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Flavonoid Myricetin as Potent Anticancer Agent: A Possibility towards Development of Potential Anticancer Nutraceuticals

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Chinese Journal of Integrative Medicine 2024年第1期30卷 75-84页

作者： Anchal Trivedi Adria Hasan Rumana Ahmad Sahabjada Siddiqui Aditi Srivastava Aparna Misra Snober S.Mir Department of Biochemistry Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India molecular cell biology Laboratory Integral Information and Research Centre-4(IIRC-4)Department of BioengineeringFaculty of EngineeringIntegral UniversityLucknow(226026)India Department of Biotechnology Era's Lucknow Medical College&HospitalEra UniversityLucknow(226003)India Department of Biosciences Faculty of ScienceIntegral UniversityLucknow(226026)India

Good nutrition plays a crucial role in maintaining a balanced lifestyle. The beneficial effects of nutrition have been found to counteract nutritional disturbances with the expanded use of nutraceuticals to treat and manage cardiovascular diseases, cancer, and other developmental defects over the last decade. Flavonoids are found abundantly in plant-derived foods such as fruits, vegetables, tea, cocoa, and wine. Fruits and vegetables contain phytochemicals like flavonoids, phenolics, alkaloids, saponins, and terpenoids. Flavonoids can act as anti-inflammatory, anti-allergic, anti-microbial(antibacterial, antifungal, and antiviral) antioxidant, anti-cancer, and anti-diarrheal agents. Flavonoids are also reported to upregulate apoptotic activity in several cancers such as hepatic, pancreatic, breast, esophageal, and colon. Myricetin is a flavonol which is naturally present in fruits and vegetables and has shown possible nutraceutical value. Myricetin has been portrayed as a potent nutraceutical that may protect against cancer. The focus of the present review is to present an updated account of studies demonstrating the anticancer potential of myricetin and the molecular mechanisms involved therein. A better understanding of the molecular mechanism(s) underlying its anticancer activity would eventually help in its development as a novel anticancer nutraceutical having minimal side effects.

关键词： myricetin flavonoids anticancer nutraceuticals Chinese medicine Ayurveda complementary and alternative medicine

Mesenchymal stem cells’“garbage bags”at work:Treating radial nerve injury with mesenchymal stem cell-derived exosomes

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World Journal of Stem cells 2024年第5期16卷 467-478页

作者： Mazhar Mushtaq Doaa Hussein Zineldeen Muhammad Abdul Mateen Khawaja Husnain Haider Department of Basic Sciences Sulaiman AlRajhi UniversityAlbukairiyah 52736AlQaseemSaudi Arabia Medical Biochemistry and molecular biology Department Faculty of MedicineTanta UniversityTanta 6632110Egypt

Unlike central nervous system injuries,peripheral nerve injuries(PNIs)are often characterized by more or less successful axonal ***,structural and functional recovery is a senile process involving multifaceted cellular and molecular *** contemporary treatment options are limited,with surgical intervention as the gold-standard method;however,each treatment option has its associated limitations,especially when the injury is severe with a large *** advancements in cell-based therapy and cell-free therapy approaches using stem cell-derived soluble and insoluble components of the cell secretome are fast-emerging therapeutic approaches to treating acute and chronic *** recent pilot study is a leap forward in the field,which is expected to pave the way for more enormous,systematic,and well-designed clinical trials to assess the therapeutic efficacy of mesenchymal stem cell-derived exosomes as a bio-drug either alone or as part of a combinatorial approach,in an attempt synergize the best of novel treatment approaches to address the complexity of the neural repair and regeneration.

关键词： Exosome Mesenchymal stem cells Nerve injury Stem cells Secretome Regeneration

Stay in touch with the endoplasmic reticulum

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Science China(Life Sciences) 2024年第2期67卷 230-257页

作者： Sha Sun Gan Zhao Mingkang Jia Qing Jiang Shulin Li Haibin Wang Wenjing Li Yunyun Wang Xin Bian Yan G.Zhao Xun Huang Ge Yang Huaqing Cai Jose C.Pastor-Pareja Liang Ge Chuanmao Zhang Junjie Hu National Laboratory of Biomacromolecules Institute of BiophysicsUniversity of Chinese Academy of SciencesChinese Academy of SciencesBeijing 100101China The Ministry of Education Key Laboratory of cell Proliferation and Differentiation College of Life SciencesPeking UniversityBeijing 100871China State Key Laboratory of Membrane biology Tsinghua-Peking Center for Life SciencesSchool of Life SciencesTsinghua UniversityBeijing 100084China Laboratory of Computational biology&Machine Intelligence School of Artificial IntelligenceUniversity of Chinese Academy of SciencesBeijing 100049China State Key Laboratory of Medicinal Chemical biology College of Life SciencesNankai UniversityTianjin 300071China Brain Research Center Department of BiologySchool of Life SciencesSouthern University of Science and TechnologyShenzhen 518055China State Key Laboratory of molecular Developmental biology Institute of Genetics and Developmental BiologyInnovation Academy for Seed DesignChinese Academy of SciencesBeijing 100101China Institute of Neurosciences Consejo Superior de Investigaciones Científicas-Universidad Miguel HernándezSan Juan de Alicante 03550Spain

The endoplasmic reticulum(ER),which is composed of a continuous network of tubules and sheets,forms the most widely distributed membrane system in eukaryotic *** a result,it engages a variety of organelles by establishing membrane contact sites(MCSs).These contacts regulate organelle positioning and remodeling,including fusion and fission,facilitate precise lipid exchange,and couple vital signaling ***,we systematically review recent advances and converging themes on ER-involved organellar *** molecular basis,cellular influence,and potential physiological functions for ER/nuclear envelope contacts with mitochondria,Golgi,endosomes,lysosomes,lipid droplets,autophagosomes,and plasma membrane are summarized.

关键词： endoplasmic reticulum nuclear envelope mitochondria Golgi apparatus endosome lysosome lipid droplets autophagosome plasma membrane membrane contact site

Non-proteolytic ubiquitination of HBx controls HBV replication

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Virologica Sinica 2024年第2期39卷 338-342页

作者： Xiangpeng Sheng Yi Yang Min Zhu Linlin Zhou Fang Zhu Yuanfei Zhu Siying Dong Hui Kong Honghua Wang Ji Jiang Mingyue Wan Mingyang Feng Qiang Deng Yumin Xu Qing You Ronggui Hu State Key Laboratory for Animal Disease Control and Prevention Harbin Veterinary Research InstituteChinese Academy of Agricultural SciencesHarbin 150069China State Key Laboratory of molecular biology Shanghai Institute of Biochemistry and Cell BiologyCenter for Excellence in Molecular Cell ScienceChinese Academy of SciencesShanghai 200031China Key Laboratory of Systems Health Science of Zhejiang Province School of Life ScienceHangzhou Institute for Advanced StudyUniversity of Chinese Academy of SciencesHangzhou 310024China Department of Thoracic Surgery Ruijin HospitalShanghai Jiaotong University School of MedicineShanghai 200025China Shanghai Key Laboratory of Plant molecular Sciences College of Life SciencesShanghai Normal UniversityShanghai 200234China Department of Pathogenic biology West China School of Basic Medical Sciences&Forensic MedicineSichuan UniversityChengdu 610041China School of Medicine Guizhou UniversityGuiyang 550025China Key Laboratory of Medical molecular Virology(MOE&MOH) School of Basic Medical SciencesFudan UniversityShanghai 200032China Department of Hospital Infection Management Department of Infectious DiseasesRuijin HospitalShanghai Jiao Tong University School of MedicineShanghai 200025China School of Biomedical Engineering Shanghai Jiao Tong UniversityShanghai 200240China

Dear Editor,Although effective vaccines and antiviral therapies are available,hepatitis B virus(HBV)infection is still a serious global health *** HBV infection remains the principal cause of liver cirrhosis and hepatocellular carcinoma(HCC).HBV is a small DNA virus,owning a~3.2 kb genome that encodes several proteins:viral DNA polymerase,core antigen(HBcAg),E antigen(HBeAg),three surface antigens(PreS1/PreS2/HBsAg),and a regulatory X protein(HBx)(Lamontagne et al.,2016).X protein,named for its lack of homology with any known proteins,is a 154 aa protein that plays an essential role in HBV biology and regulates the development of HCC(Yang et al.,2022).Although previous studies have strongly expanded our understanding of HBx,the regulation of HBx is not completely elucidated.

关键词： infection cirrhosis

DNA-delivered monoclonal antibodies targeting the p53 R175H mutant epitope inhibit tumor development in mice

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Genes & Diseases 2024年第4期11卷 368-380页

作者： Dafei Chai Xu Wang Praveen Neeli Shan Zhou Xingfang Yu Kanaga Sabapathy Yong Li Department of Medicine Section of Epidemiology and Population SciencesDan L Duncan Comprehensive Cancer CenterBaylor College of MedicineHoustonTX 77030USA Division of cellular&molecular Research Humphrey Oei Institute of Cancer ResearchNational Cancer Centre SingaporeSingapore 168583Singapore

tThe tumor suppressor p53 is the most common mutated gene in cancer,with the R175H as the most frequent p53 missense ***,there are currently no approved targeted therapies or immunotherapies against mutant ***,we characterized and inves-tigated a monoclonal antibody(mAb)that recognizes the mutant p53-R175H for its affinity,specificity,and activity against tumor cells in *** then delivered DNA plasmids expres-sing the anti-R175H mAb or a bispecific antibody(BsAb)into mice to evaluate their therapeutic *** results showed that the anti-R175H mAb specifically bound to the p53-R175H an-tigen with a high affinity and recognized the human mutant p53-R175H antigen expressed on HEK293T or MC38 cells,with no cross-reactivity with wild-type *** cultured cells,the anti-R175H mAb showed higher cytotoxicity than the control but did not induce antibody-dependent cellular *** made a recombinant MC38 mouse cell line(MC38-p53-R175H)that overexpressed the human p53-R175H after knocking out the endogenous mutant p53 *** vivo,administration of the anti-R175H mAb plasmid elicited a robust anti-tumor effect against MC38-p53-R175H in *** administration of the anti-R175H BsAb plasmid showed no therapeutic effects,yet potent anti-tumor activity was observed in combination with the anti-PD-1 *** results indicate that targeting specific mutant epitopes using DNA-delivered mAbs or BsAbs presents a form of improved natural immunity derived from tumor-infiltrating B cells and plasma cells against intracellular tumor antigens.

关键词： BsAb Cytotoxicity mAb Mutant p53 PD-1 R175H

Small extrachromosomal circular DNA in amyotrophic lateral sclerosis matter

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Neural Regeneration Research 2025年第5期20卷 1411-1413页

作者： Marcos J.Arauzo-Bravo Daniela Gerovska Matthias Schwab Alexandra Kretz Computational biology and Systems Biomedicine Biodonostia Health Research InstituteSan SebastianSpain Basque Foundation for Science IKERBASQUEBilbaoSpainMax Planck Institute for Molecular BiomedicineComputational Biology and Bioinformatics GroupMünsterNorth Rhine-WestphaliaGermany Department of cell biology and Histology Faculty of Medicine and NursingUniversity of Basque Country(UPV/EHU)LeioaSpain Department of Neurology Jena University HospitalJenaThuringiaGermany

Comprehensive studies identify motor neuron spectrum disorders including amyotrophic lateral sclerosis(ALS)as globally rising fatal disorders with the highest prevalence in aging populations,influenced by ethnicity and ancestry(GBD 2016 Motor Neuron Disease Colla borators,2018).While~10% of diagnoses involve a family history(fALS),most cases are considered sporadic(sALS).However,population-based studies suggest that even cases without a common index mutation impart heritability(Ryan et al.,2019),indicating a crucial role of rare and as yet unknown genetic denominators.

关键词： amyotrophic sclerosis

Reevaluation by the CRISPR/Cas9 knockout approach revealed that multiple pluripotency-associated lncRNAs are dispensable for pluripotency maintenance while Snora73a/b is essential for pluripotency exit

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Science China(Life Sciences) 2024年第10期67卷 2198-2212页

作者： Zhen Li Xuefei Li Jingxia Lin Yangming Wang Huiqing Cao Jiajian Zhou Institute of molecular Medicine College of Future TechnologyPeking UniversityBeijing 100871China Dermatology Hospital Southern Medical UniversityGuangzhou 510091China Beijing Advanced Center of RNA biology(BEACON) Peking UniversityBeijing 100871China

Many long noncoding RNAs(lncRNAs)have been identified through siRNA-based screening as essential regulators of embryonic stem cell(ESC)***,the biological and molecular functions of most lncRNAs remain ***,we employed CRISPR/Cas9-mediated knockout technology to explore the functions of 8 lncRNAs previously reported to promote pluripotency in mouse ***,all of these lncRNAs were dispensable for pluripotency maintenance and proliferation in mouse ESCs when disrupted individually or in ***-cell transcriptomic analysis also showed that the knockout of these lncRNAs has a minimal impact on pluripotency gene expression and cell *** further showed that several small hairpin RNAs(shRNAs)previously used to knock down lncRNAs caused the downregulation of pluripotency genes in the corresponding lncRNA-knockout ESCs,indicating that off-target effects likely responsible for the pluripotency defects caused by these ***,linc1343-knockout and linc1343-knockdown ESCs failed to form cystic structures and exhibited high expression of pluripotency genes during embryoid body(EB)*** reintroducing RNA products generated from the linc1343 locus,we found that two snoRNAs,Snora73a and Snora73b,but not lncRNAs,could rescue pluripotency silencing defects during EB differentiation of linc1343 knockout *** results suggest that the 8 previously annotated pluripotency-regulating lncRNAs have no overt functions in conventional ESC culture;however,we identified snoRNA products derived from an annotated lncRNA locus as essential regulators for silencing pluripotency genes.

关键词： long noncoding RNAs embryonic stem cells CRISPR/Cas9 snoRNAs stem cell differentiation

Genetic insights into adaptation of alfalfa

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molecular Plant 2024年第8期17卷 1170-1171页

作者： Yafei Guo Lipeng Kang Fei Lu State Key Laboratory of Plant cell and Chromosome Engineering Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina Key Laboratory of Seed Innovation Institute of Genetics and Developmental BiologyChineseAcademyof SciencesBeijingChina University of Chinese Academy of Sciences BeijingChina CAS-JIC Centre of Excellence for Plant and Microbial Science(CEPAMS) Institute of Genetics and Developmental BiologyChinese Academy of SciencesBeijingChina

Climate change is increasingly affecting agricultural outputs,as evidenced by the changing global temperature and extreme weather events that significantly impact crop yields(Lesk et al.,2016).To address this challenge,there is a growing interest in developing crops that can endure these adverse conditions to ensure food *** examples in nature show how crops have adapted to diverse environments(Gutaker and Purugganan,2023),leaving behind a rich genomic *** genomics has started to provide insights into these adaptive processes from evolutionary and genetic perspectives(Savolainen et al.,2013;Aguirre-Liguori et al.,2021;Sang et al.,2022).Recently,Zhang et al.(Zhang et al.,2024)investigated alfalfa(Medicago sativa ***),known as the"queen of forages,"for its broad *** analyzing whole-genome sequencing data of 702 accessions from 24 Medicago species,this study enriches our understanding of how to develop crops and meet the challenges of climate change.

关键词： sativa crops environments

5-Fluorouracil dose escalation generated desensitized colorectal cancer cells with reduced expression of protein methyltransferases and no epithelial-to-mesenchymal transition potential

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Oncology Research 2024年第6期32卷 1047-1061页

作者： KIMBERLY FENECH ISAAC MICALLEF BYRON BARON Centre for molecular Medicine and Biobanking University of MaltaMsidaMSD 2080Malta Department of Tumor Genetics and biology Graduate School of Medical SciencesFaculty of Life SciencesKumamoto UniversityKumamoto860-8556Japan

Background:Colorectal cancer(CRC)is one of the most frequently diagnosed *** many cases,the poor prognosis of advanced CRC is associated with resistance to treatment with chemotherapeutic drugs such as 5-Fluorouracil(5-FU).The epithelial-to-mesenchymal transition(EMT)and dysregulation in protein methylation are two mechanisms associated with chemoresistance in many *** study looked into the effect of 5-FU dose escalation on EMT and protein methylation in *** and Methods:HCT-116,Caco-2,and DLD-1 CRC cell lines were exposed to dose escalation treatment of *** motility and invasive potentials of the cells before and after treatment with 5-FU were investigated through wound healing and invasion *** was followed by aWestern blot which analyzed the protein expressions of the epithelial marker E-cadherin,mesenchymal marker vimentin,and the EMT transcription factor(EMTTF),the snail family transcriptional repressor 1(Snail)in the parental and desensitized *** blotting was also conducted to study the protein expressions of the protein methyltransferases(PMTs),Euchromatic histone lysine methyltransferase 2(EHMT2/G9A),protein arginine methyltransferase(PRMT5),and SET domain containing 7/9(SETD7/9)along with the global lysine and arginine methylation ***:The dose escalation method generated 5-FU desensitized CRC cells with distinct morphological features and increased tolerance to high doses of *** 5-FU desensitized cells experienced a decrease in migration and invasion when compared to the parental *** was reflected in the observed reduction in E-cadherin,vimentin,and Snail in the desensitized cell ***,the protein expressions of EHMT2/G9A,PRMT5,and SETD7/9 also decreased in the desensitized cells and global protein lysine and arginine methylation became dysregulated with 5-FU ***:This study showed that continuous,dose-escalation treatment of 5-FU in CRC cells generated 5-FU

关键词： Chemoresistance Epithelial-to-mesenchymal transition Protein methylation Protein methyltransferases