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Pannexins in the musculoskeletal system:new targets for development and disease progression

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Bone Research 2024年第2期12卷 255-269页

作者： Yan Luo Shengyuan Zheng Wenfeng Xiao Hang Zhang Yusheng Li department of Orthopedics Xiangya HospitalCentral South UniversityChangshaHunan 410008China National clinical Research Center for Geriatric Disorders Xiangya HospitalCentral South UniversityChangshaHunan 410008China department of clinical Medicine Xiangya Medicine SchoolCentral South UniversityChangshaHunan 410008China Shenzhen Institute of Advanced Technology Chinese Academy of SciencesShenzhen 518055China

During cell differentiation,growth,and development,cells can respond to extracellular stimuli through communication ***(Panx)family and connexin(Cx)family are two important types of channel-forming *** family contains three members(Panx1-3)and is expressed widely in bone,cartilage and *** there is no sequence homology between Panx family and Cx family,they exhibit similar configurations and *** to Cxs,the key roles of Panxs in the maintenance of physiological functions of the musculoskeletal system and disease progression were gradually revealed ***,we seek to elucidate the structure of Panxs and their roles in regulating processes such as osteogenesis,chondrogenesis,and muscle *** also focus on the comparison between Cx and *** a new key target,Panxs expression imbalance and dysfunction in muscle and the therapeutic potentials of Panxs in joint diseases are also discussed.

关键词： skeletal diseases system

Red cell distribution width/platelet ratio estimates the 3-year risk of decompensation in Metabolic Dysfunction-Associated Steatotic Liver Disease-induced cirrhosis

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World Journal of Gastroenterology 2024年第7期30卷 685-704页

作者： Marcello Dallio Mario Romeo Paolo Vaia Salvatore Auletta Simone Mammone Marina Cipullo Luigi Sapio Angela Ragone Marco Niosi Silvio Naviglio Alessandro Federico department of Precision Medicine Hepatogastroenterology DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy department of Precision Medicine Clinical Biochemistry DivisionUniversity of Campania Luigi VanvitelliNaples 80138Italy

BACKGROUND For compensated advanced chronic liver disease(cACLD)patients,the first decompensation represents a dramatically worsening prognostic *** on the first decompensation event(DE),the transition to decompensated advanced chronic liver disease(dACLD)can occur through two modalities referred to as acute decompensation(AD)and non-AD(NAD),*** Significant Portal Hypertension(CSPH)is considered the strongest predictor of decompensation in these ***,due to its invasiveness and costs,CSPH is almost never evaluated in clinical ***,recognizing noninvasively predicting tools still have more appeal across healthcare *** red cell distribution width to platelet ratio(RPR)has been reported to be an indicator of hepatic fibrosis in Metabolic Dysfunction-Associated Steatotic Liver Disease(MASLD).However,its predictive role for the decompensation has never been *** In this observational study,we investigated the clinical usage of RPR in predicting DEs in MASLD-related cACLD *** Fourty controls and 150 MASLD-cACLD patients were consecutively enrolled and followed up(FUP)semiannually for 3 *** baseline,biochemical,clinical,and Liver Stiffness Measurement(LSM),Child-Pugh(CP),Model for End-Stage Liver Disease(MELD),aspartate aminotransferase/platelet count ratio index(APRI),Fibrosis-4(FIB-4),Albumin-Bilirubin(ALBI),ALBI-FIB-4,and RPR were *** FUP,DEs(timing and modaities)were *** was assessed at the baseline and on DE occurrence according to the available clinical Practice *** Of 150 MASLD-related cACLD patients,43(28.6%)progressed to dACLD at a median time of 28.9 months(29 NAD and 14 AD).Baseline RPR values were significantly higher in cACLD in comparison to controls,as well as MELD,CP,APRI,FIB-4,ALBI,ALBI-FIB-4,and LSM in dACLD-progressing compared to cACLD individuals[all P<0.0001,except for FIB-4(P:0.007)and ALBI(P:0.011)].Receiving operator curve a

关键词： Liver cirrhosis Red blood cell distribution width Red blood cell distribution width to platelet ratio Translational Medicine Prognostic biomarker

Quantitative hepatitis B core antibody and quantitative hepatitis B surface antigen:Novel viral biomarkers for chronic hepatitis B management

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World Journal of Hepatology 2024年第4期16卷 550-565页

作者： Wattana Leowattana Pathomthep Leowattana Tawithep Leowattana department of clinical Tropical Medicine Mahidol UniversityRachatawee 10400BangkokThailand department of Medicine Srinakharinwirot UniversityWattana 10110BangkokThailand

The management of hepatitis B virus(HBV)infection now involves regular and appropriate monitoring of viral activity,disease progression,and treatment *** HBV infection biomarkers are limited in their ability to predict clinical outcomes or therapeutic *** of HBV core antibodies(qAnti-HBc)is a novel non-invasive biomarker that may help with a variety of diagnostic *** was shown to correlate strongly with infection stages,hepatic inflammation and fibrosis,chronic infection exacerbations,and the presence of occult ***,qAnti-HBc levels were shown to be predictive of spontaneous or treatment-induced HBeAg and HBsAg seroclearance,relapse after medication termination,re-infection following liver transplantation,and viral reactivation in the presence of ***-HBc,on the other hand,cannot be relied on as a single diagnostic test to address all problems,and its diagnostic and prognostic potential may be greatly increased when paired with *** qAnti-HBc diagnostic kits are currently not widely *** many methodologies are only semi-quantitative,comparing data from various studies and defining universal cut-off values remains *** review focuses on the clinical utility of qAnti-HBc and qHBsAg in chronic hepatitis B management.

关键词： Quantitative hepatitis B core antibody Quantitative hepatitis B surface antigen Chronic hepatitis B management Novels viral biomarkers

Treatment of multisystem inflammatory syndrome in children

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World Journal of Pediatrics 2024年第4期20卷 325-339页

作者： Tong Tong Yi-Hua Jin Min Wang Fang-Qi Gong department of Cardiology Children's HospitalZhejiang University School of MedicineNational Clinical Research Center for Child HealthNo.3333 Binsheng RoadHangzhou 310052China

Background Multisystem inflammatory syndrome in children(MIS-C),a relatively uncommon but severe pediatric complication,is associated with coronavirus disease 2019(COVID-19).A variety of treatment approaches,including intravenous immunoglobulins(IVIGs),glucocorticoids(GCs)and biologic agents,such as anakinra and infliximab,have been described for the management of COVID-19-related *** therapy is also ***,a well-developed treatment system has not been established,and many issues remain *** recently published articles related to the treatment of MIS-C have been ***,in this review,we identified relevant articles published recently and summarized the treatment of MIS-C more comprehensively and *** sources We reviewed the literature on the treatment of MIS-C through 20 September *** PubMed/Medline,Web of Science,EMBASE,and Cochrane Library databases were searched with the combination of the terms"multisystem inflammatory syndrome","MIS-C","PIMS-TS","therapy","treatment","drug","IVIG","GCs","intravenous immunoglobulin","corticosteroids","biological agent",and"aspirin".Results The severity of MIS-C varies,and different treatment schemes should be used according to the specific *** research and data collection are vital to better understand the pathophysiology and optimal management of *** MIS-Cis a disease involving multiple systems and has great *** the accumulation of additional experience,we have garnered fresh insights into its treatment ***,there remains a critical need for greater standardization in treatment protocols,alongside the pressing necessity for more robust and meticulously conducted studies to deepen our understanding of these protocols.

关键词： Coronavirus disease 2019-Corticosteroids Intravenous immunoglobulin Multisystem inflammatory syndrome in children-Treatment

Thymoquinone affects hypoxia-inducible factor-1αexpression in pancreatic cancer cells via HSP90 and PI3K/AKT/mTOR pathways

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World Journal of Gastroenterology 2024年第21期30卷 2793-2816页

作者： Zhan-Xue Zhao Shuai Li Lin-Xun Liu department of General Surgery Qinghai Provincial People's HospitalXining 810007Qinghai ProvinceChina department of clinical Pharmacy The Affiliated Hospital of Qinghai UniversityXining 810001Qinghai ProvinceChina

BACKGROUND Pancreatic cancer(PC)is associated with some of the worst prognoses of all major ***(TQ)has a long history in traditional medical practice and is known for its anti-cancer,anti-inflammatory,anti-fibrosis and antioxidant pharmacological *** studies on hypoxia-inducible factor-1α(HIF-1α)and PC have shown that HIF-1αaffects the occurrence and development of PC in many *** addition,TQ could inhibit the development of renal cancer by decreasing the expression of HIF-1α.Therefore,we speculate whether TQ affects HIF-1αexpression in PC cells and explore the *** To elucidate the effect of TQ in PC cells and the regulatory mechanism of HIF-1α*** Cell counting kit-8 assay,Transwell assay and flow cytometry were performed to detect the effects of TQ on the proliferative activity,migration and invasion ability and apoptosis of PANC-1 cells and normal pancreatic duct epithelial(hTERTHPNE)*** real-time polymerase chain reaction and western blot assay were performed to detect the expression of HIF-1αmRNA and protein in PC *** effects of TQ on the HIF-1αprotein initial expression pathway and ubiquitination degradation in PANC-1 cells were examined by western blot assay and *** TQ significantly inhibited proliferative activity,migration,and invasion ability and promoted apoptosis of PANC-1 cells;however,no significant effects on hTERT-HPNE cells were *** significantly reduced the mRNA and protein expression levels of HIF-1αin PANC-1,AsPC-1,and BxPC-3 *** significantly inhibited the expression of the HIF-1αinitial expression pathway(PI3K/AKT/mTOR)related proteins,and promoted the ubiquitination degradation of the HIF-1αprotein in PANC-1 *** had no effect on the hydroxylation and von Hippel Lindau protein mediated ubiquitination degradation of the HIF-1αprotein but affected the stability of the HIF-1αprotein by inhibiting the interaction between HI

关键词： Thymoquinone Pancreatic cancer Hypoxia-inducible factor-1α PI3K/AKT/mTOR HSP90

Gastric cancer secreted miR 214-3p inhibits the anti-angiogenesis effect of apatinib by suppressing ferroptosis in vascular endothelial cells

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Oncology Research 2024年第3期32卷 489-502页

作者： WEIXUE WANG TONGTONG WANG YAN ZHANG TING DENG HAIYANG ZHANG YI BA department of GI Medical Oncology Tanjin Medical University Cancer Institute and HospitalNational Clinical Research Center for CancerTianjin's Clinical Research Center for CancerTianjin Key Iaboratory of Digestive CancerKey Laboratory of Cancer Prevention and TherapyTianjin300060China

Diferent from necrosis,apoptosis,autophagy and other forms of cell death,ferroptosis is a mechanism that catalyzes lipid peroxidation of polyunsaturated ftty acids under the action of iron divalent or lipoxygenase,leading to cell *** is currently used in the third line standard treatment of advanced gastric cancer,targeting the anti-angiogenesis ***,Apatinib mediated ferroptosis in vascular endothelial cells has not been reported *** exosomes can be taken up into target cells to regulate tumor development,but the mechanism related to vascular endothelial cell ferroptosis has not yet been ***,we show that exosomes secreted by gastric cancer cells carry miR-214.3p into vascular endothelial cells and directdy target zinc finger protein A20 to negatively regulate ACSL4,a key enzyme of lipid peroxidation during frroptosis thereby inhibiting ferroptosis in vascular endothelial cells and reducing the eficiency of *** conclusion,inhibition of miR-214-3p can increase the sensitivity of vascular endothelial cells to Apatinib,thereby promoting the antiangiogenic efect of Apatinib,suggesting a potential combination therapy for advanced gastric cancer.

关键词： Cellular ferroptosis Exosome Tyrosine kinase inhibitor Gastrointestinal tumors miRNA

Testosterone replacement therapy and vascular thromboembolic events: a systematic review and meta-analysis

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Asian Journal of Andrology 2024年第2期26卷 144-154页

作者： Rossella Cannarella Carmelo Gusmano Claudia Leanza Vincenzo Garofalo Andrea Crafa Federica Barbagallo Rosita A Condorelli Sandro La Vignera Aldo E Calogero department of clinical and Experimental Medicine University of CataniaCatania 95123Italy Glickman Urological&Kidney Institute Cleveland Clinic FoundationClevelandOH44195USA

To evaluate the relationship between testosterone replacement therapy(TRT)and arterial and/or venous thrombosis in patients with pre-treatment total testosterone(TT)<12 nmol I^(-1),we performed a meta-analysis following the Population Intervention Comparison Outcome ***:men with TT<12 nmol I^(-1) or clear mention of hypogonadism in the inclusion criteria of patients;intervention:TRT;comparison:placebo or no therapy;outcomes:arterial thrombotic events(stroke,myocardial infarction[MI],upper limbs,and lower limbs),VTE(deep vein thrombosis[DVT],portal vein thrombosis,splenic thrombosis,and pulmonary embolism),and mortality.A total of 2423 abstracts were assessed for ***-four studies,including 14 randomized controlled trials(RCTs),were finally included,with a total of 4027 and 310288 hypotestosteronemic male patients,from RCTs and from observational studies,*** on RCT-derived data,TRT did not influence the risk of arterial thrombosis(odds ratio[OR]=1.27,95%confidence interval[CI]:0.47-3.43,P=0.64),stroke(OR=1.34,95%CI:0.09-18.97,P=0.83),MI(OR=0.51,95%CI:0.11-2.31,P=0.39),VTE(OR=1.42,95%CI:0.22-9.03,P=0.71),pulmonary embolism(OR=1.38,95%CI:0.27-7.04,P=0.70),and mortality(OR=0.70,95%CI:0.20-2.38,P=0.56).Meanwhile,when only observational studies are considered,a significant reduction in the risk of developing arterial thrombotic events,Ml,venous thromboembolism,and mortality was *** risk for DVT remains uncertain,due to the paucity of RCT-based *** in men with TT<12 nmol I^(-1) is safe from the risk of adverse cardiovascular *** studies specifically assessing the risk of DVT in men on TRT are needed.

关键词： hypogonadism testosterone testosterone replacement therapy thromboembolism thrombosis TRT

The pathogenic mechanism of TAR DNA-binding protein 43(TDP-43)in amyotrophic lateral sclerosis

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Neural Regeneration Research 2024年第4期19卷 800-806页

作者： Xinxin Wang Yushu Hu Renshi Xu Medical College of Nanchang University department of Neurology Jiangxi Provincial People's HospitalThe First Affiliated Hospital of Nanchang Medical CollegeThe Clinical College of Nanchang Medical College

The onset of amyotrophic lateral sclerosis is usually characterized by focal death of both upper and/or lower motor neurons occurring in the motor cortex,basal ganglia,brainstem,and spinal cord,and commonly involves the muscles of the upper and/or lower extremities,and the muscles of the bulbar and/or respiratory ***,as the disease progresses,it affects the adjacent body regions,leading to generalized muscle weakness,occasionally along with memory,cognitive,behavioral,and language impairments;respiratory dysfunction occurs at the final stage of the *** disease has a complicated pathophysiology and currently,only riluzole,edaravone,and phenylbutyrate/taurursodiol are licensed to treat amyotrophic lateral sclerosis in many industrialized *** TAR DNA-binding protein 43 inclusions are observed in 97%of those diagnosed with amyotrophic lateral *** review provides a preliminary overview of the potential effects of TAR DNAbinding protein 43 in the pathogenesis of amyotrophic lateral sclerosis,including the abnormalities in nucleoplasmic transport,RNA function,post-translational modification,liquid-liquid phase separation,stress granules,mitochondrial dysfunction,oxidative stress,axonal transport,protein quality control system,and non-cellular autonomous functions(e.g.,glial cell functions and prion-like propagation).

关键词： amyotrophic lateral sclerosis axonal transport liquid-liquid phase separation noncellular autonomous functions oxidative stress pathogenesis post-translational modification protein quality control system stress granules TAR DNA-binding protein 43(TDP-43)

Rationale and design of Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events III (TRACE III): a randomised, phase III, open- label, controlled trial

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Stroke & Vascular Neurology 2024年第1期9卷 82-89页

作者： Yunyun Xiong Bruce C V Campbell Marc Fisher Lee H Schwamm Mark Parsons Hao Li Yuesong Pan Xia Meng Xingquan Zhao Yongjun Wang Neurology Beijing Tiantan HospitalBeijingChina China National clinical Research Center for Neurological Diseases BeijingChina department of Medicine and Neurology The University of MelbourneMelbourneVictoriaAustralia Neurology Beth Israel Deaconess Medical CenterBostonMassachusettsUSA department of Neurology and Comprehensive Stroke Center Massachusetts General HospitalBostonMassachusettsUSA department of Neurology University of New South Wales South Western Sydney Clinical SchoolLiverpoolNew South WalesAustralia

Background and purpose Recombinant human TNK tissue-type plasminogen activator(rhTNK-tPA)was not inferior to alteplase for ischaemic stroke within *** study aimed to investigate the efficacy and safety of rhTNK-tPA in patients who had an ischaemic stroke due to large vessel occlusion(LVO)of anterior circulation beyond *** and design Tenecteplase Reperfusion Therapy in Acute Ischaemic Cerebrovascular Events-III(TRACE III)is a multicentre,prospective,randomised,open-label,blind endpoint,controlled clinical *** who had an ischaemic stroke due to anterior circulation LVO(internal carotid artery,middle cerebral artery M1 and M2 segments)within 4.5–24hours from last known well(including wake-up stroke and no witness stroke)and with salvageable tissue(ischaemic core volume6s at 24 hours and NIHSS score change from baseline at *** outcomes are symptomatic intracerebral haemorrhage within 36 hours and mortality at 90 *** TRACE III will provide evidence for the efficacy and safety of rhTNK-tPA in patients who had an ischaemic strokes due to anterior circulation LVO beyond *** registration number NCT05141305.

关键词： Therapy random Rational