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Glucagon-like peptide (GLP)-1 regulation of lipid and lipoprotein metabolism

Medical Review 2024年第4期4卷 301-311页

作者： Simon Hoffman Khosrow Adeli molecular Medicine Research InstituteThe Hospital for Sick ChildrenUniversity of TorontoTorontoONCanada Cardiovascular&Metabolic Disease Merck Research LaboratoriesSouth San FranciscoCAUSA molecular Medicine Research InstituteThe Hospital for Sick ChildrenUniversity of Toronto555 University Avenue M5G 1X8TorontoONCanada

Metabolic health is highly dependent on intestinal and hepatic handling of dietary and endogenous lipids and *** of lipid and lipoprotein metabolism are commonly observed in patients with insulin resistant states such as obesity,metabolic syndrome,and type 2 ***-idence from both animal models and human studies indicates that a major underlying factor in metabolic or diabetic dysli-pidemia is the overproduction of hepatic and intestinal apoli-poprotein(apo)B-containing lipoprotein *** particles are catabolized down into highly proatherogenic remnants,which can be taken up into the arterial intima and promote plaque *** gut-derived peptides have been identiﬁed as key regulators of energy metabolism;one such peptide is the incretin hormone glucagon-like peptide(GLP)-*** laboratory has previously demonstrated that GLP-1 can signal both centrally and peripherally to reduce postprandial and fasting lipoprotein ***,we have demonstrated that GLP-1 receptor(GLP-1R)agonists can ameliorate diet-induced ***,we published evidence for a novel vagal neuroendocrine signalling pathway by which native GLP-1 may exert its anti-lipemic eﬀ***,we demonstrated a novel role for other gut-derived peptides in regulating intestinal lipoprotein ***,ample evidence supports a key role for GLP-1R on the portal vein aﬀerent neurons and nodose ganglion in modulating intestinal fat absorption and lipoprotein produc-tion and identiﬁes other gut-derived peptides as novel regula-tors of postprandial *** from these data may support identiﬁcation of potential drug targets and the development of new therapeutics targeting treatment of dia-betic dyslipidemia.

关键词： glucagon-like peptide-1 lipid lipoprotein intes-tine neuroendocrine

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Interdigital MnO_(2)/PEDOT Alternating Stacked Microelectrodes for High-Performance On-Chip Microsupercapacitor and Humidity Sensing

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Energy & Environmental Materials 2024年第2期7卷 257-267页

作者： Muhammad Tahir Lihong Li Liang He Zhongyuan Xiang Zeyu Ma Waqas Ali Haider Xiaoqiao Liao Yanlin Song Key Laboratory of Green Printing CAS Research/Education Centre for Excellence in Molecular SciencesInstitute of Chemistry Chinese Academy of Sciences(ICCAS)Beijing 100190China School of Mechanical Engineering Sichuan UniversityChengdu 610065China A.S.Chemical laboratories Inc. Concord L4K 4M4ON Canada

For microelectronic devices,the on-chip microsupercapacitors with facile construction and high performance,are attracting researchers'prior consideration due to their high compatibility with modern ***,we proposed interchanging interdigital Au-/MnO_(2)/polyethylene dioxythiophene stacked microsupercapacitor based on a microfabrication process followed by successive electrochemical *** stacked configuration of two pseudocapacitive active microelectrodes meritoriously leads to an enhanced contact area between MnO_(2)and the conductive and electroactive layer of polyethylene dioxythiophene,hence providing excellent electron transport and diffusion pathways of electrolyte ions,resulting in increased pseudocapacitance of MnO_(2)and polyethylene *** stacked quasi-solid-state microsupercapacitors delivered the maximum specific capacitance of 43 mF cm^(-2)(211.9 F cm^(-3)),an energy density of 3.8μWh cm^(-2)(at a voltage window of 0.8 V)and 5.1μWh cm^(-2)(at a voltage window of 1.0 V)with excellent rate capability(96.6%at 2 mA cm^(-2))and cycling performance of 85.3%retention of initial capacitance after 10000 consecutive cycles at a current density of 5 mA cm^(-2),higher than those of ever reported polyethylene dioxythiophene and MnO_(2)-based planar *** from the favorable morphology,bilayer microsupercapacitor is utilized as a flexible humidity sensor with a response/relaxation time superior to those of some commercially available integrated *** strategy will be of significance in developing high-performance on-chip integrated microsupercapacitors/microsensors at low cost and environment-friendly routes.

关键词： electrochemical polymerization microsensor microsupercapacitor stacked microelectrode

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Discovery of a potent and selective cell division cycle 7 inhibitor from 6-(3-fluoropyridin4-yl)thieno[3,2-d]pyrimidin-4(3H)-one derivatives as an orally active antitumor agent

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Acta Pharmaceutica Sinica B 2024年第2期14卷 893-896页

作者： Mingwei Fu Min Ge Wanxiang Yang Chunchen Hu Xiaowei Li Yuanjiang Wang Shaohua Gou Pharmaceutical research Center and School of Chemistry and Chemical Engineering Southeast UniversityNanjing 211189China Jiangsu Province Hi-Tech Key Laboratory for Biomedical research Southeast UniversityNanjing 211189China Zenji research laboratories Nanjing 211189China

To the Editor:Kinase cell division cycle 7(CDC7),a cell division cycle protein,takes a vital role in mediating DNA ***7 complexes in the nucleus can phosphorylate the minichromosome maintenance complex(MCM)family members that bind to *** addition,CDC7 kinase,as a molecular switch regulating DNA replication,can mediate DNA damage signaling pathways to stimulate cell cycle termination as well as DNA *** have shown that CDC7 is overexpressed in many types of cancer cells,and its overexpression was related to poor patient survival,tumor grade,genetic instability,aneuploidy and so ***,CDC7 is a promising target for antitumor therapy.

关键词： Cell division cycle 7 DNA replication CDC7 inhibitor Anti-tumor

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Population genomic analysis unravels the evolutionary roadmap of pericarp color in rice

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Plant Communications 2024年第3期5卷 156-166页

作者： Lingjuan Xie Dongya Wu Yu Fang Chuyu Ye Qian-Hao Zhu Xinghua Wei Longjiang Fan Institute of Crop Sciences&Institute of Bioinformatics Zhejiang UniversityHangzhou 310058China Shandong(Linyi)Institute of Modern Agriculture Zhejiang UniversityLinyi 310014China Shanghai ZKW molecular Breeding Technology Co. Ltd.Shanghai 200234China CSIRO Agriculture and Food Black Mountain LaboratoriesCanberraACT 2601Australia China National Rice research Institute Chinese Academy of Agricultural SciencesHangzhou 311401China

Pigmented rice stands out for its nutritional value and is gaining more and more *** rice,domes-ticated red rice,and weedy rice all have a red pericarp and a comprehensive genetic background in terms of the red-pericarp *** performed population genetic analyses using 5104 worldwide rice acces-sions,including 2794 accessions with red or black pericarps,85 of which were newly sequenced in this *** results suggested an evolutionary trajectory of red landraces originating from wild rice,and the split times of cultivated red and white rice populations were estimated to be within the past 3500 *** red rice was found to feralize to weedy rice,and weedy rice could be further re-domesticated to cultivated red rice.A genome-wide association study based on the 2794 accessions with pigmented peri-carps revealed several new candidate genes associated with the red-pericarp trait for further functional *** results provide genomic evidence for the origin of pigmented rice and a valuable genomic resource for genetic investigation and breeding of pigmented rice.

关键词： red rice population genomics pericarp color re-domestication divergence time

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Development of Chinese herbal medicine for sensorineural hearing loss

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Acta Pharmaceutica Sinica B 2024年第2期14卷 455-467页

作者： Yunhao Wu Jingwen Zhang Qiuping Liu Zhuang Miao Renjie Chai Wenyong Chen State Key Laboratory of Bioelectronics Department of Otolaryngology Head and Neck SurgeryZhongda HospitalSchool of Life Sciences and TechnologyAdvanced Institute for Life and HealthJiangsu Province HighTech Key Laboratory for Bio-Medical ResearchSoutheast UniversityNanjing 210096China Department of otolaryngology-Head and Neck the Second Affiliated Hospital of Guangzhou University of Chinese MedicineGuangzhou 510120China Department of otolaryngology-Head and Neck Surgery Affiliated Hospital of Jiangnan UniversityWuxi 214000China Department of otolaryngology Head and Neck Surgery Sichuan Provincial People’s HospitalUniversity of Electronic Science and Technology of ChinaChengdu 610000China Co-Innovation Center of Neuroregeneration Nantong UniversityNantong 226001China Institute for Stem Cell and Regeneration Chinese Academy of ScienceBeijing 100085China Beijing Key Laboratory of Neural Regeneration and Repair Capital Medical UniversityBeijing 100069China

According to the World Health Organization’s world report on hearing,nearly 2.5 billion people worldwide will suffer from hearing loss by 2050,which may contribute to a severe impact on individual life quality and national *** hearing loss(SNHL)occurs commonly as a result of noise exposure,aging,and ototoxic drugs,and is pathologically characterized by the impairment of mechanosensory hair cells of the inner ear,which is mainly triggered by reactive oxygen species accumulation,inflammation,and mitochondrial *** recent advances have been made in understanding the ability of cochlear repair and regeneration,there are still no effective therapeutic drugs for *** herbal medicine which is widely distributed and easily accessible in China has demonstrated a unique curative effect against SNHL with higher safety and lower cost compared with Western *** we present trends in research for Chinese herbal medicine for the treatment of SNHL,and elucidate their molecular mechanisms of action,to pave the way for further research and development of novel effective drugs in this field.

关键词： Sensorineural hearing loss Chinese herbal medicine molecular mechanism Active ingredients Prescriptions Ototoxic drugs Noise Hair cells

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A bHLH transcription factor,CsSPT,regulates high-temperature resistance in cucumber

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Horticultural Plant Journal 2024年第2期10卷 503-514页

作者： Yonggui Liang Chenyu Yang Fangyan Ming Bingwei Yu Zhihua Cheng Yixi Wang Zhengkun Qiu Xiaolan Zhang Bihao Cao Shuangshuang Yan Key Laboratory of Biology and Genetic Improvement of Horticultural Crops(South China) Ministry of Agriculture and Rural AffairsGuangdong Vegetable Engineering and Technology Research CenterCollege of HorticultureSouth China Agricultural UniversityGuangzhouGuangdong 510642China State Key laboratories of Agrobiotechnology Beijing Key Laboratory of Growth and Developmental Regulation for Protected Vegetable CropsMOE Joint Laboratory for International Cooperation in Crop Molecular BreedingChina Agricultural UniversityBeijing 100193China

High-temperature stress threatens the growth and yield of crops. Basic helix-loop-helix(bHLH) transcription factors(TFs) have been shown to play important roles in regulating high-temperature resistance in plants. However, the bHLH TFs responsible for high-temperature tolerance in cucumbers have not been identified. We used transcriptome profiling to screen the high temperature-responsive candidate bHLH TFs in cucumber. Here, we found that the expression of 75 CsbHLH genes was altered under high-temperature stress. The expression of the CsSPT gene was induced by high temperatures in TT(Thermotolerant) cucumber plants. However, the Csspt mutant plants obtained by the CRISPR-Cas9 system showed severe thermosensitive symptoms, including wilted leaves with brown margins and reduced root density and cell *** Csspt mutant plants also exhibited elevated H_(2)O_(2) levels and down-regulated photosystem-related genes under normal ***, there were high relative electrolytic leakage(REC), malondialdehyde(MDA), glutathione(GSH), and superoxide radical(O_(2)^(·-)) levels in the Csspt mutant plants, with decreased Proline content after the high-temperature treatment. Transcriptome analysis showed that the photosystem and chloroplast activities in Csspt mutant plants were extremely disrupted by the high-temperature stress compared with wildtype(WT) plants. Moreover, the plant hormone signal transduction, as well as MAPK and calcium signaling pathways were activated in Csspt mutant plants under high-temperature stress. The HSF and HSP family genes shared the same upregulated expression patterns in Csspt and WT plants under high-temperature conditions. However, most bHLH, NAC, and bZIP family genes were significantly down-regulated by heat in Csspt mutant plants. Thus, these results demonstrated that CsSPT regulated the high-temperature response by recruiting photosynthesis components, signaling pathway molecules, and transcription factors. Our results pro

关键词： Cucumber bHLH CsSPT Photosynthesis High temperature

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Tau in the pancreas:understanding the link between type 2 diabetes mellitus and Alzheimer's disease

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Signal Transduction and Targeted Therapy 2024年第1期9卷 6-7页

作者： Wenlu Li Steffen Tiedt Eng H.Lo Neuroprotection research laboratories Departments of Radiology and NeurologyMassachusetts General HospitalHarvard Medical SchoolCharlestownMA02129USA Consortium International pour la Recherche Circadienne sur l’AVC(CIRCA) BostonUSA Institute for Stroke and Dementia research LMU University HospitalLMU MunichMunichGermany

A recent study published in molecular Psychiatry proposes a cellular mechanism that may contribute to decreased insulin production in individuals with type 2 diabetes mellitus(T2DM).1 Using a combination of cell culture experiments,animal models and studies in T2DM patients,the authors show that an up-regulation of tau inβ-islet cells can inhibit pancreatic insulin secretion through changes in microtubule assembly.

关键词： T2DM Alzheimer tau

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m^(6)A modification of lncRNA in middle ear cholesteatoma

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中南大学学报（医学版） 2024年第5期49卷 667-678页

作者： HE Jun XIE Shumin JIN Li FU Jinfeng YUAN Qiulin LIU Wei Department of otolaryngology-Head and Neck Surgery Second Xiangya HospitalCentral South UniversityChangsha 410011 Clinical Medical research Center for Otology in Hunan Province Changsha 410011 Department of otolaryngology-Head and Neck Surgery Xiangya HospitalCentral South UniversityChangsha 410008 otolaryngology Major Disease research Key Laboratory of Hunan Province Changsha 410008 Clinical research Center for Pharyngolaryngeal Diseases and Voice Disorders in Hunan Province Changsha 410008 National Clinical research Center for Geriatric Disorders Xiangya HospitalChangsha 410008China

Objective:Middle ear cholesteatoma is a non-tumorous condition that typically leads to hearing loss,bone destruction,and other severe *** surgery being the primary treatment,the recurrence rate remains ***,exploring the molecular mechanisms underlying cholesteatoma is crucial for discovering new therapeutic *** study aims to explore the involvement of N6-methyladenosine(m^(6)A)methylation in long non-coding RNAs(lncRNAs)in the biological functions and related pathways of middle ear ***:The m^(6)A modification patterns of lncRNA in middle ear cholesteatoma tissues(n=5)and normal post-auricular skin tissues(n=5)were analyzed using an lncRNA m^(6)A transcriptome *** Ontology(GO)and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway analyses were conducted to identify potential biological functions and signaling pathways involved in the pathogenesis of middle ear *** RNA immunoprecipitation(MeRIP)-PCR was used to validate the m^(6)A modifications in cholesteatoma and normal skin ***:Compared with normal skin tissues,1525 lncRNAs were differentially methylated in middle ear cholesteatoma tissues,with 1048 showing hypermethylation and 477 showing hypomethylation[fold change(FC)≥3 or<1/3,P<0.05].GO enrichment analysis indicated that hypermethylated lncRNAs were involved in protein phosphatase inhibitor activity,neuron-neuron synapse,and regulation ofα-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid(AMPA)receptor *** lncRNAs were associated with mRNA methyltransferase activity,secretory granule membrane,and mRNA *** analysis revealed that hypermethylated lncRNAs were mainly associated with 5 pathways:the Hedgehog signaling pathway,viral protein interaction with cytokines and cytokine receptors,mitogen-activated protein kinase(MAPK)signaling pathway,cytokine-cytokine receptor interaction,and adrenergic signaling in ***

关键词： long non-coding RNA m6A modifications middle ear cholesteatoma

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The evolution of cancer genomic medicine in Japan and the role of the National Cancer Center Japan

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Cancer Biology & Medicine 2024年第1期21卷 29-44页

作者： Teruhiko Yoshida Yasushi Yatabe Ken Kato Genichiro Ishii Akinobu Hamada Hiroyuki Mano Kuniko Sunami Noboru Yamamoto Takashi Kohno Department of Genetic Medicine and Services National Cancer Center HospitalTokyo 104-0045Japan Department of Diagnostic Pathology National Cancer Center HospitalTokyo 104-0045Japan Clinical research Support Offce Clinical Research Coordinating SectionBiobank Translational Research Support SectionNational Cancer Center HospitalTokyo 104-0045Japan Department of Pathology and Clinical laboratories National Cancer Center Hospital EastChiba 277-8577Japan Division of molecular Pharmacology National Cancer Center Research InstituteTokyo 104-0045Japan National Cancer Center research Institute Tokyo 104-0045Japan Department of Laboratory Medicine National Cancer Center HospitalTokyo 104-0045Japan Department of Experimental Therapeutics National Cancer Center HospitalTokyo 104-0045Japan Division of Genome Biology National Cancer Center Research InstituteTokyo 104-0045Japan

The journey to implement cancer genomic medicine(CGM)in oncology practice began in the 1980s,which is considered the dawn of genetic and genomic cancer *** the time,a variety of activating oncogenic alterations and their functional significance were unveiled in cancer cells,which led to the development of molecular targeted therapies in the 2000s and *** CGM is still a relatively new discipline and it is difficult to predict to what extent CGM will benefit the diverse pool of cancer patients,the National Cancer Center(NCC)of Japan has already contributed considerably to CGM advancement for the conquest of *** back at these past achievements of the NCC,we predict that the future of CGM will involve the following:1)A biobank of paired cancerous and non-cancerous tissues and cells from various cancer types and stages will be *** quantity and quality of these samples will be compatible with omics *** biobank samples will be linked to longitudinal clinical information.2)New technologies,such as whole-genome sequencing and artificial intelligence,will be introduced and new bioresources for functional and pharmacologic analyses(e.g.,a patient-derived xenograft library)will be systematically deployed.3)Fast and bidirectional translational research(bench-to-bedside and bedside-to-bench)performed by basic researchers and clinical investigators,preferably working alongside each other at the same institution,will be implemented;4)Close collaborations between academia,industry,regulatory bodies,and funding agencies will be established.5)There will be an investment in the other branch of CGM,personalized preventive medicine,based on the individual's genetic predisposition to cancer.

关键词： Cancer genomic medicine biobank patient-derived xenograft multi-gene panel test whole genome sequencing

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Emerging and multifaceted potential contributions of polyphenols in the management of type 2 diabetes mellitus

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World Journal of Diabetes 2024年第2期15卷 154-169页

作者： Ileana González Cristian Lindner Ivan Schneider Erik Diaz Miguel Angel Morales Armando Rojas Biomedical research laboratories Faculty of MedicineCatholic University of MauleTalca 34600000Chile Department of Radiology Faculty of MedicineUniversity of ConcepciónConcepción 4030000Chile Centre of Primary Attention South Metropolitan Health ServiceSantiago 3830000Chile Faculty of Medicine Catholic University of MauleTalca 3460000Chile molecular and Clinical Pharmacology Program Institute of Biomedical SciencesUniversity of ChileSantiago 8320000Chile

Type 2 diabetes mellitus(T2DM)is recognized as a serious public health concern with a considerable impact on human life,long-term health expenditures,and substantial health *** this context,the use of dietary polyphenols to prevent and manage T2DM is widely *** dietary compounds exert their beneficial effects through several actions,including the protection of pancreatic islet β-cell,the antioxidant capacities of these molecules,their effects on insulin secretion and actions,the regulation of intestinal microbiota,and their contribution to ameliorate diabetic complications,particularly those of vascular *** the present review,we intend to highlight these multifaceted actions and the molecular mechanisms by which these plant-derived secondary metabolites exert their beneficial effects on type 2 diabetes patients.

关键词： Polyphenols Antioxidants Oxidative stress Type 2 diabetes mellitus Health benefits

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