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Bile acid metabolism and signaling in health and disease:molecular mechanisms and therapeutic targets

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Signal Transduction and Targeted Therapy 2024年第5期9卷 2014-2064页

作者： Joshua S.Fleishman Sunil Kumar department of Pharmaceutical sciences College of Pharmacy and Health SciencesSt.John’s UniversityQueensNYUSA

Bile acids,once considered mere dietary surfactants,now emerge as critical modulators of macronutrient(lipid,carbohydrate,protein)metabolism and the systemic pro-inflammatory/anti-inflammatory *** acid metabolism and signaling pathways play a crucial role in protecting against,or if aberrant,inducing cardiometabolic,inflammatory,and neoplastic conditions,strongly influencing health and *** curative treatment exists for any bile acid influenced disease,while the most promising and well-developed bile acid therapeutic was recently rejected by the ***,we provide a bottom-up approach on bile acids,mechanistically explaining their biochemistry,physiology,and pharmacology at canonical and non-canonical *** this mechanistic model of bile acids,we explain how abnormal bile acid physiology drives disease pathogenesis,emphasizing how ceramide synthesis may serve as a unifying pathogenic feature for cardiometabolic *** provide an in-depth summary on pre-existing bile acid receptor modulators,explain their shortcomings,and propose solutions for how they may be ***,we rationalize novel targets for further translational drug discovery and provide future *** than dismissing bile acid therapeutics due to recent setbacks,we believe that there is immense clinical potential and a high likelihood for the future success of bile acid therapeutics.

关键词： metabolism rejected shortcomings

TBBPA rather than its main derivatives enhanced growth of endometrial cancer via p53 ubiquitination

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Journal of Environmental sciences 2024年第3期137卷 82-95页

作者： Hongyan Yu Jingxu Zhang Jing Liu Ruonan Pan Yu Wang Xiaoting Jin Rifat Zubair Ahmed Yuxin Zheng department of Occupational health and Environmental health School of Public HealthQingdao UniversityQingdao 266071China State Key Laboratory of Environmental Chemistry and Ecotoxicology Research Center for Eco-Environmental SciencesChinese Academy of SciencesBeijing 100085China department of Genetics University of KarachiKarachi 75270Pakistan

Tetrabromobisphenol A(TBBPA)and its derivatives widely exist in various environments and *** the available data indicate that TBBPA exposure is highly associated with the increased incidence of endometrial cancer(EC),the effects of TBBPA and its main derivatives on EC proliferation and the involved crucial mechanism remain *** present study aimed to investigate the effects of TBBPA and its derivatives under environmental concentrations on the proliferation of EC,and the crucial mechanism on the progression of EC caused by bromine fame retardants *** this research,TBBPA and two of the most common TBBPA derivatives including TBBPA bis(2-hydroxyethyl ether)(TBBPABHEE)and TBBPA bis(dibromopropyl ether)(TBBPA-BDBPE)were screened for their capacities in induced EC proliferation and explored the related mechanism by in vitro cell culture model and in vivo mice *** environmental concentrations,TBBPA promoted the proliferation of EC,the main derivatives of TBBPA(TBBPA-BHEE and TBBPA-BDBPE)did not present the similar facilitation *** ubiquitination degradation of p53 was crucial in TBBPA induced EC proliferation,which resulted in the increase of downstream cell cycle and decrease of *** further molecular docking result suggested the high affinity between TBBPA and ubiquitinated *** finding revealed the effects of TBBPA and its derivatives on EC proliferation,thus providing novel insights into the underlying mechanisms of TBBPA-caused EC.

关键词： Tetrabromobisphenol A(TBBPA) Endometrial cancer(EC) Derivatives Ubiquitin proteases p53

Therapeutic advances in neural regeneration for Huntington’s disease

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Neural Regeneration Research 2024年第9期19卷 1991-1997页

作者： Francesco D’Egidio Vanessa Castelli Giorgia Lombardozzi Fabrizio Ammannito Annamaria Cimini Michele d’Angelo department of Life Health and Environmental SciencesUniversity of L’AquilaL’AquilaItaly

Huntington’s disease is a neurodegenerative disease caused by the expansion mutation of a cytosine-adenine-guanine triplet in the exon 1 of the HTT gene which is responsible for the production of the huntingtin (Htt) protein. In physiological conditions, Htt is involved in many cellular processes such as cell signaling, transcriptional regulation, energy metabolism regulation, DNA maintenance, axonal trafficking, and antiapoptotic activity. When the genetic alteration is present, the production of a mutant version of Htt (mHtt) occurs, which is characterized by a plethora of pathogenic activities that, finally, lead to cell death. Among all the cells in which mHtt exerts its dangerous activity, the GABAergic Medium Spiny Neurons seem to be the most affected by the mHtt-induced excitotoxicity both in the cortex and in the striatum. However, as the neurodegeneration proceeds ahead the neuronal loss grows also in other brain areas such as the cerebellum, hypothalamus, thalamus, subthalamic nucleus, globus pallidus, and substantia nigra, determining the variety of symptoms that characterize Huntington’s disease. From a clinical point of view, Huntington’s disease is characterized by a wide spectrum of symptoms spanning from motor impairment to cognitive disorders and dementia. Huntington’s disease shows a prevalence of around 3.92 cases every 100,000 worldwide and an incidence of 0.48 new cases every 100,000/year. To date, there is no available cure for Huntington’s disease. Several treatments have been developed so far, aiming to reduce the severity of one or more symptoms to slow down the inexorable decline caused by the disease. In this context, the search for reliable strategies to target the different aspects of Huntington’s disease become of the utmost interest. In recent years, a variety of studies demonstrated the detrimental role of neuronal loss in Huntington’s disease condition highlighting how the replacement of lost cells would be a reasonable strategy to o

关键词： cell therapy exosomes extracellular vesicles Huntingtin Huntington’s disease medium spiny neurons neurodegenerative disease neurogenesis neuronal loss stem cells

Differences between lower extremity joint running kinetics captured by marker-based and markerless systems were speed dependent

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Journal of Sport and health Science 2024年第4期13卷 569-578页

作者： Hui Tang Barry Munkasy Li Li department of health sciences and Kinesiology Georgia Southern UniversityStatesboroGA 30458USA department of Kinesiology and health Education University of Texas at AustinAustinTX 78712USA

Background:The development of computer vision technology has enabled the use of markerless movement tracking for biomechanical *** research has reported the feasibility of markerless systems in motion analysis but has yet to fully explore their utility for capturing faster movements,such as *** studies using markerless systems in clinical and sports settings are still ***,the present study compared running biomechanics estimated by marker-based and markerless *** running speed not only affects sports performance but is also associated with clinical injury prevention,diagnosis,and rehabilitation,we aimed to investigate the effects of speed on the comparison of estimated lower extremity joint moments and powers between markerless and marker-based technologies during treadmill running as a concurrent validating ***:Kinematic data from marker-based/markerless technologies were collected,along with ground reaction force data,from 16 young adults running on an instrumented treadmill at 3 speeds:2.24 m/s,2.91 m/s,and 3.58 m/s(5.0 miles/h,6.5 miles/h,and 8.0 miles/h).Sagittal plane moments and powers of the hip,knee,and ankle were calculated by inverse dynamic *** series analysis and statistical parametric mapping were used to determine system ***:Compared to the marker-based system,the markerless system estimated increased lower extremity joint kinetics with faster speed during the swing phase in most ***:Despite the promising application of markerless technology in clinical settings,systematic markerless overestimation requires focused *** on segment pose estimations,the centers of mass estimated by markerless technologies were farther away from the relevant distal joint centers,which led to greater joint moments and powers estimates by markerless ***-based *** differences were amplified by running speed.

关键词： Biomechanics Motion capture Gait Statistical parametric mapping

Design of an automated robotic microinjection system for batch injection of zebrafish embryos and larvae

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Microsystems & Nanoengineering 2024年第1期10卷 89-103页

作者： Zhongyi Guo Nana Ai Wei Ge Qingsong Xu department of Electromechanical Engineering Faculty of Science and TechnologyUniversity of MacaoMacaoChina department of Biomedical sciences and Centre of Reproduction Development and Aging(CRDA)Faculty of Health SciencesUniversity of MacaoMacaoChina

This paper presents the design of a vision-based automated robotic microinjection system for batch injection of both zebrafish embryos and larvae.A novel visual recognition algorithm based on an automatic threshold and excessive dilatation is introduced to accurately identify the center of zebrafish embryos and larval yolks.A corresponding software system is developed using the producer-consumer model as the framework structure,and a friendly user interface is designed to allow operators to choose from a range of desired functions according to their different *** addition,a novel microstructural agarose device is designed and fabricated to simultaneously immobilize mixed batches of embryos and ***,a prototype microinjection system is fabricated by integrating hardware devices with visual *** experimental study is conducted to verify the performance of the robotic microinjection *** results show that the reported system can accurately identify zebrafish embryos and larvae and efficiently complete batch microinjection tasks of the mixtures with an injection success rate of 92.05%in 13.88 s per *** with manual and existing microinjection systems,the proposed system demonstrates the merits of versatility,excellent efficiency,high success rate,high survival rate,and sufficient stability.

关键词： zebra automated hardware

Prevalence of Anemia in Patients with Diabetes Mellitus:A Systematic Review and Meta-Analysis

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Biomedical and Environmental sciences 2024年第1期37卷 96-107页

作者： Monireh Faghir-Ganji Narjes Abdolmohammadi Maryam Nikbina Alireza Amanollahi Alireza Ansari-Moghaddam Rozhan Khezri Hamidreza Baradaran Student Research Committee Iran University of Medical SciencesTehranIran department of Epidemiology School of Public HealthIran University of Medical SciencesTehranIran department of Epidemiology School of Public HealthTehran University of Medical SciencesTehranIran department of Midwifery Shoushtar Faculty of Medical SciencesShoushtarIran department of Epidemiology School of Public Health and SafetyShahid Beheshti University of Medical SciencesTehranIran Trauma and Injury Research Center Iran University of Medical SciencesTehranIran health Promotion Research Center Zahedan University of Medical SciencesZahedanIran Endocrine Research Center Institute of Endocrinology and MetabolismIran University of Medical SciencesTehranIran

Objective Anemia is a common public health concern in patients with type 2 diabetes *** study aimed to identify the prevalence of anemia among patients with *** Electronic databases,including PubMed,Scopus,Web of sciences,and Google Scholar,were searched systematically for studies published between 2010 and *** removing duplicates and inappropriate reports,the remaining manuscripts were reviewed and appraised using theNewcastleOttawa Scale(NOS)tool.A random-effects model was used to calculate the pooled estimates of the extracted data using Stata version *** of the studies was assessed using the Q *** A total of 51 articles containing information on 26,485 patients with diabetes were included in this *** articles were mainly from Asia(58.82%)and Africa(35.29%).The overall prevalence of anemia was 35.45%(95%CI:30.30–40.76),with no evidence of heterogeneity by *** the two continents with the highest number of studies,the prevalence of anemia in patients with diabetes was significantly higher in Asia[40.02;95%CI:32.72–47.54]compared to Africa[28.46;95%CI:21.90–35.50](P for heterogeneity=0.029).Moreover,there has been an increasing trend in the prevalence of anemia in patients with diabetes over time,from[15.28;95%CI:9.83–22.21]in 2012 to[40.70;95%CI:10.21–75.93]in *** Globally,approximately 4 in 10 patients with diabetes suffer from ***,routine anemia screening and control programs every 3 months might be useful in improving the quality of life of these patients.

关键词： Prevalence Diabetic foot Anemia Diabetes mellitus

Protective effect of long-chain polyunsaturated fatty acids on hepatorenal syndrome in rats

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World Journal of Nephrology 2024年第3期13卷 49-61页

作者： João Bruno Beretta Duailibe Cassiana Macagnan Viau Jenifer Saffi Sabrina Alves Fernandes Marilene Porawski department of Hepatology Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Brazil department of Basic health sciences Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Brazil department of Hepatology and Basic health sciences Federal University of Health Sciences of Porto AlegrePorto Alegre 90050-170Brazil

BACKGROUND Hepatorenal syndrome(HRS)is the most prevalent form of acute kidney injury in cirrhotic *** is characterized by reduced renal blood flow and represents the most severe complication in cirrhotic patients with advanced *** research has indicated that antioxidants can delay the onset of a hyperdynamic circulatory state in cirrhosis and improve renal function in HRS *** omega-3 supplementation has significantly reduced the risk of liver *** supplementation could represent an additional therapy for individuals with *** To evaluated the antioxidant effect of omega-3 polyunsaturated fatty acid supplementation on the kidneys of cirrhotic *** Secondary biliary cirrhosis was induced in rats by biliary duct ligation(BDL)for 28 *** used 24 male Wistar rats divided into the following groups:I(control);II(treated with omega-3,1 g/kg of body weight);III(BDL treated with omega-3,1 g/kg of body weight);and IV(BDL without treatment).The animals were killed by overdose of anesthetic;the kidneys were dissected,removed,frozen in liquid nitrogen,and stored in a freezer at-80℃for later *** evaluated oxidative stress,nitric oxide(NO)metabolites,DNA damage by the comet assay,cell viability test,and apoptosis in the *** were analyzed by one-way analysis of variance,and means were compared using the Tukey test,with P≤*** Omega-3 significantly decreased the production of reactive oxygen species(P<0.001)and lipoperoxidation in the kidneys of cirrhotic rats treated with omega-3(P<0.001).The activity of the antioxidant enzymes superoxide dismutase and catalase increased in the BDL+omega-3 group compared to the BDL group(P<0.01).NO production,DNA damage,and caspase-9 cleavage decreased significantly in the omega-3-treated BDL *** was an increase in mitochondrial electrochemical potential(P<0.001)in BDL treated with omega-3 compared to *** changes in the cell survival index in HRS with omega-3 c

关键词： Long-chain polyunsaturated fatty acids Antioxidant effect Hepatorenal syndrome Liver cirrhosis Reactive oxygen species Apoptosis

Therapeutic potential and pharmacological mechanism of visnagin

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Journal of Integrative Medicine 2024年第4期22卷 399-412页

作者： Poonam Yadav Sumeet Kumar Singh Sayantap Datta Saloni Verma Aarti Verma Arnab Rakshit Anjana Bali Jasvinder Singh Bhatti Amit Khurana Umashanker Navik department of Pharmacology School of Health SciencesCentral University of PunjabBathindaPunjab 151401India department of Pharmacological and Pharmaceutical sciences College of PharmacyUniversity of HoustonHoustonTX 77204-5000USA department of Human Genetics and Molecular Medicine School of Health SciencesCentral University of PunjabBathindaPunjab 151401India

Visnagin is a furanochromone and one of the most important compound in the Ammi visnaga(L.)Lam(a synonym of Visnaga daucoides Gaertn.)plant,which is used to cure various *** investigations into the bioactive properties of visnagin have been studied to *** literature on visnagin demonstrates its biological properties,including anti-inflammatory,anti-diabetic,and beneficial effects in cardiovascular and renal ***,visnagin improves sperm quality parameters,stimulates steroidogenesis,and increases serum gonadotropins and testosterone levels,while decreasing proinflammatory cytokines,oxidative damage,genomic instability,and it modulates ***,visnagin has emerged as an exciting lead for further research,owing to its potential in various unmet clinical *** current review summarized its basic structure,pharmacokinetics,and pharmacological effects,focusing on its mechanisms of *** review will help to understand the potential of visnagin as an alternative treatment strategy for several diseases and provide insight into research topics that need further exploration for visnagin’s safe clinical use.

关键词： Visnagin Phytochemical Anti-inflammatory Ammi visnaga L. Visnaga daucoides Gaertn Cancer

Metabologenomics and network pharmacology to understand the molecular mechanism of cancer research

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World Journal of Clinical Cases 2024年第3期12卷 474-478页

作者： Yusuf Tutar department of Basic Pharmaceutical sciences Faculty of PharmacyDivision of BiochemistryUniversity of Health SciencesIstanbul 34668Turkey health sciences Faculty Recep Tayyip Erdogan UniversityRize 53350Turkey Molecular Oncology Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey Molecular Medicine Division Health Sciences InstitutesUniversity of Health SciencesIstanbul 34668Turkey

In this editorial I comment on the article“Network pharmacological and molecular docking study of the effect of Liu-Wei-Bu-Qi capsule on lung cancer”published in the recent issue of the World Journal of Clinical Cases 2023 November 6;11(31):*** all living forms are able to manufacture particular chemicals-metabolites that enable them to differentiate themselves from one another and to overcome the unique obstacles they encounter in their natural *** methods for chemical warfare,communication,nutrition acquisition,and stress prevention are made possible by these specialized *** is a popular technique for collecting direct mea-surements of metabolic activity from many biological ***,con-fusing metabolite identification is a typical issue,and biochemical interpretation is frequently constrained by imprecise and erroneous genome-based estimates of enzyme *** annotation and gene integration uses a biochemical reaction network to obtain a metabolite-gene association so called *** network uses an approach that emphasizes metabolite-gene consensus via biochemical *** metabolomics and genomics data is ***,computer networking proposes that using meta-bolomics data may improve annotations in sequenced species and provide testable hypotheses for specific biochemical *** The genome and metabolites of biological organisms are not fully characterized with current ***,increasing high-throughput metabolomics and genomics data provide promising generation of paired data sets to understand the molecular mechanism of biochemical processes as well as determining targets for pharmaceutical drug *** network infrastructures to integrate omics analysis can provide molecular mechanism of biochemical ***,clinical data may be integrated to gene expression–metabolite expression by system genetics appr

关键词： Network pharmacology Metabologenomics Genome Pathways Cancer