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Glucagon-like peptide 1 receptor activation:anti-inflammatory effects in the brain

Neural Regeneration research 2024年第8期19卷 1671-1677页

作者： Yolanda Diz-Chaves Zainab Maastor Carlos Spuch José Antonio Lamas Lucas C.González-Matías Federico Mallo Biomedical research centre(CINBIO) Laboratory of EndocrinologyUniversity of VigoGalicia Sur Health Research InstituteVigoSpain Translational Neuroscience research Group Galicia Sur Health Research InstituteCIBERSAMHospitalÁlvaro CunqueiroSala InvestigaciónEstrada Clara CampoamorVigoSpain Biomedical research centre(CINBIO) Laboratory of NeuroscienceUniversity of VigoGalicia Sur Health Research InstituteVigoSpain

The glucagon-like peptide 1 is a pleiotropic hormone that has potent insulinotropic effects and is key in treating metabolic diseases such as diabetes and ***-like peptide 1 exerts its effects by activating a membrane receptor identified in many tissues,including diffe rent brain ***-like peptide 1 activates several signaling pathways related to neuroprotection,like the support of cell growth/survival,enhancement promotion of synapse formation,autophagy,and inhibition of the secretion of proinflammatory cytokines,microglial activation,and apoptosis during neural *** glial cells,including astrocytes and microglia,maintain metabolic homeostasis and defe nse against pathogens in the central nervous *** brain insult,microglia are the first cells to respond,followed by reactive *** activated cells produce proinflammato ry mediators like cytokines or chemokines to react to the ***,under these circumstances,mic roglia can become chro nically inflammatory by losing their homeostatic molecular signature and,consequently,their functions during many *** processes promote the development of neurological disorders and influence their pathological evolution:like the formation of protein aggregates,the accumulation of abnormally modified cellular constituents,the formation and release by injured neurons or synapses of molecules that can dampen neural function,and,of critical impo rtance,the dysregulation of inflammato ry control *** glucagonlike peptide 1 receptor agonist emerges as a critical tool in treating brain-related inflammatory pathologies,restoring brain cell homeostasis under inflammatory conditions,modulating mic roglia activity,and decreasing the inflammato ry *** review summarizes recent advances linked to the anti-inflammato ry prope rties of glucagon-like peptide 1 receptor activation in the brain related to multiple sclerosis,Alzheimer’s disease,Parkins

关键词： astrocytes brain glucagon-like peptide 1 receptor inflammation microglia

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Calculus bovis in hepatocellular carcinoma:Tumor molecular basis,Wnt/β-catenin pathway role,and protective mechanism

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World Journal of Gastroenterology 2024年第35期30卷 3959-3964页

作者： Khaled Mohamed Mohamed Koriem Department of Medical Physiology Medical Research and Clinical Studies InstituteNational Research CentreGiza 12622Egypt

In this editorial,we comment on the recent article by Huang et *** editorial focuses specifically on the molecular mechanisms of hepatocellular carcinoma(HCC),mechanism of Wnt/β-catenin pathway in HCC,and protective mechanism of Calculus bovis(CB)in *** cancer is the fourth most common cause of cancer-related deaths *** most prevalent kind of primary liver cancer,HCC,is typically brought on by long-term viral infections(hepatitis B and C),non-alcoholic steatohepatitis,excessive alcohol consumption,and other conditions that can cause the liver to become chronically inflamed and *** is a wellknown traditional remedy in China and Japan and has been used extensively to treat a variety of diseases,such as high fever,convulsions,and *** in lipid metabolism,cholesterol metabolism,bile acid metabolism,alcohol metabolism,and xenobiotic detoxification lead to fatty liver disease and liver ***,which is a tricarboxylic acid cycle intermediate,is vital to energy production and mitochondrial *** is also thought to be a signaling molecule in metabolism and in the development and spread of liver *** Wnt/β-catenin pathway is made up of a group of proteins that are essential for both adult tissue homeostasis and embryonic *** is frequently caused by the dysregulation of the Wnt/β-catenin signaling *** HCC liver carcinogenesis,Wnt/β-catenin signaling is activated by the expression of downstream target *** between the liver and the gut exists via the portal vein,biliary tract,and systemic ***"gutliver axis"controls intestinal *** of the main factors contributing to the development,progression,and treatment resistance of HCC is the abnormal activation of the Wnt/β-Catenin signaling ***,understanding this pathway is essential to treating *** ingredients of CB,particularly oleanolic acid,ergosterol,and ursolic acid,have anti-p

关键词： Hepatocellular carcinoma MicroRNAs Wnt/β-catenin pathway Calculus bovis apoptosis

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Decreased eggshell strength caused by impairment of uterine calcium transport coincide with higher bone minerals and quality in aged laying hens

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Journal of Animal Science and Biotechnology 2024年第3期15卷 1258-1277页

作者： Yu Fu Jianmin Zhou Martine Schroyen Haijun Zhang Shugeng Wu Guanghai Qi Jing Wang Key Laboratory of Feed Biotechnology Ministry of Agriculture and Rural AffairsInstitute of Feed ResearchChinese Academy of Agricultural SciencesBeijing 100081China Precision Livestock and Nutrition Laboratory Gembloux Agro‑Bio TechTERRA Teaching and Research CentreUniversity of LiegeGembloux B‑5030Belgium

Background Deteriorations in eggshell and bone quality are major challenges in aged laying *** study compared the differences of eggshell quality,bone parameters and their correlations as well as uterine physiologi-cal characteristics and the bone remodeling processes of hens laying eggs of different eggshell breaking strength to explore the mechanism of eggshell and bone quality reduction and their interaction.A total of 24074-week-old Hy-line Brown laying hens were selected and allocated to a high(HBS,44.83±1.31 N)or low(LBS,24.43±0.57 N)eggshell breaking strength *** A decreased thickness,weight and weight ratio of eggshells were observed in the LBS,accompanied with ultrastructural deterioration and total Ca *** quality was negatively correlated with eggshell quality,marked with enhanced structures and increased components in the *** the LBS,the mammillary knobs and effective layer grew *** the initiation stage of eggshell calcification,a total of 130 differentially expressed genes(DEGs,122 upregulated and 8 downregulated)were identified in the uterus of hens in the LBS relative to those in the *** DEGs were relevant to apoptosis due to the cellular Ca *** values of p62 protein level,caspase-8 activity,Bax protein expression and lower values of Bcl protein expression and Bcl/Bax ratio were seen in the *** assay and hematoxylin-eosin staining showed a significant increase in TUNEL-positive cells and tissue damages in the uterus of the *** few DEGs were identified at the growth stage,similar uterine tissue damages were also observed in the *** expressions of runt-related transcription factor 2 and osteocal-cin were upregulated in humeri of the *** diameter and more structural damages of endocortical bones and decreased ash were observed in femurs of the *** The lower eggshell breaking strength may be attributed to a declined Ca transport due to uterine tissue damages,which

关键词： Bone parameter Calcium transport Eggshell quality Laying hen Tissue damage

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The Combination Effect of Daphne Extract and Imatinib on the Antiproliferative Activity of the K562 Cell Line

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Journal of Biosciences and Medicines 2024年第8期12卷 141-153页

作者： Alireza Khorshid Jafar Nouri Nojadeh Javid Sabour Takanlu Alireza Tavasoli Department of Clinical Laboratory Sciences University of Texas Medical Branch at Galveston Galveston TX USA Department of Medical Genetics Faculty of Medicine Tabriz University of Medical Sciences Tabriz Iran apoptosis research centre Department of Biochemistry School of Natural Sciences National University of Ireland Galway Galway Ireland Department of Pathology School of Medicine Fasa University of Medical Science Fasa Iran

Background: Herbal medicine is well-known among the ancient medical sciences. Healing properties have been observed in some species of Daphne plant. The effect of Daphne plant extract on the K562 cell line has been previously studied, and Gleevec is a well-known and effective medicine for the treatment of chronic myelogenous leukemia. Material and Methods: In this study, the simultaneous effects of using herbal medicine and a target therapy medicine on the K562 cell line were investigated. The presence of some species of Daphne in Iran motivated us to evaluate the cytotoxic effect of Daphne mucronata on human leukemia cancer cells. The antiproliferative activity of the dichloromethane extract of Daphne mucronate (Thymelaeaceae), a new anticancer medicinal plant, was evaluated. Cell viability was quantitated by MTT assay. Apoptotic and necrotic changes in the cell membrane were examined using flow cytometry. Changes in Bax and Bcl2 gene expression were investigated using real-time PCR. The MIC and the IC50 of the crude extract were calculated, and the MIC and IC50 of the Daphne extract in combination of imatinib were tested in the K-562 cell line. Results: K-562 cells responded to the extract treatments in a dose-dependent manner, and the increase in the expression of Bcl2 and decrease in the expression of the Bax gene intensified with increasing extract concentration. Flow cytometry revealed that most of the cells underwent necrosis. Conclusion: Daphne extract effectively decreased the viability of the K562 cell line. The necrotic effect of the Daphne extract was evaluated, and an increase in the gene expression of Bcl2 was observed in cells exposed to the Daphne extract. The combination of Daphne extracts with imatinib enhances the cytotoxic effect of imatinib.

关键词： Daphne Imatinib apoptosis Herbal Medicine Bax Bcl-2 CML

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Mitochondria-specific near-infrared photoactivation of peroxynitrite upconversion luminescent nanogenerator for precision cancer gas therapy

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Acta Pharmaceutica Sinica B 2024年第1期14卷 378-391页

作者： Hui Yu Aliya Tiemuer Xufeng Yao Mingyuan Zuo Hai-Yan Wang Yi Liu Xiaoyuan Chen Department of Biomedical Engineering School of EngineeringChina Pharmaceutical UniversityNanjing 211198China School of Mechanical Engineering Southeast UniversityNanjing 211189China Departments of Diagnostic Radiology SurgeryChemical and Biomolecular Engineeringand Biomedical EngineeringYong Loo Lin School of Medicine and College of Design and EngineeringNational University of SingaporeSingapore 119074Singapore Clinical Imaging research centre Centre for Translational MedicineYong Loo Lin School of MedicineNational University of SingaporeSingapore 117599Singapore Nanomedicine Translational research Program Yong Loo Lin School of MedicineNational University of SingaporeSingapore 117597Singapore Institute of Molecular and Cell Biology Agency for ScienceTechnologyand Research(A*STAR)ProteosSingapore 138673Singapore

Gas therapy is emerging as a highly promising therapeutic strategy for cancer ***,there are limitations,including the lack of targeted subcellular organelle accuracy and spatiotemporal release precision,associated with gas *** this study,we developed a series of photoactivatable nitric oxide(NO)donors NRh-R-NO(R=Me,Et,Bn,iPr,and Ph)based on an N-nitrosated upconversion luminescent rhodamine *** the irradiation of 808 nm light,only NRh-Ph-NO could effectively release NO and NRh-Ph with a significant turn-on frequency upconversion luminescence(FUCL)signal at 740 nm,ascribed to lower N-N bond dissociation *** also investigated the involved multistage near-infrared-controlled cascade release of gas therapy,including the NO released from NRh-Ph-NO along with one NRh-Ph molecule generation,the superoxide anion O_(2)^(⋅−)produced by the photodynamic therapy(PDT)effect of NRh-Ph,and highly toxic peroxynitrite anion(ONOO‒)generated from the co-existence of NO and O_(2)^(⋅−).After mild nano-modification,the nanogenerator(NRh-Ph-NO NPs)empowered with superior biocompatibility could target *** an 808 nm laser irradiation,NRh-Ph-NO NPs could induce NO/ROS to generate RNS,causing a decrease in the mitochondrial membrane potential and initiating apoptosis by caspase-3 activation,which further induced tumor immunogenic cell death(ICD).In vivo therapeutic results of NRh-Ph-NO NPs showed augmented RNS-potentiated gas therapy,demonstrating excellent biocompatibility and effective tumor inhibition guided by real-time FUCL ***,this versatile strategy defines the targeted RNS-mediated cancer therapy.

关键词： Near infrared Photo-triggered Mitochondrion Upconversion luminescent bioimaging Peroxynitrite Nanogenerator Gas therapy In vivo

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Androgens exert multifaceted functions in sex differences analyzed through single-cell transcriptome

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Science China Life Sciences 2024年

作者： Xinxin Tang Yinkun Fu Zhihui Zou Yue Li Ming He Key Laboratory of Cell Differentiation and apoptosis of Ministry of Education Shanghai Frontiers Science Center of Cellular Homeostasis and Human Diseases Department of Pathophysiology School o Medicine Shanghai Jiao Tong University Department of Pathology The Affiliated Hospital of Youjiang Medical University for Nationalities

Sex differences are ubiquitous in human development, aging and disease. For example, the overwhelming majority of non-reproductive system cancers are more common in males(Mauvais-Jarvis et al., 2020), while autoimmune...

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Computer-aided molecular design and optimization of potent inhibitors disrupting APC-Asef interaction

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Acta Pharmaceutica Sinica B 2024年第6期14卷 2631-2645页

作者： Xuefei Wang Zeqian Du Yuegui Guo Jie Zhong Kun Song Junyuan Wang Jianqiang Yu Xiuyan Yang Chen-Ying Liu Ting Shi Jian Zhang Department of Pathophysiology Key Laboratory of Cell Differentiation and Apoptosis of Chinese Ministry of EducationShanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China Key Laboratory of Protection Development and Utilization of Medicinal Resources in Liupanshan AreaMinistry of EducationPeptide&Protein Drug Research CenterSchool of PharmacyNingxia Medical UniversityYinchuan 750004China State Key Laboratory of Microbial Metabolism Joint International Research Laboratory of Metabolic and Developmental SciencesSchool of Life Sciences and BiotechnologyShanghai Jiao Tong UniversityShanghai 200240China Department of Colorectal and Anal Surgery Xinhua HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China Basic Science research Center Base(Pharmaceutical Science) Yantai UniversityYantai 264005China Medicinal Chemistry and Bioinformatics Center Shanghai Jiao Tong UniversitySchool of MedicineShanghai 200025China State Key Laboratory of Pharmaceutical Biotechnology Nanjing UniversityNanjing 210023China

Colorectal cancer(CRC)is the second leading cause of cancer mortality *** initial diagnosis,approximately 20%of patients are diagnosed with metastatic CRC(mCRC).Although the APC-Asef interaction is a well-established target for mCRC therapy,the discovery and development of effective and safe drugs for mCRC patients remains an urgent and challenging *** this study,we identified a novel structural scaffold based on MAI inhibitors,the first-in-class APC-Asef inhibitors we reported *** model-driven optimizations of the N-terminal cap and experimental evaluations of inhibitory activity were performed,and 24-fold greater potency was obtained with the best inhibitor compared to the parental *** addition,the cocrystal structure validated that the two-layerπ-πstacking interactions were essential for inhibitor stabilization in the bound ***,in vitro and in vivo studies have demonstrated that novel inhibitors suppressed lung metastasis in CRC by disrupting the APC-Asef *** results provide an intrinsic structural basis to further explore drug-like molecules for APC-Asef-mediated CRC therapy.

关键词： APC-Asef Peptidomimetic Computer-aided molecular design ONIOM model π-πstacking Metastatic colorectal cancer

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Selenium nanoparticles in aquaculture:Unique advantages in the production of Se-enriched grass carp(Ctenopharyngodon idella)

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Animal Nutrition 2024年第1期16卷 189-201页

作者： Chao Zhu Zifang Wu Qimin Liu Xiaolin Wang Lijuan Zheng Shuyang He Fangxia Yang Hong Ji Wuzi Dong College of Animal Science and Technology Northwest A&F UniversityYanglingShaanxi712100China College of Forestry Northwest A&F UniversityYanglingShaanxi712100China Biology research centre of Qin Mountains Wildlife Northwest A&F UniversityYanglingShaanxi712100China

The production of selenium-enriched fish can contribute to alleviating selenium deficiency in human ***,it is still unclear which selenium source,as an additive,can efficiently and costeffectively produce high-quality selenium-enriched *** study evaluated the effects of selenium nanoparticles(SeNP),selenite,and selenomethionine(SeMet)on the growth,antioxidant capacity,selenium content,selenium speciation,and meat quality of grass *** diets were prepared,including a basal diet(BD)and three concentrations(0.1,0.3,and 0.9 mg/kg)of SeNP,selenite,and SeMet.A total of600 fish(250.79±1.57 g)were randomly assigned to 30 tanks(3 tanks/group).Fish were fed the experimental diet three times daily for 60 *** this study,SeNP most significantly promoted the growth and antioxidant capacity of grass carp,with 0.3 mg/kg SeNP identified as the optimal additive ***,SeNP demonstrated equally excellent bioavailability as SeMet and significantly increased the content of SeMet in grass carp(Ctenopharyngodon idella)***,compared to SeMet and selenite,dietary SeNP could more significantly enhance the content of selenocysteine(SeCys2)and methylselenocysteine(MeSeCys)in grass carp muscle *** addition,we have demonstrated that SeCys2and MeSeCys promote apoptosis of cancer cells(HeLa)through the mitochondrial apoptotic pathway(involving Bax and Bcl-2).Furthermore,as an additive,0.3 mg/kg SeNP significantly improved the flesh quality of grass carp by reducing crude fat and heavy metal content,as well as increasing the levels of eicosapentaenoic acid(EPA)and docosahexaenoic acid(DHA)and the ratio of n-3/n-6 polyunsaturated fatty acid(PUFA).In summary,SeNP is the most suitable additive for producing selenium-enriched fish.

关键词： Selenium nanoparticle Speciation analysis Grass carp Selenium additive

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Protective mechanism of Paeoniae Radix Alba against chemical liver injury based on network pharmacology,molecular docking,and in vitro experiments

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Journal of Traditional Chinese Medical Sciences 2024年第1期11卷 55-66页

作者： Shuangqiao Liu Xin Liu Sijia Jiang Min Fu Jinxi Hu Jiaqi Liu Xiaoxu Fan Yingtong Feng Shujing Zhang Jingxia Wang School of Traditional Chinese Medicine Beijing University of Chinese MedicineBeijing 102488China School of Traditional Chinese Medicine Xinjiang Medical UniversityUrumqi 830017China The centre for Translational Biology Research Institute of McGill University Health CentreMontr eal H4A 3J1Canada

Objective:To explore and validate the potential targets of Paeoniae Radix Alba(***,Bai Shao)in protecting against chemical liver injury through network pharmacology,molecular docking technology,and in vitro cell ***:Network pharmacology was used to identify the common potential targets of *** and chemical liver *** docking was used to fit the components,which were subsequently verified in vitro.A cell model of hepatic fibrosis was established by activating hepatic stellate cell(HSC)-LX2 cells with 10 ng/mL transforming growth factor-β*** cells were exposed to different concentrations of total glucosides of paeony(TGP),the active substance of ***,and then evaluated using the cell counting kit-8 assay,enzyme-linked immunosorbent assay,and western ***:Analysis through network pharmacology revealed 13 key compounds of ***,and the potential targets for preventing chemical liver injury were IL-6,AKT serine/threonine kinase 1,jun protooncogene,heat shock protein 90 alpha family class A member 1(HSP90AA1),peroxisome proliferator activated receptor gamma(PPARG),PTGS2,and *** Ontology(GO)enrichment analysis indicated the involvement of response to drugs,membrane rafts,and peptide *** Encyclopedia of Genes and Genomes(KEGG)enrichment analysis revealed that the main pathways involved lipid and atherosclerosis and chemical carcinogenesis-receptor *** and albiflorin exhibited strong affinity for HSP90AA1,PTGS2,PPARG,and *** concentrations of TGP can inhibit the expression of COL-I,COL-III,IL-6,TNF-a,IL-1β,HSP-90a,and PTGS2 while increasing the expression of PPAR-γand CASP3 in activated HSC-LX2 ***:*** primarily can regulate targets such as HSP90AA1,PTGS2,PPARG,***,the main active compound of ***,protects against chemical liver injury by reducing the inflammatory response,activating apoptotic proteins,and promoting the apoptosis of activated HSCs.

关键词： Paeoniae Radix Alba Total glycosides of paeony Chemical liver injury Liver fibrosis Network pharmacology Hepatic stellate cells

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Vault RNAs(vtRNAs):Rediscovered non-coding RNAs with diverse physiological and pathological activities

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Genes & Diseases 2024年第2期11卷 772-787页

作者： Mahsa Aghajani Mir Deputy of research and Technology Health Research InstituteBabol University of Medical SciencesBabol 47176-4774Iran

The physicochemical characteristics of RNA admit non-coding RNAs to perform a different range of biological acts through various mechanisms and are involved in regulating a diversity of fundamental ***,some reports of pathological conditions have proved abnormal expression of many non-coding RNAs guides the *** RNAs are a class of non-coding RNAs containing stem regions or loops with well-conserved sequence patterns that play a fundamental role in the function of vault particles through RNA-ligand,RNA–RNA,or RNA-protein *** together,vault RNAs have been proposed to be involved in a variety of functions such as cell proliferation,nucleocytoplasmic transport,intracellular detoxification processes,multidrug resistance,apoptosis,and autophagy,and serve as microRNA precursors and signaling *** decades of investigations devoted,the biological function of the vault particle or the vault RNAs is not yet completely *** this review,the current scientific assertions of the vital vault RNAs functions were discussed.

关键词： ncRNA Vault complex Vault RNA vtRNA viral infection tumorigenesis

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