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Stir-Fried Semen Armeniacae Amarum Suppresses Aristolochic AcidⅠ-Induced Nephrotoxicity and DNA Adducts

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Chinese Journal of Integrative medicine 2025年第2期31卷 142-152页

作者： LI Cheng-xian XIAO Xiao-he LI Xin-yu XIAO Da-ke WANG Yin-kang WANG Xian-ling ZHANG Ping LI Yu-rong NIU Ming BAI Zhao-fang School of Chinese Materia Medica Beijing University of Chinese MedicineBeijing(100102)China Department of Hepatology Military Institute of Chinese Materiathe Fifth Medical CentreGeneral Hospital of PLABeijing(100039)China National Key Laboratory of Kidney Beijing(100039)China School of pharmacy Chengdu University of Traditional Chinese MedicineChengdu(610075)China School of traditional Chinese medicine Capital Medical UniversityBeijing(100069)China School of traditional Chinese medicine Southern Medical UniversityGuangzhou(510515)China Department of pharmacy Medical Supplies Center of PLA General HospitalBeijing(100039)China Department of Military Patient Management the Fifth Medical Center of PLA General HospitalBeijing(100039)China Department of Hematology the Fifth Medical Center of Chinese PLA General HospitalBeijing(100071)China

Objective:to investigate the protective effects of stir-fried Semen Armeniacae Amarum(SAA)against aristolochic acidⅠ(AAⅠ)-induced nephrotoxicity and DNA adducts and elucidate the underlying mechanism involved for ensuring the safe use of Asari Radix et ***:In vitro,HEK293t cells overexpressing Flag-tagged multidrug resistance-associated protein 3(MRP3)were constructed by Lentiviral transduction,and inhibitory effect of top 10 common pairs of medicinal herbs with Asari Radix et Rhizoma in clinic on MRP3 activity was verified using a self-constructed fluorescence screening *** m RNA,protein expressions,and enzyme activity levels of NAD(P)H quinone dehydrogenase 1(NQO1)and cytochrome P4501A2(CYP1A2)were measured in differentiated Hepa RG *** toxicity after inhibition of AAⅠmetabolite transport was detected using cell counting kit-8 *** vivo,C57BL/6 mice were randomly divided into 5 groups according to a random number table,including:control(1%sodium bicarbonate),AAⅠ(10 mg/kg),stir-fried SAA(1.75 g/kg)and AAⅠ+stir-fried SAA(1.75 and 8.75 g/kg)groups,6 mice in each *** 7 days of continuous gavage administration,liver and kidney damages were assessed,and the protein expressions and enzyme activity of liver metabolic enzymes NQO1 and CYP1A2 were determined ***:In vivo,combination of 1.75 g/kg SAA and 10 mg/kg AAⅠsuppressed AAⅠ-induced nephrotoxicity and reduced d A-ALI formation by 26.7%,and these detoxification effects in a dose-dependent manner(Ptically,SAA inhibited MRP3 transport in vitro,downregulated NQO1 expression in vivo,increased CYP1A2 expression and enzymatic activity in vitro and in vivo,respectively(Ptably,SAA also reduced AAⅠ-induced hepatotoxicity throughout the detoxification process,as indicated by a 41.3%reduction in the number of liver adducts(Ptirfried SAA is a novel drug candidate for the suppression of AAⅠ-induced liver and kidney dam

关键词： aristolochic acidⅠ stir-fried Semen Armeniacae Amarum detoxification principles of compatibility metabolic enzymes transporters

Apples to oranges:environmentally derived,dynamic regulation of serotonin neuron subpopulations in adulthood?

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Neural Regeneration Research 2025年第9期20卷 2596-2597页

作者： Christopher J.O’Connell Matthew J.Robson Department of Genetics College of MedicineHarvard UniversityBostonMAUSA James L.Winkle College of pharmacy Division of Pharmaceutical SciencesUniversity of CincinnatiCincinnatiOHUSA Neuroscience Graduate Program College of MedicineUniversity of CincinnatiCincinnatiOHUSA

traumatic brain injury(tBI)is a public health problem with an undue economic burden that impacts nearly every age,ethnic,and gender group across the globe(Capizzi et al.,2020).tBIs are often sustained during a dynamic range of exposures to energetic environmental forces and as such outcomes are typically heterogeneous regarding severity and pathology(Capizzi et al.,2020).

关键词： sustained orange dynamic

Blocking the PD-1 signal transduction by occupying the phosphorylated ItSM recognition site of SHP-2

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Science China(Life Sciences) 2025年第1期68卷 189-203页

作者： Wenjie Li Wenyi Mei Hewei Jiang Jie Wang Xiaoli Li Lina Quan Yanyan Diao Yanni Ma Sisi Fan Zhuwei Xie Mengdie Gong Huan Zhu Dewen Bi Feng Zhang Lei Ma Jian Zhang Yufeng Gao Aris Paschalidis Honghuang Lin Fangfang Liu Kangdong Liu Mingliang Ye Zhenjiang Zhao Yajun Duan Zhuo Chen Yufang Xu Weilie Xiao Shengce tao Lili Zhu Honglin Li Shanghai Key Laboratory of New Drug Design School of PharmacyEast China University of Science&TechnologyShanghai 200237China Shanghai Center for Systems Biomedicine Key Laboratory of Systems Biomedicine(Ministry of Education)Shanghai Jiao Tong UniversityShanghai 200240China Key Laboratory of Medicinal Chemistry for Natural Resource Ministry of EducationYunnan Characteristic Plant Extraction LaboratoryYunnan Provincial Center for Research&Development of Natural ProductsState Key Laboratory for Conservation and Utilization of Bio-Resources in YunnanSchool of Pharmacy and School of Chemical Science and TechnologyYunnan UniversityKunming650500China CAS Key Laboratory of Separation Sciences for Analytical Chemistry National Chromatographic R&A CenterDalian Institute of Chemical PhysicsChinese Academy of SciencesDalian 116023China Department of Cardiology The First Affiliated Hospital of USTCDivision of Life Sciences and MedicineUniversity of Science and Technology of ChinaHefei 230027China Department of Infectious Diseases The First Affiliated Hospital of Anhui Medical UniversityHefei 230022China Department of medicine University of Massachusetts Chan Medical SchoolWorcester MA 01655USA Department of Pathophysiology School of Basic Medical SciencesAcademy of Medical ScienceCollege of MedicineZhengzhou UniversityZhengzhou 450001China Innovation Center for AI and Drug Discovery East China Normal UniversityShanghai 200062China Lingang Laboratory Shanghai 200031China

targeting the PD-1/PD-L1 axis with small-molecular inhibitors is a promising approach for ***,we identify a natural pentacyclic triterpenoid,Pygenic Acid A(PA),as a PD-1 signaling *** exerts anti-tumor activity in hPD-1 knock-in C57BL/6 mice and enhances effector functions of t cells to promote immune responses by disrupting the PD-1 signaling ***,we identify SHP-2 as the direct molecular target of PA for inhibiting the PD-1 signaling ***,mechanistic studies suggest that PA binds to a new druggable site in the phosphorylated PD-1 ItSM recognition site of SHP-2,inhibiting the recruitment of SHP-2 by *** together,our findings demonstrate that PA has a potential application in cancer immunotherapy and occupying the phosphorylated ItSM recognition site of SHP-2 may serve as an alternative strategy to develop PD-1 signaling *** addition,our success in target recognition provides a paradigm of target identification and confirmation for natural products.

关键词： pygenic acid A programmed death-1 immunoreceptor tyrosine-based switch motif SH2 domain-containing protein-tyrosine phosphatase-2 target identification site recognition

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 SciencesShanghai 201203China School of pharmacy University of Chinese Academy of SciencesBeijing 100049China School of pharmacy Nanjing University of Chinese MedicineNanjing 210023China State Key Laboratory of Drug Research Department of Medicinal ChemistryShanghai Institute of Materia MedicaChinese Academy of SciencesShanghai 201203China Innovation Research Institute of traditional Chinese medicine Shanghai University of Traditional Chinese MedicineShanghai 201203China Experiment Center for Science and technology Shanghai University of Traditional Chinese MedicineShanghai 201203China

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).this imbalance and the discharge of inflammatory mediators perpetuate the cycle of inflammation and tissue ***,controlling inflammation and modulating osteoclastogenesis are critical therapeutic targets for managing OA.

关键词： inflammation drugs

Compound heterozygous mutation of AFG3L2 causes autosomal recessive spinocerebellar ataxia through mitochondrial impairment and MICU1 mediated Ca2+overload

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Science China(Life Sciences) 2025年第2期68卷 484-501页

作者： Hongyu Li Qingwen Ma Yan Xue Linlin Cai Liwen Bao Lei Hong Yitao Zeng Shu-Zhen Huang Richard H.Finnell Fanyi Zeng Shanghai Institute of Medical Genetics Shanghai Children’s HospitalShanghai Jiao Tong University School of MedicineShanghai 200040China Department of Histo-Embryology Genetics and Developmental BiologyShanghai Jiao Tong University School of MedicineShanghai 200025China NHC Key Laboratory of Medical Embryogenesis and Developmental Molecular Biology Shanghai Key Laboratory of Embryo and Reproduction EngineeringShanghai 200040China Center for Precision Environmental Health Baylor College of MedicineHouston 77030USA School of pharmacy Macao University of Science and TechnologyMacao 999078China

Autosomal recessive spinocerebellar ataxias(SCARs)are one of the most common neurodegenerative diseases characterized by progressive *** SCARs are known to be caused by mutations in multiple genes,there are still many cases that go undiagnosed or are *** this study,we presented a SCAR patient,and identified a probable novel pathogenic mutation(c.1A>G,p.M1V)in the AFG3L2 start *** proband's genotype included heterozygous mutations of the compound AFG3L2(p.[M1V];[R632X](c.[1A>G];[1894.C>t])),which were inherited from the father(c.1A>G,p.M1V)and mother(c.1894C>t,p.R632X).Functional studies performed on hi PSCs(human induced pluripotent stem cells)generated from the patients and HEK293t cells showed that the mutations impair mitochondrial function and the unbalanced expression of AFG3L2 mRNA and protein ***,this novel mutation resulted in the degradation of the protein and the reduction of the stability of the AFG3L2 protein,and MCU(mitochondrial calcium uniporter)complex mediated Ca2+overload.

关键词： AFG3L2 gene autosomal recessive spinocerebellar ataxia mitochondrial impairment Ca2+overload

A supramolecular nanoprodrug for prevention of gallstone formation

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Chinese Chemical Letters 2025年第2期36卷 354-359页

作者： Xiangjun Zhang Xiaodi Yang Yan Wang Zhongping Xu Sisi Yi tao Guo Yue Liao Xiyu tang Jianxiang Zhang Ruibing Wang College of pharmacy Chongqing Medical University Chongqing university Fuling Hospital Department of Pharmaceutics College of PharmacyThird Military Medical University (Army Medical University) Yu-Yue Pathology Scientific Research Center State Key Laboratory of trauma and Chemical Poisoning Third Military Medical University (Army Medical University) State Key Laboratory of Quality Research in Chinese medicine Institute of Chinese Medical SciencesUniversity of Macau

Cholelithiasis affects approximately 10%-20% of the adult population globally. And cholesterol accumulation and nucleation of cholesterol crystals are commonly recognized as the primary process in the initiation and progression of gallstones. Hydroxypropyl-β-cyclodextrin(HPCD) is a supramolecular host compound that can solubilize cholesterol, potentially serving as a preventative or therapeutic agent for cholelithiasis. However, we found that the administration of HPCD treatment did not impede the formation of gallstones in mice, mainly attributed to the pre-complexation of its cavity during the transition process. Here we synthesized a prodrug of HPCD and prepared a HPCD nanoparticle(HPCD-NP), which can be transported efficiently to the gallbladder through the hepatobiliary system following an intravenous injection. In the bile, the HPCD-NP degraded into free HPCD, bound to cholesterol crystals and gallstones within the gallbladder and effectively increased cholesterol solubilization, leading to gallstones regression. Given the established safety of both HPCD and cyclodextrin-based nanoparticles in numerous animal and human studies, HPCD-NP shows considerable promise for the prevention and treatment of human cholelithiasis.

关键词： Gallstone Hepatobiliary transport Host-guest interaction Hydroxypropyl-β-cyclodextrin Solubilization

An in-depth understanding of the role and mechanisms of t cells in immune organ aging and age-related diseases

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Science China(Life Sciences) 2025年第2期68卷 328-353页

作者： Yudai Xu Zijian Wang Shumin Li Jun Su Lijuan Gao Junwen Ou Zhanyi Lin Oscar Junhong Luo Chanchan Xiao Guobing Chen Department of Microbiology and Immunology School of MedicineInstitute of Geriatric ImmunologySchool of MedicineJinan UniversityGuangzhou 510632China Key Laboratory of Viral Pathogenesis&Infection Prevention and Control(Jinan university) Ministry of EducationGuangzhou 510632China Guangdong-Hong Kong-Macao Great Bay Area Geroscience Joint Laboratory School of MedicineJinan UniversityGuangzhou 510632China First Affiliated Hospital Jinan UniversityGuangzhou 510630China Anti Aging Medical Center Clifford HospitalGuangzhou 511495China Guangdong Provincial People’s Hospital(Guangdong Academy of Medical Sciences) Southern Medical UniversityGuangzhou 510080China Department of Systems Biomedical Sciences School of MedicineJinan UniversityGuangzhou 510632China the Sixth Affiliated Hospital of Jinan university(Dongguan Eastern Central Hospital) Jinan UniversityDongguan 523000China Zhuhai Institute of Jinan university Jinan UniversityZhuhai 519070China

t cells play a critical and irreplaceable role in maintaining overall ***,their functions undergo alterations as individuals *** is of utmost importance to comprehend the specific characteristics of t-cell aging,as this knowledge is crucial for gaining deeper insights into the pathogenesis of aging-related diseases and developing effective therapeutic *** this review,we have thoroughly examined the existing studies on the characteristics of immune organ ***,we elucidated the changes and potential mechanisms that occur in t cells during the aging ***,we have discussed the latest research advancements pertaining to t-cell agingrelated *** findings provide a fresh perspective for the study of t cells in the context of aging.

关键词： t cell aging immune organ age-related diseases

Purinergic signaling by tCRaβ~+double-negative t regulatory cells ameliorates liver ischemia–reperfusion injury

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Science Bulletin 2025年第2期70卷 241-254页

作者： Hua Jin Mingyang Li Xiyu Wang Lu Yang Xinjie Zhong Zihan Zhang Xiaotong Han Jingjing Zhu Mengyi Li Songlin Wang Simon C.Robson Guangyong Sun Dong Zhang Immunology Research Center for Oral and Systemic Health Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Medical Research Center Beijing Institute of Respiratory Medicine and Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China Department of Gastroenterology Beijing Chao-Yang HospitalCapital Medical UniversityBeijing 100020China General Surgery Department Beijing Friendship HospitalCapital Medical UniversityBeijing 100050China Beijing Laboratory of Oral Health Capital Medical University School of Basic MedicineBeijing 100069China Center for Inflammation Research Department of AnesthesiaCritical Care&Pain Medicineand Department of MedicineBeth Israel Deaconess Medical CenterHarvard Medical SchoolBostonMA 02115USA

Hepatic ischemia–reperfusion injury(HIRI)is an important cause of liver injury following liver transplantation and major resections,and neutrophils are the key effector cells in ***-negative t regulatory cells(DNt)are increasingly recognized as having critical regulatory functions in the immune *** DNt expresses distinct immunoregulatory mechanisms to modulate neutrophils,as in HIRI,remains largely *** this study,we found that murine and human DNt highly expressed CD39that protected DNt from extracellular AtP-induced apoptosis and generated adenosine in tandem with CD73,to induce high levels of neutrophil ***,extracellular adenosine enhanced DNt survival and suppressive function by upregulating survivin and NKG2D expression via the A2AR/pAKt/FOXO1 signaling *** transfer of DNt ameliorated HIRI in mice through the inhibition of neutrophils in a CD39-dependent ***,the adoptive transfer of A2ar^(-/-)DNt validated the importance of adenosine/A2AR signaling,in promoting DNt survival and immunomodulatory function to protect against HIRI in *** conclusion,purinergic signaling is crucial for DNt homeostasis in *** of CD39 or activation of A2AR signaling in DNt may provide novel therapeutic strategies to target innate immune disorders.?2024 the *** by Elsevier *** behalf of Science China *** is an open accessarticle under the CC BY-NC-ND license(http://***/licenses/by-nc-nd/4.0/).

关键词： Double-negative t regulatory cells Hepatic ischemia and reperfusion injury CD39 Adenosine A2AR

thymus serpyllum *** Oil:Phytochemistry and in Vitro and in Silico Screening of Its Antimicrobial,Antioxidant and Anti-Inflammatory Properties

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Phyton-International Journal of Experimental Botany 2025年第1期94卷 209-227页

作者： Samiah Hamad Al-Mijalli Hanae Naceiri Mrabti Amine Elbouzidi Naglaa S.Ashmawy Amine Batbat Emad M.Abdallah Wafa Laaboudi Mohammed Aladhadh Fahad M.Alshabrmi Sulaiman Mohammed Alnasser Mohamed Addi Naoufal El Hachlafi Department of Biology College of SciencesPrincess Nourah bint Abdulrahman UniversityRiyadh11671Saudi Arabia Department of Pharmcology Laboratory of Epidemiology and Research in Health SciencesFaculty of MedicinePharmacy and DentistrySidi Mohamed Ben Abdellah UniversityFez30000Morocco Laboratoire d’Amélioration des Productions Agricoles Biotechnologie et Environnement(LAPABE)Facultédes SciencesMoroccodes SciencesUniversitéMohammed PremierOujda60000Morocco Department of Pharmaceutical Sciences College of PharmacyGulf Medical UniversityAjmanP.O.Box 4184United Arab Emirates Department of Pharmacognosy Faculty of PharmacyAin Shams UniversityAbbassiaCairo11566Egypt Laboratory of Applied Organic Chemistry Faculty of Sciences and TechniquesSidi Mohamed Ben Abdellah UniversityImouzzer RoadFez30000Morocco Department of Biology College of ScienceQassim UniversityQassim51452Saudi Arabia High Institute of Nursing Professions and Health techniques Fez Fez30050Morocco Department of Food Science and Human Nutrition College of Agriculture and FoodQassim UniversityBuraydah51452Saudi Arabia Department of Medical Laboratories College of Applied Medical SciencesQassim UniversityBuraydah51452Saudi Arabia Department of Pharmacology and toxicology College of PharmacyQassim UniversityBuraydah52571Saudi Arabia Faculty of medicine and pharmacy Ibn Zohr UniversityGuelmim81000Morocco

thymus serpyllum L.,often known as wild thyme,has been used since ancient times due to its multifaceted culinary and medicinal *** is usually utilized in folk medicine to manage different health *** work aimed to investigate the chemical composition and biological characteristics of *** essential oil(EO),including its antimicrobial,antioxidant,and anti-inflammatory ***,we have prompted an in-silico simulation to reveal the underlying mode of action of these *** chemical characterization of ***(EO)by Gas Chromatography-Mass Spectrometry(GC-MS)indicated sabinene(17.33%),terpinen-4-ol(11.73%),phellandral(13.18%),and thymol(10.54%)as main *** antimicrobial screening utilized the disc-diffusion technique,MIC,and MBC *** disc-diffusion test’s results revealed significant anti-Candida activity and notable antibacterial *** MIC and MBC tests showed that *** EO effectively stops bacterial growth,including Gram-positive and Gram-negative strains and Candida *** tolerance level ratio demonstrated that this EO exhibits bactericidal and fungicidal effects on all tested bacteria and Candida ***,*** EO presented effective inhibitory activity against the 5-lipoxygenase(5-LOX)enzyme(IC50=744.19±0.1µg/mL)(pt also effectively affected FRAP,β-carotene,DPPH,and ABtS *** light of these findings,*** holds promise for diverse applications across pharmaceuticals,nutraceuticals,and the food ***,further research and collaboration between traditional knowledge and modern medicine are crucial to fully realizing its potential benefits in these fields.

关键词： thymus serpyllum GC-MS antimicrobial oxidative stress anti-inflammatory in silico