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Chemical warfare agent countermeasures based on macrocycle supramolecular chemistry

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Science China Chemistry 2024年

作者： Junyi Chen Yahan Zhang Chunju Li Qingbin Meng State Key Laboratory of National Security Specially Needed Medicines Beijing Institute of Pharmacology and Toxicology Tianjin Key Laboratory of Structure and Performance for Functional Molecules College of Chemistry Tianjin Normal University

Given that chemical warfare agents(CWAs) pose some of the largest threats to humankind, social stability, and world peace,considerable attention has been drawn to the development of the corresponding detection, decontamination, and treatment techniques. The versatile functionality and distinctive recognition potency of macrocycles enable their customized design for specific tasks, such as chemical sensing, catalysis, or separation. Hence, supramolecular materials are well suited for the establishment of CWA countermeasures. Herein, we summarize the recent progress in the development of macrocycle-based materials for counteracting several representative CWAs, including nerve, blister, blood, incapacitating, choking, and irritating agents, providing a foundation for further advances in this field and fostering practical translational terms.

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Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik Department of pharmacology School of Health SciencesCentral University of PunjabBathindaPunjab 151401India Department of Pharmacological and Pharmaceutical Sciences College of PharmacyUniversity of HoustonHoustonTX 77204-5000USA Department of Human Genetics and Molecular Medicine School of Health SciencesCentral University of PunjabBathindaPunjab 151401India

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various *** investigations into the bioactive properties of visnagin have been studied to *** literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal ***,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates ***,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical *** current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of *** review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Visnagin Phytochemical Anti-inflammatory Ammi visnaga L. Visnaga daucoides Gaertn Cancer

LncR NA CCRR maintains Cahomeostasis against myocardial infarction through the FTO-SERCA2a pathway

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Science China Life Sciences 2024年

作者： Hua Yang Lina Xuan Shengjie Wang Huishan Luo Xiaomeng Duan Jianjun Guo Shijia Cui Jieru Xin Junwei Hao Xiufang Li Jun Chen Feihan Sun Xiaolin Hu Siyun Li Ying Zhang Lei Jiao Baofeng Yang Lihua Sun Department of pharmacology Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular DiseaseJoint International Research Laboratory of Cardiovascular Medicine Research Ministry of Education China) College of Pharmacy Harbin Medical University Department of pharmacology Harbin Medical University (State Key Laboratory of Frigid Zone Cardiovascular Disease Joint International Research Laboratory of Cardiovascular Medicine Research Ministry of Education China) College of Pharmacy Harbin Medical University

Cardiac conduction regulatory RNA(CCRR) has been documented as an antiarrhythmic lncRNA in our earlier investigation. This study aimed to evaluate the effects of CCRR on SERCA2a and the associated Ca2+homeostasis in myocardial infarction(MI). Overexpression of CCRR via AAV9-mediated delivery not only partially reversed ischemia-induced contractile dysfunction but also alleviated abnormal Ca2+homeostasis and reduced the heightened methylation level of SERCA2a following MI. These effects were also observed in CCRR overexpressing transgenic mice. A conserved sequence domain of CCRR mimicked the protective function observed with the full ***, silencing CCRR in healthy mice led to intracellular Ca2+overloading of cardiomyocytes. CCRR increased SERCA2a protein stability by upregulating FTO expression. The direct interaction between CCRR and FTO protein was characterized by RNA-binding protein immunoprecipitation(RIP) analysis and RNA pulldown experiments. Activation of NFATc3 was identified as an upstream mechanism responsible for CCRR downregulation in MI. This study demonstrates that CCRR is a protective lncRNA that acts by maintaining the function of FTO, thereby reducing the m6A RNA methylation level of SERCA2a, ultimately preserving calcium homeostasis for myocardial contractile function in MI. Therefore, CCRR may be considered a promising therapeutic strategy with a beneficial role in cardiac pathology.

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Commentary on“Synchronized activity of sensory neurons initiates cortical synchrony in a model of neuropathic pain”

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Neural Regeneration Research 2024年第4期19卷 728-728页

作者： Lorenzo Di Cesare Mannelli Carla Ghelardini Department of Neuroscience PsychologyDrug Research and Child Health-Neurofarba-Section of Pharmacology and ToxicologyUniversity of Florence

In pat i e nt s,a s well as in animal mod e l s,hypersensitivity to external stimuli(hyperalgesia and allodynia)or spontaneous pain is often the first,and the most disabling,symptom of neuropathy(Davis et al.,2020).The increased activity of sensitive neurons drives pain development,making ion channel modulation a fundamental target for current pharmacotherapy as well as one of the most investigated by the R&D departments of pharmaceutical companies(Bennett et al.,2019).

关键词： companies pain ent

Compartmentalized regulation of organelle integrity in neurodegenerative diseases:lessons from the Drosophila motor neuron

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Neural Regeneration Research 2025年第1期20卷 195-196页

作者： Hyun Sung Department of Neurology Johns Hopkins University School of MedicineBaltimoreMDUSA Medical Research Institute and Department of PharmacologyPusan National University School of MedicineYangsanRepublic of Korea

Neurons are highly polarized,morphologically asymmetric,and functionally compartmentalized cells that contain long axons extending from the cell *** this reason,their maintenance relies on spatiotemporal regulation of organelle distribution between the somatodendritic and axonal *** some organelles,such as mitochondria and smooth endoplasmic reticulum,are widely distributed throughout the neuron,others are segregated to either the somatodendritic or axonal *** example,Golgi outposts and acidified lysosomes are predominantly present in the somatodendritic domain and rarely distributed along the axon,whereas newly formed autophagosomes and synaptic vesicles are mainly distributed in the distal axon(Britt et al.,2016).

关键词： organelle regulation distribution

具有快上转化速率的窄光谱蓝光多重共振发光材料（英文）

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Science China Materials 2024年

作者：田杨苏蓉川刘俊杰雷搏文刘旻昊宾正杨 College of Chemistry Sichuan University Department of pharmacology North Sichuan Medical University

如何提高蓝光多重共振发光材料的反隙间窜跃速率(kRISC),并维持较快的辐射跃迁速率(kR)是促进其进一步发展和应用的关键.本论文报道了一种简单且高效的“空间限制的受体-供体-受体(SCADA)”策略,旨在加速蓝色多重共振发光分子的上转化过...

如何提高蓝光多重共振发光材料的反隙间窜跃速率(kRISC),并维持较快的辐射跃迁速率(kR)是促进其进一步发展和应用的关键.本论文报道了一种简单且高效的“空间限制的受体-供体-受体(SCADA)”策略,旨在加速蓝色多重共振发光分子的上转化过程.在多重共振中心骨架的最高占据轨道(HOMO)分布位点引入两个氰基苯受体,并在最低位占据轨道(LUMO)引入一个叔丁基咔唑给体,使发射波长蓝移的同时,减小发射的半峰宽(FWHM).此外,供体单元和受体单元呈现近距离的面对面取向,产生分子内给受体相互作用,进而增强自旋轨道耦合,加速反隙间窜跃过程.基于“SCADA”策略,本文成功开发出蓝光多重共振发光分子2DCNCz-BN,其FWHM仅为19 nm,并同时具有较快的kRISC(1.8×106s-1)和kR(2.0×108s-1).以2DCNCz-BN为发光分子的OLED器件,最大外量子效率(EQEmax)为30.2%,并展现出较低的效率滚降,在1000 cd m-2的亮度下, EQE可以维持22.3%.

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Regulation of sleep by astrocytes in the hypothalamic ventrolateral preoptic nucleus

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Neural Regeneration Research 2025年第4期20卷 1098-1100页

作者： Jae-Hong Kim Ruqayya Afridi Il-Sung Jang Maan Gee Lee Kyoungho Suk Brain Korea 21 four KNU Convergence Educational Program of Biomedical Sciences for Creative Future Talents School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of pharmacology School of MedicineKyungpook National UniversityDaeguRepublic of Korea Department of pharmacology School of DentistryKyungpook National UniversityDaeguRepublic of Korea Brain Science&Engineering Institute Kyungpook National UniversityDaeguRepublic of Korea

Astrocytes are functionally dynamic cells that support neurons in multiple ways throughout an organism’s *** astrocytic regulation of neuronal activity has been increasingly recognized in recent *** are now recognized as playing a more complex role than mere bystanders in the central nervous ***,their role in regulating the sleep neurocircuitry is not well *** this perspective,we highlight the role of astrocytes in sleep modulation,with a particular focus on regulatory mechanisms related to the ventrolateral preoptic nucleus(VLPO)of the *** briefly discuss recent literature reporting the role of VLPO astrocytes in regulating sleep-associated behaviors.

关键词： sleep ventrolateral astrocytes

Allosterically activating SHP2 by oleanolic acid inhibits STAT3-Th17 axis for ameliorating colitis

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2598-2612页

作者： Jinbo Hu Wen Liu Yi Zou Chenyang Jiao Jiazhen Zhu Qiang Xu Jianjun Zou Yang Sun Wenjie Guo State Key Laboratory of Pharmaceutical Biotechnology Nanjing Drum Tower HospitalSchool of Life SciencesNanjing UniversityNanjing 210093China Department of Clinical pharmacology Nanjing First HospitalNanjing Medical UniversityNanjing 210006China Jiangsu Key Laboratory of New Drug Research and Clinical Pharmacy Xuzhou Medical UniversityXuzhou 221004China

Src homology 2 domain-containing tyrosine phosphatase 2(SHP2)is an essential tyrosine phosphatase that is pivotal in regulating various cellular signaling pathways such as cell growth,differentiation,and *** activation of SHP2 has been shown to have a therapeutic effect in colitis and Parkinson's ***,the identification of SHP2 activators and a complete understanding of their mechanism is *** used a two-step screening assay to determine a novel allosteric activator of SHP2 that stabilizes it in an open *** acid was identified as a suitable *** binding to R362,K364,and K366 in the active center of the PTP domain,oleanolic acid maintained the active open state of SHP2,which facilitated the binding between SHP2 and its *** oleanolic acid-activated SHP2 hindered Th17 differentiation by disturbing the interaction between STAT3 and IL-6Rαand inhibiting the activation of ***,via the activation of SHP2 and subsequent attenuation of the STAT3-Th17 axis,oleanolic acid effectively mitigated colitis in *** protective effect was abrogated by SHP2 knockout or administration of the SHP2 inhibitor *** findings underscore the potential of oleanolic acid as a promising therapeutic agent for treating inflammatory bowel diseases.

关键词： Oleanolic acid SHP2 STAT3 Th17 Colitis Allosteric activator

Pro-resolving lipid mediator reduces amyloid-β42–induced gene expression in human monocyte–derived microglia

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Neural Regeneration Research 2025年第3期20卷 873-886页

作者： Ying Wang Xiang Zhang Henrik Biverstål Nicolas GBazan Shuai Tan Nailin Li Makiko Ohshima Marianne Schultzberg Xiaofei Li Department of Neurobiology Care Sciences&SocietyDivision of NeurogeriatricsKarolinska InstitutetStockholmSweden Department of Neurology Neuroscience CenterThe First Hospital of Jilin UniversityChangchunJilin ProvinceChina Department of Physiology and pharmacology Karolinska InstitutetStockholmSweden Department of Biosciences and Nutrition Karolinska InstitutetHuddingeSweden Neuroscience Center of Excellence Louisiana State UniversityNew OrleansLAUSA Department of Medicine SolnaClinical Pharmacology GroupKarolinska University HospitalStockholmSweden

Specialized pro-resolving lipid mediators including maresin 1 mediate resolution but the levels of these are reduced in Alzheimer's disease brain, suggesting that they constitute a novel target for the treatment of Alzheimer's disease to prevent/stop inflammation and combat disease pathology. Therefore, it is important to clarify whether they counteract the expression of genes and proteins induced by amyloid-β. With this objective, we analyzed the relevance of human monocyte–derived microglia for in vitro modeling of neuroinflammation and its resolution in the context of Alzheimer's disease and investigated the pro-resolving bioactivity of maresin 1 on amyloid-β42–induced Alzheimer's disease–like inflammation. Analysis of RNA-sequencing data and secreted proteins in supernatants from the monocyte-derived microglia showed that the monocyte-derived microglia resembled Alzheimer's disease–like neuroinflammation in human brain microglia after incubation with amyloid-β42. Maresin 1 restored homeostasis by down-regulating inflammatory pathway related gene expression induced by amyloid-β42 in monocyte-derived microglia, protection of maresin 1 against the effects of amyloid-β42 is mediated by a re-balancing of inflammatory transcriptional networks in which modulation of gene transcription in the nuclear factor-kappa B pathway plays a major part. We pinpointed molecular targets that are associated with both neuroinflammation in Alzheimer's disease and therapeutic targets by maresin 1. In conclusion, monocyte-derived microglia represent a relevant in vitro microglial model for studies on Alzheimer's disease-like inflammation and drug response for individual patients. Maresin 1 ameliorates amyloid-β42–induced changes in several genes of importance in Alzheimer's disease, highlighting its potential as a therapeutic target for Alzheimer's disease.

关键词： Alzheimer's disease amyloid-β maresin microglia monocyte neuroinflammation resolution RNA-sequencing specialized pro-resolving lipid mediator