such as T cell immunoreceptor with Ig and ITIM domains(TIGIT),mucin domain containing-3(TIM-3),lymphocyte activation gene-3(LAG-3),V-domain immunoglobulin suppressor of T cell activation(VISTA),B and T lymphocyte attenuator(BTLA),and signal-regulatory proteinα(SIRPα).Functional m Abs targeting these molecules are under ***-4,PD-1/PD-L1,and other recently discovered immune checkpoint proteins with distinct structures are at the forefront of *** review discusses these structures,as well as clinical progress in m Abs targeting these immune checkpoint molecules and their potential applications.

关键词： Immunotherapy cancer ICIs PD-1 CTLA-4

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