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World Journal of Gastroenterology 2024年第40期30卷 4393-4398页

作者： Hang Zhang Xuan Dong Lei Zhu Fu-Shan Tang Department of Clinical Pharmacy Key Laboratory of Basic Pharmacology of Guizhou Province and School of PharmacyZunyi Medical UniversityZunyi 563006Guizhou ProvinceChina key laboratory of basic pharmacology of ministry of Education and Joint International Research laboratory of Ethnomedicine of ministry of Education Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina key laboratory of Clinical Pharmacy in Zunyi City Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina

Liver diseases pose a significant threat to human *** effective therapeutic agents exist for some liver diseases,there remains a critical need for advancements in research to address the gaps in treatment options and improve patient *** article reviews the assessment of Elafibranor's effects on liver fibrosis and intestinal barrier function in a mouse model of alcoholic liver disease(ALD),as reported by Koizumi et al in the World Journal of *** summarize the impact and mechanisms of Elafibranor on ALD,metabolic-associated fatty liver disease,and cholestatic liver disease based on current *** also explore its potential as a dual agonist of PPARα/δ,which is undergoing Phase III clinical trials for metabolic-associated *** goal is to stimulate further investigation into Elafibranor's use for preventing and treating these liver diseases and to provide insights for its clinical application.

关键词： Elafibranor Peroxisome proliferator activated receptor Liver fibrosis Alcoholic liver disease Metabolic-associated fatty liver disease Metabolic-associated steatohepatitis Cholestatic liver disease Primary biliary cholangitis Liver diseases

lncRNA Gm20257 alleviates pathological cardiac hypertrophy by modulating the PGC-1α–mitochondrial complexⅣaxis

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Frontiers of Medicine 2024年第4期18卷 664-677页

作者： Tong Yu Qiang Gao Guofang Zhang Tianyu Li Xiaoshan Liu Chao Li Lan Zheng Xiang Sun Jianbo Wu Huiying Cao Fangfang Bi Ruifeng Wang Haihai Liang Xuelian Li Yuhong Zhou Lifang Lv Hongli Shan Department of Physiology School of Basic MedicineHarbin Medical UniversityHarbin150081China State key laboratory of Frigid Zone Cardiovascular Disease Department of Pharmacology(State-Province Key Laboratories of Biomedicine-Pharmaceutics of China key laboratory of Cardiovascular Research Ministry of Education)College of PharmacyHarbin Medical UniversityHarbin150081China The Center of Functional Experiment Teaching School of Basic MedicineHarbin Medical UniversityHarbin150081China

Pathological cardiac hypertrophy,a major contributor to heart failure,is closely linked to mitochondrial *** roles of long noncoding RNAs(lncRNAs),which regulate mitochondrial function,remain largely unexplored in this ***,a previously unknown lncRNA,Gm20257,was *** markedly increased under hypertrophic stress in vivo and in *** suppression of Gm20257 by using small interfering RNAs significantly induced cardiomyocyte ***,the overexpression of Gm20257 through plasmid transfection or adeno-associated viral vector-9 mitigated angiotensinⅡ-induced hypertrophic phenotypes in neonatal mouse ventricular cells or alleviated cardiac hypertrophy in a mouse TAC model respectively,thus restoring cardiac ***,Gm20257 restored mitochondrial complexⅣlevel and enhanced mitochondrial *** prediction showed that Gm20257 had a high binding score with peroxisome proliferator–activated receptor coactivator-1(PGC-1α),which could increase mitochondrial complex ***,Western blot analysis results revealed that Gm20257 substantially affected the expression of PGC-1α.Further analyses through RNA immunoprecipitation and immunoblotting following RNA pull-down indicated that PGC-1αwas a direct downstream target of *** interaction was demonstrated to rescue the reduction of mitochondrial complex IV induced by hypertrophic stress and promote the generation of mitochondrial *** findings suggest that Gm20257 improves mitochondrial function through the PGC-1α-mitochondrial complexⅣaxis,offering a novel approach for attenuating pathological cardiac hypertrophy.

关键词： lncRNA Gm20257 cardiac hypertrophy PGC-1α mitochondrial complexⅣ ATP

Formulation,characterization and in vivo and in vitro evaluation of aloe-emodin-loaded solid dispersions for dissolution enhancement

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Journal of Traditional Chinese Medicine 2024年第1期44卷 54-62页

作者： LI Xiuyan LUO Yuting WANG Jinhui DU Zhimin key laboratory of basic and Application Research of Beiyao Heilongjiang University of Chinese MedicineMinistry of EducationHarbin 150040China College of Pharmacy Harbin Medical UniversityHarbin 150081China Institute of Clinical pharmacology the Second Affliated Hospital of Harbin Medical University(University Key aboratory of Drug ResearchHeilongjiang Province)Harbin 150086China Department of Clinical pharmacology College of Pharmacy Harbin Medical UniversityHarbin 150081China State key laboratory of Quality Research in Chinese Medicines Macao University of Science and TechnologyMacao 999078China

OBJECTIVE:To prepare aloe-emodin solid dispersion(AE-SD)and determine the metabolic process of AE and AE-SD in ***:AE-SD was prepared via solvent evaporation or solvent melting using PEG-6000 and PVP-K30 as *** analysis,X-ray diffraction spectroscopy,differential scanning calorimetry,Fourier transform infrared spectroscopy and scanning electron microscopy were used to identify the physical state of *** prescriptions were screened via the dissolution degree determination *** Phoenix software,AE suspension and AE-SD were subjected to a pharmacokinetic comparison study analyzing the alteration of behavior in vivo after AE was prepared as a solid *** toxicity was assessed in mice,and the physiological toxicity was used as the determination criterion for ***:AE-SD showed that AE existed in the carrier in an amorphous *** with polyethylene glycol,polyvinylpyrrolidone(PVP)inhibited AE crystallization,causing the drug to transform from a dense crystalline state to an amorphous form and increasing the degree of drug ***,it was more suitable as a carrier material for *** addition of poloxamer(POL)was more beneficial to the stability of solid dispersions and could reduce the amount of *** dissolution test confirmed that the optimal ratio of AE to the composite vector AE-PVP-POL was 1:2:2,and its dissolution effect was also *** on the pharmacokinetic comparison,the drug absorption was faster and quickly reached the peak of blood drug concentration in AE-SD compared to AE,the Cmax of AE-SD was greater than that of AE,and t1/2 and mean residence time of AE-SD were less than *** results showed that the drug metabolism in AE-SD was better,and the residence time was *** toxicology study showed that both AE and AE-SD had no ***:This paper established that the solubility of the drug could be increased after preparing a solid dispersion,

关键词： aloe-emodin solid dispersion solvent evaporation drug liberation pharmacokinetics

Hydroxysafflor Yellow A Inhibits Pyroptosis and Protecting HUVECs from OGD/R via NLRP3/Caspase-1/GSDMD Pathway

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Chinese Journal of Integrative Medicine 2024年第11期30卷 1027-1034页

作者： GUO Fan HAN Xiao YOU Yue XU Shu-juan ZHANG Ye-hao CHEN Yuan-yuan XIN Gao-jie LIU Zi-xin REN Jun-guo CAO Ce LI Ling-mei FU Jian-hua Institute of basic Medical Sciences of Xiyuan Hospital China Academy of Chinese Medical Sciences Beijing key laboratory of Chinese Materia pharmacology Department of Central laboratory Kunshan Hospital of Chinese Medicine

Objective: To observe the protective effect and mechanism of hydroxyl safflower yellow A(HSYA)from myocardial ischemia-reperfusion injury on human umbilical vein endothelial cells(HUVECs). Methods:HUVECs were treated with oxygen-glucose deprivation reperfusion(OGD/R) to simulate the ischemia reperfusion model, and cell counting kit-8 was used to detect the protective effect of different concentrations(1.25–160 μmol/L)of HSYA on HUVECs after OGD/R. HSYA 80 μmol/L was used for follow-up experiments. The contents of inflammatory cytokines interleukin(IL)-18, IL-1β, monocyte chemotactic protein 1(MCP-1), tumor necrosis factor α(TNF-α) and IL-6 before and after administration were measured by enzyme-linked immunosorbent assay. The protein expressions of toll-like receptor, NOD-like receptor containing pyrin domain 3(NLRP3), gasdermin D(GSDMD) and GSDMD-N-terminal domain(GSDMD-N) before and after administration were detected by Western blot. NLRP3 inflammasome inhibitor cytokine release inhibitory drug 3 sodium salt(CRID3 sodium salt, also known as MCC950) and agonist were added, and the changes of NLRP3, cysteine-aspartic acid protease 1(Caspase-1), GSDMD and GSDMD-N protein expressions were detected by Western blot. Results: HSYA inhibited OGD/R-induced inflammation and significantly decreased the contents of inflammatory cytokines IL-18,IL-1β, MCP-1, TNF-α and IL-6(P<0.01 or P<0.05). At the same time, by inhibiting NLRP3/Caspase-1/GSDMD pathway, HSYA can reduce the occurrence of pyroptosis after OGD/R and reduce the expression of NLRP3,Caspase-1, GSDMD and GSDMD-N proteins(P<0.01). Conclusions: The protective effect of HSYA on HUVECs after OGD/R is related to down-regulating the expression of NLRP3 inflammasome and inhibiting pyroptosis.

关键词： Chinese medicine NLRP3 inflammasome human umbilical vein endothelial cells hydroxysafflor yellow A myocardial reperfusion injury oxygen-glucose deprivation reperfusion pyroptosis

Antitumor effects of a novel photosensitizer-mediated photodynamic therapy and its influence on the cell transcriptome

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Oncology Research 2024年第5期32卷 911-923页

作者： JINGJING CHEN DAN WANG ZEQUN WANG MENGYUAN HAN HOUQING YIN WENTING ZHOU RIBAI YAN YAN PAN Department of pharmacology School of PharmacyChangzhi Medical CollegeChangzhiChina2 Department of PharmacologySchool of Basic Medical SciencesHealth Science CenterPeking UniversityBeijingChina3 Beijing Key Laboratory of Tumor Systems BiologyPeking UniversityBeijingChina4 Department of PharmacologyXinjiang Medical UniversityUrumqiChina5 School of Pharmaceutical SciencesPeking UniversityBeijingChina

Photodynamic therapy(PDT)is a promising cancer *** study investigated the antitumor effects and mechanisms of a novel photosensitizer meso-5-[ρ-diethylene triamine pentaacetic acid-aminophenyl]−10,15,20-triphenyl-porphyrin(DTP)mediated PDT(DTP-PDT).Cell viability,reactive oxygen species(ROS),and apoptosis were measured with a Cell Counting Kit-8 assay,DCFH-DA fluorescent probe,and Hoechst staining,*** apoptosis-and autophagy-related proteins were examined using western *** sequencing was used to screen differentially expressed mRNAs(DERs),and bioinformatic analysis was performed to identify the major biological events after *** results show that DTP-PDT inhibited cell growth and induced ROS generation in MCF-7 and SGC7901 *** ROS scavenger N-acetyl-L-cysteine(NAC)and the P38 MAPK inhibitor SB203580 alleviated DTP-PDT-induced ***-PDT induced cell apoptosis together with upregulated Bax and downregulated Bcl-2,which could also be inhibited by NAC or *** level of LC3B-Ⅱ,a marker of autophagy,was increased by DTP-PDT.A total of 3496 DERs were obtained after *** Ontology and Kyoto Encyclopedia of Genes and Genomes analyses indicated that DERs included those involved in cytosolic ribosomes,the nuclear lumen,protein binding,cell cycle,protein targeting to the endoplasmic reticulum,and ribosomal DNA *** Ontology and Reactome enrichment analyses indicated that DERs were associated with a variety of cancers and cell cycle ***-protein interaction results demonstrated that cdk1 and rps27a ranked in the top 10 interacting ***,DTP-PDT could inhibit cell growth and induce cell apoptosis and autophagy,partly through ROS and the P38 MAPK signaling *** associated with the cell cycle,ribosomes,DNA replication,and protein binding may be the key changes in DTP-PDT-mediated cytotoxicity.

关键词： Photodynamic therapy ROS Apoptosis Autophagy Bioinformatic analysis

The response and anti-stress mechanisms of nitrifying sludge under long-term exposure to Cd Se quantum dots

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Journal of Environmental Sciences 2024年第1期135卷 174-184页

作者： Linkai Guo Lei Yang Yongxiang Ren Shen Cui Xiaotong Li Jia Wang Jun Lan Haoqi Lu Yuchao Wang Shaanxi key laboratory of Environmental Engineering Xi’an University of Architecture and TechnologyXi’an 710055China key lab of Northwest Water Resource Environment and EcologyMinistry of EducationXi’an University of Architecture and TechnologyXi’an 710055China

The wide application of CdSe quantum dots(QDs)increases its stress risk to sewage treatment *** study evaluated the response of nitrification performance,floc characteristics and microbial community of nitrifying sludge under long-term exposure to CdSe *** showed CdSe QDs(≥1 mg/L)would decrease the activity of ammonia monooxygenase(AMO).Under the stress of 30 mg/L CdSe QDs,the activity of AMO was reduced by 66%,while the activities of hydroxylamine oxidase and nitrite oxidoreductase were enhanced by 19.1%and 26%,***,the final nitrification effects were not adversely affected,and the production rates of NO_(2)^(-)-N and NO_(3)^(-)-N were ***,CdSe QDs improved biomass concentration in sludge and maintained the stability of sludge *** throughput sequencing analysis showed that CdSe QDs evidently reduced the abundance and diversity of microbial community in nitrifying *** abundances of amino acid metabolism and lipid metabolism were ***,CdSe QDs decreased the fluorescence intensity of tryptophan-like protein from 2,326 to 1,179 *** loosely bound extracellular polymeric substances(EPSs)and from 3,792 to 3,117 *** tightly bound *** relieve CdSe QD stress,the polysaccharide content increased from0.31 to 0.61 mg/g MLSS and intracellular antioxidant defense was *** CdSe QD level increasing to 30 mg/L,the total antioxygenic capacity and the activities of catalase were enhanced up to 411%and 143.2%,***,CdSe QDs had little adverse effects on cell membrane integrity,microbial metabolism and the abundance of Nitrospirae.

关键词： Quantum dots Activated sludge Extracellular polymeric substances Microbial community Antioxidant effect

Strengthening pharmacotherapy research for COVID-19-induced pulmonary fibrosis

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World Journal of Clinical Cases 2024年第5期12卷 875-879页

作者： Yan-Miao Liu Jing Zhang Jing-Jing Wu Wei-Wei Guo Fu-Shan Tang The First Clinical Institute Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina key laboratory of Clinical Pharmacy in Zunyi City Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina Department of Respiratory Medicine Central Hospital in Jinchang CityJinchang 737102Gansu ProvinceChina Department of Clinical Pharmacy Key Laboratory of Basic Pharmacology of Guizhou Province and School of PharmacyZunyi Medical UniversityZunyi 563006Guizhou ProvinceChina key laboratory of basic pharmacology of ministry of Education and Joint International Research laboratory of Ethnomedicine of ministry of Education Zunyi Medical UniversityZunyi 563006Guizhou ProvinceChina

The global spread of severe acute respiratory syndrome coronavirus 2 has resulted in a significant number of individuals developing pulmonary fibrosis(PF),an irreversible lung *** condition can manifest within a short inter-val following the onset of pneumonia symptoms,sometimes even within a few *** lung transplantation is a potentially lifesaving procedure,its limited availability,high costs,intricate surgeries,and risk of immunological rejection present significant *** optimal timing of medication administration for coronavirus disease 2019(COVID-19)-induced PF remains *** this,it is crucial to explore pharmacotherapy interventions,involving early and preventative treatment as well as pharmacotherapy options for advanced-stage ***,studies have demonstrated disparities in anti-fibrotic treatment based on race and gender *** mutations may also impact therapeutic *** research efforts on pharmacotherapy interventions,while considering relevant pharmacological factors and optimizing the timing and dosage of medication administration,will lead to enhanced,personalized,and fair treatment for individuals impacted by COVID-19-related *** measures are crucial in lessening the burden of the disease on healthcare systems and improving patients'quality of life.

关键词： COVID-19 Pulmonary fibrosis Pharmacotherapy intervention Medication administration Timing Dosage

Prenatal amoxicillin exposure induces developmental toxicity in fetal mice and its characteristics

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Journal of Environmental Sciences 2024年第3期137卷 287-301页

作者： Yongguo Dai Yu Peng Wen Hu Yi Liu Hui Wang Department of pharmacology Wuhan University School of Basic Medical SciencesWuhan 430071China Department of Pharmacy Zhongnan Hospital of Wuhan UniversityWuhan 430071China Hubei Provincial key laboratory of Developmentally Originated Disease Wuhan 430071China

Amoxicillin,a widely used antibiotic in human and veterinary pharmaceuticals,is now considered as an“emerging contaminant”because it exists widespreadly in the environment and brings a series of adverse ***,systematic studies about the developmental toxicity of amoxicillin are still *** explored the potential effects of amoxicillin exposure on pregnancy outcomes,maternal/fetal serum phenotypes,and fetal multiple organ development in mice,at different doses(75,150,300 mg/(kg·day))during late-pregnancy,or at a dose of 300 mg/(kg·day)during different stages(mid-/latepregnancy)and courses(single-/multi-course).Results showed that prenatal amoxicillin exposure(PAmE)had no significant infuence on the body weights of dams,but it could inhibit the physical development and reduce the survival rate of fetuses,especially during the ***,PAmE altered multiple maternal/fetal serum phenotypes,especially in *** multi-organ function results showed that PAmE inhibited testicular/adrenal steroid synthesis,long bone/cartilage and hippocampal development,and enhanced ovarian steroid synthesis and hepatic glycogenesis/lipogenesis,and the order of severity might be gonad(testis,ovary)>liver>*** analysis found that PAmE-induced multiorgan developmental and functional alterations had differences in stages,courses and fetal gender,and the most obvious changes might be in high-dose,late-pregnancy and multicourse,but there was no typical rule of a dose-response *** conclusion,this study confirmed that PAmE could cause abnormal development and multi-organ function alterations,which deepens our understanding of the risk of PAmE and provides an experimental basis for further exploration of the long-term harm.

关键词： Amoxicillin Prenatal exposure Fetal development Organ function Developmental toxicity

A selective HK2 degrader suppresses SW480 cancer cell growth by degrading HK2

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Chinese Chemical Letters 2024年第8期35卷 201-204页

作者： Yang Liu Yan Liu Kaiyin Yang Zhiruo Zhang Wenbo Zhang Bingyou Yang Hua Li Lixia Chen Wuya College of Innovation Key Laboratory of Structure-Based Drug Design&DiscoveryMinistry of EducationShenyang Pharmaceutical UniversityShenyang 110016China key laboratory of basic and Application Research of Beiyao Ministry of EducationHeilongjiang University of Chinese MedicineHarbin 150006China Institute of Structural pharmacology&TCM Chemical Biology College of PharmacyFujian University of Traditional Chinese MedicineFuzhou 350122China Hubei key laboratory of Natural Medicinal Chemistry and Resource Evaluation School of PharmacyTongji Medical CollegeHuazhong University of Science and TechnologyWuhan 430030China

Hexokinase 2(HK2)is the rate-limiting enzyme in the first step of glycolysis,catalyzing glucose to glucose-6-phosphate,and overexpressed in most cancer ***2 also binds to voltage-dependent anion channel(VDAC)to stabilize the mitochondrial outer membrane,which inhibits cancer cell ***,HK2 has become a potential target for cancer *** targeting chimeras(PROTACs)are hetero-bifunctional molecules that recruit an E3 ubiquitin ligase to a given substrate protein resulting in its targeted *** potent and specific PROTACs targeting dissimilar targets have been *** this study,an HK2 PROTAC,4H-5P-M,was developed and induced the degradation of HK2 relying on the ubiquitin-proteasome *** was found that 4H-5P-M as an effective HK2 degrader induced HK2 degradation in a dose-and time-dependent manner and suppressed the growth of SW480 cells.4H-5P-M selectively induced HK2 degradation at a lower concentration than other hexokinase ***,it could suppress glycolysis and accelerate the apoptosis of cancer ***,it provided a new insight into the development of anti-tumor drugs.

关键词： HK2 PROTACs Degrader Anti-tumor SW480

Eubacterium coprostanoligenes alleviates chemotherapy-induced intestinal mucositis by enhancing intestinal mucus barrier

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Acta Pharmaceutica Sinica B 2024年第4期14卷 1677-1692页

作者： Dongsheng Bai Jiawei Zhao Runde Wang Jiaying Du Chen Zhou Chunyang Gu Yuxiang Wang Lulu Zhang Yue Zhao Na Lu State key laboratory of Natural Medicines Jiangsu Key Laboratory of Carcinogenesis and InterventionDepartment of PhysiologySchool of Basic Medicine and Clinical PharmacyChina Pharmaceutical UniversityNanjing 210009China Department of Clinical pharmacology School of PharmacyNanjing Medical UniversityNanjing 211166China

Chemotherapy-induced mucositis represents a severe adverse outcome of cancer treatment,significantly curtailing the efficacy of these treatments and,in some cases,resulting in fatal *** identifying intestinal epithelial cell damage as a key factor in chemotherapy-induced mucositis,the paucity of effective treatments for such damage is *** our study,we discovered that Eubacterium coprostanoligenes promotes mucin secretion by goblet cells,thereby fortifying the integrity of the intestinal mucus *** enhanced barrier function serves to resist microbial invasion and sub-sequently reduces the inflammatory ***,this effect remains unobtrusive to the anti-tumor efficacy of chemotherapy ***,*** up-regulates the expression of AUF1,leading to the stabilization of Muc2 mRNA and an increase in mucin synthesis in goblet *** espe-cially significant finding is that *** activates the AhR pathway,thereby promoting the expression of *** summary,our results strongly indicate that *** enhances the intestinal mucus barrier,effec-tively alleviating chemotherapy-induced intestinal mucositis by activating the AhR/AUFl pathway,consequently enhancing Muc2 mRNA stability.

关键词： Chemotherapy Mucositis Eubacterium coprostanoligenes MUC2 AUF1