{"title":"Identification of steroidal cardenolides from Calotropis procera as novel HIV-1 PR inhibitors: A molecular docking & molecular dynamics simulation study.","authors":"Kandagatla Swapna, M Srujana, Estari Mamidala","doi":"10.25259/IJMR_2115_23","DOIUrl":"10.25259/IJMR_2115_23","url":null,"abstract":"<p><p>Background & objectives Despite advancements in antiretroviral therapy, drug-resistant strains of HIV (human immunodeficiency virus) remain a global health concern. Natural compounds from medicinal plants offer a promising avenue for developing new HIV-1 PR (protease) inhibitors. This study aimed to explore the potential of compounds derived from Calotropis procera, a medicinal plant, as inhibitors of HIV-1 PR. Methods This in silico study utilized natural compound information and the crystal structure of HIV-1 PR. Molecular docking of 17 steroidal cardenolides from Calotropis procera against HIV-1 PR was performed using AutoDock 4.2 to identify compounds with higher antiviral potential. A dynamic simulation study was performed to provide insights into the stability, binding dynamics, and potential efficacy of the top potential antiviral compound as an HIV-1 therapeutic. Results We found that all tested cardenolides had higher binding affinities than Amprenavir, indicating their potential as potent HIV-1 PR inhibitors. Voruscharin and uscharidin displayed the strongest interactions, forming hydrogen bonds and hydrophobic interactions with HIV-1 PR. Voruscharin showed improved stability with lower RMSD (Root Mean Square Deviation) values and reduced fluctuations in binding site residues but increased flexibility in certain regions. The radius of gyration analysis confirmed a stable binding pose between HIV-1 PR and Voruscharin. Interpretation & conclusions These findings suggest that Calotropis procera could potentially be a source of compounds for developing novel HIV-1 PR inhibitors, contributing to the efforts to combat HIV. Further studies and clinical trials are needed to evaluate the safety and efficacy of these compounds as potential drug candidates for the treatment of HIV-1 infection.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"78-86"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463882/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390306","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Abdul Ghani, Harvinder Singh, Hemanth Kumar, Kim Vaiphei
{"title":"MicroRNA expression signature in gastrointestinal stromal tumour & their molecular & histological features.","authors":"Abdul Ghani, Harvinder Singh, Hemanth Kumar, Kim Vaiphei","doi":"10.25259/ijmr_2567_22","DOIUrl":"10.25259/ijmr_2567_22","url":null,"abstract":"<p><p>Background & objectives In gastrointestinal stromal tumour (GIST), not only genetic abnormalities are responsible for adverse clinical events, but epigenetic modifications also play a crucial role. MicroRNA (miRNA) dysregulation plays a significant role in carcinogenesis as miRNAs serve as natural silencer for their targets. Our study aimed to explore the miRNAs expression and its association with molecular and histopathological characteristics of GIST. Methods Fifty GIST samples, including 45 formalin fixed paraffin embedded (FFPE) and fresh tissues were included. Peripheral non-tumour tissues were used as controls. All the cases were confirmed using immunohistochemistry. RNA was extracted using miRNA-specific kit, and the expression was performed using RT-qPCR. The data were evaluated using AriaMx software version 1.5 (Agilent, US). MiRNAs expression was analyzed by using the relative quantification method (ΔΔCT). Results miR-221, miR-222, miR-494 and miR-34a showed significant down-regulation in tumours relative to non-tumour tissues. The expression levels of these miRNAs were significantly down-regulated in c-KIT (proto-oncogene encoding the tyrosine kinase transmembrane receptor)-positive tumours compared to c-KIT-negative. Further analysis revealed that reduced expression was associated with spindle subtypes and gastric localization. However, there was no significant correlation with other histological features. Additionally, miR-221/222, and miR-494 were down-regulated in most of the KIT exon 11 mutant subtypes, while miRNA-34a was associated with platelet derived growth factor receptor alpha (PDGFRA) mutations. Interpretation & conclusions The present study showed that the down-regulation of these miRNAs may help better molecular classification and characterization of GISTs. Our results offer new insight into the association between miRNAs and histological features, enabling a more thorough understanding of GISTs at the molecular level.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"118-127"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463855/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390309","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Presence of multiple van genes among glycopeptide non-susceptible Staphylococcus aureus exhibiting in vitro MIC creep phenomenon: A study from north-east India.","authors":"Monalisha Hazarika, Kathakali Nath, Deepshikha Bhowmik, K Melson Singha, Debadatta Dhar, Amitabha Bhattacharjee","doi":"10.25259/ijmr_2224_22","DOIUrl":"10.25259/ijmr_2224_22","url":null,"abstract":"<p><p>Background & objectives The global prevalence of vancomycin-resistant Staphylococcus aureus (VRSA) has increased two fold since 2010, accounting for 2.4 per cent of S. aureus infections. The emerging hVISA isolates and their increasing trends pose a serious therapeutic challenge. The present study investigated in vitro vancomycin and teicoplanin minimum inhibitory concentration (MIC) creep in S. aureus and assessed their revertants. Methods A total of 845 isolates were collected for this study, and 246 were confirmed as S. aureus. Molecular characterization of vancomycin resistance was carried out by PCR assay targeting genes types viz: vanA, vanB, vanC, vanC2/C3, vanD, vanE, and vanG. MIC was determined for vancomycin and teicoplanin by agar dilution method. MIC creep and revertant analysis were done by broth dilution method in the presence and absence of antibiotics. Results PCR assay confirmed 12 isolates were harboured vanA, followed by vanD (n=8) and vanB (n=7). The study showed 69 isolates were screened positive for glycopeptide non-susceptibility. While analyzing vancomycin MIC creep, four isolates showed a significant increase in MIC, whereas no creep phenomenon was observed for the rest. In the case of teicoplanin, seven isolates showed the MIC creep phenomenon. Revertant analysis of all the isolates that showed MIC creep phenomenon for vancomycin and teicoplanin reverted to their original MIC when the antibiotic pressure was withdrawn. Interpretation & conclusions In the present study setting, glycopeptide non-susceptibility was found in eight per cent of the isolates, and the present study found the occurrence of multiple van genes from isolates calculated from a single study center will impose a serious challenge in infection control and antibiotic policy. This study also underscores that heterogenic resistant isolates, upon exposure to vancomycin and teicoplanin at a minimum level, exhibited an increase in MIC, which will impact individuals receiving glycopeptide therapy.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"109-117"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463864/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390312","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"High prevalence of alcohol use disorder & psychiatric comorbidity among coal mine workers: Observations from a cross-sectional study in West Bengal.","authors":"Amit Chakrabarti, Indranil Saha, Manoj Kalita, Debangana Bhattacharya, Bidisha Haque, Alisha Nagraj, Sovonlal Mukherjee, Vivek Benegal","doi":"10.25259/ijmr_2407_23","DOIUrl":"10.25259/ijmr_2407_23","url":null,"abstract":"<p><p>Background & objectives Tobacco (30%), alcohol (21.4%) and cannabis (3%) are the three most commonly abused substances in India. Tobacco and alcohol abuse have higher prevalence rates among different occupational groups as compared to that in general population in the country. Both tobacco and alcohol lead to significant occupational harm in terms of absenteeism, injuries, sickness and lost productivity. This study estimated the patterns of substance use and associated common psychiatric comorbidity in a sample of coal mine workers. Methods Coal mine workers at the age of 18 yr or above engaged in mining activities (skilled/semi-skilled/unskilled) were recruited from the Raniganj - Asansol coal mining areas of Eastern Coalfields Limited (ECL). Participants were screened to identify patterns of substance use and other common mental health problems. All participants were administered ASSIST (The Alcohol, Smoking and Substance Involvement Screening Test); GENACIS (Gender, Alcohol and Culture: An International Study) modified questionnaire; and Hospital Anxiety and Depression Scale (HADS) for primary screening for anxiety and depression. Results Out of 202 participants 69 per cent (n=140) were found with either 'hazardous and harmful' (moderate risk); or 'dependent' (high risk) patterns of use of either tobacco or alcohol or cannabis or of more than one substance. Only 31 per cent (n=62) were 'low-risk' for all substances. Almost 65 per cent (n=132) and 49 per cent (n=99) participants out of the whole sample (n=202) belonged to 'hazardous and harmful' (moderate risk) and 'dependent' (high risk) pattern of tobacco and alcohol consumption, respectively. About 28.8 per cent (n=38) and 23.7 per cent (n=31) of all participants had anxiety and depression, respectively. Combined moderate to high use of both alcohol and tobacco use was significantly associated with the risk of having anxiety [adjusted odds ratio (AOR)=4.896, P<0.015] and depression (AOR=5.335, P<0.012). Interpretation & conclusions Alcohol and tobacco are major substance abuse problems among coal mine workers. This population requires early community and primary care based brief intervention as well as additional community-based pharmacotherapy for substance dependence problems as well as intervention for common mental health issues.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"95-101"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463852/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390305","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Parth Sharma, Varad Putambekar, Peeyush Kumar, David Mathew Thomas, Sudheer K Vuyyuru, Bhaskar Kante, Sandeep Kumar Mundhra, Raju Sharma, Nihar Ranjan Dash, Govind Makharia, Saurabh Kedia, Vineet Ahuja
{"title":"Incidence of intestinal & extra-intestinal cancers among individuals with Crohn's disease in northern India.","authors":"Parth Sharma, Varad Putambekar, Peeyush Kumar, David Mathew Thomas, Sudheer K Vuyyuru, Bhaskar Kante, Sandeep Kumar Mundhra, Raju Sharma, Nihar Ranjan Dash, Govind Makharia, Saurabh Kedia, Vineet Ahuja","doi":"10.25259/ijmr_1722_23","DOIUrl":"10.25259/ijmr_1722_23","url":null,"abstract":"<p><p>Background & objectives Crohn's disease (CD) is associated with a higher risk of malignancy, which is attributed to disease behaviour and the usage of immunosuppressants. The burden of malignancy in CD is scarcely reported from Asia. We report real-world data on CD-related malignancy from a northern Indian cohort. Methods This retrospective analysis included individuals with CD who were followed up at the All India Institute of Medical Sciences, New Delhi, from 2005 to 2021. The standardized incidence ratio (SIR) was used to calculate the relative risk of malignancy in CD affected individuals compared to the general population. Results In this study, 952 study participants were included, with a mean age at diagnosis of 36.9±15.11 yr; 61.1 per cent were male. The median follow-up duration was 34 months [IQR (interquartile range): 19-73]. Most study participants received steroids (76.7%), immunomodulators (68.7%), or anti-TNF therapy (10.8%). The overall incidence of malignancy was 1.05 per cent, indicating a 10.45 times higher risk in CD [SIR: 10.45; 95% Confidence interval (CI):4.98-17.96]. Eight out of 826, 1 of 106 and 1 of 25 study participants developed malignancy in the first, second and third decades, respectively. The cumulative risk of malignancy was 2.7, 5.5, and 13.4 per cent in the first, second, and third decades, respectively. Regarding bowel malignancies, one study participant each developed ileocaecal adenocarcinoma, anorectal adenocarcinoma, malignant rectal fibrous histiocytoma, and gastric adenocarcinoma. Extraintestinal malignancies included single cases each of follicular neoplasia of the thyroid, neuroendocrine tumour of the pancreatic tail, breast cancer, hepatocellular cancer, oral cancer, and prostate cancer. No cases of lymphoma or skin malignancy were reported. Interpretation & conclusions At 30 yr, the cumulative risk of malignancy among Indian CD-affected individuals was 13.4 per cent, with a SIR of 10.45 (95% CI: 4.98- 17.96). The risk increased with increasing age at disease onset and duration.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"61-69"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463866/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390307","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Silambu Chelvi Kannayan, Basilea Watson, Kannan Thiruvengadam, M H Ghazala Shamail, Banurekha Velayutham, Rajendran Krishnan, Saravanan Natarajan
{"title":"Malnutrition in tribal people living with tuberculosis in India: A systematic review & meta-analysis.","authors":"Silambu Chelvi Kannayan, Basilea Watson, Kannan Thiruvengadam, M H Ghazala Shamail, Banurekha Velayutham, Rajendran Krishnan, Saravanan Natarajan","doi":"10.25259/IJMR_2188_23","DOIUrl":"10.25259/IJMR_2188_23","url":null,"abstract":"<p><p>Background & objectives Tuberculosis (TB) remains a persistent public health challenge in India. The country also has high proportions of malnutrition in different areas, making the population susceptible to TB. Among vulnerable populations, such as tribal communities, TB and malnutrition pose significant threats. Tribal populations exhibit disproportionately higher TB prevalence rates compared to non-tribal groups. Also, malnutrition prevalence among tribal communities far exceeds national averages in India. Amidst fragmented data, a systematic review of nutritional status among tribal populations with TB in India is imperative to inform comprehensive intervention strategies. Methods Cross-sectional, case-control, cohort and interventional studies reporting the nutritional status of active TB affected individuals among tribal populations in India were specifically included if terms such as \"malnutrition\" or \"low BMI\" were used. This systematic review followed PRISMA guidelines and was registered with PROSPERO (CRD42020168328). The data was assessed using a random-effects model and standardized mean with 95% confidence interval (CI). The I2 statistics indicated heterogeneity. Publication bias was evaluated using funnel plots. Results Out of 124 studies, 20 were selected for initial screening, 15 were excluded due to a lack of appropriate data, and five were included for the final analysis. The pooled prevalence estimates of malnutrition among Indian tribes living with TB was 514 per 1000 people, with 95% CI: 232-791. The sensitivity analysis showed that no individual study influenced the estimation of pooled prevalence. Interpretation & conclusions In the background of India, contributing considerably to the burden of TB-related morbidity and mortality alongside undernutrition, reviews have underscored undernutrition as the predominant risk factor for TB, affecting over 50 per cent of the population in some States. This situation is exacerbated among the tribal communities in India due to the dual burdens of undernutrition and TB being more pronounced. Our systematic review consolidates evidence from five studies, revealing the prevalence of malnutrition among tribal TB patients. Conducting well-planned implementation research to address this dual burden among the underprivileged population would help achieve the ambitious goal of a TB-free India 2025.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"23-30"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463873/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390308","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Hepatitis C virus genotypes among population with reported risk factors in Assam, north-east India: Emergence of genotype-8.","authors":"Sagarika Das, Devyashree Medhi, Anjan Jyoti Talukdar, Dina Raja, Kishore Sarma, Anisha Sarma, Lahari Saikia","doi":"10.25259/ijmr_1222_23","DOIUrl":"10.25259/ijmr_1222_23","url":null,"abstract":"<p><p>Background & objectives Hepatitis C virus (HCV) exhibits extensive genetic diversity in infected hosts. There are few published reports of HCV genotype (GT) distribution from the north-east Indian States lying close to the 'Golden Triangle' known for illicit drug trafficking. Real-time knowledge of HCVGT distribution is important for studies on epidemiologic aspects and virus evolution and for the development of new target-specific, direct-acting antiviral drugs. This study aims to examine the distribution of HCVGTs and their subtypes in different risk groups from Assam, north-east India. Methods It is a hospital-based cross-sectional study. Plasma samples reactive for anti-HCV antibody in enzyme-linked immunosorbent assay (ELISA) were subjected to viral load test and genotyping by real-time Reverse Transcription-Polymerase Chain Reaction (RT-PCR) or characterization of non-structural protein NS5B region by nested PCR. Nucleotide sequences were subjected to phylogenetic analysis. Results The most common HCVGT detected was GT-3 (95.89%), followed by GT-1 (3.42%), GT-6xa (0.34%) and GT-8 (0.34%). The mean age of subjects was 30.24 yr, and males outnumbered females. The most commonly associated risk factor was injecting drug use (IDU) (74.31%), followed by tattooing and/or piercing (33.22%), transfusion of blood/blood products (10.27%), and haemodialysis (9.25%). Co-infection with human immunodeficiency virus (HIV) was found in 17.8 per cent, and with Hepatitis B virus (HBV) in 3.42 per cent of the cases. Interpretation & conclusions The detection of HCVGT-8 makes this the first report from Assam and the second from India as per the authors' knowledge. This may indicate strain's endemic nature in India. The increasing trend of HCV infection among young IDUs and HCV-HIV co-infection indicates the need for enhancing surveillance and intensified prevention efforts among young adults.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"43-50"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463879/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390304","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Perception towards electronic health records & uptake of digital health IDs among the urban residents in northern India: A mixed methods study.","authors":"Aravind P Gandhi, Kathirvel Soundappan","doi":"10.25259/ijmr_664_23","DOIUrl":"10.25259/ijmr_664_23","url":null,"abstract":"<p><p>Background & objectives Ayushman Bharat Digital Mission (ABDM) envisages a unique digital health ID for all citizens of India, to create electronic health records (EHR) of individuals. The present study assessed the uptake of Digital Health IDs by the patient and general population, their attitude toward EHR, and explored the barriers to digital ID and utilizing electronic health records services. Methods A concurrent explanatory mixed methods study was undertaken in Chandigarh, India, with an analytical cross-sectional design as a quantitative part and a qualitative descriptive study. The study participants were 419 individuals aged ≥18 yr who attended the urban primary healthcare centre (n=399) and the community-based screening camps (n=20) between July 2021 and January 2022. Latent Class Analysis (LCA) was undertaken to identify hidden sub-population characteristics. In-depth interviews were done to identify the barriers to health ID uptake. Results The digital health ID uptake rate was 78 per cent (n=327). Among the study participants, those who were aware of EHR, those who wanted a national EHR system, those who were confident with the government on EHR security, and those who were willing to make national EHR accessible for research showed significantly higher digital health ID uptake than their counterparts. The themes identified under barriers of uptake from the qualitative interviews were lack of awareness, technology-related (including digital literacy) and utility-related. Interpretation & conclusions Increasing EHR awareness, digital health literacy, and enacting data protection laws may improve the acceptance of the digital health ecosystem in India.</p>","PeriodicalId":13349,"journal":{"name":"Indian Journal of Medical Research","volume":"160 1","pages":"51-60"},"PeriodicalIF":2.7,"publicationDate":"2024-07-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC11463868/pdf/","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142390311","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}