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Role of prostate cancer stem-like cells in the development of antiandrogen resistance

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Cancer Drug Resistance 2022年第2期5卷 459-471页

作者： prem prakash kushwaha Shiv Verma Shashank Kumar Sanjay Gupta Department of Urology Case Western Reserve UniversityClevelandOH 44106USA. The Urology Institute University Hospitals Cleveland Medical CenterClevelandOH 44106USA. Molecular Signaling and Drug Discovery Laboratory Department of BiochemistryCentral University of PunjabBathinda 151401India. Department of Pathology Case Western Reserve UniversityClevelandOH 44106USA. Department of Pharmacology Case Western Reserve UniversityClevelandOH 44106USA. Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA. Divison of General Medical Sciences Case Comprehensive Cancer CenterClevelandOH 44106USA.

Androgen deprivation therapy(ADT)is the standard of care treatment for advance stage prostate *** with ADT develops resistance in multiple ways leading to the development of castration-resistant prostate cancer(CRPC).Present research establishes that prostate cancer stem-like cells(CSCs)play a central role in the development of treatment resistance followed by disease *** CSCs are capable of self-renewal,differentiation,and regenerating tumor *** stemness properties in prostate CSCs arise due to various factors such as androgen receptor mutation and variants,epigenetic and genetic modifications leading to alteration in the tumor microenvironment,changes in ATP-binding cassette(ABC)transporters,and adaptations in molecular signaling *** reprograms prostate tumor cellular machinery leading to the expression of various stem cell markers such as Aldehyde Dehydrogenase 1 Family Member A1(ALDH1A1),Prominin 1(PROM1/CD133),Indian blood group(CD44),SRY-Box Transcription Factor 2(Sox2),POU Class 5 Homeobox 1(POU5F1/Oct4),Nanog and ABC *** markers indicate enhanced self-renewal and stemness stimulating CRPC evolution,metastatic colonization,and resistance to *** this review,we discuss the role of ADT in prostate CSCs differentiation and acquisition of CRPC,their isolation,identification and characterization,as well as the factors and pathways contributing to CSCs expansion and therapeutic opportunities.

关键词： Prostate cancer second-generation antiandrogens cancer stem cells castration resistance prostate cancer androgen deprivation therapy

Bulbine frutescens phytochemicals as novel ABC-transporter inhibitor:a molecular docking and molecular dynamics simulation study

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Journal of Cancer Metastasis and Treatment 2021年第1期7卷 20-32页

作者： prem prakash kushwaha Santosh Kumar Maurya Amit Singh Kumari Sunita Prajapati Atul Kumar Singh Mohd Shuaib Shashank Kumar Molecular Signaling&Drug Discovery Laboratory Department of BiochemistryCentral University of PunjabBathinda 151401India Department of Computational Sciences Central University of PunjabBathinda 151401India.

Aim:The present in silico study aimed to evaluate the ATP-binding cassette(ABC)transporter inhibition potential of Bulbine frutescens(***)***:Several previous studies and databases were used to retrieve the ligands and target protein *** molecular docking study was performed using the Auto Dock Tools,and the GROMACS package was applied to accomplish molecular dynamics ***:Utilizing the molecular docking and simulation approach,~25 phytochemicals were screened against the ABC transporter *** score analysis revealed that *** phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside exhibited strong binding on the ABC transporter protein with a minimum binding score-9.8 kcal/mol in comparison to the standard ABC transporter inhibitor diltiazem(-6.86 kcal/mol).Furthermore,molecular dynamics simulation for 4’-Demethylknipholone 2’-β-D-glucopyranoside showed an acceptable root mean square deviation,radius of gyration,root mean square fluctuation,and hydrogen bond,in addition to other lead ***:The in-silico study demonstrated that *** phytochemical 4’-Demethylknipholone 2’-β-D-glucopyranoside possesses anti-drug resistance properties and requires further testing in preclinical settings.

关键词： Cancer drug resistance ABC-transporter natural inhibitors Bulbine frutescens MM-GBSA

Resistance to second generation antiandrogens in prostate cancer: pathways and mechanisms

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Cancer Drug Resistance 2020年第4期3卷 742-761页

作者： Shiv Verma Kumari Sunita Prajapati prem prakash kushwaha Mohd Shuaib Atul Kumar Singh Shashank Kumar Sanjay Gupta Department of Urology Case Western Reserve UniversityClevelandOH 44106USA The Urology Institute University Hospitals Cleveland Medical CenterClevelandOH 44106USA School of Basic and Applied Sciences Department of Biochemistry and Microbial SciencesCentral University of PunjabBathinda 151001India Department of Nutrition Case Western Reserve UniversityClevelandOH 44106USA Divison of General Medical Sciences Case Comprehensive Cancer CenterClevelandOH 44106USA Department of Urology Louis Stokes Cleveland Veterans Affairs Medical CenterClevelandOH 44106USA

Androgen deprivation therapy targeting the androgens/androgen receptor(AR)signaling continues to be the mainstay treatment of advanced-stage prostate *** use of second-generation antiandrogens,such as abiraterone acetate and enzalutamide,has improved the survival of prostate cancer patients;however,a majority of these patients progress to castration-resistant prostate cancer(CRPC).The mechanisms of resistance to antiandrogen treatments are complex,including specific mutations,alternative splicing,and amplification of oncogenic proteins resulting in dysregulation of various signaling *** this review,we focus on the major mechanisms of acquired resistance to second generation antiandrogens,including AR-dependent and AR-independent resistance mechanisms as well as other resistance mechanisms leading to CRPC *** knowledge of resistance mechanisms to AR targeted treatments will lead to additional research on designing more effective therapies for advanced-stage prostate cancer.

关键词： Prostate cancer second-generation antiandrogens androgen receptor castration resistance prostate cancer

Proximate Composition,Mineral Content and Fatty Acids Analyses of Aromatic and Non-Aromatic Indian Rice

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Rice science 2017年第1期24卷 21-31页

作者： Deepak Kumar VERMA prem prakash SRIVASTAV Agricultural and Food Engineering Department Indian Institute of TechnologyKharagpur 721302India

Awareness on nutritive value and health benefits of rice is of vital importance in order to increase the consumption of rice in daily diet of the human beings. In this study, a total of six aromatic and two non-aromatic rice accessions grown in India were analysed for their nutritional quality attributes including proximate composition, mineral contents and fatty acids. Data with three replications were used to measure Pearson＇s simple correlation co-efficient in order to establish the relationship among various nutritional quality attributes. The result on proximate composition showed that Govind Bhog had the highest moisture（13.57%） and fat（0.92%） content, which signifies its tasty attribute. Badshah Bhog exhibited the highest fibre content（0.85%）, carbohydrate content（82.70%） and food energy（365.23 k Cal per 100 g）. Among the minerals, the higher Ca（98.75 mg/kg）, Zn（17.00 mg/kg） and Fe（31.50 mg/kg） were in Gopal Bhog, whereas the highest Na（68.85 mg/kg） was in Badshah Bhog, the highest K（500.00 mg/kg） was in Swetganga, Khushboo and Sarbati. The highest contents of unsaturated fatty acids viz. oleic acid（49.14%）, linoleic acid（46.99%） and linolenic acid（1.27%） were found in Sarbati, whereas the highest content of saturated fatty acids viz. myristic acid（4.60%） and palmitic acid（31.91%） were found in Govind Bhog and stearic acid（6.47%） in Todal. The identified aromatic rice accessions Gopal Bhog, Govind Bhog and Badshah Bhog and non-aromatic rice accession Sarbati were found nutritionally superior among all eight tested accessions. The nutritional quality oriented attributes in this study were competent with recognized prominent aromatic and non-aromatic rice accessions as an index of their nutritional worth and recommend to farmers and consumers which may be graded as export quality rice with good unique nutritional values in international market.

关键词： aromatic unsaturated nutritional proximate accession carbohydrate oleic vital competent attribute

Assessing anthropogenic pressure and threats on Paeonia emodi *** Royle habitats in Garhwal Himalaya

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Journal of Mountain Science 2023年第3期20卷 810-820页

作者： Praveen JOSHI prem prakash Vijay Kant PUROHIT Department of Botany Govt.M.B.P.G.CollegeHaldwani 263641Indial High Altitude Plant Physiology Research Centre H.N.B.Garhwal Central UniversitySrinagar Garhwal 263671India

The Garhwal Himalaya is among the major repositories of immensely valuable wild edible plants and provides food security to the local *** the valuable plant species that grow in this region,Paeonia emodi(family Paeoniaceae)is an important wild edible species that found in temperate regions with an altitude range between 1800 and 2800 *** species is facing a severe threat to its sustainability due to overharvesting,habitat disturbances,and a lack of effort regarding *** the first time,this study investigated anthropogenic pressure,population decline perceptions in the natural habitat,and vulnerability assessment of *** under selected study sites(n=23 villages).A semi structured questionnaire was used to interview approximately 45%of the local inhabitants,including herbal practitioners(Vaidhyas or Dais)of each *** the basis of demographic characteristics,the perceptions and responses of 464 local people were documented regarding potential causes of deterioration and feasible options for sustainable *** the weight survey method,we estimated the actual amount of collection based on personal interaction and direct *** order to determine the threats status,a rapid vulnerability assessment(RVA)was performed and were used based on the current exploitation and *** present study revealed that leaf(100%)was the most frequently harvested part,followed by stem(95.65%),seed(26.09%),root(21.74%)and flower(13.04%).The village Triyuginarayan and Pothivasa recorded the highest collection scores while the purpose of the collection was mostly edible(100%),medicinal(100%),and least commercial(8.70%).According to the literature review and the present survey,the RVA(total=21)is categorized as category II(intermediate side of the RVA index),indicating a degree of *** study revealed that *** faces extinction in the Garhwal *** this species through agro-production techniques may alleviate th

关键词： Anthropogenic pressure Conservational strategies Garhwal Himalaya Paeonia emodi Rapid vulnerability assessment Wild edibles

Threshold for initiation of motion of unimodal and bimodal sediments

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International Journal of Sediment Research 2013年第1期28卷 24-33页

作者： Shaileshkumar B.PATEL prem Lal PATEL prakash Devidas POREY Water Resources Engineering CEDSardar Vallabhbhai National Institute of TechnologySurat-395007India Department of Civil Engineering Sardar Vallabhbhai National Institute of TechnologySurat-395007India Sardar Vallabhbhai National Institute of Technology Surat-395007India

Experimental data,obtained from previous studies,on Critical Tractive Stress(CTS) of non-uniform sediments, have been used to verify the adequacy of existing relationships for CTS of non-uniform bimodal *** in view the performance of such relationships,a new relationship for computation of dimensionless CTS of individual size fraction of non-uniform unimodal and bimodal sediments has been proposed in the form of power *** coefficient and exponent of the proposed power law have been empirically correlated with sediment characteristics for available sediment *** proposed relationship has been validated with independent flume and field data to assess their applicability for unimodal and bimodal sediments.

关键词： Bimodal Critical tractive stress Non-uniform sediment Scaling size Unimodal

Enhancement of bioactives, functional and nutraceutical attributes of banana peels and de-oiled groundnut cake through submerged fermentation employing Calocybe indica

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FOOD BIOSCIENCE 2023年第3期53卷 3197-3207页

作者： Kapri, Mandira Singh, Umesh Srivastav, prem prakash Sharma, Satyawati Indian Inst Technol IIT Delhi New Delhi India Indian Inst Technol IIT Kharagpur Kharagpur India Indian Inst Technol Delhi Ctr Rural Dev & Technol Block 3Room 289 New Delhi 110016 India

In the current study, agro-industrial waste (banana peels and de-oiled groundnut cake) was valorised through submerged fermentation employing Calocybe indica. The fermented agro-waste revealed an increase in Ergosta-compounds, (3.57%), which include Ergosta-5,7,9(11),22-tetraen-3-ol,(***.,22E)-(1.87%), Ergosta-5,7,22- trien-3-ol,(***.,22e)-(1.24%) and Ergosta-7,22-dien-3-ol,(***.,***.,22E)-(0.46%). A reduction of phytic acid (26.25-6.84 mg/100g), oxalate (81.82-18.69 mg/100g), water holding capacity (34.29-30.97 ml/g), least gelation concentration (18-12.5%), bulk density (6.82-2.28 g/ml) and swelling volume (9.5-6.1 ml/g) with an increase in beta-glucan (8-24.57%), dispersibility (78.27-92.92%), oil holding capacity (0.59-1.73 ml/g), valine (ten-fold) and threonine (four-fold) seen in the fermented product makes it suitable for the food industry. GC-MS analysis confirmed the enriched levels of bioactive compounds namely, (S)-(-)-Perillyl alcohol, alpha.-Longipinene, isozonarol, widdrol, hydroxy valerenic acid, reynosin, beta-Eudesmol, lupenone, etc. in fermented agro-waste mixture. The valorised agro-waste-mycelia mixture can be used as a potential nutraceutically enriched health supplement in the food and pharma industries.

关键词： Agro-waste Fermentation Bioactives Nutraceuticals Health supplement

Assessment of tumor markers CA 19-9,CEA,CA 125,and CA 242 for the early diagnosis and prognosis prediction of gallbladder cancer

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World Journal of Gastrointestinal Surgery 2022年第11期14卷 1272-1284页

作者： Seema Rani Sinha prem prakash Rakesh Kumar Singh Dinesh Kumar Sinha Biochemistry Indira Gandhi Institute of Medical SciencesPatna 800014India General Surgery Indira Gandhi Institute of Medical SciencesPatna 800014India Surgical Gastroenterology Indira Gandhi Institute of Medical SciencesPatna 800014India Radiation Oncology State Cancer InstituteIndira Gandhi Institute of Medical SciencesPatna 800014BiharIndia

BACKGROUND Gallbladder cancer(GBC)is one of the leading and aggressive cancers in this region of *** is very difficult to diagnose in the early stage,as it lacks typical early signs and symptoms;thus,the diagnosis is often in the advanced stage,which ultimately leads to a poor 5-year survival *** markers including carbohydrate antigen 19-9(CA 19-9),carcinoembryonic antigen(CEA),CA 125,CA 242,and alpha fetoprotein are used as indicators in the diagnosis and prognosis of *** To compare tumor marker levels between GBC and benign GB diseases(GBDs)and to assess the combined use of tumor markers to increase the diagnostic accuracy for *** Patients of either sex aged≥18 years,with suspected GBC(GB polyp,irregular thick GB wall,GB mass,porcelain GB)on the basis of radiological imaging were included in this *** wall thickness using ultrasonography and tumor markers CEA,CA 125,CA 19-9,and CA 242 in all patients were *** cases after surgical intervention were divided into two groups,GBC and benign GBD,according to histopathological examination *** cases were followed up and clinical findings,radiological findings,and levels of tumor markers were *** A total of 200 patients were included in this study,of whom 80 patients had GBC and 120 patients had benign *** median(interquartile range)age was 52.0(41.0-60.0)years and the majority of patients(132,66.0%)were *** markers including CA 19-9,CA 125,CEA,and CA 242 were significantly elevated in patients with GBC(P<0.001).There was a significant reduction in tumor markers at 3 and 6 mo from baseline(P<0.001).The mean survival of patients with normal and elevated levels of tumor markers CA 125,CA 19-9,and CEA was comparable;however lymph node metastasis and CA 242 expression level were independent prognostic *** Serum levels of tumor markers including CA 19-9,CA 125,CEA,and CA 242 were significantly associated with ***,no significant asso

关键词： Benign gallbladder Tumor markers Survival Benign lesions Sensitivity Specificity

Recent trends in extraction,identification and quantification methods of Centella asiatica phytochemicals with potential applications in food industry and therapeutic relevance:A review

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Food Bioscience 2022年第5期49卷 282-306页

作者： Soubhagya Tripathy Deepak Kumar Verma Mamta Thakur Nishant Chakravorty Smita Singh prem prakash Srivastav Agricultural and Food Engineering Department Indian Institute of Technology KharagpurKharagpur721302West BengalIndia Department of Food Technology School of SciencesITM UniversityGwalior474001Madhya PradeshIndia School of Medical Science and Technology Indian Institute of Technology Kharagpur721302West BengalIndia Department of Nutrition and Dietetics University Institute of Applied Health SciencesChandigarh UniversityChandigarh140413PunjabIndia

Centella asiatica,a pre-historically utilized medicinal herb that is well recognized as a traditional phytotherapeutic substance for treating a variety of ***,its phytochemicals use as a functional component in food and beverage has recently attracted the attentions of food researchers and *** possesses pharmacological value due to the presence of phytochemicals like flavonoids and terpenoids,mainly asiatic acid,asiaticoside,and *** role as a functional component in developing various processed food products and packaging films is continuously being *** improves the micronutrient profile and antioxidant potential of developed food products like noodles,chocolates,soups,pasta,***,comprehensive scientific validation based on clinical trials is inadequate,which impede the perception of health benefits and nutritional importance of *** rich food ***,there is a need to extensively examine the composition of *** active compounds in order to maximise its application in the food processing and preservation ***,the goal of this paper is to investigate into the existing information on the extraction,identification,and quantification of *** phytochemicals,as well as to explore their biological *** potential of *** for developing functional foods and beverages,as well as their processing and preservation to improve human health,is also highlighted.

关键词： Centella asiatica Asiatic acid Phytochemicals Extraction techniques Food applications Anti-cancerous activity Antidiabetic effect