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Osteoclast precursor differentiation by MCPIP via oxidative stress,endoplasmic reticulum stress,and autophagy

分子细胞生物学报:英文版 2011年第6期3卷 360-368页

作者： Kangkai Wang Jianli Niu Hyunbae Kim pappachan e.kolattukudy Burnett School of Biomedical Sciences College of MedicineUniversity of Central FloridaOrlandoFL 32816USA

Osteoclasts(OCs)are responsible for bone resorption in inflammatory joint *** chemotactic protein-1(MCP-1)has been shown to induce differentiation of monocytes to OC precursors,but nothing is known about the underlying ***,we elucidate how MCPIP,induced by MCP-1,mediates this *** of MCPIP abolished MCP-1-mediated expression of OC markers,tartrate-resistant acid phosphatase,and serine protease cathepsin *** of MCPIP induced p47PHOX and its membrane translocation,reactive oxygen species formation,and induction of endoplasmic reticulum(eR)stress chaperones,up-regulation of autophagy marker,Beclin-1,and lipidation of LC3,and induction of OC *** of oxidative stress attenuated eR stress and autophagy,and suppressed expression of OC *** of eR stress by a specific inhibitor or by knockdown of IRe1 blocked autophagy and induction of OC *** stress inducers,tunicamycin and thapsigargin,induced expression of OC *** inhibition by 3′-methyladenine,LY294002,wortmannin or by knockdown of Beclin-1 or Atg 7 inhibited MCPIP-induced expression of OC *** results strongly suggest that MCP-1-induced differentiation of OC precursor cells is mediated via MCPIP-induced oxidative stress that causes eR stress leading to autophagy,revealing a novel mechanistic insight into the role of MCP-1 in OCs differentiation.

关键词： MCP-1 MCPIP osteoclast differentiation reactive oxygen species eR stress

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Metabolic-associated fatty liver disease and sarcopenia:A double whammy

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World Journal of Hepatology 2024年第2期16卷 152-163页

作者： Aditya Viswanath Sherouk Fouda Cornelius James Fernandez Joseph M pappachan School of Medicine Leicester UniversityLeicester LE17RHUnited Kingdom School of Health and Biomedical Sciences Rmit UniversityMelbourne VICAustralia Department of endocrinology and Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPreston PR29HTUnited Kingdom Faculty of Science Manchester Metropolitan UniversityManchester M156BHUnited Kingdom Faculty of Biology Medicine and HealthThe University of ManchesterManchester M139PLUnited Kingdom

The prevalence of metabolic-associated fatty liver disease(MAFLD)has increased substantially in recent years because of the global obesity ***,now recognized as the number one cause of chronic liver disease in the world,not only increases liver-related morbidity and mortality among sufferers but also worsens the complications associated with other comorbid conditions such as cardiovascular disease,type 2 diabetes mellitus,obstructive sleep apnoea,lipid disorders and *** the interplay between MAFLD and these comorbidities is important to design optimal therapeutic *** can be either part of the disease process that results in MAFLD(e.g.,obesity or adiposity)or a consequence of MAFLD,especially in the advanced stages such as fibrosis and *** can also worsen MAFLD by reducing exercise capacity and by the production of various muscle-related chemical ***,it is crucial to thoroughly understand how we deal with these diseases,especially when they *** explore the pathobiological interlinks between MAFLD and sarcopenia in this comprehensive clinical update review article and propose evidence-based therapeutic strategies to enhance patient care.

关键词： Metabolic-associated fatty liver disease Sarcopenia Sarcopenic obesity Lean metabolic-associated fatty liver disease Cardiovascular disease Liver-muscle axis

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Hemoglobin A1c in early postpartum screening of women with gestational diabetes

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World Journal of Diabetes 2013年第3期4卷 76-81页

作者： Mahesh V Katreddy Joseph M pappachan Sarah e Taylor Radha Indusekhar Ananth U Nayak Alan M Nevill the combined Antenatal Diabetes Clinic University Hospital of North Staffordshire NHS TrustStoke on Trent ST4 6QGUnited Kingdom Department of endocrinology University Hospital of North Staffordshire NHS TrustStoke-on-Trent ST4 6QGUnited Kingdom Research Institute in Health Care Sciences University of WolverhamptonWolverhampton WV1 1LYUnited Kingdom

AIM:To assess the utility of hemoglobin A1c(HbA1c) in the early postpartum screening of women with gestational diabetes mellitus(GDM).MeTHODS:Over a 3 years period,HbA1c estimations were undertaken in addition to and simultaneously with the traditional oral glucose tolerance test(OGTT),in 203 women with GDM as a part of early postpartum screening for dysglycaemia,at 6 wk *** Health Organization criteria was used for diagnosing diabetes:fasting blood glucose(FBG) ≥ 7.0 mmol/Land/or 2-h postprandial blood glucose(PPBG) ≥ 11.1 mmol/L and/or HbA1c ≥ 48 mmol/mol;and impaired glycaemiastate:impaired fasting glucose 6.1-6.9 mmol/L and/or impaired glucose tolerance 7.8-11.0 mmol/L and/or HbA1c:42-47 mmol/***:Mean FBG,2-h PPBG and HbA1c were 4.9 ± 0.7 mmol/L,5.6 ± 2.0 mmol/L and 38 ± 5 mmol/mol ***,2-h PPBG and HbA1c detected 6(3%),7(3.5%) and 11(5.4%) cases of diabetes respectively,and 11(5.4%),25(12.3%) and 23(11.3%) cases of pre-diabetes state ***1c values ≥ 48 mmol/mol(≥ 6.5%) showed a diagnostic sensitivity of 71.4% and specificity of 98.5% for diabetes in comparison to OGTT in receiver operating characteristics curve *** HbA1c cut-off 44 mmol/mol,sensitivity and specificity were 100% and 92.3% respectively [area under the curve:0.98(95%CI:0.96-1.00)].Sensitivity and specificity for detecting high risk "impaired glycaemia" state [HbA1c 42 mmol/mol(6.0%)] were 28% and 80%,***:HbA1c level ≥ 48 mmol/mol(≥ 6.5%) has reasonable sensitivity and high specificity in comparison to OGTT for early postpartum screening of diabetes in *** 6 th week postpartum screening,if FBG is normal and HbA1c ecommended.

关键词： Postpartum screening Glycated haemoglobin Gestational diabetes mellitus Impaired glycaemia

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