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Microtubule acetylation dyshomeostasis in Parkinson’s disease

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Translational Neurodegeneration 2023年第1期12卷 576-600页

作者： Padmashri Naren Khan Sabiya Samim Kamatham Pushpa Tryphena Lalitkumar K.Vora Saurabh Srivastava Dharmendra Kumar Khatri shashi bala singh Molecular and Cellular Neuroscience Lab Department of Pharmacology and ToxicologyNational Institute of Pharmaceutical Education and Research(NIPER)HyderabadTelangana 500037India School of Pharmacy Queen’s University Belfast97 Lisburn RoadBelfast BT97BLUK Department of Pharmaceutics National Institute of Pharmaceutical Education and Research(NIPER)HyderabadTelangana 500037India

The inter-neuronal communication occurring in extensively branched neuronal cells is achieved primarily through the microtubule(MT)-mediated axonal transport *** mechanistically regulated system delivers cargos(proteins,mRNAs and organelles such as mitochondria)back and forth from the soma to the *** proteins like kinesins and dynein mechanistically regulate polarized anterograde(from the soma to the synapse)and retrograde(from the synapse to the soma)commute of the cargos,*** axonal transport of such cargos is achieved by altering the microtubule stability via post-translational modifications(PTMs)ofα-andβ-tubulin heterodimers,core components constructing the *** within the lumen of MTs,K40 acetylation ofα-tubulin viaα-tubulin acetyl transferase and its subsequent deacetylation by HDAC6 and SIRT2 are widely scrutinized PTMs that make the MTs highly flexible,which in turn promotes their *** movement of various motor proteins,including kinesin-1(responsible for axonal mitochondrial commute),is enhanced by this PTM,and dyshomeostasis of neuronal MT acetylation has been observed in a variety of neurodegenerative conditions,including Alzheimer’s disease and Parkinson’s disease(PD).PD is the second most common neurodegenerative condition and is closely associated with impaired MT dynamics and deregulated tubulin acetylation *** the relationship between status of MT acetylation and progression of PD pathogenesis has become a chicken-and-egg question,our review aims to provide insights into the MT-mediated axonal commute of mitochondria and dyshomeostasis of MT acetylation in *** enzymatic regulators of MT acetylation along with their synthetic modulators have also been briefly *** towards a tubulin-based therapy that enhances MT acetylation could serve as a disease-modifying treatment in neurological conditions that lack it.

关键词： Parkinson’s disease Microtubule acetylation Tubulin PTMs Mitochondria Axonal transport HDAC6 SIRT2 inhibitors

Clinical profile and outcomes of hepatocellular carcinoma in primary Budd-Chiari syndrome

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World Journal of Gastrointestinal Oncology 2024年第3期16卷 699-715页

作者： Ankit Agarwal Sagnik Biswas Shekhar Swaroop Arnav Aggarwal Ayush Agarwal Gautam Jain Anshuman Elhence Arun Vaidya Amit Gupte Ravi Mohanka Ramesh Kumar Ashwani Kumar Mishra Shivanand Gamanagatti shashi bala Paul Subrat Kumar Acharya Akash Shukla Shalimar Department of Gastroenterology and Human Nutrition All India Institute of Medical SciencesNew Delhi 110029DelhiIndia Department of Gastroenterology Seth Gordhandas Sunderdas Medical College and KEM HospitalMumbai 400012MaharashtraIndia Department of Gastroenterology Sir HN Reliance Foundation HospitalMumbai 400004India Department of Liver Transplant and HPB Sir HN Reliance Foundation HospitalMumbai 400004India Department of Gastroenterology All India Institute of Medical SciencesPatna 801507India Professor of Biostatistics National Drug Dependence Treatment Centre(NDDTC)All India Institute of Medical SciencesNew Delhi 110029India Department of Radiodiagnosis All India Institute of Medical SciencesNew Delhi 110029DelhiIndia

BACKGROUND There is scant literature on hepatocellular carcinoma(HCC)in patients with Budd-Chiari syndrome(BCS).AIM To assess the magnitude,clinical characteristics,feasibility,and outcomes of treatment in *** A total of 904 BCS patients from New Delhi,India and 1140 from Mumbai,India were *** prevalence and incidence of HCC were determined,and among patients with BCS-HCC,the viability and outcomes of interventional therapy were *** In the New Delhi cohort of 35 BCS-HCC patients,18 had HCC at index presentation(prevalence 1.99%),and 17 developed HCC over a follow-up of 4601 person-years,[incidence 0.36(0.22-0.57)per 100 person-years].BCS-HCC patients were older when compared to patients with BCS alone(P=0.001)and had a higher proportion of inferior vena cava block,cirrhosis,and long-segment vascular *** median alpha-fetoprotein level was higher in patients with BCS-HCC at first presentation than those who developed HCC at follow-up(13029 ng/mL vs 500 ng/mL,P=0.01).Of the 35 BCS-HCC,26(74.3%)underwent radiological interventions for BCS,and 22(62.8%)patients underwent treatment for HCC[transarterial chemoembolization in 18(81.8%),oral tyrosine kinase inhibitor in 3(13.6%),and transarterial radioembolization in 1(4.5%)].The median survival among patients who underwent interventions for HCC compared with those who did not was 3.5 years vs 3.1 mo(P=0.0001).In contrast to the New Delhi cohort,the Mumbai cohort of BCS-HCC patients were predominantly males,presented with a more advanced HCC[Barcelona Clinic Liver Cancer C and D],and 2 patients underwent liver *** HCC is not uncommon in patients with *** interventions and liver transplantation are feasible in select primary BCS-HCC patients and may improve outcomes.

关键词： Budd chiari syndrome Cancer Cirrhosis Thrombosis Liver Varices Transarterial chemoembolization Hepatic venous outflow tract obstruction

Alcoholic liver disease and the gut-liver axis

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World Journal of Gastroenterology 2010年第11期16卷 1321-1329页

作者： Gyongyi Szabo shashi bala Liver Center Department of Medicine University of Massachusetts Medical School

Alcoholic liver disease (ALD) is one of the leading causes of liver diseases and liver-related death worldwide. Of the many factors that contribute to the pathogenesis of ALD, gut-derived lipopolysaccharide (LPS) plays a central role in induction of steatosis, inflammation, and fi brosis in the liver. In this review, we discuss the mechanisms by which alcohol contributes to increased gut permeability, the activation of Kupffer cells, and the infl ammatory cascade by LPS. The role of the Toll-like receptor 4 (TLR4) complex in LPS recognition and the importance of the TLR4-induced signaling pathways are evaluated in ALD.

关键词： Kupffer cell Gut permeability microRNA Tumor necrosis factor-α Endotoxin

Emerging role of microRNAs in liver diseases

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World Journal of Gastroenterology 2009年第45期15卷 5633-5640页

作者： shashi bala Miguel Marcos Gyongyi Szabo Department of Medicine University of Massachusetts Medical School WorcesterMA 01605 United States

MicroRNAs are a class of small non-coding RNAs that are found in plants, animals, and some viruses. They modulate the gene function at the post-transcriptional level and act as a fine tuner of various processes, such as development, proliferation, cell signaling, and apopto-sis. They are associated with different types and stages of cancer. Recent studies have shown the involvement of microRNAs in liver diseases caused by various factors, such as Hepatitis C, Hepatitis B, metabolic disorders, and by drug abuse. This review highlights the role of microRNAs in liver diseases and their potential use as therapeutic molecules.

关键词： MicroRNA Hepatitis Fatty liver Fibrosis Cirrhosis

Plasma microRNA profiles distinguish lethal injury in acetaminophen toxicity: A research study

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World Journal of Gastroenterology 2012年第22期18卷 2798-2804页

作者： Jeanine Ward shashi bala Jan Petrasek Gyongyi Szabo Department of Emergency Medicine University of Massachusetts Medical School 55 Lake Avenue North Worcester MA 01655 United States Division of Gastroenterology Department of Medicine University of Massachusetts Medical School 364 Plantation Street Worcester MA 01655 United States

AIM: To investigate plasma microRNA (miRNA) profiles indicative of hepatotoxicity in the setting of lethal acetaminophen (APAP) toxicity in mice. METHODS: Using plasma from APAP poisoned mice, either lethally (500 mg/kg) or sublethally (150 mg/kg) dosed, we screened commercially available murine microRNA libraries (SABiosciences, Qiagen Sciences, MD) to evaluate for unique miRNA profiles between these two dosing parameters. RESULTS: We distinguished numerous, unique plasma miRNAs both up- and downregulated in lethally compared to sublethally dosed mice. Of note, many of the greatest up- and downregulated miRNAs, namely 574-5p, 466g, 466f-3p, 375, 29c, and 148a, have been shown to be associated with asthma in prior studies. Interestingly, a relationship between APAP and asthma has been previously well described in the literature, with an as yet unknown mechanism of pathology. There was a statistically significant increase in alanine aminotransferase levels in the lethal compared to sublethal APAP dosing groups at the 12 h time point (P < 0.001). There was 90% mortality in the lethally compared to sublethally dosed mice at the 48 h time point (P = 0.011). CONCLUSION: We identified unique plasma miRNAs both up- and downregulated in APAP poisoning which are correlated to asthma development.

关键词： Plasma microRNA Hepatotoxicity Acet-aminophen Drug-induced liver injury Alanine amino-transferase

Design and simulation of nanoscale double-gate TFET/tunnel CNTFET

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Journal of Semiconductors 2018年第4期39卷 34-38页

作者： shashi bala Mamta Khosla Department of Electronic and Communication Engineering Dr B R Ambedkar Natrional Institute of Technology Jalandhar-144011 India

A double-gate tunnel field-effect transistor （DG tunnel FET） has been designed and investigated for various channel materials such as silicon （Si）, gallium arsenide （GaAs）, alminium gallium arsenide （A1xGa1-xAs） and CNT using a nano ViDES Device and TCAD SILVACO ATLAS simulator. The proposed devices are com- pared on the basis of inverse subthreshold slope （SS）, ION/IoFF current ratio and leakage current. Using Si as the channel material limits the property to reduce leakage current with scaling of channel, whereas the A1xGa1-xAs based DG tunnel FET provides a better ION/IOFF current ratio （2.51 × 10^6） as compared to other devices keeping the leakage current within permissible limits. The performed silmulation of the CNT based channel in the double-gate tunnel field-effect transistor using the nano ViDES shows better performace for a sub-threshold slope of 29.4 mV/dec as the channel is scaled down. The proposed work shows the potential of the CNT channel based DG tunnel FET as a futuristic device for better switching and high retention time, which makes it suitable for memory based circuits.

关键词： band-to-band tunneling (BTBT) double gate (DG) silicon (Si) gallium arsenide (GaAs) aluminum gallium arsenide (AlxGa1 xAs) tunnel field effect transistor (FET) carbon nanotube (CNT)

Microstructural analysis and hot corrosion behavior of HVOF-sprayed Ni–22Cr–10Al–1Y and Ni–22Cr–10Al–1Y–SiC(N) coatings on ASTM-SA213-T22 steel

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International Journal of Minerals,Metallurgy and Materials 2020年第3期27卷 401-416页

作者： Gurmail singh Niraj bala Vikas Chawla Department of Mechanical Engineering IKGPTUJalandhar 144603PunjabIndia Department of Aerospace Engineering Chandigarh UniversityGharuan 140413PunjabIndia Department of Mechanical Engineering BBSBECFatehgarh Sahib 140407PunjabIndia

The present paper deals with the investigation of microstructure and high-temperature hot corrosion behavior of high-velocity oxy fuel(HVOF)-produced coatings. Two powder coating compositions, namely, Ni22Cr10Al1Y alloy powder and Ni22Cr10Al1Y(80 wt%;microsized)–silicon carbide(SiC)(20 wt%;nano(N)) powder, were deposited on a T-22 boiler tube steel. The hot corrosion behavior of bare and coated steels was tested at 900°C for 50 cycles in Na2SO4–60 wt%V2O5 molten-salt environment. The kinetics of corrosion was established with weight change measurements after each cycle. The microporosity and microhardness of the as-coated samples have been reported. The X-ray diffraction,field emission-scanning electron microscopy/energy dispersive spectroscopy, and X-ray mapping characterization techniques have been utilized for structural analysis of the as-coated and hot-corroded samples. The results showed that both coatings were deposited with a porosity less than2%. Both coated samples revealed the development of harder surfaces than the substrate. During hot corrosion testing, the bare T22 steel showed an accelerated corrosion in comparison with its coated counterparts. The HVOF-sprayed coatings were befitted effectively by maintaining their adherence during testing. The Ni22Cr10Al1Y–20 wt%SiC(N) composite coating was more effective than the Ni–22Cr–10Al–1Y coating against corrosion in the high-temperature fluxing process.

关键词： high-velocity oxy fuel thermal spray hot corrosion oxide scale nano-structured coating

ON APPROXIMATE EFFICIENCY FOR NONSMOOTH ROBUST VECTOR OPTIMIZATION PROBLEMS

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Acta Mathematica Scientia 2020年第3期40卷 887-902页

作者： Tadeusz ANTCZAK Yogendra PANDEY Vinay singh shashi Kant MISHRA Faculty of Mathematics and Computer Science University of LódźBanacha 2290-238 LódźPoland Department of Mathematics Satish Chandra CollegeBallia 277001India Department of Mathematics National Institute of TechnologyAizawl-796012MizoramIndia Department of Mathematics Banaras Hindu UniversityVaranasi-221005India

In this article,we use the robust optimization approach(also called the worst-case approach)for findingε-efficient solutions of the robust multiobjective optimization problem defined as a robust(worst-case)counterpart for the considered nonsmooth multiobjective programming problem with the uncertainty in both the objective and constraint ***,we establish both necessary and sufficient optimality conditions for a feasible solution to be anε-efficient solution(an approximate efficient solution)of the considered robust multiobjective optimization *** also use a scalarizing method in proving these optimality conditions.

关键词： Robust optimization approach robust multiobjective optimization ε-efficient solution ε-optimality conditions scalarization

Development of islet organoids from human induced pluripotent stem cells in a cross-linked collagen scaffold

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Cell Regeneration 2021年第1期10卷 388-399页

作者： Shruti Sandilya shashi singh CSIR-Centre for Cellular and Molecular Biology Uppal RoadHyderabad 500007India

Islets organoids would have value in the cell replacement therapy for diabetes apart from usual personalized drug screening *** of a large number of Islets like clusters,with ability to respond to glucose stimulation appears to be an ideal *** this study we have generated islet organoids with the ability to respond to glucose stimulation by insulin *** source of the cells was an iPSC cell line differentiated into the pancreatic *** cells were assembled in matrigel or cross-linked collagen scaffold and compared for their efficacy to release insulin upon stimulation with *** assembled organoids were examined by immunohistochemistry and expression of the relevant marker *** organoids showed expression of islet like markers in both-matrigel and crosslinked collagen *** islet organoids in both the cases showed release of insulin upon stimulation with *** crosslinked collagen scaffold is quite stable and supports islet cells growth and function.

关键词： Endocrine Exocrine Marker genes Crosslinked collagen Functional Insulin release