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Chaperone-assisted E3 ligase CHIP:A double agent in cancer

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Genes & Diseases 2022年第6期9卷 1521-1555页

作者： sunny kumar Malini Basu Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata-700091&4Raja S.C.Mullick RoadJadavpurKolkata 700032India Department of Microbiology Dhruba Chand Halder CollegeDakshin BarasatSouth 24 ParaganasWest Bengal 743372India

The carboxy-terminus of Hsp70-interacting protein(CHIP)is a ubiquitin ligase and co-chaperone belonging to Ubox family that plays a crucial role in the maintenance of cellular homeostasis by switching the equilibrium of the folding-refolding mechanism towards the proteasomal or lysosomal degradation *** links molecular chaperones ***70,HSP70 and HSP90 with ubiquitin proteasome system(UPS),acting as a quality control *** contains charged domain in between N-terminal tetratricopeptide repeat(TPR)and C-terminal Ubox *** domain interacts with the aberrant client proteins via chaperones while Ubox domain facilitates the ubiquitin transfer to the client proteins for ***,CHIP is a classic molecule that executes ubiquitination for degradation of client ***,CHIP has been found to be indulged in cellular differentiation,proliferation,metastasis and ***,CHIP can play its dual role as a tumor suppressor as well as an oncogene in numerous malignancies,thus acting as a double ***,in this review,we have reported almost all substrates of CHIP established till date and classified them according to the hallmarks of *** addition,we discussed about its architectural alignment,tissue specific expression,sub-cellular localization,folding-refolding mechanisms of client proteins,E4 ligase activity,normal physiological roles,as well as involvement in various diseases and tumor ***,we aim to discuss its importance in HSP90 inhibitors mediated cancer ***,this report concludes that CHIP may be a promising and worthy drug target towards pharmaceutical industry for drug development.

关键词： Chaperones(HSC70/HSP70&HSP90) CHIP Oncogene Therapy Tumor suppressor Ubiquitin proteasome system(UPS)

COVID-19 therapeutics:Clinical application of repurposed drugs and futuristic strategies for target-based drug discovery

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Genes & Diseases 2023年第4期10卷 1402-1428页

作者： sunny kumar Malini Basu Pratyasha Ghosh Uttam Pal Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata-700091&4Raja S.C.Mullick RoadJadavpurKolkata 700032India Department of Microbiology Dhruba Chand Halder CollegeDakshin BarasatWest Bengal 743372India Department of Economics Bethune CollegeUniversity of CalcuttaKolkata 700006India

Severe acute respiratory syndrome coronavirus-2(SARS-CoV-2)causes the compli-cated disease *** are continuously facing huge problems in the treatment of patients,as COVID-19-specific drugs are not available,hence the principle of drug repurpos-ing serves as a one-and-only ***,the repurposing of many drugs is underway;few of them are already approved by the regulatory bodies for their clinical use and most of them are in different phases of clinical *** in this review,our main aim is to discuss in detail the up-to-date information on the target-based pharmacological classification of repurposed drugs,the potential mechanism of actions,and the current clinical trial status of various drugs which are under repurposing since early *** last,we briefly proposed the probable phar-macological and therapeutic drug targets that may be preferred as a futuristic drug discovery approach in the development of effective medicines.

关键词： Clinical trials COVID-19 Drug discovery Pharmacology Repurposing of drugs SARS-CoV-2

Targeting PD-1/PD-L1 in cancer immunotherapy:An effective strategy for treatment of triple-negative breast cancer(TNBC)patients

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Genes & Diseases 2023年第4期10卷 1318-1350页

作者： sunny kumar Mouli Chatterjee Pratyasha Ghosh Kirat K.Ganguly Malini Basu Mrinal K.Ghosh Cancer Biology and Inflammatory Disorder Division Council of Scientific and Industrial Research-Indian Institute of Chemical Biology(CSIR-IICB)TRUE CampusCN-6SectoreVSalt LakeKolkata 700091JadavpurKolkataPIN 700032India Department of Economics Bethune CollegeUniversity of CalcuttaKolkataPIN 700006India Department of Microbiology Michael Madhusudan Memorial CollegeDurgapurPIN 713216India Department of Microbiology Dhruba Chand Halder CollegeUniversity of CalcuttaKolkataPIN 743372India

Maintaining the balance between eliciting immune responses against foreign pro-teins and tolerating self-proteins is crucial for maintenance of *** functions of programmed death protein 1(PD-1)and its ligand programmed death ligand 1(PD-L1)are to inhibit immune responses so that over-reacting immune cells does not cause any damage to its own body ***,cancer cells hijack this mechanism to attenuate immune cells functions and create an immunosuppressive environment that fuel their continuous growth and *** the past few years’rapid development in cancer immunotherapy has opened a new avenue in cancer *** of PD-1 and PD-L1 has become a potential strategy that rescue the functions of immune cells to fight against cancer with high ***,immune checkpoint monotherapies were not very successful,making breast cancer less ***,recent reports support the presence of tumor infiltrating lympho-cytes(TILs)in breast cancer that make it favorable for PD-1/PD-L1 mediated immunotherapy,which is effective in PD-L1 positive ***,anti-PD-1(pembrolizumab)and anti-PD-L1(atezolizumab)gets FDA approval for breast cancer treatment and make PD-1/PD-L1 immunotherapy is meaningful for further ***,this article gathered understand-ing of PD-1 and PD-L1 in recent years,their signaling networks,interaction with other mole-cules,regulations of their expressions and functions in both normal and tumor tissue microenvironments are crucial to find and design therapeutic agents that block this pathway and improve the treatment ***,authors collected and highlighted most of the important clinical trial reports on monotherapy and combination therapy.

关键词： Breast cancer Cancer Clinical trial Immunotherapy PD-1/PD-L1 TNBC

中外大学生饮酒态度、动机和酒精障碍的比较研究

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中外大学生饮酒态度、动机和酒精障碍的比较研究

Translocator protein and neurodegeneration: insights from Alzheimer’s disease

四川省医学会第十五次精神病学学术会议暨第三次心身医学学术会议

作者： sunny kumar 雷威陈晶梁雪梅刘可智西南医科大学附属医院精神科西南医科大学精神病学教研室

目的:研究中国和外国在校大学生饮酒态度、动机和酒文化知识的差异,及其与酒精使用障碍的关系。方法:采用《酒精依赖疾患识别测验》,《饮酒动机问卷》,《饮酒态度问卷》,《酒桌文化问卷》和方便取样的方法,选取四川省某高校58名中国大...

目的:研究中国和外国在校大学生饮酒态度、动机和酒文化知识的差异,及其与酒精使用障碍的关系。方法:采用《酒精依赖疾患识别测验》,《饮酒动机问卷》,《饮酒态度问卷》,《酒桌文化问卷》和方便取样的方法,选取四川省某高校58名中国大学生和43名外国大学生(主要来自印度、巴基斯坦、斯里兰卡、厄瓜多尔、尼泊尔、尼日利亚

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Neural Regeneration Research 2025年第4期20卷 1090-1091页

作者： Arpit kumar Pradhan Rainer Rupprecht Gerhard Rammes Klinik für Anaesthesiologie und Intensivmedizin der Technischen Universität München Klinikum rechts der IsarMunichGermany Graduate School of Systemic Neurosciences Ludwig-Maximilians-Universität MünchenMartinsriedGermany Department of Psychiatry and Psychotherapy University RegensburgRegensburgGermany

The 18 kDa translocator protein(TSPO)located on the outer mitochondrial membrane regulates several key cellular processes including mitochondrial homeostasis,cholesterol transport,apoptosis,cell proliferation,and maintenance of mitochondrial health(Rupprecht et al.,2022,2023).TSPO is expressed in both peripheral organs and the central nervous system,with a more pronounced expression in tissues that produce *** main reason why TSPO has garnered so much attention is because it plays a key role in neurosteroidogenesis by transferring cholesterol from the outer to the inner mitochondrial membrane,which is the rate-limiting step in neurosteroid synthesis.A cholesterol-recognizing amino acid consensus domain has been identified in the cytosolic C terminus of the TSPO protein by both in vitro and site-directed mutagenesis experiments(Li et al.,2001).However,the role of TSPO in the process of neurosteroid synthesis has been challenged by several studies,particularly TSPO knockout models,which suggest that TSPO removal does not affect the phenotype or the system’s viability(Tu et al.,2014).However,ligands targeting TSPO have been shown to enhance levels of neurosteroids which suggests that neurosteroidogenesis is one of the major functional roles mediated by the TSPO protein.

关键词： cholesterol organs

Natural and artificial small RNAs:a promising avenue of nucleic acid therapeutics for cancer

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Cancer Biology & Medicine 2017年第3期14卷 242-253页

作者： sunny Yadav Mamta Shekhawat Devashree Jahagirdar Nilesh kumar Sharma Cancer and Translational Research Lab Dr.D.Y Patil Biotechnology&Bioinformatics InstituteDr.D.Y.Patil VidyapeethPune 411033MaharashtraIndia

Since the failure of traditional therapy, gene therapy using functional DNA sequence and small RNA/DNA molecules(oligonucleotide) has become a promising avenue for cancer treatment. The discovery of RNA molecules has impelled researchers to investigate small regulatory RNA from various natural and artificial sources and determine a cogent target for controlling tumor progression. Small regulatory RNAs are used for therapeutic silencing of oncogenes and aberrant DNA repair response *** their advantages, therapies based on small RNAs exhibit limitations in terms of stability of therapeutic drugs, precisionbased delivery in tissues, precision-based intercellular and intracellular targeting, and tumor heterogeneity-based responses. In this study, we summarize the potential and drawbacks of small RNAs in nucleic acid therapeutics for cancer.

关键词： Cancer drug targeting gene intracellular therapeutics tumor heterogeneity

Atomic structure calculations for F-like tungsten

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Chinese Physics B 2014年第9期23卷 174-179页

作者： sunny Aggarwal Department of Physics and Astrophysics University of Delhi

Energy levels, wavefunction compositions and lifetimes have been computed for all levels of ls^22s^22p^5, ls^22s^2p^6, ls^22s^22p^43s, ls^22s^22p^43p, and ls^22s^22p^43d configurations in highly charged F-like tungsten ion. The multiconfigurational Dirac-Fock method （MCDF） is adopted to generate the wavefunctions. We have also presented the transition wavelengths, oscillator strengths, transition probabilities, and line strengths for the electric dipole （El） and magnetic quadrupole （M2） transition from the ls^22s^22p^5 ground configuration. We have performed parallel calculations with the flexible atomic code （FAC） for comparing the atomic data. The reliability of present data is assessed by comparison with other theoretical and experimental data available in the literature. Good agreement is found between our results and those obtained using different approaches confirm the quality of our results. Additionally, we have predicted some new atomic data for F-like W that were not available so far and may be important for plasma diagnostic analysis in fusion plasma.

关键词： atomic data transition probability

Comparative studies of lightweight deflectometer and Benkelman beam deflectometer in low volume roads

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Journal of Traffic and Transportation Engineering(English Edition) 2016年第5期3卷 438-447页

作者： sunny Deol Guzzarlapudi Vinod kumar Adigopula Rakesh kumar Department of Civil Engineering Sardar Vallabhbhai National Institute of Technology

A comparative subgrade moduli study is carried out by static and dynamic deflection methods using lightweight deflectometer and conventional Benkelman beam deflec- tometer on low volume road. Field and laboratory tests are performed at 40 test locations on in-service road of 2 km stretch that contains three common types of cohesive soils （CH, CI, and CL）. Pavement static and dynamic responses are estimated to ascertain static, backcalculated, and composite moduli of subgrade. The backcalculated and composite moduli of subgrade is validated at given moisture content using repeated triaxial test. Static moduli values are on lower side as compared with dynamic moduli values whereas the composite, and laboratory moduli of subgrade are approximately consistent with 2% to 7% variation, respectively. Correlation analyses between static and dynamic moduli of different types of subgrade soils depict good correlation of determination （R2） varies between 0.75 and 0.91. Subsequently, validation of static moduli with California bearing ratio （CBR） related subgrade moduli shows moderate correlation of 0.67 to 0.74 whereas dynamic moduli shows good correlation of 0.74 to 0.93 for different types of soils, respectively. Therefore, the comparative analysis shows that lightweight deflectometer provides reliable subgrade moduli values, and it can be used as a quick subgrade strength evaluating tool for low volume roads.

关键词： Low volume road Lightweight deflectometer Backcalculated subgrade moduli Composite moduli of subgrade Static moduli of subgrade

A Study on the Effect of Low Calcium Ultra-fine Fly Ash as a Partial Sustainable Supplementary Material to Cement in Self-compacting Concrete

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Journal of Wuhan University of Technology(Materials Science) 2023年第2期38卷 330-341页

作者： Adapala sunny Suprakash Karthiyaini S School of Civil Engineering Vellore Institute of TechnologyChennaiTamil Nadu600127India

The aim and scope of the present study were to determine the efficacy of UFFA in evaluating the workability,static and dynamic stabilization properties,retention period,and slump loss of SCC systems in their fresh state,as well as their compressive strength at various ***(SEM and XRD)of blended SCC systems were ***,the thermogravimetry behavior of blended SCC specimens were *** to the evaluated results,incorporating up to 20%UFFA into fresh concrete improved its performance due to its engineered fine particle size and spherical geometry,both of which contribute to the enhancement of *** of 25%and 30%of UFFA show effect on the water-binder ratio and chemical enhancer dosage,resulting in a loss of homogeneity in fresh SCC *** reduced particle size,increased amorphous content,and increased surface area all contribute to the pozzolanic reactivity of the early and later ages,resulting in denser packing and thus an increase in compressive *** experimental results indicate that UFFA enhances the properties of SCC in both its fresh and hardened states,which can be attributed to the particles’fineness and their relative effect on SCC.

关键词： ultra fine fly ash self-compacting concrete workability segregation compressive strength microstructure TGA