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WNT/β-catenin signaling in urothelial carcinoma of bladder

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World Journal of Nephrology 2019年第5期8卷 83-94页

作者： minal garg Niharika Maurya Department of Biochemistry University of Lucknow

Urothelial carcinoma of bladder is the second most prevalent genitourinary *** is a highly heterogeneous disease as it represents a spectrum of neoplasms,including non-muscle invasive bladder cancer(NMIBC),muscle invasive bladder cancer(MIBC)and metastatic ***-wide approaches and candidate gene analysis suggest that malignant transformation of the bladder is multifactorial and a multitude of genes are involved in the development of MIBC or NMIBC *** signaling is being examined to control and maintain balance between stemness and differentiation in adult stem cell *** to its participation in urothelial development and maintenance of adult urothelial tissue homeostasis,the components of Wnt signaling are reported as an important diagnostic and prognostic markers as well as novel therapeutic ***/epigenetic alterations in the key molecules of Wnt/β-catenin canonical pathway have been linked with tumorigenesis,development of drug resistance and enhanced *** review extends our understanding on the functions of key regulatory molecules of canonical Wnt/β-catenin pathway in urothelial tumorigenesis by inducing cancer stem cell phenotype(UCSCs).UCSCs may be responsible for tumor heterogeneity,high recurrence rates and complex biological behavior of bladder ***,understanding the role of UCSCs and the regulatory mechanisms that are responsible for high relapse rates and metastasis could help to develop pathway inhibitors and augment current *** implications in the treatment of urothelial carcinoma of bladder by targeting this pathway primarily in UCSCs as well as in bulk tumor population that are responsible for high relapse rates and metastasis may facilitate potential therapeutic avenues and better prognosis.

关键词： Chemoresistance Therapeutic approaches Urothelial carcinoma of bladder Urothelial cancer stem cells Wnt/β-catenin

MicroRNAs,stem cells and cancer stem cells

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World Journal of Stem Cells 2012年第7期4卷 62-70页

作者： minal garg Department of Biochemistry University of LucknowLucknow 226007India

This review discusses the various regulatory charac-teristics of microRNAs that are capable of generating widespread changes in gene expression via post translational repression of many mRNA targets and control self-renewal, differentiation and division of cells. It controls the stem cell functions by controlling a wide range of pathological and physiological processes, including development, differentiation, cellular proliferation, programmed cell death, oncogenesis and metastasis. Through either mRNA cleavage or translational repression, miRNAs alter the expression of their cognate target genes; thereby modulating cellular pathways that affect the normal functions of stem cells, turning them into cancer stem cells, a likely cause of relapse in cancer patients. This present review further emphasizes the recent discoveries on the functional analysis of miRNAs in cancer metastasis and implications on miRNA based therapy using miRNA replacement or anti-miRNA technologies in specific cancer stem cells that are required to establish their efficacy in controlling tumorigenic potential and safe therapeutics.

关键词： Stem cell functions Cancer stem cells Cellular pathways miRNA oncomiR Tumor suppressor miRNAs miRNA based therapeutics

garg incontinence scores: New scoring system on the horizon to evaluate fecal incontinence. Will it make a difference?

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World Journal of Gastroenterology 2024年第3期30卷 204-210页

作者： Petr Tsarkov Inna Tulina Parvez Sheikh Darya D Shlyk Pankaj garg Department of Colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Oncologic Colorectal Surgery Sechenov First Moscow State Medical UniversityMoscow 119991Russia Department of Colorectal Surgery Saifee HospitalMumbai 400004MaharashtraIndia Department of Colorectal Surgery Garg Fistula Research InstitutePanchkula 134113HaryanaIndia

The main aim of this opinion review is to comment on the recent article published by garg et al in the World Journal of Gastroenterology 2023;29:4593–*** authors in the published article developed a new scoring system,garg incon-tinence scores(GIS),for fecal incontinence(FI).FI is a chronic debilitating disease that has a severe negative impact on the quality of life of the *** IV criteria define FI as multiple episodes of solid or liquid stool passed into the clothes at least twice a *** associated social stigmatization often leads to significant under-reporting of the condition,which further impairs *** important point is that the complexity and vagueness of the disease make it difficult for the patients to properly define and report the magnitude of the problem to their *** to this,the management becomes even more *** issue is resolved up to a considerable extent by a scoring *** were several scoring systems in use for the last three *** prominent of them were the Cleveland Clinic scoring system or the Wexner scoring system,*** Hospital or Vaizey’s scores,and the FI severity ***,there were several shortcomings in these scoring *** the opinion review,we tried to analyze the strength of GIS and compare it to the existing scoring *** main pitfalls in the existing scoring systems were that most of them gave equal weightage to different types of FI(solid,liquid,flatus,etc.),were not comprehensive,and took only the surgeon’s perception of FI into *** GIS,almost all shortcomings of previous scoring systems had been addressed:different weights were assigned to different types of FI by a robust statistical methodology;the scoring system was made comprehensive by including all types of FI that were previously omitted(urge,stress and mucus FI)and gave priority to patients’rather than the physicians’perceptions while developing the scoring *** to this,GIS in

关键词： Fecal incontinence Scoring system Urge Stress Flatus

Emerging role of microRNAs in cancer stem cells:Implications in cancer therapy

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World Journal of Stem Cells 2015年第8期7卷 1078-1089页

作者： minal garg Department of Biochemistry University of Lucknow

A small subset of cancer cells that act as tumor initiating cells or cancer stem cells(CSCs) maintain self-renewal and growth promoting capabilities of cancer and are responsible for drug/treatment resistance,tumor recurrence and metastasis. Due to their potential clinical importance,many researchers have put their efforts over decades to unravel the molecular mechanisms that regulate CSCs functions. Micro RNAs(mi RNAs) which are 21-23 nucleotide long,endogenous noncoding RNAs,regulate gene expression through gene silencing at post-transcriptional level by binding to the 3'-untranslated regions or the open reading frames of target genes,thereby result in target mR NA degradation or its translational repression and serve important role in several cellular,physiological and developmental processes. Aberrant mi RNAs expression and their implication in CSCs regulation by controlling asymmetric cell division,drug/treatment resistance and metastasis make mi RNAs a tool of great therapeutic potential against cancer. Recent advancements on the biological complexities of CSCs,modulation in CSCs properties by mi RNA network and development of mi RNA based treatment strategies specifically targeting the CSCs as an attractive therapeutic targets for clinical application are being critically analysed.

关键词： Cancer stem cells Drug resistance Tumor recurrence

Epithelial plasticity in urothelial carcinoma: Current advancements and future challenges

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World Journal of Stem Cells 2016年第8期8卷 260-267页

作者： minal garg Department of Biochemistry University of Lucknow

Urothelial carcinoma(UC) of the bladder is characterized by high recurrence rate where a subset of these cells undergoes transition to deadly muscle invasive disease and later metastasizes. Urothelial cancer stem cells(UroC SCs), a tumor subpopulation derived from trans-formation of urothelial stem cells, are responsible for heterogeneous tumor formation and resistance to systemic treatment in UC of the bladder. Although the precise reason for pathophysiologic spread of tumor is not clear, transcriptome analysis of microdissected cancer cells expressing multiple progenitor/stem cell markers validates the upregulation of genes that derive epithelial-to-mesenchymal transition. Experimental studies on human bladder cancer xenografts describe the mechanistic functions and regulation of epithelial plasticity for its cancer-restraining effects. It has been further examined to be associated with the recruitment of a pool of Uro CSCs into cell division in response to damages induced by adjuvant therapies. This paper also discusses the various probable therapeutic approaches to attenuate the progressive manifestation of chemoresistance by co-administration of inhibitors of epithelial plasticity and chemotherapeutic drugs by abrogating the early tumor repopulation as well as killing differentiated cancer cells.

关键词： Cancer stem cells Clinical management Cytotoxic effects Epithelial plasticity Therapeutic resistance Urothelial carcinoma Urothelial stem cells

Mutational analysis of Ras hotspots in patients with urothelial carcinoma of the bladder

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World Journal of Clinical Oncology 2020年第8期11卷 614-628页

作者： Kiran Tripathi Apul Goel Atin Singhai minal garg Department of Biochemistry University of LucknowLucknow 226007India Department of Urology King George Medical UniversityLucknow 226003 Department of Pathology King George Medical UniversityLucknow 226003India

BACKGROUND Mutational activation of Ras genes is established as a prognostic factor for the genesis of a constitutively active RAS-mitogen activated protein kinase pathway that leads to *** among the distribution of the most frequent mutations in Ras isoforms is reported in different patient populations with urothelial carcinoma of the bladder(UCB).AIM To determine the presence/absence of mutations in Ras isoforms in patients with UCB in order to predict disease *** This study was performed to determine the mutational spectrum at the hotspot regions of H-Ras,K-Ras and N-Ras genes by polymerase chain reaction-restriction fragment length polymorphism(PCR-RFLP)and DNA sequencing followed by their clinical impact(if any)by examining the relationship of mutational spectrum with clinical histopathological variables in 87 UCB *** None of the 87 UCB patients showed point mutations in codon 12 of H-Ras gene;codon 61 of N-Ras gene and codons 12,13 of K-Ras gene by *** DNA sequencing of tumor and normal control bladder mucosal specimens followed by Blastn alignment with the reference wild-type sequences failed to identify even one nucleotide difference in the coding exons 1 and 2 of H-Ras,NRas and K-Ras genes in the tumor and control bladder mucosal *** Our findings on the lack of mutations in H-Ras,K-Ras and N-Ras genes could be explained on the basis of different etiological mechanisms involved in tumor development/progression,inherent genetic susceptibility,tissue specificity or alternative Ras dysfunction such as gene amplification and/or overexpression in a given cohort of patients.

关键词： Coding exons Oncogenic activation Polymerase chain reaction-restriction fragment length polymorphism Point mutations Ras genes Urothelial carcinoma of bladder

Covalent Bond Based Android Malware Detection Using Permission and System Call Pairs

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Computers, Materials & Continua 2024年第3期78卷 4283-4301页

作者： Rahul Gupta Kapil Sharma R.K.garg Department of Information Technology Delhi Technological UniversityNew Delhi110042India Department of Mechanical Engineering Deenbandhu Chhotu Ram University of Science and TechnologyMurthal131039India

The prevalence of smartphones is deeply embedded in modern society,impacting various aspects of our *** versatility and functionalities have fundamentally changed how we communicate,work,seek entertainment,and access *** the many smartphones available,those operating on the Android platform dominate,being the most widely used *** widespread adoption of the Android OS has significantly contributed to increased malware attacks targeting the Android ecosystem in recent ***,there is an urgent need to develop new methods for detecting Android *** literature contains numerous works related to Android malware *** far as our understanding extends,we are the first ones to identify dangerous combinations of permissions and system calls to uncover malicious behavior in Android *** introduce a novel methodology that pairs permissions and system calls to distinguish between benign and malicious *** approach combines the advantages of static and dynamic analysis,offering a more comprehensive understanding of an application’s *** establish covalent bonds between permissions and system calls to assess their combined *** introduce a novel technique to determine these pairs’Covalent Bond Strength *** pair is assigned two scores,one for malicious behavior and another for benign *** scores serve as the basis for classifying applications as benign or *** correlating permissions with system calls,the study enables a detailed examination of how an app utilizes its requested permissions,aiding in differentiating legitimate and potentially harmful *** comprehensive analysis provides a robust framework for Android malware detection,marking a significant contribution to the *** results of our experiments demonstrate a remarkable overall accuracy of 97.5%,surpassing various state-of-the-art detection techniques proposed in the current literature.

关键词： Android malware android security hybrid analysis permission and system call pairs

Clinicohistopathological implications of phosphoserine 9 glycogen synthase kinase-3β/β-catenin in urinary bladder cancer patients

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World Journal of Clinical Oncology 2019年第4期10卷 166-182页

作者： Niharika Maurya Rinni Singh Apul Goel Atin Singhai Uday Pratap Singh Vinita Agrawal minal garg Department of Biochemistry Lucknow University Department of Urology King George Medical University Department of Pathology King George Medical University Department of Urology and Renal Transplantation Sanjay Gandhi Post Graduate Institute of Medical Sciences Department of Pathology Sanjay Gandhi Post Graduate Institute of Medical Sciences

BACKGROUND Aberrant activation of phosphorylated form of glycogen synthase kinase-3β[pS9 GSK-3β(Serine 9 phosphorylation)] is known to trigger Wnt/β-catenin signal cascade but its clinicohistopathological implications in bladder carcinogenesis remain *** To investigate the diagnostic and prognostic relevance of expressions of pS9 GSK-3β, β-catenin and its target genes in the pathobiology of bladder *** Bladder tumor tissues from ninety patients were analyzed for quantitative expression and cellular localization of pS9 GSK-3β by immunohistochemical(IHC) staining. Real time-quantitative polymerase chain reaction and IHC were done to check the expression of β-catenin, Cyclin D1, Snail and Slug at transcriptome and protein level respectively. Clinicohistopathological variables were obtained from histology reports, follow up and OPD visits of *** of the markers were statistically correlated with these variables to determine their significance in clinical setting. Results were analysed using SPSS20.0 *** Aberrant(low or no membranous/high nuclear/high cytoplasmic) expression of pS9 GSK-3β was noted in 51% patients and found to be significantly associated with tumor stage and tumor grade(P = 0.01 and 0.04; Mann Whitney U test).Thirty one percent tumors exhibited aberrant co-expression of pS9 GSK-3β andβ–catenin proteins and showed strong statistical association with tumor stage,tumor type, smoking/tobacco chewing status(P = 0.01, 0.02 and 0.04, MannWhitney U test) and shorter overall survival probabilities of patients(P = 0.02;Kaplan Meier test). Nuclear immunostaining of Cyclin D1 in tumors with altered pS9 GSK-3β/β–catenin showed relevance with tumor stage, grade and ***β–catenin and pS9 GSK-3β proteins are identified as markers of diagnostic/prognostic significance in disease pathogenesis. Observed histopathological association of Cyclin D1 identifies it as marker of potential relevance in tumors with altered

关键词： Pathobiology Target genes Tumor stage and grade Wnt/β–catenin signal cascade Urothelial carcinoma of bladder

Exploring the combination of biochar‐amended soil and automated irrigation technology for water regulation and preservation in green infrastructure

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Deep Underground Science and Engineering 2024年第1期3卷 39-52页

作者： Honghu Zhu Yuanxu Huang Haihong Song Jian Chen Songlei Han Tanwee Mazumder Ankit garg School of Earth Sciences and Engineering Nanjing UniversityNanjingChina Department of Civil and Smart Engineering Construction Guangdong Engineering Center for Structure Safety and Health MonitoringShantou UniversityShantouChina Shanghai Municipal Engineering Design Co. LtdShanghaiChina Indian Institute of Technology Madras ChennaiIndia

Biochar is a carbon sink material with the potential to improve water retention in various ***,for the long‐term maintenance of green infrastructure,there is an additional need to regulate the water contents in the covers to maintain vegetation growth in semiarid *** this study,biochar‐amended soil was combined with subsurface drip irrigation,and the water preservation characteristics of this treatment were investigated through a series of one‐dimensional soil column *** ascertain the best treatment method specific to semiarid climatic conditions,the test soil was amended with 0%,1%,3%,and 5%*** irrigation devices equipped with soil moisture sensors were used to control the subsurface water content with the aim of enhancing vegetation *** soil column test lasted 150 h,during which the volumetric water contents and soil suction data were *** experimental results reveal that the soil specimen amended with 3%biochar is the most water‐saving regardless of the time *** with a higher biochar content(e.g.,5%)consumes a more significant amount of water due to the enhancement of the water‐holding *** on the experimental results,it can be concluded that the appropriate ratio can be determined within 1%–3%,which can reduce not only the amount of irrigated/used water but also the time *** technology can be explored for water content regulation in green infrastructure and the development of barriers for protecting the environment around deep underground waste containment.

关键词： biochar drip irrigation underground water preservation water regulation