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Identification of lineariifolianoid A as a novel dual NFAT1 and MDM2 inhibitor for human cancer therapy

The Journal of Biomedical Research 2016年第4期30卷 322-333页

作者： Jiang-Jiang Qin Sushanta Sarkar Sukesh Voruganti Rajesh agarwal Wei Wang Ruiwen Zhang Department of pharmaceutical Sciences Texas Tech University Health Sciences CenterAmarilloTX 79106USA Cancer Biology Center School of PharmacyTexas Tech University Health Sciences CenterAmarilloTX 79106USA Department of pharmaceutical Sciences Skaggs School of Pharmacy and Pharmaceutical Sciences University of Colorado Cancer Center University of Colorado DenverAuroraCO 80045USA

There is an increasing interest in development of novel anticancer agents that target oncogenes. We have recently discovered that nuclear factor of activated T cells 1 （NFAT1） is a novel regulator of the Mouse Double Minute 2 （MDM2） oncogene and the NFAT1-MDM2 pathway has been implicated in human cancer development and pro- gression, justifying that targeting the NFAT1-MDM2 pathway could be a novel strategy for discovery and develop- ment of novel cancer therapeutics. The present study was designed to examine the anticancer activity and underlying mechanisms of action of lineariifolianoid A （LinA）, a novel natural product inhibitor of the NFAT 1-MDM2 pathway. The cytotoxicity of LinA was first tested in various human cancer cell lines in comparison with normal cell lines. The results showed that the breast cancer cells were highly sensitive to LinA treatment. We next demonstrated the effects of LinA on cell proliferation, colony formation, cell cycle progression, and apoptosis in breast cancer MCF7 and MDA-MB-231 cells, in dose-dependent and p53-independent manners. LinA also inhibited the migration and invasion of these cancer cells. Our mechanistic studies further indicated that its anticancer activities were attributed to its inhibitory effects on the NFAT 1-MDM2 pathway and modulatory effects on the expression of key proteins involved in cell cycle progression, apoptosis, and DNA damage. In summary, LinA is a novel NFAT 1-MDM2 inhib- itor and may be developed as a preventive and therapeutic agent against human cancer.

关键词： lineariifolianoid A NFAT1 MDM2 breast cancer p53 apoptosis

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Assessing the Effect of Disease progression on Spirituality

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psychology Research 2012年第12期2卷 729-736页

作者： Siddharth agarwal Vijai Kumar preetvanti Singh p. K. Saxena Saran Ashram Hospital Siddharth Hospital Agra India Saran Ashram Hospital Agra India Dayalbagh Educational Institute DeemedUniversity Agra India Dayalbagh Educational Institute Agra India

Disease and sufferings lead religious persons nearer to almighty in search of mercy. Not much is known about how to design and disseminate programs of spiritual exercises and spiritual indicators for persons suffering with some disease (sufferers). Research is required to advance the understanding of prioritized internal and external indicators responsible for spiritual awakening among these sufferers. In this paper, an attempt is made to compute OFDp (overall futuristic decision priority) weights to generate spiritual scenarios for spiritual awakening by using MCFDM (multi-criteria futuristic decision-making) methodology. The generated prioritized spiritual scenarios responsible for spiritual awakening among sufferers were then used to assess the effect of some kind of disease (physical problem, suffering, disorder, etc.) on strengthening their religious faith and defining their optimal spiritual trajectories towards ultimate reality. In this research work, a two-phased DRFI (disease-religious faith-interaction) experiment is also designed and developed. The results derived from phase-I pilot research study based on prioritized spiritual scenarios on 20 male and female sufferers are also presented.

关键词：疾病评估宗教信仰实验设计多准则决策优先级指标方案未来主义

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Female Sex Workers and Their Association with Self-Help Groups in Thane, Maharashtra, India: A Comparative Analysis in the Context of HIV program Outcome

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World Journal of AIDS 2016年第4期6卷 186-196页

作者： Awdhesh Yadav Saravanamurthy p. Sakthivel Shaikh Tayyaba Uma Shah Ashok agarwal public Health Foundation of India New Delhi India

Objectives: Understanding the role of Self-Help Group (SHG) in light of the evolving dynamics of sex work needs to be delved into to strategize HIV interventions among FSWs in India. This paper aims to study the HIV program outcome among the FSWs associated with SHGs and FSWs not associated with SHGs in Thane, Maharashtra. Study Design: This cross-sectional study was undertaken from the Behavioral Tracking Survey (BTS) conducted among 503 FSWs in Thane in 2015. Two-stage probability based conventional sampling was done for selection of brothel and bar based FSWs, while Time Location Cluster (TLC) sampling was done for home, lodge and street based sex workers. Methods: Bivariate and multivariate logistic regression were performed to compare and contrast between FSWs associated with SHG and those not associated with SHG with respect to the utilization of HIV related services by them. “Condom use”, “consistent condom use”, “contact with peer-educators”, “counseling sessions” and “HIV testing” were chosen as indicators on HIV service utilization. Results: 8% (38) of FSWs are registered with SHG;92% aged ≥25 years, 47% illiterate, and 71% are currently married. The likelihood of utilizing HIV services including, knowledge on HIV/AIDS and its mode of transmission (OR: 5.54;CI: 1.87 - 16.60;p Conclusions: Considering the improved HIV program outcomes among FSWs associated with SHG, HIV interventions among FSWs could consider facilitating the formation of SHGs with FSWs as one of the key strategies to empower the community for ensuring better program outcomes.

关键词： Female Sex Workers Self-Help Group HIV Thane Empowerment

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Green tea extract as a cryoprotectant additive to preserve the motility and DNA integrity of human spermatozoa

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Asian Journal of Andrology 2021年第2期23卷 150-156页

作者： Odai AM Alqawasmeh Mingpeng Zhao Carol pS Chan Maran BW Leung Ki C Chow Nikunj agarwal Jennifer SM Mak Chi C Wang Chi p pang Tin C Li Wai K Chu David YL Chan Assisted Reproductive Technology Unit Department of Obstetrics and GynaecologyFaculty of MedicineThe Chinese University of Hong KongHong KongChina Department of Ophthalmology and Visual Sciences The Chinese University of Hong KongHong KongChina

Cryopreservation impairs sperm quality and functions,including motility and DNA *** additives in sperm freezing media have previously brought improvements in postthawed sperm *** tea extract(GTE)is widely considered as an excellent antioxidant,and its beneficial role has been proven in other human *** study aims to evaluate the GTE as a potential additive in cryopreservation media of human *** part one,the semen of 20 normozoospermic men was used to optimize the concentration of GTE that maintains sperm motility and DNA integrity against oxidative stress,induced by hydrogen peroxide(H_(2)O_(2)).Spermatozoa were treated with GTE at different concentrations before incubation with H_(2)O_(2).In part two,the semen of 45 patients was cryopreserved with or without 1.0 ng ml^(-1)*** 2 weeks,the semen was thawed,and the effect on sperm motility and DNA fragmentation was *** data showed that GTE significantly protected sperm motility and DNA integrity against oxidative stress induced by H_(2)O_(2)when added at a final concentration of 1.0 ng ml^(-1).We found that the addition of 1.0 ng ml^(-1)GTE to cryopreservation media significantly increased sperm motility and DNA integrity(both ppatients with high sperm DNA damage benefited similarly from the GTE ***,there was no significant change in the reactive oxygen species(ROS)*** conclusion,supplementing sperm freezing media with GTE has a significant protective effect on human sperm motility and DNA integrity,which may be of clinical interest.

关键词： antioxidants cryopreservation additives sperm cryopreservation sperm DNA fragmentation sperm motility

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Risk factors of COVID-19 infection among policemen: A case-control study

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Journal of Acute Disease 2020年第6期9卷 263-269页

作者： Neeraj agarwal Bijit Biswas Department of Community and Family Medicine All India Institute of Medical SciencesPatnaBiharIndia

Objective:To investigate the risk factors and protective measures of COVID-19 among policemen in an eastern state of ***:This case-control study was conducted in Bihar,located in the eastern part of *** total,6 confirmed COVID-19 cases(the case group)and 11 negative contacts of these cases(the control group)of Bihar Military police participated in the ***:All subjects were male with a median age of 51(range:23-60)*** these 6 confirmed cases,5 cases were *** third(33.3%)of the case group and the majority(90.9%)of the control group reported maintenance of physical distance of at least 1 meter with others all the time,which was significantly different(p=0.028).There was no other statistically significant difference between the case group and the control ***:physical distancing is the most effective public health measure to control contagious diseases like COVID-19,especially in the absence of an effective vaccine in police settings.

关键词： COVID-19 police Epidemiology Risk factors protective factors

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Cardioprotective activity of alcoholic extract of Tinospora cordifolia (Willd.) Miers in calcium chloride-induced cardiac arrhythmia in rats

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The Journal of Biomedical Research 2011年第4期25卷 280-286页

作者： Ashish Kumar Sharma Kunal Kishore Divya Sharma B.p Srinivasan Shyam Sunder agarwal Ashok Sharma Santosh Kumar Singh Samir Gaur Vijay Singh Jatav Department of pharmacology Gyan Vihar School of PharmacySuresh Gyan Vihar UniversityJagatpuraJaipur (Rajasthan)302025India Delhi Institute of pharmaceutical Sciences & Research Department of PharmacologyPushpviharSector Ⅲ.New Delhi 110017India

The present study investigated the antiarrhythmic activity of alcoholic extract of Tinospora cordifolia （T. cordifolia） in CaCl2 induced arrhythmia. CaCl2 （25 mg/kg） was administered by intravenous infusion （iv） to produce arrhythmia in rats. The animals were then treated with T. cordifolia extract （150, 250, and 450 mg/kg） and verapamil （5 mg/kg,iv）. Lead II electrocardiogram was monitored. plasma calcium, sodium and potassium levels were measured. In CaCl2 induced arrhythmia, heart rate was decreased by 41.10%, T. cordifolia at 150, 300, and 450 mg/kg decreased the heart rate by 26.30%, 29.16%, and 38.29%, respectively, and verapamil reduced the heart rate by 9.70% compared to the normal group. The pQRST waves were normalized and atrial and ventricular fibrillation was controlled in rats treated with verapamil and T. cordifolia. CaCl2 increased calcium and sodium levels and decreased potassium levels in blood. T. cordifolia dose-dependently decreased calcium and sodium levels and increased potassium levels. Hence, T. cordifolia can be used in antiarrhythmic clinical settings and beneficial in atrial and ventricular fibrillation and flutter and may be indicated in ventricular tachyarrhythmia.

关键词： Tinospora cordifolia arrhythmia cardioprotection.

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Correlation between tear fluid and serum vitamin D levels

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Eye and Vision 2016年第1期3卷 178-182页

作者： Swaminathan Sethu Rohit Shetty Kalyani Deshpande Natasha pahuja Nandini Chinnappaiah Aarti agarwal Anupam Sharma Arkasubhra Ghosh GROW Research Laboratory Narayana Nethralaya Foundation#258/A Hosur RoadNarayana Health CityBommasandra560099 BangaloreIndia Cornea and Refractive Surgery Division Narayana NethralayaBangaloreIndia

Background:Vitamin D deficiency is associated with a range of systemic diseases including ocular *** objective of this study is to measure tear vitamin D levels and investigate the correlation between serum and tear vitamin D ***:A total of 48 healthy volunteers without any systemic and ocular disease were recruited for this observational cohort *** was collected using clot activator coated Vacutainer®plus *** fluid was collected using Schirmer’s *** and tear total 25-hydroxyvitamin D levels were measured by competitive chemiluminescent ELISA and the correlation between the levels were ***:The measured serum 25-hydroxyvitamin D level ranged between 3.3 and 27.5 ng/ml(Mean±SEM,9.4±0.7 ng/ml;Median 8.4 ng/ml).Significantly(ppared to *** average of~2 fold(Mean±SEM,1.9±0.2;Range 0.4–5.8;Median,1.7)higher 25-hydroxyvitamin D was observed in tears compared to serum in the *** addition,a positive correlation was observed between serum and tear 25-hydroxyvitamin D levels(r=0.5595;ppared to that of the *** would be beneficial to consider tear vitamin D levels to study its role with reference to ocular surface diseases.

关键词： Vitamin D 25-hydroxyvitamin D 1,25-dihydroxyvitamin D Tears Serum

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Gastroenteropancreatic neuroendocrine neoplasms:A clinical snapshot

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World Journal of Gastrointestinal Surgery 2021年第3期13卷 231-255页

作者： Cornelius J Fernandez Mayuri agarwal Biju pottakkat Nisha Nigil Haroon Annu Susan George Joseph Mpappachan Department of Endocrinology and Metabolism Pilgrim HospitalUnited Lincolnshire Hospitals NHS TrustBoston PE219QSUnited Kingdom Department of Surgical Gastroenterology Jawaharlal Institute of Post Graduate Medical Education and Research(JIPMER)Puducherry 605006India Department of Endocrinology and Internal Medicine Northern Ontario School of MedicineSudbury P3E 2C6OntarioCanada Department of Medical Oncology VPS Lakeshore HospitalCochin 682040KeralaIndia Department of Endocrinology and Metabolism Lancashire Teaching Hospitals NHS TrustPR29HTPrestonThe University of ManchesterOxford Road M139PLManchester Metropolitan UniversityAll Saints Building M156BHManchesterUnited Kingdom.

Our understanding about the epidemiological aspects,pathogenesis,molecular diagnosis,and targeted therapies of neuroendocrine neoplasms(NENs)have drastically advanced in the past ***(GEp)NENs originate from the enteroendocrine cells of the embryonic gut which share common endocrine and neural differentiation *** NENs are welldifferentiated,and slow *** neuroendocrine biomarkers that are used in the diagnosis of functional NENs include insulin,glucagon,vasoactive intestinal polypeptide,gastrin,somatostatin,adrenocorticotropin,growth hormone releasing hormone,parathyroid hormone-related peptide,serotonin,histamine,and 5-hydroxy indole acetic acid(5-HIAA).Biomarkers such as pancreatic polypeptide,human chorionic gonadotrophin subunits,neurotensin,ghrelin,and calcitonin are used in the diagnosis of non-functional NENs.5-HIAA levels correlate with tumour burden,prognosis and development of carcinoid heart disease and mesenteric fibrosis,however several diseases,medications and edible products can falsely elevate the 5-HIAA ***-specific transcription factors are useful in the differential diagnosis of metastasis from an unknown primary of well-differentiated *** novel biomarkers include circulating tumour cells,circulating tumour DNA,circulating micro-RNAs,and neuroendocrine neoplasms test(NETest)(simultaneous measurement of 51 neuroendocrine-specific marker genes in the peripheral blood).NETest has high sensitivity(85%-98%)and specificity(93%-97%)for the detection of gastrointestinal NENs,and is useful for monitoring treatment response,recurrence,and *** terms of management,surgery,radiofrequency ablation,symptom control with medications,chemotherapy and molecular targeted therapies are all considered as *** is the mainstay of treatment,but depends on factors including age of the individual,location,stage,grade,functional status,and the heredity of the tumour(sporadic vs inherited).Me

关键词： Gastroenteropancreatic neuroendocrine neoplasms Neuroendocrine tumours Neuroendocrine carcinoma Targeted molecular therapy Octreoscan Chemotherapy

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Link between Friesinger Index and Lipid profile in patients Undergoing Diagnostic Coronary Angiography

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International Journal of Clinical Medicine 2015年第8期6卷 538-546页

作者： Deepesh agarwal Ramanand p. Sinha Ram Mohan Jaiswal Nikhil pursnani Nirlep Gajiwala Ashok Thakkar Mahatma Gandhi Cardiac and Critical Care Center Jaipur India Sahajanand Medical Technologies pvt. Ltd. Surat India

Background: A strong association between abnormal lipid variables and development of atherosclerosis is widely established. However, few data exist on the association between lipid levels and the extent or severity of coronary lesions in patients with coronary artery disease. Objective: We aimed to determine the link between lipid levels and the extent or severity of coronary lesions in patients with suspected coronary artery disease using Friesinger index (FR). Methodology: In this prospective and singe-center study, consecutive patients who underwent coronary angiography for diagnostic purposes were analyzed. Each participant was evaluated for lipid levels i.e. total cholesterol, triglycerides, high-density lipoprotein (HDL) cholesterol, low-density lipoprotein (LDL) cholesterol, very-low-density lipoprotein (VLDL) cholesterol, non-HDL cholesterol, triglycerides/ HDL cholesterol, and triglycerides/non-HDL cholesterol. The extent of coronary disease was evaluated using FR index. Results: A total of 566 patients (mean age: 56.17 ± 9.99 years) were included in the study. The mean FR index was 5.40 ± 3.78. A significantly positive correlation was observed between FR index and total cholesterol (p = 0.002), triglycerides (p p p = 0.006), triglycerides/HDL cholesterol ratio (p = 0.008), and triglycerides/non-HDL cholesterol ratio (p = 0.002). On the contrary, an inverse correlation was observed between FR index and HDL cholesterol (p played no role in governing the FR index severity, while body-mass index, hypertension, diabetes, and smoking showed significant association with FR index (p present study demonstrates a significant link between the extent of coronary artery disease and levels of certain lipid variables.

关键词： Cholesterol Coronary Angiography Coronary Artery Disease Friesinger Index Lipid profile Triglyceride

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<i>In-Silico</i>Validation and Development of Chlorogenic Acid (CGA) Loaded polymeric Nanoparticle for Targeting Neurodegenerative Disorders

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Journal of Biomaterials and Nanobiotechnology 2020年第4期11卷 279-303页

作者： Vinayak agarwal Shriya agarwal Ramneek Kaur pranav pancham Harleen Kaur Siddhi Bhardwaj Manisha Singh Department of Biotechnology Jaypee Institute of Information Technology (JIIT) Noida U.P. India School of Medicine Western Sydney University Campbelltown New South Wales Australia Amity Institute of Biotechnology Amity University Noida U.P. India

Background: Recent decades witnessed a significant growth in terms of phytocompounds based therapeutics, extensively explored for almost all types of existing disorders. They have also been widely investigated in Neurodegenerative disorders (NDDs) and Chlorogenic acid (CGA), a polyphenolic compound having potential anti-inflammatory and anti-oxidative properties, emerged as a promising compound in ameliorating NDDs. Owing to its poor stability, bioavailability and release kinetics, CGA needed a suitable nanocarrier based pharmaceutical design for targeting NDDs. Objective: The current study is aimed at the in-silico validation of CGA as an effective therapeutic agent targeting various NDDs followed by the fabrication of polymeric nanoparticles-based carrier system to overcome its pharmacological limitations and improve its stability. Methods: A successful in-silico validation using molecular docking techniques along with synthesis of CGA loaded polymeric nanoparticles (CGA-Nps) by ionic gelation method was performed. The statistical optimisation of the developed CGA-Nps was done by Box Behnken method and then the optimized formulation of CGA-Nps was characterised using particle size analysis (pSA), Transmission electron microscopy (TEM), Fourier Transform Infrared spectroscopy (FTIR) along with in-vitro release kinetics analysis. Results & Conclusion: The results attained exhibited average particle size of 101.9 ± 1.5 nm, polydispersibility (pDI) score of 0.065 and a Zp of −17.4 mV. On a similar note, TEM results showed a size range of CGA-Nps between 90 - 110 nm with a spherical shape of Nps. Also, the data from in-vitro release kinetics showed a sustained release of CGA from the Nps following the first-order kinetics suggesting the appropriate designing of nanoformulation.

关键词： Antioxidant Anti-Inflammatory polymeric Nanoparticles Release Kinetics Box Behnken Design Molecular Docking particle Size Analysis

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