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Reference gene panel for urinary exosome-based molecular diagnostics in patients with kidney disease

World Journal of Nephrology 2024年第3期13卷 62-72页

作者： Deendayal D Mishra Pramod K Maurya Swasti Tiwari Department of Molecular medicine and Biotechnology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknow 226014Uttar PradeshIndia

BACKGROUND Kidney disease is a severe complication of diabetes that often leads to end-stage renal *** diagnosis is crucial for prevention or ***,the current diagnostic methods,with their limitations in detecting the disease in its early stages,underscore the urgency and importance of finding new *** encapsulated inside urinary exosomes(UEs)have potential as early biomarkers for kidney *** need for reference miRNAs for accurate interpretation currently limits their translational *** To identify consistently expressing reference miRNAs from UEs of controls and patients with type 2 diabetesmellitus(T2DM)and biopsy-confirmed kidney *** miRNA profiling was performed on UEs from 31 human urine samples using a rigorous and unbiased *** UEs were isolated from urine samples collected from healthy individuals(n=6),patients with T2DM(n=13),and T2DM patients who also had kidney diseases(including diabetic nephropathy,n=5;membranous nephropathy,n=5;and IgA nephropathy,n=2)through differential *** characterizing the UEs,miRNA expression profiling using microarray technology was *** Microarray data analysis identified 14 miRNAs that were consistently expressed in UEs from 31 human samples,representing various kidney conditions:diabetic controls,diabetic nephropathy,membrane nephropathy,IgA nephropathy,and healthy *** in silico analysis,we determined that 10 of these miRNAs had significant potential to serve as reference genes in *** We identified uniformly expressing UE miRNAs that could serve as reference genes kidney disease biomarkers.

关键词： miRNA Microarray Urinary exosomes Diabetic nephropathy Type 2 diabetes mellitus Kidney disease

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ABCD^(2) risk score does not predict the presence of cerebral microemboli in patients with hyper-acute symptomatic critical carotid artery stenosis

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Stroke & Vascular Neurology 2017年第2期2卷 41-46页

作者： Mahmud Saedon Charles E Hutchinson Christopher H E Imray Donald R J Singer Warwick Medical School University of WarwickCoventryUK University Hospitals Coventry Warwickshire NHS Trust CoventryUK fellowship of postgraduate medicine LondonUK Yale School of medicine New HavenConnecticutUSA

Introduction:ABCD^(2) risk score and cerebral microemboli detected by transcranial Doppler(TCD)have been separately shown to the predict risk of recurrent acute *** studied whether ABCD2 risk score predicts cerebral microemboli in patients with hyper-acute symptomatic carotid artery *** and methods:We studied 206 patients presenting within 2 weeks of transient ischaemic attack or minor stroke and found to have critical carotid artery stenosis(≥50% ).86 patients(age 70±1(SEM:years),58 men,83 Caucasian)had evidence of microemboli;72(84% )of these underwent carotid endarterectomy(CEA).120 patients(age 72±1 years,91 men,113 Caucasian)did not have microemboli detected;102(85% )of these underwent *** were analysed using X2 and Mann–Whitney U tests and receiver operating characteristic(ROC)***:140/206(68% :95% CI 61.63 to 74.37)patients with hyper-acute symptomatic critical carotid stenosis had an ABCD2 risk score≥*** was no significant difference in the NICE red flag criterion for early assessment(ABCD^(2) risk score≥4)for patients with cerebral microemboli versus those without microemboli(59/86 vs 81/120 patients:OR 1.05 ABCD2 risk score≥4(95% CI 0.58 to 1.90,p=0.867)).The ABCD2 risk score was<4 in 27 of 86(31% :95% CI 21 to 41)embolising patients and in 39 of 120(31% :95% CI 23 to 39)without cerebral *** adjusting for pre-neurological event antiplatelet treatment(APT),area under the curve(AUC)of ROC for ABCD2 risk score showed no prediction of cerebral microemboli(no pre-event APT,n=57:AUC 0.45(95% CI 0.29 to 0.60,p=0.531);preevent APT,n=147:AUC 0.51(95% CI 0.42 to 0.60,p=0.804)).Conclusions:The ABCD2 score did not predict the presence of cerebral microemboli or carotid disease in over one-quarter of patients with symptomatic critical carotid artery *** the basis of NICE guidelines(refer early if ABCD2≥4),assessment of high stroke risk based on ABCD2 scoring may lead to inappropriate delay in urgent treat

关键词： patients cerebral emboli

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Registry report on prediction by Pocock cardiovascular score of cerebral microemboli acutely following carotid endarterectomy

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Stroke & Vascular Neurology 2018年第3期3卷 147-152页

作者： Mahmud Saedon Athanasios Saratzis Rachel W S Lee Charles E Hutchinson Christopher H E Imray Donald R J Singer Nottingham University Hospitals NHS Trust NottinghamUK University Hospitals Coventry and Warwickshire NHS Trust CoventryUK Leicester Royal Infirmary LeicesterUK Yale School of medicine New HavenConnecticutUSA fellowship of postgraduate medicine LondonUK

background Cerebral microemboli may lead to ischaemic neurological complications after carotid endarterectomy(CEA).The association between classical cardiovascular risk factors and acute cerebral microemboli following carotid surgery has not been *** aim of this study was to explore whether an established cardiovascular risk score(Pocock score)predicts the presence of cerebral microemboli acutely after *** and methods Pocock scores were assessed for the 670 patients from the Carotid Surgery Registry(age 71±1(SEM)years,474(71%)male,652(97%)Caucasian)managed from January 2002 to December 2012 in the Regional Vascular Centre at University Hospitals Coventry and Warwickshire NHS Trust,which serves a population of *** was undertaken in 474(71%)patients for symptomatic carotid stenosis and in 196(25%)asymptomatic patients during the same period.74% of patients were hypertensive,71%were smokers and 49% had *** A high Pocock score(≥2.3%)was significantly associated with evidence of cerebral microemboli acutely following CEA(P=0.039,Mann-Whitney(MW)test).A Pocock score(≥2.3%)did not predict patients who required additional antiplatelet therapy(microemboli signal(MES)rate>50 hour-1:P=0.164,MW test).Receiver operating characteristic analysis also showed that the Pocock score predicts acute postoperative microemboli(area under the curve(AUC)0.546,95%CI 0.502 to 0.590,P=0.039)but not a high rate of postoperative microemboli(MES>50 hour−1:AUC 0.546,95% CI 0.482 to 0.610,P=0.164).A Pocock score≥2.3% showed a sensitivity of 74% for the presence of acute postoperative cerebral microemboli.A Pocock score≥2.3% also showed a sensitivity of 77% and a negative predictive value of 90% for patients who developed a high microembolic rate>50 hour−1 after carotid *** These findings demonstrate that the Pocock score could be used as a clinical tool to identify patients at high risk of developing acute postoperative microemboli.

关键词： cerebral Surgery Registry

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Aberrant promoter methylation of p16 in colorectal adenocarcinoma in North Indian patients

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World Journal of Gastrointestinal Oncology 2010年第7期2卷 295-303页

作者： Pooja Malhotra Rakesh Kochhar Kim Vaiphei Jai Dev Wig Safrun Mahmood Department of Gastroenterology Postgraduate Institute of Medical Education and Research Department of Histopathology Postgraduate Institute of Medical Education and Research Department of General Surgery Postgraduate Institute of Medical Education and Research Department of Experimental medicine and Biotechnology Postgraduate Institute of Medical Education and Research

AIM:To investigate p16 gene methylation and its expression in 30 patients with sporadic colorectal adenocarcinoma in a North Indian population. METHODS:Methylation specific polymerase chain reaction was used to detect p16 gene methylation and immunohistochemistry was used to study the p16 expression in 30 sporadic colorectal tumors as well as adjoining and normal tissue ***:Aberrant promoter methylation of p16 gene was detected in 12(40%)tumor specimens,whereas no promoter methylation was observed in adjoining and normal *** showed expression of p16 protein in 26(86.6%)colorectal tumors whereas complete loss of expression was seen in 4(13.3%)and reduced expression was observed in 12(40%)tumors. In the adjoining mucosa,expression of p16 was in 11 (36.6%)whereas no clear positivity for p16 protein was seen in normal *** was a significant difference in the expression of p16 protein in tumor tissue and adjoining mucosa(P0.05). CONCLUSION:Our study demonstrated that promoter hypermethylation of the p16 gene results in loss/reduced expression of p16 protein and this loss/reduced expression may contribute to tumor enlargement.

关键词： Methylation specific polymerase chain reaction p16 Methylation Immunohistochemistry Colorectal cancer

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Anti-endothelial cell antibody rich sera from rheumatic heart disease patients induces proinflammatory phenotype and methylation alteration in endothelial cells

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Genes & Diseases 2018年第3期5卷 275-289页

作者： Mukul Rastogi Subendu Sarkar Ankita Makol Rana Sandip Singh Uma Nahar Saikia Dibyajyoti Banerjee Seema Chopra Anuradha Chakraborti Department of Experimental medicine and Biotechnology Postgraduate Institute of Medical Education and ResearchChandigarh160012India Department of Cardiothoracic and Vascular Surgery Postgraduate Institute of Medical Education and ResearchChandigarh160012India Department of Histopathology Postgraduate Institute of Medical Education and ResearchChandigarh160012India Department of Obstetrics and Gynaecology Postgraduate Institute of Medical Education and ResearchChandigarh160012India

Rheumatic heart disease(RHD)is a major cause of cardiovascular morbidity and mortality in developing nations like *** commonly affects the mitral valve which is lined by a single layer of endothelial cells(ECs).The role of ECs in mitral valve damage during RHD is not well *** here,anti-endothelial cell antibody from RHD patients has been used to stimulate the ECs(HUVECs and HMVECs).ECs proinflammatory phenotype with increased expression of TNFa,IL-6,IL-8,IFNg,IL-1b,ICAM1,VCAM1,E-selectin,laminin B,and vimentin was documented in both *** promoter hypomethylation of various key inflammatory cytokines(TNFa,IL-6,and IL-8),integrin(ICAM1)associated with leukocyte transendothelial migration,and extracellular matrix genes(vimentin,and laminin)were also ***,the in-vitro data was in accordance with ex-vivo observations which correlated significantly with the etiological factors such as smoking,socioeconomic status,and ***,the study sheds light on the role of ECs in RHD which is a step forward in the elucidation of disease pathogenesis.

关键词： Anti-Endothelial cell antibodies DNA methylation Endothelial cells Inflammation Rheumatic heart disease

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Vitamins and non-alcoholic fatty liver disease: A molecular insight

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Liver Research 2021年第2期5卷 62-71页

作者： Sana Raza Archana Tewari Sangam Rajak Rohit A.Sinha Department of Endocrinology Sanjay Gandhi Postgraduate Institute of Medical SciencesLucknowIndia

The incidence of non-alcoholic fatty liver disease(NAFLD)is rising rapidly across the *** pathogenesis is largely driven by an imbalance in hepatic energy metabolism,and at present,there is no approved drug for its *** liver plays a crucial role in micronutrient metabolism,and deregulation of this micronutrient metabolism may contribute to the pathogenesis of *** regulate several enzymatic processes in the liver,and derangement in vitamin metabolism is believed to play a critical role in NAFLD *** anti-oxidant activities of vitamins C and E have been attributed to mitigate hepatocyte injury,and alterations in the serum levels of vitamin D,vitamin B12 and folate have shown a strong correlation with NAFLD *** review aims to highlight the role of these vitamins,which represent promising therapeutic targets for the management of NAFLD.

关键词： Anti-oxidant Autophagy Non-alcoholic fatty liver disease(NAFLD) Non-alcoholic steatohepatitis(NASH) Vitamin A Vitamin B Vitamin C Vitamin D Vitamin E

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Land cover change and carbon stores in a tropical montane cloud forest in the Sierra Madre Oriental,Mexico

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Journal of Mountain Science 2018年第10期15卷 2136-2147页

作者： Edgar G.LEIJA-LOREDO Numa P.PAVóN Arturo SáNCHEZ-GONZáLEZ Rodrigo RODRIGUEZ-LAGUNA GregorioáNGELES-PéREZ Center for Biological Research Autonomous University of Hidalgo.42184 HidalgoMexico Institute oJ:Ag ricultural Sciences Academic Area of Forestry EngineeringAutonomous University of Hidalgo.43600 HidalgoMexico postgraduate School Campus MontecilloPostgraduate in Forest Sciences.56230 Estado de MexicoMexico

Tropical montane cloud forest is one of the ecosystems with the highest biomass worldwide, representing an important carbon store. Globally its deforestation index is –1.1%, but in Mexico it is higher than –3%. Carbon estimates are scarce globally, particularly in Mexico. The objective of this study was to simulate future land-cover scenarios for the Sierra Madre Oriental in Mexico, by analyzing past forest cover changes. Another objective was to estimate stored carbon in the two study areas. These objectives involve the generation of information that could be useful inputs to anti-deforestation public policy such as the REDD+ strategy. Remote sensing was used to measure land cover change and estimate carbon stocks. Satellite images from 2015, 2000 and 1986 were used, and Dinamica EGO freeware generatedmodels of future projections. Between 1986 and 2015, 5171 ha of forest were converted to pasture. The annual deforestation rates were –1.5% for Tlanchinol and –1.3% for the San Bartolo Tutotepec sites. Distance to roads and marginalization were highly correlated with deforestation. By 2030, an estimated 3608 ha of forest in these sites will have been converted to pasture. Stored carbon was estimated at 16.35 Mg C ha-1 for the Tlanchinol site and 12.7 Mg C ha-1 for the San Bartolo site. In the Sierra Madre Oriental deforestation due to land cover change(–1.4%) is higher than levels reported worldwide. Besides having high values of stored carbon(14.5 Mg C ha-1), these forests have high biodiversity. The models' outputs show that the deforestation process will continue if action is not taken to avoid the expansion of livestock pasturing. This can be done by paying incentives for forest conservation to the owners of the land. The results suggest that REDD+ is currently the most viable strategy for reducing deforestation rates in tropical montane cloud forests in Sierra Madre Oriental.

关键词： Cloud forest Carbon stores C mitigation Climate change Dinamica EGO Forest management Remote sensing.

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Polymer Sensitized Quasi Solid-State Photovoltaic Cells Using Derivatives of Polythiophene

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Journal of Materials Science & Technology 2006年第6期22卷 811-816页

作者： G.K.R.Senadeera J.M.R.C.Fernando Institute of Fundamental Studies Hantane RoadKandySri Lanka Institute of Fundamental Studies Hantane RoadKandySri Lanka Postgraduate Institute of ScienceUniversity of PeradeniyaPeradeniyaSri Lanka

Substituted thiophene sensitized, nanocrystalline TiO2-based quasi solid-state solar cells were fabricated by using either poly （3-thiophene acetic acid）（P3TAA） or a copolymer with poly （3-thiophene acetic acid）-poly （hexyl thiophene）（P3TAA-PHT） polymers and copper iodide （Cul） as a hole conducting material together with an ionic liquid 1-ethyl-3-methylimidazolium bis （trifluoromethylsulfonyl） amide and lithium bis （triflu- oromethanesulfone） imide as additives for charge transport promotion. Dramatic enhancements in the cell performances were observed with the additives in Cul. While the cell sensitized with P3TAA generated a short-circuit photocurrent of -1.45 ***^-2, an open-circuit photovoltage of -345 mV with a total power conversion efficiency of -0.3% under simulated full sunlight of 100 mW-cm^-2 （air mass： 1.5）, the cell sensitized with copolymer P3TAA-PHT delivered -0.25% efficiency under the same conditions with -1.23 mA-cm^-2 as photocurrent and -371 mV as photovoltage.

关键词： Solar cells Polymers Titanium dioxide

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Cell-type specific role of autophagy in the liver and its implications in non-alcoholic fatty liver disease

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World Journal of Hepatology 2023年第12期15卷 1272-1283页

作者： Sana Raza Sangam Rajak Rajani Singh Jin Zhou Rohit A Sinha Amit Goel Department of Endocrinology Sanjay Gandhi Postgraduate Institute of Medical SciencesUttar PradeshLucknow 226014India Department of Hepatology Sanjay Gandhi Postgraduate Institute of Medical SciencesUttar PradeshLucknow 226014India CVMD Duke-NUS Medical SchoolSingapore 169857Singapore

Autophagy,a cellular degradative process,has emerged as a key regulator of cellular energy production and stress *** autophagy is a common phenomenon observed in several human diseases,and its restoration offers curative ***-alcoholic fatty liver disease(NAFLD),more recently renamed metabolic dysfunction-associated steatotic liver disease,is a major metabolic liver disease affecting almost 30%of the world ***,NAFLD has no pharmacological therapies available to *** regulates several hepatic processes including lipid metabolism,inflammation,cellular integrity and cellular plasticity in both parenchymal(hepatocytes)and non-parenchymal cells(Kupffer cells,hepatic stellate cells and sinusoidal endothelial cells)with a profound impact on NAFLD *** cell type-specific autophagy in the liver is essential in order to develop targeted treatments for liver diseases such as *** autophagy in specific cell types can have varying effects on liver function and pathology,making it a promising area of research for liver-related *** review aims to summarize our present understanding of cell-type specific effects of autophagy and their implications in developing autophagy centric therapies for NAFLD.

关键词： Autophagy Non-alcoholic fatty liver disease Hepatocytes Macrophages Hepatic stellate cells

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Cytokines-activated nuclear IKKα-FAT10 pathway induces breast cancer tamoxifen-resistance

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Science China(Life Sciences) 2024年第7期67卷 1413-1426页

作者： Xueyan Chen Weilin Wu Ji-Hak Jeong Matjaz Rokavec Rui Wei Shaolong Feng Werner Schroth Hiltrud Brauch Shangwei Zhong Jun-Li Luo Department of Oncology Xiangya HospitalCentral South UniversityChangsha 410008China Department of Molecular medicine The Scripps Research InstituteJupiter 33458USA Dr.Margarete Fischer-Bosch-Institute of Clinical Pharmacology Stuttgart 70376Germany iFIT Cluster of Excellence University of TübingenTübingen 72074Germany The Cancer Research Institute and the Second Affiliated Hospital Henyang Medical SchoolUniversity of South ChinaHengyang 421001China National Health Commission Key Laboratory of Birth Defect Research and Prevention Hunan Provincial Maternal and Child Health Care HospitalChangsha 410008China

Endocrine therapy that blocks estrogen signaling is the most effective treatment for patients with estrogen receptor positive(ER+)breast ***,the efficacy of agents such as tamoxifen(Tam)is often compromised by the development of *** we report that cytokines-activated nuclear IKKαconfers Tam resistance to ER+breast cancer by inducing the expression of FAT10,and that the expression of FAT10 and nuclear IKKαin primary ER+human breast cancer was correlated with lymphotoxinβ(LTB)expression and significantly associated with relapse and metastasis in patients treated with adjuvant ***αactivation or enforced FAT10 expression promotes Tam-resistance while loss of IKKαor FAT10 augments Tam *** induction of FAT10 by IKKαis mediated by the transcription factor Pax5,and coordinated via an IKKα-p53-miR-23a circuit in which activation of IKKαattenuates p53-directed repression of ***,our findings establish IKKα-to-FAT10 pathway as a new therapeutic target for the treatment of Tam-resistant ER+breast cancer.

关键词： nuclear IKKα breast cancer Tam-resistance FAT10 Pax5 lymphotoxin nuclear IKKα-FAT0 pathway

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