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T cell interactions with microglia in immune-inflammatory processes of ischemic stroke

Neural Regeneration Research 2025年第5期20卷 1277-1292页

作者： Yuxiao Zheng Zilin Ren ying Liu Juntang Yan Congai chen Yanhui He Yuyu Shi Fafeng cheng Qingguo Wang Changxiang Li Xueqian Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijingChina Library Beijing University of Chinese MedicineBeijingChina Dongzhimen Hospital Beijing University of Chinese MedicineBeijingChina

The primary mechanism of secondary injury after cerebral ischemia may be the brain inflammation that emerges after an ischemic stroke,which promotes neuronal death and inhibits nerve tissue *** the first immune cells to be activated after an ischemic stroke,microglia play an important immunomodulatory role in the progression of the *** an ischemic stroke,peripheral blood immune cells(mainly T cells)are recruited to the central nervous system by chemokines secreted by immune cells in the brain,where they interact with central nervous system cells(mainly microglia)to trigger a secondary neuroimmune *** review summarizes the interactions between T cells and microglia in the immune-inflammatory processes of ischemic *** found that,during ischemic stroke,T cells and microglia demonstrate a more pronounced synergistic ***1,Th17,and M1 microglia can co-secrete proinflammatory factors,such as interferon-γ,tumor necrosis factor-α,and interleukin-1β,to promote neuroinflammation and exacerbate brain ***2,Treg,and M2 microglia jointly secrete anti-inflammatory factors,such as interleukin-4,interleukin-10,and transforming growth factor-β,to inhibit the progression of neuroinflammation,as well as growth factors such as brain-derived neurotrophic factor to promote nerve regeneration and repair brain *** interactions between microglia and T cells influence the direction of the subsequent neuroinflammation,which in turn determines the prognosis of ischemic stroke *** trials have been conducted on the ways to modulate the interactions between T cells and microglia toward anti-inflammatory communication using the immunosuppressant fingolimod or overdosing with Treg cells to promote neural tissue repair and reduce the damage caused by ischemic ***,such studies have been relatively infrequent,and clinical experience is still *** summary,in ischemic stroke,T cell subsets and activated micro

关键词： brain immune inflammation interaction ischemic stroke mechanism microglia neuron secondary injury T cells

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Unveiling phosphofructokinase as the key target: an innovative strategy combining pull-down assays with optical imaging for snail-killing mechanism exploration

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Science China Chemistry 2025年

作者： Yuxun Lu Weisi Wang Le Yu Yuqiang Zhao ying chen Yunhai Guo Bingrong Luo Yuhua Liu Shizhu Li Liping Duan ying Zhou Yunnan Characteristic Plant Extraction Laboratory College of Chemical Science and Technology Yunnan University College of Biological and Chemical Engineering Guangxi University of Science and Technology National Institute of Parasitic Diseases Chinese Center for Disease Control and Prevention (Chinese Center for Tropical Diseases Research)NHC Key Laboratory of Parasite and Vector Biology WHO Collaborating Centre for Tropical Diseases National Center for International Research on Tropical Diseases School of Chemistry and Environment Yunnan Minzu University Dali Institute of Schistosomiasis Control

The Pomacea canaliculata, also known as apple snail, is an invasive species in China, posing a serious threat to agricultural production and public health. To prevent its rampant infestation, we developed a highly efficient snail-killing lead compound, 1-(4-chlorophenyl)-3-(pyridin-3-yl)urea (PBQ). However, the killing mechanism of PBQ remains unclear. To elucidate this, two novel compounds, B-PBQ and J-PBQ, were developed through structural modification of PBQ and were used, through both protein pull-down assay and confocal laser scanning microscopy imaging, to identify and confirm that phosphofructokinase(PFK) in the apple snail is the primary target protein of PBQ. Further studies revealed that PBQ successfully inhibits the activity,content, and expression of PFK in apple snail, disrupting the glycolysis pathway and leading to abnormal energy *** disruptions impair the snail’s tolerance to low oxygen, resulting in its efficient eradication. These findings offer a promising direction for developing next-generation PFK-targeted snail-killing pesticides. Furthermore, the strategy of combining pull-down assays with optical imaging used in this work provides a novel approach for the exploration of mechanisms of other pesticide candidates.

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Deciphering fungal metabolon coupling tandem inverse-electrondemand Diels-Alder reaction and semipinacol rearrangement for the biosynthesis of spiro polycyclic alkaloids

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Science China Chemistry 2025年第1期68卷 288-296页

作者： Shuai Liu Wen-qiang Xu ying-Tong Di Man-cheng Tang Ding-Kang chen Ming-Ming Cao Yao-Wen Chang Hong-Yu Tang Chun-Mao Yuan Jun-Bo Yang Zhi-Li Zuo Han Guo Zi-Fei Xu ying Zeng Yun-Dong Wu Xiao-Jiang Hao Key Laboratory of Phytochemistry and Natural Medicines (Chinese Academy of Sciences) Kunming Institute of Botany Chinese Academy of Sciences University of Chinese Academy of Sciences Lab of Computational Chemistry and Drug Design State Key Laboratory of Chemical Oncogenomics Peking University Shenzhen Graduate School Shenzhen Bay Laboratory State Key Laboratory of Microbial Metabolism School of Life Sciences & Biotechnology Shanghai Jiao Tong University State Key Laboratory of Functions and Applications of Medicinal Plants Guizhou Medical University Molecular Biology Experimental Center Germplasm Bank of Wild Species in Southwest China Kunming Institute of Botany Chinese Academy of Sciences Yunnan Key Laboratory for Wild Plant Resources Kunming Institute of Botany Chinese Academy of Sciences Research Unit of Chemical Biology of Natural Anti-Virus Products Chinese Academy of Medical Sciences

In the intricate process of natural product biosynthesis, a metabolon can enhance metabolic flux by associating sequential enzymes. A fungal metabolon, comprising of flavin-dependent monooxygenase Spe F and P450 monooxygenase Spe G, is identified in the biosynthesis of spiro polycyclic alkaloids(+)-notoamide B and its diastereomer(+)-versicolamide B. Using notoamide E as a substance, Spe F/Spe G metabolon can control the stereoselectivity of its 2,3-epoxidation, followed by hydrogen atom ion at C-17 to generate reactive epoxide tau-m A with dienyl iminium unit. Subsequently,(+)-notoamide B and(+)-versicolamide B are produced via tandem nonenzymatic inverse-electron-demand Diels-Alder reaction and semipinacol rearrangement. This provides the first example of metabolon in the biosynthesis of spiro-prenylated indole alkaloids.

关键词： metabolon Diels-Alder reaction semipinacol rearrangement biosynthesis notoamides spiro polycyclic alkaloids

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Exploring the interaction between the gut microbiota and cyclic adenosine monophosphate-protein kinase A signaling pathway:a potential therapeutic approach for neurodegenerative diseases

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Neural Regeneration Research 2025年第11期20卷 3095-3112页

作者： Fengcheng Deng Dan Yang Lingxi Qing Yifei chen Jilian Zou Meiling Jia qian Wang Runda Jiang Lihua Huang College of Pharmacy Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina State Key Laboratory of Southwestern Chinese Medicine Resources Chengdu University of Traditional Chinese MedicineChengduSichuan ProvinceChina

The interaction between the gut microbiota and cyclic adenosine monophosphate(cAMP)-protein kinase A(PKA)signaling pathway in the host's central nervous system plays a crucial role in neurological diseases and enhances communication along the gut–brain *** gut microbiota influences the cAMP-PKA signaling pathway through its metabolites,which activates the vagus nerve and modulates the immune and neuroendocrine ***,alterations in the cAMP-PKA signaling pathway can affect the composition of the gut microbiota,creating a dynamic network of microbial-host *** reciprocal regulation affects neurodevelopment,neurotransmitter control,and behavioral traits,thus playing a role in the modulation of neurological *** coordinated activity of the gut microbiota and the cAMP-PKA signaling pathway regulates processes such as amyloid-β protein aggregation,mitochondrial dysfunction,abnormal energy metabolism,microglial activation,oxidative stress,and neurotransmitter release,which collectively influence the onset and progression of neurological *** study explores the complex interplay between the gut microbiota and cAMP-PKA signaling pathway,along with its implications for potential therapeutic interventions in neurological *** pharmacological research has shown that restoring the balance between gut flora and cAMP-PKA signaling pathway may improve outcomes in neurodegenerative diseases and emotional *** can be achieved through various methods such as dietary modifications,probiotic supplements,Chinese herbal extracts,combinations of Chinese herbs,and innovative dosage *** findings suggest that regulating the gut microbiota and cAMP-PKA signaling pathway may provide valuable evidence for developing novel therapeutic approaches for neurodegenerative diseases.

关键词： cyclic adenosine monophosphate emotional disorders gut microbiota neurodegenerative diseases neurological diseases protein kinase A reciprocal regulation signaling pathway strategy therapies

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Pharmacological targeting cGAS/STING/NF-κB axis by tryptanthrin induces microglia polarization toward M2 phenotype and promotes functional recovery in a mouse model of spinal cord injury

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Neural Regeneration Research 2025年第11期20卷 3287-3301页

作者： Ziwei Fan Mengxian Jia Jian Zhou Zhoule Zhu Yumin Wu Xiaowu Lin Yiming qian Jiashu Lian Xin Hua Jianhong Dong Zheyu Fang Yuqing Liu Sibing chen Xiumin Xue Juanqing Yue Minyu Zhu ying Wang Zhihui Huang Honglin Teng Department of Orthopedics(Spine Surgery) the First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina School of Pharmacy Hangzhou Normal UniversityHangzhouZhejiang ProvinceChina Department of Neurology The First Affiliated Hospital of Wenzhou Medical UniversityWenzhouZhejiang ProvinceChina Department of Pathology Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina Department of Clinical Research Center Affiliated Hangzhou First People’s HospitalSchool of MedicineWestlake UniversityHangzhouZhejiang ProvinceChina

The M1/M2 phenotypic shift of microglia after spinal cord injury plays an important role in the regulation of neuroinflammation during the secondary injury phase of spinal cord *** of shifting microglia polarization from M1(neurotoxic and proinflammatory type)to M2(neuroprotective and anti-inflammatory type)after spinal cord injury appears to be *** possesses an anti-inflammatory biological ***,its roles and the underlying molecular mechanisms in spinal cord injury remain *** this study,we found that tryptanthrin inhibited microglia-derived inflammation by promoting polarization to the M2 phenotype in *** promoted M2 polarization through inactivating the cGAS/STING/NF-κB ***,we found that targeting the cGAS/STING/NF-κB pathway with tryptanthrin shifted microglia from the M1 to M2 phenotype after spinal cord injury,inhibited neuronal loss,and promoted tissue repair and functional recovery in a mouse model of spinal cord ***,using a conditional co-culture system,we found that microglia treated with tryptanthrin suppressed endoplasmic reticulum stress-related neuronal *** together,these results suggest that by targeting the cGAS/STING/NF-κB axis,tryptanthrin attenuates microglia-derived neuroinflammation and promotes functional recovery after spinal cord injury through shifting microglia polarization to the M2 phenotype.

关键词： cGAS/STING functional recovery microglia neuroinflammation neuroprotection nuclear factor-κB polarization spinal cord injury tryptanthrin

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Insufficient MIRO1 contributes to declined oocyte quality during reproductive aging

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Science China Life Sciences 2025年

作者： Zhen-Nan Pan Hao-Lin Zhang Kun-Huan Zhang Jia-qian Ju Jing-Cai Liu Shao-chen Sun College of Animal Science and Technology Nanjing Agricultural University Reproductive Medicine Centre The Affiliated Yantai Yuhuangding Hospital of Qingdao University

Mitochondrial Rho-GTPase 1 (MIRO1) is an outer mitochondrial membrane protein which regulates mitochondrial transport and mitophagy in mitosis. In present study, we reported the crucial roles of MIRO1 in mammalian oocyte meiosis and its potential relationship with aging. We found that MIRO1 expressed in mouse and porcine oocytes, and its expression decreased in aged mice. MIRO1 deficiency caused the failure of meiotic resumption and polar body extrusion in both mouse and porcine oocytes, which could be rescued by exogenous MIRO1supplementation. Mass spectrometry data indicated that MIRO1 associated with several cytoskeleton and cell cycle-related proteins, and MIRO1 regulated motor protein Dynein for microtubule-organizing centers (MTOCs) dynamics at germinal vesicle (GV) stage, which determined meiotic resumption. Furthermore, we found that MIRO1 regulated Aurora A and kinesin family member 11 (KIF11) for meiotic spindle assembly in oocytes. Besides, MIRO1 associated with several mitochondria-related proteins dynamic-related protein 1 (DRP1),Parkin and lysosomal-associated membrane protein 2 (LAMP2) for mitochondrial dynamics and mitophagy during oocyte meiosis. Taken together, our results suggested that MIRO1 played pivotal roles in meiotic resumption, spindle assembly and mitochondrial function in mouse and porcine oocytes, and its insufficiency might contribute to the oocyte maturation defects during aging.

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Identification of a dual functional betulinic acid analog for the treatment of osteoarthritis by phenotypic screening

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Science China Life Sciences 2025年第1期68卷 300-302页

作者： Ze-Min Lin Mai Xiang Wen-Hui Wei Shu-Hui Fan Li chen Jie Wang Xiao-qian Yang Chun-Hao Yang Shi-Jun He Jian-Ping Zuo Laboratory of Immunopharmacology State Key Laboratory of Drug ResearchShanghai Institute of Materia MedicaChinese Academy of Sciences School of Pharmacy University of Chinese Academy of Sciences School of Pharmacy Nanjing University of Chinese Medicine State Key Laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of Sciences Innovation Research Institute of Traditional Chinese Medicine Shanghai University of Traditional Chinese Medicine Experiment Center for Science and Technology Shanghai University of Traditional Chinese Medicine

Dear Editor, Phenotypic drug discovery, which observes compound effects on physiology,has given way to targeting specific molecules, but has revived by using modern methods to find drugs based on therapeutic outcomes in disease models(Vincent et al., 2022). Osteoarthritis(OA) is a prevalent chronic joint disorder, primarily affecting knee joints, with osteoclast activation due to low-grade inflammation resulting in increased bone resorption and structural changes in the joint(Katz et al.,2021).

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成人EB病毒阳性T细胞淋巴组织增殖性疾病13例临床分析

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中华血液学杂志 2017年第3期38卷 243-246页

作者：施鹏飞谢亚萍徐颖钱申贤陈况高大泉黄细莲杭州市第一人民医院血液科、南京医科大学附属杭州医院血液科 310006

2008年WHO关于造血和淋巴组织肿瘤分类中列入2种EBV阳性T细胞淋巴增殖性疾病（***-cell lymphoproliferative disorders，EBV＋T-LPD），包括种痘水疱病样淋巴瘤和儿童系统性EBV＋T-LPD。

关键词：淋巴组织增殖性疾病 EBV阳性 T细胞临床分析 EB病毒淋巴增殖性疾病成人淋巴组织肿瘤

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皮肤科门诊男性患者人乳头瘤病毒感染情况及分型

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中国感染控制杂志 2024年第10期23卷 1258-1263页

作者：左安欣钱影臣张晓妹周丹仝放仇玮南京市江宁医院病理科江苏南京211100

目的分析皮肤科门诊男性患者人乳头瘤病毒(HPV)感染情况及基因亚型分布,为防治男性HPV感染提供参考。方法回顾性调查2022年1月-2023年3月在某院皮肤科门诊就诊并进行HPV检测的男性患者,并将全部受检患者分为5组:病毒性疣组、皮炎皮疹组... 详细信息

目的分析皮肤科门诊男性患者人乳头瘤病毒(HPV)感染情况及基因亚型分布,为防治男性HPV感染提供参考。方法回顾性调查2022年1月-2023年3月在某院皮肤科门诊就诊并进行HPV检测的男性患者,并将全部受检患者分为5组:病毒性疣组、皮炎皮疹组、泌尿道感染组、包皮阴茎炎组、无症状组。统计分析患者年龄组成、临床诊断、症状类型与基因型分布之间的关系。结果共有1035例男性患者进行了HPV检测,567例检测阳性,阳性率54.78%。其中病毒性疣组286例,皮炎皮疹组164例,泌尿道感染组6例,包皮阴茎炎组109例,无症状组470例。21种HPV亚型均被检出,检出率位于前3位的亚型依次是6型(17.97%)、11型(12.37%)、52型(8.70%)。单一型HPV感染阳性率为29.86%,占54.50%。不同年龄组的感染阳性率、低危感染阳性率和多重混合型感染阳性率比较,差异均有统计学意义(均P<0.05)。<20岁年龄组感染阳性率高于20~<30岁组、30~<40岁组和40~<50岁组,差异均有统计学意义(均P<0.05)。阳性患者中199例(35.10%)无临床症状,368例(64.90%)有临床症状,主要表现为病毒性疣(40.74%,231例)。病毒性疣组中HPV阳性患者以低危型为主,占80.95%;包皮阴茎炎组中HPV阳性患者以高危型为主,占84.78%;无症状组中HPV阳性患者以高危型感染为主,占86.43%。结论皮肤科门诊男性HPV感染以单一型感染为主,低危型感染临床诊断主要表现为病毒性疣,高危型感染主要表现为包皮阴茎炎,无症状组中阳性感染者以高危型为主。

关键词：人乳头瘤病毒男性基因型临床症状 HPV

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阳离子抗菌肽溶血性的研究进展

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药物生物技术 2016年第6期23卷 535-539页

作者：李绘春荣炜炜钱康英陈玉清南京师范大学生命科学学院江苏省分子医学生物技术重点实验室江苏南京210000

阳离子抗菌肽是一类小分子多肽,具有抗细菌、抗真菌、病毒等微生物感染以及杀伤恶性肿瘤细胞等多种生物学功能,具有发展为新型抗菌、抗癌药物的重要应用前景。然而,抗菌肽的溶血毒性仍然是阻碍抗菌肽应用的关键因素。该文主要从螺旋度... 详细信息

阳离子抗菌肽是一类小分子多肽,具有抗细菌、抗真菌、病毒等微生物感染以及杀伤恶性肿瘤细胞等多种生物学功能,具有发展为新型抗菌、抗癌药物的重要应用前景。然而,抗菌肽的溶血毒性仍然是阻碍抗菌肽应用的关键因素。该文主要从螺旋度、两亲性、疏水性、电荷等阳离子抗菌肽自身的结构参数以及膜脂、膜蛋白、糖分子等红细胞膜的结构组分两方面对抗菌肽溶血机制的研究进展进行了综述,并简述了降低溶血性的研究进展,期望能有助于设计治疗潜力的抗菌肽应用于临床。

关键词：阳离子抗菌肽溶血性结构参数红细胞细胞膜

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