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Potential role of tubulin glutamylation in neurodegenerative diseases

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Neural Regeneration Research 2024年第6期19卷 1191-1192页

作者： Abdullah Md.Sheikh Shatera Tabassum Department of Laboratory medicine Shimane University Faculty of Medicine

The differentiation of neuronal stem cells into mature neurons is a complex process that involves both structural and functional changes. As cells undergo differentiation, there are notable functional changes, including the expression of various transcription factors, cytokines, and neurotransmitiers. Additionally, structural changes occur as the cells develop various processes from the cell body and establish synaptic contacts with other cells.

关键词： POLARITY

Metabolic disease and the liver: A review

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World Journal of Hepatology 2024年第1期16卷 33-40页

作者： Márcia Vargas Sheila de Castro Cardoso Toniasso Patricia G Riedel Camila Pereira Baldin Francielle Lopes dos Reis Robson Martins Pereira Maria Carlota Borba Brum Dvora Joveleviths Mario Reis Alvares-da-Silva Program of Graduate Science in Gastroenterology and Hepatology Federal University of Rio Grande do SulPorto Alegre 90040-060Rio Grande do SulBrazil School of medicine Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Program of Graduate Science in Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90410000Brazil medicine faculty Federal university of Rio Grande do Sul Federal University of Rio Grande do SulPorto Alegre 90040-060Brazil Division of Gastroenterology and Hepatology Clinicas Hospital of Porto AlegrePorto Alegre 90035007Brazil

Metabolic dysfunction-associated steatotic liver disease(MASLD)is the most common liver disease worldwide,with an estimated prevalence of 31%in Latin America.The presence of metabolic comorbidities coexisting with liver disease varies substantially among populations.It is acknowledged that obesity is boosting the type 2 diabetes mellitus“epidemic,”and both conditions are significant contributors to the increasing number of patients with MASLD.Nonalcoholic steatohepatitis represents a condition of chronic liver inflammation and is considered the most severe form of MASLD.MASLD diagnosis is based on the presence of steatosis,noninvasive scores and altered liver tests.Noninvasive scores of liver fibrosis,such as serum biomarkers,which should be used in primary care to rule out advanced fibrosis,are simple,inexpensive,and widely available.Currently,guidelines from international hepatology societies recommend using noninvasive strategies to simplify case finding and management of high-risk patients with MASLD in clinical practice.Unfortunately,there is no definite pharmacological treatment for the condition.Creating public health policies to treat patients with risk factors for MASLD prevention is essential.

关键词： Nonalcoholic fatty liver disease Primary care Metabolic risk Liver Metabolism

Suppression of mature TAU isoforms prevents Alzheimer's disease-like amyloid-beta oligomer-induced spine loss in rodent neurons

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Neural Regeneration Research 2024年第8期19卷 1655-1657页

作者： Sarah Buchholz Hans Zempel Institute of Human Genetics Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany Center for Molecular medicine Cologne(CMMC) Faculty of Medicine and University Hospital CologneUniversity of CologneCologneGermany

Introduction:TAU isoforms as disease mediators:The microtubule-associated protein TAU is predominantly present in the axons of neurons under physiological conditions.In Alzheimer’s disease(AD)and related tauopathies,TAU also mislocalizes("TAU missorting")to the soma and the dendrites,where it eventually forms aggregates,the so-called neurofibrillary tangles(for review see Zimmer-Bensch and Zempel,2021;Zempel,2023).

关键词： Alzheimer Zimmer tau

On the functions of astrocyte-mediated neuronal slow inward currents

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Neural Regeneration Research 2024年第12期19卷 2602-2612页

作者： Balázs Pál Department of Physiology Faculty of MedicineUniversity of DebrecenDebrecenHungary

Slow inward currents are known as neuronal excitatory currents mediated by glutamate release and activation of neuronal extra synaptic N-met hyl-D-aspartate receptors with the contribution of astrocytes.These events are significantly slower than the excitatory postsynaptic currents.Parameters of slow inward currents are determined by seve ral factors including the mechanisms of astrocytic activation and glutamate release,as well as the diffusion pathways from the release site towards the extra synaptic recepto rs.Astrocytes are stimulated by neuronal network activity,which in turn excite neurons,forming an astrocyte-neuron feedback loop.Mostly as a consequence of brain edema,astrocytic swelling can also induce slow inward currents under pathological conditions.There is a growing body of evidence on the roles of slow inward currents on a single neuron or local network level.These events often occur in synchro ny on neurons located in the same astrocytic domain.Besides synchronization of neuronal excitability,slow inward currents also set synaptic strength via eliciting timing-dependent synaptic plasticity.In addition,slow inward currents are also subject to non-synaptic plasticity triggered by long-la sting stimulation of the excitatory inputs.Of note,there might be important regionspecific differences in the roles and actions triggering slow inward currents.In greater networks,the pathophysiological roles of slow inward currents can be better understood than physiological ones.Slow inward currents are identified in the pathophysiological background of autism,as slow inward currents drive early hypersynchrony of the neural networks.Slow inward currents are significant contributors to paroxysmal depolarizational shifts/interictal spikes.These events are related to epilepsy,but also found in Alzheimer's disease,Parkinson's disease,and stroke,leading to the decline of cognitive functions.Events with features overlapping with slow inward currents(excitatory,N-methyl-Daspartate-receptor mediated currents with astrocyti

关键词： astrocyte cortical spreading depolarization gliotransmission glutamate neural synchronization NMDA receptor paroxysmal depolarizational shift slow inward current

Quantitative and qualitative subgenomic RNA profiles of SARS-CoV-2 in respiratory samples: A comparison between Omicron BA.2 and non-VOC-D614G

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Virologica Sinica 2024年第2期39卷 218-227页

作者： Zigui Chen Rita Way Yin Ng Grace Lui Lowell Ling Agnes S.Y.Leung Chit Chow Siaw Shi Boon Wendy C.S.Ho Maggie Haitian Wang Renee Wan Yi Chan Albert Martin Li David Shu Cheong Hui Paul Kay Sheung Chan Department of Microbiology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of medicine and Therapeutics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anaesthesia and Intensive Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Paediatrics Faculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Anatomical and Cellular Pathology Faculty of MedicineThe Chinese University of Hong KongHong KongChina Jockey Club School of Public Health and Primary Care Faculty of MedicineThe Chinese University of Hong KongHong KongChina Stanley Ho Centre for Emerging Infectious Diseases Faculty of MedicineThe Chinese University of Hong KongHong KongChina

The SARS-CoV-2 Omicron variants are notorious for their transmissibility,but little is known about their subgenomic RNA(sgRNA)expression.This study applied RNA-seq to delineate the quantitative and qualitative profiles of canonical sgRNA of 118 respiratory samples collected from patients infected with Omicron BA.2 and compared with 338 patients infected with non-variant of concern(non-VOC)-D614G.A unique characteristic profile depicted by the relative abundance of 9 canonical sgRNAs was reproduced by both BA.2 and non-VOCD614G regardless of host gender,age and presence of pneumonia.Remarkably,such profile was lost in samples with low viral load,suggesting a potential application of sgRNA pattern to indicate viral activity of individual patient at a specific time point.A characteristic qualitative profile of canonical sgRNAs was also reproduced by both BA.2 and non-VOC-D614G.The presence of a full set of canonical sgRNAs carried a coherent correlation with crude viral load(AUC¼0.91,95%CI 0.88–0.94),and sgRNA ORF7b was identified to be the best surrogate marker allowing feasible routine application in characterizing the infection status of individual patient.Further potentials in using sgRNA as a target for vaccine and antiviral development are worth pursuing.

关键词： Coronavirus SARS-CoV-2 Omicron BA.2 Non-VOC-D614G RNA-seq Subgenomic RNA(sgRNA)

Hepatocellular carcinoma-the role of the underlying liver disease in clinical practice

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World Journal of Gastroenterology 2024年第19期30卷 2488-2495页

作者： Angelo Zambam de Mattos Isadora Zanotelli Bombassaro Arndt Vogel Jose D Debes Department of Internal medicine Universidade Federal de Ciências da Saúde de Porto AlegreRSPorto Alegre 90020090Brazil Graduate Program in medicine:Hepatology Federal University of Health Sciences of Porto AlegreRSPorto Alegre 90050-170Brazil Division of Gastroenterology Hepatology University of TorontoHannover M5R 0A3Canada Department of medicine University of MinnesotaMinneapolisMN 55455United States

Hepatocellular carcinoma(HCC)is one of the most common causes of cancerrelated mortality.This particular type of cancer has the distinctive characteristic of mostly happening in individuals with an underlying liver disease.This makes the management of patients more challenging,since physicians must take into consideration two different conditions,the chronic liver disease and the tumor.The underlying liver disease has several implications in clinical practice,because different kinds of chronic liver disease can lead to varying degrees of risk of developing HCC,obstacles in surveillance,and differences in the efficacy of the treatment against HCC.A shift in the prevalence of liver diseases has been evident over the last few years,with viral hepatitis gradually losing the leading position as cause of HCC and metabolic dysfunction-associated steatotic liver disease gaining importance.Therefore,in an era of personalized medicine,it is imperative that physicians are aware of the underlying liver disease of individuals with HCC and its impact in the management of their tumors.

关键词： Hepatocellular carcinoma Etiology Epidemiology Surveillance Therapy

A discussion about the limitations of the Eurocode’s high-speed load model for railway bridges

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Railway Engineering Science 2024年第2期32卷 211-228页

作者： Gonçalo Ferreira Pedro Montenegro JoséRui Pinto António Abel Henriques Rui Calçada CONSTRUCT-LESE Faculty of EngineeringUniversity of PortoRua Dr.Roberto Frias4200-465 PortoPortugal CONSTRUCT-LABEST Faculty of EngineeringUniversity of PortoRua Dr.Roberto Frias4200-465 PortoPortugal

High-speed railway bridges are subjected to normative limitations concerning maximum permissible deck accelerations.For the design of these structures,the European norm EN 1991-2 introduces the high-speed load model(HSLM)—a set of point loads intended to include the effects of existing high-speed trains.Yet,the evolution of current trains and the recent development of new load models motivate a discussion regarding the limits of validity of the HSLM.For this study,a large number of randomly generated load models of articulated,conventional,and regular trains are tested and compared with the envelope of HSLM effects.For each type of train,two sets of 100,000 load models are considered:one abiding by the limits of the EN 1991-2 and another considering wider limits.This comparison is achieved using both a bridge-independent metric(train signatures)and dynamic analyses on a case study bridge(the Canelas bridge of the Portuguese Railway Network).For the latter,a methodology to decrease the computational cost of moving loads analysis is introduced.Results show that some theoretical load models constructed within the stipulated limits of the norm can lead to effects not covered by the HSLM.This is especially noted in conventional trains,where there is a relation with larger distances between centres of adjacent vehicle bogies.

关键词： High-speed load model Dynamic analysis High-speed railways Train signature Railway bridges Deck acceleration

Lacidipine,thiamine pyrophosphate and their combination on the ocular ischemic syndrome induced by bilateral common carotid artery ligation

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International Journal of Ophthalmology(English edition) 2024年第5期17卷 815-821页

作者： Ibrahim Cicek Ahmet Mehmet Somuncu Durdu Altuner Bahadir Suleyman Renad Mammadov Seval Bulut Taha Abdulkadir Coban Tugba Bal Tastan Halis Suleyman Department of Ophthalmology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Pharmacology Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Clinical Biochemistry Faculty of MedicineErzincan Binali Yildirim UniversityErzincan 24100Turkey Department of Histology and Embryology Faculty of MedicineErzincan Binali Yildirim University ErzincanErzincan 24100Turkey

AIM:To investigate the effect of lacidipine,thiamine pyrophosphate(TPP)and the combination of lacidipine and TPP against oxidative and inflammatory eye damage induced by bilateral common carotid artery ligation in rats.METHODS:Male albino Wistar rats were categorized as those who underwent sham surgery(SG),right and left common carotid cross-clamping and unclamping procedure(CCU),lacidipine+CCU(LCCU),TPP+CCU(TCCU),and combination of lacidipine and TPP(LTC)+CCU(LTCCU).One hour before anesthesia,the LCCU(n=6)received lacidipine(4 mg/kg,orally)and the TCCU(n=6)received TPP(20 mg/kg,intraperitoneally).The SG(n=6)and CCU(n=6)received the same volume of distilled water from the same route.After anesthesia(60 mg/kg ketamine,intraperitoneally),the necks of the rats were opened in the midline.Ischemia was created for 10min by placing clips on the right and left common carotid arteries.Rats in the SG only underwent subcutaneous incision.After 10min,the clips were removed and reperfusion was achieved for six days.Then,the animals were euthanized(120 mg/kg ketamine,intraperitoneally)and the levels of oxidant,antioxidant and proinflammatory cytokines in the eye tissues were determined.The retinal tissue of the eye was also examined histopathologically.RESULTS:Lacidipine,TPP,and LTC significantly prevent the increase in malondialdehyde,tumor necrosis factoralpha,interleukin-1β(IL-1β),and IL-6 levels,decrease in total glutathione levels,superoxide dismutase and catalase activities and histopathological retinal damage in eye tissue induced by bilateral common carotid artery ligation in rats.The impact of these drugs on protection is determined to be LTC>lacidipine>TPP.CONCLUSION:As a result of the study,it is concluded that LTC may be more effective than lacidipine and TPP alone in treating ocular ischemic syndrome.

关键词： ocular ischemic syndrome lacidipine thiamine pyrophosphate oxidative stress

Aberrant bile duct communicating with the cystic duct:From early detection to management of late surgical complications

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Hepatobiliary & Pancreatic Diseases International 2024年第4期23卷 412-416页

作者： Phonthep Angsuwatcharakon Pradermchai Kongkam Wiriyaporn Ridtitid Panida Piyachaturawat Phuphat Vongwattanakit Prooksa Ananchuensook Natee Faknak Kunvadee Vanduangden Rungsun Rerknimitr Department of Anatomy Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand Division of Gastroenterology Department of MedicineFaculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand Department of Surgery Faculty of MedicineChulalongkorn University and King Chulalongkorn Memorial HospitalBangkokThailand Center of Excellence for Innovation and Endoscopy in Gastrointestinal Oncology Faculty of MedicineChulalongkorn UniversityBangkokThailand

The aberrant hepatic duct is classified by Huang et al.[1]into type A(right intrahepatic duct variant)and type B(left intrahepatic duct variant).Type A and B are further classified into 5(A1-5)and 6(B1-6)subtypes,respectively.The variation of cystic duct involves only in type A.Type A1 or classic arrangement refers to the formation of the common hepatic duct(CHD)by the left hepatic duct(LHD)and the right hepatic duct(RHD).The RHD has two tributaries composed of the right anterior hepatic duct(RAHD)and the right posterior hepatic duct(RPHD).Then,the common bile duct(CBD)is formed when the cystic duct joins with the CHD(Fig.1).Type A2 refers to the RAHD and RPHD joining with LHD at hepatic hilum,and the absence of the RHD.Type A3 refers to the RAHD or RPHD directly draining to the LHD.Type A4 refers to the RAHD or RPHD directly draining to the CHD.Type A5 refers to the RAHD,RPHD or RHD directly draining to the cystic duct(or aberrant bile duct communicating with the cystic duct,ACC)(Fig.1)[1].

关键词： bile hepatic RPH