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Estrogen receptor expression in chronic hepatitis C and hepatocellular carcinoma pathogenesis

World Journal of Gastroenterology 2017年第37期23卷 6802-6816页

作者： Janaki K Iyer Mamta Kalra Anil kaul Mark E Payton rashmi kaul Department of Biochemistry and Microbiology Oklahoma State University-Center for Health Sciences Department of Natural Sciences Northeastern State University Immatics US Inc Health Care Administration Oklahoma State University-Center for Health Sciences Department of Statistics Oklahoma State University

AIM To investigate gender-specific liver estrogen receptor(ER) expression in normal subjects and patients with hepatitis C virus(HCV)-related cirrhosis and hepatocellular carcinoma(HCC).METHODS Liver tissues from normal donors and patients diagnosed with HCV-related cirrhosis and HCV-related HCC were obtained from the NIH Liver Tissue and Cell Distribution System. The expression of ER subtypes, ERα and ERβ, were evaluated by Western blotting and real-time RT-PCR. The subcellular distribution of ERα and ERβ was further determined in nuclear and cytoplasmic tissue lysates along with the expression ofinflammatory [activated NF-κB and IκB-kinase(IKK)] and oncogenic(cyclin D1) markers by Western blotting and immunohistochemistry. The expression of ERα and ERβ was correlated with the expression of activated NF-κB, activated IKK and cyclin D1 by Spearman's correlation. RESULTS Both ER subtypes were expressed in normal livers but male livers showed significantly higher expression of ERα than females(P < 0.05). We observed significantly higher m RNA expression of ERα in HCV-related HCC liver tissues as compared to normals(P < 0.05) and ERβ in livers of HCV-related cirrhosis and HCV-related HCC subjects(P < 0.05). At the protein level, there was a significantly higher expression of nuclear ERα in livers of HCV-related HCC patients and nuclear ERβ in HCV-related cirrhosis patients as compared to normals(P < 0.05). Furthermore, we observed a significantly higher expression of phosphorylated NF-κB and cyclin D1 in diseased livers(P < 0.05). There was a positive correlation between the expression of nuclear ER subtypes and nuclear cyclin D1 and a negative correlation between cytoplasmic ER subtypes and cytoplasmic phosphorylated IKK in HCV-related HCC livers. These findings suggest that dysregulated expression of ER subtypes following chronic HCVinfection may contribute to the progression of HCVrelated cirrhosis to HCV-related *** Gender differences were observed in ER

关键词： Estrogen receptor α Estrogen receptor β Hepatitis C virus-related cirrhosis Hepatitis C virusrelated hepatocellular carcinoma Sex and gender Normal liver

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A comparative review of HLA associations with hepatitis Band C viral infections across global populations

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World Journal of Gastroenterology 2007年第12期13卷 1770-1787页

作者： rashmi Singh rashmi kaul Anil kaul Khalid Khan Department of Biochemistry and Microbiology Center of Health Sciences Oklahoma State University Tulsa OK 74107 United States Department of Pediatrics Division ofGastroenterology University of Minnesota United States

Hepatitis B （HBV） and hepatitis C （HCV） viral infection or co-infection leads to risk of development of chronic infection, cirrhosis and hepatocellular carcinoma （HCC）. Immigration and globalization have added to the challenges of public health concerns regarding chronic HBV and HCV infections worldwide. The aim of this study is to review existing global literature across ethnic populations on HBV and HCV related human leukocyte antigen （HLA） associations in relation to susceptibility, viral persistence and treatment. Extensive literature search was conducted to explore the HLA associations in HBV and HCV infections reported across global populations over the past decade to understand the knowledge status, weaknesses and strengths of this information in different ethnic populations. HLA DR13 is consistently associated with HBV clearance globally. HLADRB1＊11/＊12 alleles and DQB1＊0301 are associated with HBV persistence but with HCV clearance worldwide. Consistent association of DRB1＊03 and ＊07 is observed with HCV susceptibility and non-responsiveness to HBV vaccination across the population. HLA DR13 is protective for vertical HBV and HCV transmission in Chinese and Italian neonates, but different alleles are associated with their susceptibility in these populations. HLA class I molecule interactions with Killer cell immunoglobulin like receptors （KIR） of natural killer （NK） cells modulate HCV infection outcome via regulating immune regulatory cells and molecules. HLA associations with HBV vaccination, interferon therapy in HBV and HCV, and with extra hepatic manifestations of viral hepatitis are also discussed. Systematic studies in compliance with global regulatory standards are required to identify the HLA specific viral epitope, stage specific T cell populations interacting with different HLA alleles during disease progression and viral clearance of chronic HBV or HCV infections among different ethnic populations. These studies would facilitate stage specific th

关键词： Human leukocyte antigen HBV persistence HCV persistence Interferon response to HBV and HCV HBV vaccination response

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Unveiling the effect of estrogen receptors in alcoholic liver disease:A novel outlook

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Liver Research 2023年第4期7卷 333-341页

作者： Sukriti Baweja Ashmit Mittal Swati Thangariyal P.Debishree Subudhi Shivani Gautam rashmi kaul Department of Molecular and Cellular Medicine Institute of Liver and Biliary SciencesNew DelhiIndia Department of Biochemistry and Microbiology Oklahoma State University Center for Health SciencesTulsaOKUSA

Alcoholic liver disease(ALD)has a multifaceted development,progressing from alcoholic steatosis to alcoholic hepatitis and ultimately to alcoholic cirrhosis,irreversible liver damage that can even result in hepatocellular *** prevalence of ALD is increasing globally,particularly among middle-aged ***-based studies have revealed that ALD affects more men;however,disease progression differs between men and *** this,the molecular understanding of alcohol-induced liver injury among genders and its association with changes in sex hormone metabolism,particularly with estrogen and estrogen receptors(ERs)in ALD,remains *** review focuses on experimental and human studies describing alcohol and its association with estrogen metabolism and signaling via *** alcohol consumption affects the immune response,and whether estrogen has any contributory effect remains inadequately *** review also discusses various therapeutic approaches currently in use and future approaches that can affect the response or progression via estrogen *** role of gender on alcohol consumption and its association with steroid hormones must be elucidated for a better understanding of the pathogenesis of ALD,the development of effective therapeutic approaches,and better disease management in both men and women,as ALD remains a major public health concern.

关键词： Alcoholic liver disease(ALD) Estrogen Estrogen receptors(ERs) Inflammation Immune response Therapeutic target

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Role of sex steroid receptors in pathobiology of hepatocellular carcinoma

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World Journal of Gastroenterology 2008年第39期14卷 5945-5961页

作者： Mamta Kalra Jary Mayes Senait Assefa Anil K kaul rashmi kaul Department of Biochemistry and Microbiology Oklahoma State University Center for Health SciencesTulsaOklahoma 74107United States

The striking gender disparity observed in the incidence of hepatocellutar carcinoma （HCC） suggests an important role of sex hormones in HCC pathogenesis. Though the studies began as early as in 1980s, the precise role of sex hormones and the significance of their receptors in HCC still remain poorly understood and perhaps contribute to current controversies about the potential use of hormonal therapy in HCC. A comprehensive review of the existing literature revealed several shortcomings associated with the studies on estrogen receptor （ER） and androgen receptor （AR） in normal liver and HCC. These shortcomings include the use of less sensitive receptor ligand binding assays and immunohistochemistry studies for ERα alone until 1996 when ERβ isoform was identified. The animal models of HCC utilized for studies were primarily based on chemical-induced hepatocarcinogenesis with less similarity to virus-induced HCC pathogenesis. However, recent in vitro studies in hepatoma cells provide newer insights for hormonal regulation of key cellular processes including interaction of ER and AR with viral proteins. In light of the above facts, there is an urgent need for a detailed investigation of sex hormones and their receptors in normal liver and HCC. In this review, we systematically present the information currently available on androgens, estrogens and their receptors in normal liver and HCC obtained from in vitro, in vivo experimental models and clinical studies. This information will direct future basic and clinical research to bridge the gap in knowledge to explore the therapeutic potential of hormonal therapy in HCC.

关键词： Sex hormones Estrogen receptor Androgen receptor Hepatocellular carcinoma Hepatocarcinogenesis

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KarXT治疗精神分裂症患者的临床研究

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中国临床药理学杂志 2024年第3期40卷 439-439页

作者： kaul I 戴荣源

Xanomeline-trospium(KarXT)是将占诺美林与外周限制性毒蕈碱受体拮抗药曲司氯铵联合使用,其目的是改善与外周毒蕈碱受体相关的占诺美林相关不良事件。EMERGENT-2试验旨在评估KarXT对患有急性精神分裂症患者的疗效和安全性。

关键词：急性精神分裂症受体拮抗药疗效和安全性精神分裂症患者曲司氯铵毒蕈碱受体占诺美林相关不良事件

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Mortalin imaging in normal and cancer cells with quantum dot immuno conjugates

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Cell Research 2003年第6期13卷 503-507页

作者： ZEENIA kaul,TOMOKO YAGUCHI,SUNIL C kaul,TAKASHI HIRANO,RENU WADHWA,KAZUNARI TAIRA National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan National Institute of Advanced Industrial Science and Technology (AIST) 1-1-1 Higashi Tsukuba Ibaraki3058562 Japan

Quantum dots are the nanoparticles that are recently emerging as an alternative to organic fluorescence probes in cell biology and biomedicine, and have several predictive advantages. These include their i) broad absorption spectra allowing visualization with single light source, ii) exceptional photo-stability allowing long term studies and iii) narrow and symmetrical emission spectrum that is controlled by their size and material composition. These unique properties allow simultaneous excitation of different size of quantum dots with a single excitation light source, their simultaneous resolution and visualization as different colors. At present there are only a few studies that have tested quantum dots in cellular imaging. We describe here the use of quantum dots in mortalin imaging of normal and cancer cells. Mortalin staining pattern with quantum dots in both normal and cancer cells mimicked those obtained with organic florescence probes and were considerably stable.

关键词： quantum dots immunofluorescence mortalin visualization.

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A computational analysis of the impact of mass transport and shear on three-dimensional stem cell cultures in perfused micro-bioreactors

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Chinese Journal of Chemical Engineering 2016年第1期24卷 163-174页

作者： Himanshu kaul Yiannis Ventikos Zhanfeng Cui Institute of Biomedical Engineering Department of Engineering Science University of Oxford Old Road Campus Research Building Headington Oxford OX3 7DQ UK Department of Computer Science University of Sheffield Regent Court Sheffield S1 4DP UK Department of Mechanical Engineering University College London Torrington Place London WCIE 7JE UK

In this study, Computational Fluid Dynamics(CFD) is used to investigate and compare the impact of bioreactor parameters(such as its geometry, medium flow-rate, scaffold configuration) on the local transport phenomena and, hence, their impact on human mesenchymal stem cell(hM SC) expansion. The geometric characteristics of the TissueFlex174;(Zyoxel Limited, Oxford, UK) microbioreactor were considered to set up a virtual bioreactor containing alginate(in both slab and bead configuration) scaffolds. The bioreactor and scaffolds were seeded with cells that were modelled as glucose consuming entities. The widely used glucose medium, Dulbecco's Modified Eagle Medium(DMEM), supplied at two inlet flow rates of 25 and 100 μl·h^(-1), was modelled as the fluid phase inside the bioreactors. The investigation, based on applying dimensional analysis to this problem, as well as on detailed three-dimensional transient CFD results, revealed that the default bioreactor design and boundary conditions led to internal and external glucose transport, as well as shear stresses, that are conducive to h MSC growth and expansion. Furthermore, results indicated that the ‘top-inout' design(as opposed to its symmetric counterpart) led to higher shear stress for the same media inlet rate(25 μl·h^(-1)), a feature that can be easily exploited to induce shear-dependent differentiation. These findings further confirm the suitability of CFD as a robust design tool.

关键词： Alginate scaffolds Bioreactors Fluid mechanics Dimensionless quantities Mass transfer Modelling Perfusion

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Clinical efficacy of the over-the-scope clip device: A systematic review

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World Journal of Gastroenterology 2020年第24期26卷 3495-3516页

作者： Nicholas Bartell Krystle Bittner Vivek kaul Truptesh H Kothari Shivangi Kothari Division of Gastroenterology and Hepatology University of Rochester Medical CenterRochesterNY 14642United States

BACKGROUND The over-the-scope clip(OTSC)system has been increasingly utilized as a nonsurgical option to endoscopically manage refractory gastrointestinal(GI)hemorrhage,perforations/luminal defects and *** data exist evaluating the efficacy and safety of *** To determine the clinical success and adverse event(AE)rates of OTSC across all GI *** A PubMed search was conducted for eligible articles describing the application of the OTSC system for any indication in the GI *** article or case series reporting data for less than 5 total patients was *** primary outcome was the rate of clinical *** outcomes included:Technical success rate,OTSC-related AE rate and requirement for surgical intervention despite-OTSC *** rates(per-indication and overall)were calculated as the number of patients with the event of interest divided by the total number of *** A total of 85 articles met our inclusion criteria(n=3025 patients).OTSC was successfully deployed in 94.4%of patients(n=2856/3025).The overall rate of clinical success(all indications)was 78.4%(n=2371/3025).Per-indication clinical success rates were as follows:(1)86.0%(1120/1303)for GI hemorrhage;(2)85.3%(399/468)for perforation;(3)55.8%(347/622)for fistulae;(4)72.6%(284/391)for anastomotic leaks;(5)92.8%(205/221)for defect closure following endoscopic resection(e.g.,following endoscopic mucosal resection or endoscopic submucosal dissection);and(6)80.0%(16/20)for stent ***’s related to the deployment of OTSC were only reported in 64 of 85 studies(n=1942 patients),with an overall AE rate of 2.1%(n=40/1942).Salvage surgical intervention was required in 4.7%of patients(n=143/3025).CONCLUSION This systematic review demonstrates that the OTSC system is a safe and effective endoscopic therapy to manage GI hemorrhage,perforations,anastomotic leaks,defects created by endoscopic resections and for stent *** success in fistula

关键词： Over-the-scope clip Hemostasis Perforation Fistula closure Endoscopic resection Anastomotic leak Ovesco Endoscopy

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Ionic liquid passivated black phosphorus for stabilized compliant electronics

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Nano Research 2023年第5期16卷 7858-7866页

作者： Ravindra Mehta Misook Min Ridwan F.Hossain Gustavo A.Saenz Gerardo Gamboa Anupama B.kaul Department of Materials Science and Engineering PACCAR Technology InstituteUniversity of North TexasDentonTX 76207USA Department of Electrical Engineering University of North TexasDentonTX 76207USA

Black phosphorus(BP)is an attractive material for two-dimensional(2D)electronics and optoelectronics given its direct optical band gap in the ***,the vulnerability of BP to oxygen and moisture under ambient conditions has been a significant impediment for the adoption of this material towards practical *** vulnerability has also curtailed the development of additively manufactured,solution processed,ink-jet printed BP devices,which are cost-effective alternatives to lithographically patterned rigid electronics and optoelectronics based on *** this work,we have fabricated stable BP electronic devices on flexible and compliant substrates using low-cost,additive manufacturing techniques with ink-jet printing through scalable chemical exfoliation *** address the stability issues with BP,ionic liquids(ILs)were used as a passivation layer on the surface of the BP to minimize oxidative *** enhanced stability of BP was inferred through Raman spectroscopy and scanning probe microscopy techniques,where no observable changes in the A^(1)_(g)and A^(2)_(g)Raman vibrational modes were observed with time for the BP films passivated with ILs over a period of 168 h under ambient *** the other hand,a blue-shift in these Raman modes was evident for unpassivated *** probe microscopy measurements clearly revealed the difference in the surface characteristics through localized regions of degradation that intensified with time,which was clearly absent in IL/BP *** stability measurements were also conducted in electronic device platforms for IL coated BP devices,where the temperature T dependence of the I_(ds)-V_(ds)characteristic was measured from T~5.4 to 335 *** demonstrations of stabilized ILs/BP devices at ambient printed on flexible polyimide substrates were also *** irradiation with broadband radiation appears to have a significant influence on the electrical behavior of BP,evident through t

关键词： 2D materials black phosphorus ionic liquids ink-jet printing flexible electronics

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Phytochemical profiling and biological activity of Plectranthus amboinicus(Lour.) mediated by various solvent extracts against Aedes aegypti larvae and toxicity evaluation

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Asian Pacific Journal of Tropical Medicine 2020年第11期13卷 494-502页

作者： Deepak Paramasivam Balamuralikrishnan Balasubramanian Sungkwon Park Palanisamy Alagappan Tanushri kaul Wenchao Liu Perumal Pachiappan Department of Biotechnology School of BiosciencesPeriyar UniversitySalemTamil Nadu-636011India Department of Biotechnology Rathnavel Subramaniam College of Arts and ScienceSulur-641402Tamil NaduIndia Department of Food Science and Biotechnology College of Life ScienceSejong UniversitySeoul-05006South Korea Nutritional Improvement of Crops International Centre for Genetic Engineering and BiotechnologyAruna Asaf Ali MargNew Delhi 110067India Department of Animal Science College of AgricultureGuangdong Ocean UniversityZhanjiangGuangdong 524088China Department of Marine Science School of Marine SciencesBharathidasan UniversityTiruchirappalli-620024Tamil NaduIndia

Objective:To analyze the phytochemical compounds and to investigate the bio-toxic efficacy of various solvent extracts of Plectranthus amboinicus against mosquito larvae activity and lethality on non-targeting ***:The methanol,ethyl acetate,hexane,and aqueous extracts of Plectranthus amboinicus were subjected to analyze the mosquitocidal activity against the dengue vector,Aedes aegypti and toxicity assays on zebra fish and brine *** replications were performed,and negative control was also ***,ethyl acetate extract of Plectranthus amboinicus was chosen for the determination of bio-active ***:The mosquitocidal assays of methanol and ethyl acetate extracts of Plectranthus amboinicus showed the maximal activity with minimal concentration against the 4 th instar mosquito-larvae of Aedes aegypti through the following lethal concentration(LC50 and LC90)values:53.36&92.51μg/m L and 13.64&86.09μg/mL,*** addition,the plant extracts showed no toxicity on zebra fish embryo and brine shrimp *** gas-chromatography analysis of the ethyl acetate extract of Plectranthus amboinicus revealed the presence of seven different *** them,PAEA-fraction 60 contained a major active bioactive compound,hexadecanoic acid,methyl ester(270.0).Conclusions:Plectranthus amboinicus possesses mosquitocidal properties and could be used as a potential alternative source for preparing the mosquitocidal agents.

关键词： Plectranthus amboinicus Cold percolation Indian borage Mosquitocidal

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