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Jatonik polyherbal mixture induced rat liver MMPT pore opening in normal Wistar rat:In vitro and in vivo studies

Chinese Herbal Medicines 2024年第1期16卷 113-120页

作者： Olabinri P.Folashade Ibrahim Damilare Boyenle Tolulope A.Oyedeji Fiyinfoluwa Demilade Ojeniyi Adisa Ayobami Damilare Leonard O.Ehigie Adeola Folasade Ehigie Membrane biochemistry and biophysics Research laboratory Department of BiochemistryLadoke Akintola University of TechnologyOgbomoso 210214Nigeria Computational Biology/Drug Discovery laboratory Department of BiochemistryLadoke Akintola University of TechnologyOgbomoso 210214Nigeria College of Health Sciences Crescent University AbeokutaAbeokuta 111105Nigeria Department of biochemistry University of LagosLagos 101017Nigeria

Objective:To assess acute toxicity,the in vitro and in vivo effects of methanol and ethyl acetate extracts(JME and JEE)of Jatonik polyherbal mixture on some mitochondria-related parameters and their effect on the activity of some liver ***:Acute toxicity of JME and JEE was determined using Lorke’s *** vitro and in vivo opening of the mitochondrial membrane permeability transition pore(MMPT pore)was spectrophotometrically *** of malondialdehyde(MDA)as an index of lipid peroxidation and the activity of mitochondrial ATPase was evaluated in vitro and in vivo and the effect of JME and JEE on the activity of liver enzymes such as alkaline phosphatase(ALP),aspartate and alanine aminotransferase(AST and ALT)and gamma-glutamyl transferase(GGT)was also ***:JME had an LD_(50) of 3808 mg/kg b.w whereas JEE had an LD_(50) greater than 5000 mg/kg *** *** the rats have been fed with both extracts,a photomicrograph of a piece of liver tissue showed no apparent symptoms of *** the in vitro and in vivo studies,both extracts prompted intact mitochondria to open their MMPT *** compared to the control,lipid peroxide product release and ATPase activity were significantly increased(P<0.05)in vitro and in *** activities of AST,ALT,and GGT were all reduced at 50 mg/kg when treated with JME,but the activity of AST was considerably enhanced when treated with JEE(P<0.05).The results revealed that both JME and JEE of the Jatonik polyherbal mixture had low toxicity,profound MMPTpore induction,and enhanced ATPase activity,but an increased MDA ***:Jatonik extracts may be a promising target for drug development in diseases where there is dysregulation of apoptosis,however,further studies are needed to better clarify the molecular mechanism involved in these phenomena.

关键词： acute toxicity Ageratum conyzoides Linn. apoptosis Hunteria umbellate(K.Schum.)Hallier f. Lepidium meyenii Walp. mitochondrial ATPase mitochondrial lipid peroxidation mitochondrial membrane permeability transition pore polyherbal mixture Xylopia aethiopica(Dunal)A.Rich

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Dormancy heterogeneity among Arabidopsis thaliana seeds is linked to individual seed size

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Plant Communications 2024年第2期5卷 215-227页

作者： Michal Krzyszton Sebastian P.Sacharowski Veena Halale Manjunath Katarzyna Muter Grzegorz Bokota Ce Wang Dariusz Plewczynski Tereza Dobisova Szymon Swiezewski laboratory of Seeds Molecular Biology Institute of Biochemistry and BiophysicsPAS02-106 WarsawPoland laboratory of Functional and Structural Genomics Centre of New TechnologiesUniversity of WarsawWarsawPoland laboratory of Bioinformatics and Computational Genomics Faculty of Mathematics and Information ScienceWarsaw University of TechnologyWarsawPoland Labdeers Ltd. 680-01 BoskoviceCzech Republic

Production of morphologically and physiologically variable seeds is an important strategy that helps plants to survive in unpredictable natural ***,the model plant Arabidopsis thaliana and most agronomically essential crops produce visually homogenous *** automated phenotype analysis,we observed that small seeds in Arabidopsis tend to have higher primary and secondary dormancy levels than large *** analysis revealed distinct gene expression profiles between large and small *** seeds have higher expression of translation-related genes implicated in germination *** contrast,small seeds have elevated expression of many positive regulators of dormancy,including a key regulator of this process,the DOG1 *** in DOG1 expression are associated with differential production of its alternative cleavage and polyadenylation isoforms;in small seeds,the proximal poly(A)site is selected,resulting in a short mRNA ***,single-seed RNA sequencing analysis demonstrated that large seeds resemble DOG1 knockout mutant ***,on the single-seed level,expression of genes affected by seed size is correlated with expression of genes that position seeds on the path toward *** results demonstrate an unexpected link between seed size and dormancy phenotypes in a species that produces highly homogenous seed pools,suggesting that the correlation between seed morphology and physiology is more widespread than initially assumed.

关键词： seed size dormancy DOG1 Arabidopsis

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A multi-platform analysis of human gingival crevicular fluid reveals ferroptosis as a relevant regulated cell death mechanism during the clinical progression of periodontitis

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International Journal of Oral Science 2024年第2期16卷 265-279页

作者： Alfredo Torres M.Angélica Michea Ákos Végvári Marion Arce Valentina Pérez Marcela Alcota Alicia Morales Rolando Vernal Mauricio Budini Roman A.Zubarev Fermín E.González laboratory of Experimental Immunology&Cancer Faculty of DentistryUniversity of ChileSantiagoChile Department of Conservative Dentistry Faculty of DentistryUniversity of ChileSantiagoChile Division of Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSweden Periodontal Biology laboratory Faculty of DentistryUniversidad de ChileSantiagoChile laboratory of Cellular and Molecular Pathology Institute for Research in Dental SciencesFaculty of DentistryUniversity of ChileSantiagoChile

Ferroptosis is implicated in the pathogenesis of numerous chronic-inflammatory diseases,yet its association with progressive periodontitis remains *** investigate the involvement and significance of ferroptosis in periodontitis progression,we assessed sixteen periodontitis-diagnosed *** progression was clinically monitored over twelve weeks via weekly clinical evaluations and gingival crevicular fluid(GCF)collection was performed for further *** metrics,proteomic data,in silico methods,and bioinformatics tools were combined to identify protein profiles linked to periodontitis progression and to explore their potential connection with *** western blot analyses validated key ***,a single-cell RNA sequencing(scRNA-seq)dataset(GSE164241)for gingival tissues was analyzed to elucidate cellular dynamics during periodontitis *** progression was identified as occurring at a faster rate than traditionally *** samples from progressing and non-progressing periodontal sites showed quantitative and qualitatively distinct proteomic *** addition,specific biological processes and molecular functions during progressive periodontitis were revealed and a set of hub proteins,including SNCA,CA1,HBB,SLC4A1,and ANK1 was strongly associated with the clinical progression status of ***,we found specific proteins-drivers or suppressors-associated with ferroptosis(SNCA,FTH1,HSPB1,CD44,and GCLC),revealing the co-occurrence of this specific type of regulated cell death during the clinical progression of ***,the integration of quantitative proteomic data with scRNA-seq analysis suggested the susceptibility of fibroblasts to *** analyses reveal proteins and processes linked to ferroptosis for the first time in periodontal patients,which offer new insights into the molecular mechanisms of progressive periodontal *** findings may le

关键词： finding progression faster

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Exploring noncoding variants in genetic diseases:from detection to functional insights

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Journal of Genetics and Genomics 2024年第2期51卷 111-132页

作者： Ke Wu Fengxiao Bu Yang Wu Gen Zhang Xin Wang Shunmin He Mo-Fang Liu Runsheng Chen Huijun Yuan Institute of Rare Diseases West China Hospital of Sichuan UniversityChengduSichuan 610041China Key laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhouZhejiang 310024China Key laboratory of RNA Biology Center for Big Data Research in HealthInstitute of BiophysicsChinese Academy of SciencesBeijing 100101China University of Chinese Academy of Sciences Beijing 100049China State Key laboratory of Molecular Biology State Key Laboratory of Cell BiologyShanghai Key Laboratory of Molecular AndrologyShanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China

Previous studies on genetic diseases predominantly focused on protein-coding variations, overlooking the vast noncoding regions in the human genome. The development of high-throughput sequencing technologies and functional genomics tools has enabled the systematic identification of functional noncoding variants. These variants can impact gene expression, regulation, and chromatin conformation, thereby contributing to disease pathogenesis. Understanding the mechanisms that underlie the impact of noncoding variants on genetic diseases is indispensable for the development of precisely targeted therapies and the implementation of personalized medicine strategies. The intricacies of noncoding regions introduce a multitude of challenges and research opportunities. In this review, we introduce a spectrum of noncoding variants involved in genetic diseases, along with research strategies and advanced technologies for their precise identification and in-depth understanding of the complexity of the noncoding genome. We will delve into the research challenges and propose potential solutions for unraveling the genetic basis of rare and complex diseases.

关键词： Noncoding variation Genetic disease Research approach Challenge

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Distinct molecular targets of ProEGCG from EGCG and superior inhibition of angiogenesis signaling pathways for treatment of endometriosis

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Journal of Pharmaceutical Analysis 2024年第1期14卷 100-114页

作者： Sze Wan Hung Massimiliano Gaetani Yiran Li Zhouyurong Tan Xu Zheng Ruizhe Zhang Yang Ding Gene Chi Wai Man Tao Zhang Yi Song Yao Wang Jacqueline Pui Wah Chung Tak Hang Chan Roman A.Zubarev Chi Chiu Wang Department of Obstetrics&Gynaecology The Chinese University of Hong KongHong KongChina Division of Physiological Chemistry I Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Chemical Proteomics Core Facility Department of Medical Biochemistry and BiophysicsKarolinska InstitutetStockholmSE 17177Sweden Unit of Chemical Proteomics Science for Life Laboratory(SciLifeLab)StockholmSE 17177Sweden Center for Reproductive Medicine Henan Key Laboratory of Reproduction and GeneticsThe First Affiliated Hospital of Zhengzhou UniversityZhengzhou450003China Department of Chemistry McGill UniversityMontrealH3A2K6Canada Department of Pharmacological&Technological Chemistry I.M.Sechenov First Moscow State Medical UniversityMoscow119146Russia Reproduction and Development Li Ka Shing Institute of Health SciencesThe Chinese University of Hong KongHong KongChina School of Biomedical Sciences The Chinese University of Hong KongHong KongChina Chinese University of Hong Kong-Sichuan University Joint laboratory in Reproductive Medicine The Chinese University of Hong KongHong KongChina

Endometriosis is a common chronic gynecological disease with endometrial cell implantation outside the *** is a major pathophysiology in *** previous studies have demonstrated that the prodrug of epigallocatechin gallate(ProEGCG)exhibits superior anti-endometriotic and anti-angiogenic effects compared to epigallocatechin gallate(EGCG).However,their direct binding targets and underlying mechanisms for the differential effects remain *** this study,we demonstrated that oral ProEGCG can be effective in preventing and treating ***,1D and 2D Proteome Integral Solubility Alteration assay-based chemical proteomics identified metadherin(MTDH)and PX domain containing serine/threonine kinase-like(PXK)as novel binding targets of EGCG and ProEGCG,*** simulation and BioLayer interferometry were used to confirm their binding *** results showed that MTDH-EGCG inhibited protein kinase B(Akt)-mediated angiogenesis,while PXK-ProEGCG inhibited epidermal growth factor(EGF)-mediated angiogenesis via the EGF/hypoxia-inducible factor(HIF-1a)/vascular endothelial growth factor(VEGF)*** vitro and in vivo knockdown assays and microvascular network imaging further confirmed the involvement of these signaling ***,our study demonstrated that ProEGCG has superior therapeutic effects than EGCG by targeting distinct signal transduction pathways and may act as a novel antiangiogenic therapy for endometriosis.

关键词： Molecular targets ProEGCG EGCG Angiogenesis Treatment Endometriosis

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The Role of E3 Ligases in Macrophage-mediated Inflammation

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生物化学与生物物理进展 2024年第9期51卷 2037-2060页

作者： JIN Jia-Bei GE Yi-Dong JIN Xiao-Feng Zhejiang Key laboratory of Pathophysiology Department of Biochemistry and Molecular BiologyHealth Science CenterNingbo UniversityNingbo 315211China

Macrophages,existed in almost all organs of the body,are responsible for detecting tissue injury,pathogens,playing a key role in host defense against a variety of invading pathogens triggering inflammatory *** evidence suggests that macrophage-mediated immune responses are efficiently regulated by the ubiquitination modification,which is responsible for normal immune ***,numerous studies indicates that the aberrant activation or inhibition of macrophage-mediated immune responses occurs in inflammation,mainly caused by dysregulated ubiquitination modification due to E3 ubiquitin ligases mutations or abnormal ***,E3 ubiquitin ligases,responsible for recognizing the substrates,are key enzymes in the ubiquitin proteasome system(UPS)composed of ubiquitin(Ub),ubiquitin-activating E1 enzymes,ubiquitin-conjugating E2 enzymes,E3 ubiquitin ligases,26S proteasome,and deubiquitinating ***,several E3 ubiquitin ligases are involved in the regulation of some common signal pathways in macrophage-mediated inflammation,including Toll-like receptors(TLRs),nucleotide-binding oligomerization domain(NOD)-like receptors(NLRs),RIG-I-like receptors(RLRs),C-type lectin receptors(CLRs)and the receptor for advanced glycation end products(RAGE).Herein,we summarized the physiological and pathological roles of E3 ligases in macrophage-mediated inflammation,as well as the inhibitors and agonists targeting E3 ligases in macrophage mediated inflammation,providing the new ideas for targeted therapies in macrophage-mediated inflammation caused aberrant function of E3 ligases.

关键词： E3 ligases macrophage NLRs/RLRs/TLRs targeted therapies

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Innovative insights into extrachromosomal circular DNAs in gynecologic tumors and reproduction

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Protein & Cell 2024年第1期15卷 6-20页

作者： Ning Wu Ling Wei Zhipeng Zhu Qiang Liu Kailong Li Fengbiao Mao Jie Qiao Xiaolu Zhao State Key laboratory of Female Fertility Promotion Center for Reproductive MedicineDepartment of Obstetrics and GynecologyCenter for Reproductive MedicinePeking University Third HospitalBeijing 100191China National Clinical Research Center for Obstetrics and Gynecology Peking University Third HospitalBeijing 100191China Key laboratory of Assisted Reproduction(Peking University) Ministry of EducationBeijing 100191China Beijing Key laboratory of Reproductive Endocrinology and Assisted Reproductive Technology Beijing 100191China Institute of Medical Innovation and Research Peking University Third HospitalBeijing 100191China Cancer Center Peking University Third HospitalBeijing 100191China Department of biochemistry and biophysics Beijing Key Laboratory of Protein Posttranslational Modifications and Cell FunctionSchool of Basic Medical SciencesPeking University Health Science CenterBeijing 100191China Beijing Advanced Innovation Center for Genomics Beijing 100191China Peking-Tsinghua Center for Life Sciences Peking UniversityBeijing 100191China

Originating but free from chromosomal DNA,extrachromosomal circular DNAs(eccDNAs)are organized in circular form and have long been found in unicellular and multicellular *** biogenesis and function are poorly understood as they are characterized by sequence homology with linear DNA,for which few detection methods are *** advances in high-throughput sequencing technologies have revealed that eccDNAs play crucial roles in tumor formation,evolution,and drug resistance as well as aging,genomic diversity,and other biological processes,bringing it back to the research *** mechanisms of eccDNA formation have been proposed,including the breakage-fusion-bridge(BFB)and translocation-deletion-amplification *** tumors and disorders of embryonic and fetal development are major threats to human reproductive *** roles of eccDNAs in these pathological processes have been partially elucidated since the first discovery of eccDNA in pig sperm and the double minutes in ovarian cancer *** present review summarized the research history,biogenesis,and currently available detection and analytical methods for eccDNAs and clarified their functions in gynecologic tumors and *** also proposed the application of eccDNAs as drug targets and liquid biopsy markers for prenatal diagnosis and the early detection,prognosis,and treatment of gynecologic *** review lays theoretical foundations for future investigations into the complex regulatory networks of eccDNAs in vital physiological and pathological processes.

关键词： extrachromosomal circular DNAs gynecologic tumors reproduction liquid biopsy non-invasive prena-tal testing

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Establishment of a cholangiocarcinoma risk evaluation model based on mucin expression levels

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World Journal of Gastrointestinal Oncology 2024年第4期16卷 1344-1360页

作者： Chun-Yuan Yang Li-Mei Guo Yang Li Guang-Xi Wang Xiao-Wei Tang Qiu-Lu Zhang Ling-Fu Zhang Jian-Yuan Luo Department of Pathology Institute of Systems BiomedicineSchool of Basic Medical Sciences Peking UniversityPeking University Third HospitalPeking University Health Science CenterBeijing 100191China Department of General Surgery Peking University Third HospitalBeijing 100191China Department of Medical Genetics Department of Biochemistry and BiophysicsSchool of Basic Medical Sciences Peking UniversityPeking University Health Science CenterBeijing 100191China

BACKGROUND Cholangiocarcinoma(CCA)is a highly malignant cancer,characterized by frequent mucin ***1 has been identified as a critical oncogene in the progression of ***,the comprehensive understanding of how the mucin family influences CCA progression and prognosis is still *** To investigate the functions of mucins on the progression of CCA and to establish a risk evaluation formula for stratifying CCA *** Single-cell RNA sequencing data from 14 CCA samples were employed for elucidating the roles of mucins,complemented by bioinformatic ***-quent validations were conducted through spatial transcriptomics and *** construction of a risk evaluation model utilized the least absolute shrinkage and selection operator regression algorithm,which was further confirmed by independent cohorts and diverse data *** CCA tumor cells with elevated levels of MUC1 and MUC4 showed activated nucleotide metabolic pathways and increased ***5AC-high cells were found to promote CCA progression through WNT ***5B-high cells exhibited robust cellular oxidation activities,leading to resistance against antitumoral ***13-high cells were observed to secret chemokines,recruiting and transforming macrophages into the M2-polarized state,thereby suppressing antitumor ***16-high cells were found to promote tumor progression through interleukin-1/nuclear factor kappa-light-chain-enhancer of activated B cells signaling upon interaction with *** the expression levels of these mucins,a risk factor evaluation formula for CCA was developed and validated across multiple *** samples with higher risk factors exhibited stronger metastatic potential,chemotherapy resistance,and poorer *** Our study elucidates the functional mechanisms through which mucins contribute to CCA development,and provides tools for risk stratification in CCA.

关键词： Mucin Cholangiocarcinoma Single-cell RNA sequencing Spatial transcriptomics Prognosis

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生物信息学资源助力蛋白质磷酸化的系统层次理解

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Science Bulletin 2024年第8期69卷 989-992页

作者：彭迪贾大夏宏光张珞颖黄鹏宇薛宇 Department of Bioinformatics and Systems Biology MOE Key Laboratory of Molecular BiophysicsHubei Bioinformatics and Molecular Imaging Key LaboratoryCollege of Life Science and TechnologyHuazhong University of Science and TechnologyWuhan 430074China Key laboratory of Birth Defects and Related Diseases of Women and Children Department of PaediatricsWest China Second University HospitalState Key Laboratory of BiotherapySichuan UniversityChengdu 610041China Department of biochemistry&Research Center of Clinical Pharmacy of The First Affiliated Hospital Zhejiang University School of MedicineHangzhou 310058China Institute of Biomedical Engineering Chinese Academy of Medical Sciences and Peking Union Medical CollegeTianjin 300192China Nanjing University Institute of Artificial Intelligence Biomedicine Nanjing 210031China

Protein phosphorylation,catalyzed by protein kinases(PKs),is one of the most prevalent post-translational modifications(PTMs)in *** occurring at different positions in a protein sequence can possess distinct functional impacts,and sitespecific phosphorylation may drastically alter a protein’s conformation,activity,and ***,biologists usually focused on studying regulatory mechanisms of phosphorylation in a limited number of proteins,mainly due to a lack of highthroughput *** the past two decades,advances in liquid chromatography coupled with tandem mass spectrometry(LC-MS/MC)have boomed a revolutionary technology named phosphoproteomics,which can simultaneously quantify thousands of phosphorylation sites(p-sites),and provide a great opportunity for a systems-level understanding of *** LCMS/MC,other approaches such as immunohistochemistry(IHC)and immune-detection by sequencing(ID-seq)have also emerged.

关键词： positions catalyzed translational

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Optical-neural Stimulation in Non-human Primates:Modulating Brain Function and Behavior

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生物化学与生物物理进展 2024年第10期51卷 2379-2391页

作者： CHEN Yi-Bing WANG Huan YANG Yan State Key laboratory of Brain and Cognitive Science Institute of BiophysicsChinese Academy of SciencesBeijing 100101China Sino-Danish College University of Chinese Academy of SciencesBeijing 100049China

Optical-neural stimulation,which encompasses cutting-edge techniques such as optogenetics and infrared neurostimulation,employs distinct mechanisms to modulate brain function and *** advanced neuromodulation techniques offer accurate manipulation of targeted areas,even selectively modulating specific neurons,in the *** makes it possible to investigate the cause-and-effect connections between neural activity and behavior,allowing for a better comprehension of the intricate brain dynamics towards complex ***-human primates serve as an essential animal model for investigating these complex functions in brain research,bridging the gap between the basic research and clinical *** of the earliest optical studies utilizing optogenetic neuromodulation in monkeys was conducted in *** then,the optical-neural stimulations have been effectively applied in non-human *** review summarises recent research that employed optogenetics or infrared neurostimulation techniques to regulate brain function and behavior in non-human *** current state of optical-neural stimulations discussed here demonstrates their efficacy in advancing the understanding of brain ***,there are still challenges that need to be addressed before they can fully achieve their potential.

关键词： optical-neural stimulation optogenetics infrared neurostimulation non-human primates

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