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Background: A hospital-based cross-sectional case-control study was conducted to investigate the association between exposure through various pesticide residues detected in the plasma and serum 8-OHdG levels among farmers and non-farmers diagnosed with leukaemia, lymphoma and breast cancers and compare the same with healthy controls with no cancer and no exposure. Methodology: The present study was conducted among the farmers and non-farmers visiting a regional tertiary cancer care hospital in Hyderabad, Telangana State, India. Data were collected by administering a pre-tested questionnaire through an interview followed by the collection of blood samples which were analyzed for pesticide residues using LC-MS/MS while the serum levels of 8-OHdG were measured using ELISA. Data were analyzed using SPSS 24. Results: The pesticide residues detected were chlorpyrifos, dimethoate, malathion, phosalone, and quinalphos which were approved and recommended for their use on the crops that were cultivated by the farmers in their plasma samples along with banned pesticide residues like monocrotophos, diazinon, and dichlorvos among farmers diagnosed with all three types of cancers while the non-farmers and healthy controls were not detected with any such residues. In addition, farmers diagnosed with leukemia had higher levels of all the pesticide residues in their plasma than those diagnosed with lymphoma and breast cancers. Further, a significant difference was also observed between profenofos residues in plasma and serum 8-OHdG levels. Conclusion: In the present study, though the farmers diagnosed with three types of cancers were detected with various types of pesticide residues analysed, only residues of profenofos showed a significant difference with serum levels of 8-OHdG suggesting the need for an in-depth follow up molecular studies in a larger cohort to assess the possible association between 8-OHdG levels with the pesticide residues among the exposed. [ABSTRACT FROM AUTHOR]

Background. Human papillomavirus (HPV) infection is largely responsible for the development of invasive cervical cancer (ICC). Its prevalence, risk factors and genotype distribution among women residing in Bihar (third most populous Indian state) with and without ICC are not well known. Methods. In this hospital-based study, we followed up 1439 participants with cytology and HPV report. HPV detection and genotyping were performed using the TaqMan-based real-time PCR method. Clinical and sociodemographic data were collected and analysed using statistical methods. Results. The overall prevalence of HPV infection was 37.3% (537/1439) and 11 different types of HPV genotypes were observed. Higher HPV positivity was found in premalignant, intraepithelial and invasive malignant lesions of the cervix; 73.8% (93/126) of atypical squamous cells, cannot exclude high-grade squamous intraepithelial lesion (ASC-H) and high-grade squamous intraepithelial lesions (HSIL) and 93.4% (114/122) of invasive malignancies were infected with HPV in comparison to only 26.1% (245/938) of negative for intraepithelial lesion or malignancy (NILM) cytology. Moreover, HPV was found in 95.2% (236/248) of histologically confirmed cases of carcinoma cervix. HPV16 and HPV18 infections were reported in 78.2% (194/248) and 8.9% (22/248), respectively. The remaining patients had infection with other high-risk strains/co-infection with multiple strains or were HPV-negative. Various sociodemographic factors including women >50 years of age, >10 years of marriage and high parity were significantly associated with HPV infection. Conclusion. Our data suggest that HPV16 infection may be the major cause for ICC among women residing in Bihar. Our findings may serve as a baseline for developing an appropriate screening and vaccination strategy for Bihar. [ABSTRACT FROM AUTHOR]

Epidemiological studies suggest suppression of the lymphocytes function through cholinergic stimulation due to organophosphorus pesticide exposure. The study aimed to assess the alteration in the levels of immune cell phenotypes among farm women (FW) and farm children (FC) who were occupationally exposed to pesticides and age/gender-matched control subjects belonging to Rangareddy district (Telangana, India). A total of 129 FW, 129 FC and 268 age/gender-matched controls were recruited. Blood samples were collected from the selected subjects to estimate the levels of nine organophosphorus pesticide residues and CD (CD3+, CD4+, CD8+, CD16+ and CD19+) cell markers using LC-MS/MS and flow cytometry, respectively. Independent t-test analysis was conducted to compare the immune cell phenotypes between exposed and control groups. Spearman's rank correlation test was further carried out to identify any possible correlation between the pesticide residues and CD markers. The mean percentage for CD4+, CD8+ and CD16+ was found to be significantly low, while for CD19 + itwas significantly high in the FW as compared to the CW group (p < 0.01). Further, the residues of chlorpyrifos and monocrotophos among FW were found to be significantly correlating with the mean percentages of CD19+ and CD8+ markers, respectively. The cell marker subsets of CD4+ and CD8+ were significantly low in FC children 9–12 years and 13–15 years age groups, respectively (p < 0.05). Also, these levels were significantly correlating with the residues of malathion and monocrotophos. The present study could indicate an alteration in the lymphocytes' subpopulations, which may thereby infer the toxicity in the first phase assessment of immunotoxicity. Therefore, further studies may be conducted to understand the suspected pesticides' mechanism along with various other factors in causing immune suppression coupled with nutritional and other related disorders. [ABSTRACT FROM AUTHOR]

Byline: Sangeeta. Pankaj, Anita. Kumari, Vijayanand. Choudhary, Babban. JeeThe state of Bihar covers an area of 94,163 km2 and is one of the less economically developed states of India. Approximately [...]

The prognosis of hepatocellular carcinoma (HCC) with portal vein tumor thrombosis (PVTT) is dismal. Despite best treatment and care, the patients with this malignancy only showed 2.7–4 months of overall survival. It is debatable whether liver transplantation helps PVTT sufferers. The effectiveness of radiation therapy in treating HCC patients with PVTT should not be undervalued. By limiting the high dosage region to a small planning target volume, stereotactic radiation delivery has shifted toward hypofractionation, limiting the radiation exposure to healthy organs and tissues. Stereotactic body radiotherapy (SBRT) has a local control rate of 75–100%, depending on the treatment. The major limitation in SBRT for hepatocellular carcinoma with PVTT is the paucity of prospective evidence for longer periods beyond the first two years after treatment. More prospective studies/randomized clinical trials with a longer follow-up, larger sample size, and adequate statistical power are the dire need of the present situation to ascertain the curative effect of SBRT as primary therapy for advanced HCC with PVTT. SBRT can improve survival, particularly for patients receiving multidisciplinary treatment. This review sums up our most current understanding of how radiation therapy, notably SBRT, can be used to treat hepatocellular carcinoma when combined with PVTT. Recent research has led us to believe that irradiation in the form of SBRT may cure hepatocellular carcinoma complicated by PVTT. [ABSTRACT FROM AUTHOR]

Nutritional status plays a major role in determining the possible adverse health outcomes due to pesticide toxicity. The objective of the present study was to assess the organophosphorus pesticide residue levels among farm women (FW) (24-45years) and farm children (FC) (9-12 and 13-15years) belonging to the Rangareddy district (Telangana, India) along with their micronutrient status, inhibition of acetylcholinesterase activity, and oxidative stress levels. Residues of Chlorpyrifos, Diazinon, Malathion, Monocrotophos and Phosalone were found in the serum samples of FW and FC along with significantly low levels of vitamins and minerals. Inhibition of AChE activity was observed in FW and FC and altered oxidative stress parameters among FW. Correlation studies have found significant associations between the pesticide residues, micronutrients and antioxidant enzymes. The study suggests an association between pesticide exposure coupled with micronutrient deficiency, induced AChE inhibition, and oxidative stress. [ABSTRACT FROM AUTHOR]

Human papilloma virus (HPV) has emerged as a primary cause of cervical cancer worldwide. HPV is a relatively small (55 nm in diameter) and non-enveloped virus containing approximately 8 kb long double stranded circular DNA genome. To date, 228 genotypes of HPV have been identified. Although all HPV infections do not lead to the development of malignancy of cervix, only persistent infection of high-risk types of HPV (mainly with HPV16 and HPV18) results in the disease. In addition, the immunity of the patients also acts as a key determinant in the carcinogenesis. Since, no HPV type specific medication is available for the patient suffering with cervical cancer, hence, a deep understanding of the disease etiology may be vital for developing an effective strategy for its prevention and management. From the immunological perspectives, the entire mechanisms of disease progression still remain unclear despite continuous efforts. In the present review, the recent developments in immunology of HPV-mediated cervix carcinoma were discussed. At the end, the prevention of disease using HPV type specific recombinant vaccines was also highlighted. [ABSTRACT FROM AUTHOR]

Oxidative stress has been reported as one of the adverse effects caused due to pesticides, which is the main mechanism of the toxicity in humans and animals and is a useful parameter in monitoring studies. It involves an imbalance in the equilibrium state of ROS and antioxidant defenses leading to alterations in various antioxidant enzyme levels and lipid peroxidation. The objective of the current paper is to present a review of the potential role and protective mechanism action of the antioxidant micronutrient supplementation to ameliorate the oxidative stress induced by pesticides. Studies in animal models and human were retrieved through the relevant search of the literature and categorized. Various animal studies were categorized according to the type of supplementation. Animal studies provide evidence to conclude the potential protective role of antioxidants in ameliorating the adverse effects of pesticides. Similar studies in humans are meager suggesting for further comprehensive research. [ABSTRACT FROM AUTHOR]

In the current scenario of medical sciences, homeopathy, the most popular system of therapy, is recognized as one of the components of complementary and alternative medicine (CAM) across the world. Despite, a long debate is continuing whether homeopathy is just a placebo or more than it, homeopathy has been considered to be safe and cost-effectiveness therapeutic modality. A number of human ailments ranging from common to serious have been treated with homeopathy. However, selection of appropriate medicines against a disease is cumbersome task as total spectrum of symptoms of a patient guides this process. Available data suggest that homeopathy has potency not only to treat various types of cancers but also to reduce the side effects caused by standard therapeutic modalities like chemotherapy, radiotherapy or surgery. Although homeopathy has been widely used for management of cancers, its efficacy is still under question. In the present review, the anti-cancer effect of various homeopathic drugs against different kinds of cancers has been discussed and future course of action has also been suggested. [ABSTRACT FROM AUTHOR]

Small heat shock proteins (sHSPs) are one of the five families of proteins acting as molecular chaperone. sHSPs possess a universally conserved alpha-crystallin domain, hence, also known as alpha-crystallin family. Mycobacterium tuberculosis (MTB) is an etiological agent of tuberculosis, a disease claiming million of lives every year across the world. MTB has two sHSPs: sHSP16.3 (a 16.3 kDa protein) and Acr2 (a 17.8 kDa protein). Of these, sHSP16.3 has been reported to be crucial for survival of MTB during prolonged period of dormancy, in addition to indispensable role in its growth, virulence and cell wall thickening. Additionally, this mycobacterial protein is also beneficial for host as well. Due to strong immunogenic properties and consistent presence in patients sera, sHSP16.3 has largely been implicated in vaccine development and diagnosis of latent and active infections of MTB in the clinical cases of TB. Recently, our study provided the substantial evidence to exploit this mycobacterial protein as a good drug target for developing novel therapeutic intervention. In the present review, a comprehensive analysis of various attributes of sHSP16.3 has been done and major gaps in area have been highlighted for future course of action. [ABSTRACT FROM AUTHOR]

Lysosomal storage disorders (LSDs) are a group of seventy different metabolic storage diseases due to accumulation of substrate mainly in the form of carbohydrate, lipids, proteins, and cellular debris. They occur due to variant in different genes that regulate lysosomal enzymes synthesis, transport, and secretion. In recent years, due to an increased availability of various therapies to treat these disorders, and increased diagnostic tools, there has been an escalated awareness of LSDs. Due to heterogeneous population and various social reasons, India is likely to have a high frequency of LSDs. Therefore, to understand the burden of various LSDs, its molecular spectrum, and understanding the phenotype-genotype correlation, Indian Council of Medical Research (ICMR) and Department of Health Research (DHR), Government of India had set up a task force in the year 2015. It has resulted in identifying common LSDs, and founder variant for some of the storage disorders and molecular spectrum of various LSDs across the country. This review describes in detail the spectrum of LSDs, its molecular epidemiology and prevention in context to Indian population., Competing Interests: J.S. received research grant from (i) ICMR-DHR-NTF (GIA/31(ii)/2014-DHR) and the funds were used to study the mutation spectrum of different LSDs in the country, (ii) GSBTM-DST/JDR and D/608/2020/459-461 and the funds were used to develop and validate smMIP-based NGS technology for genetic diagnosis of LSD patients, and (iii) BT/PR39587/MED/12/851/2020 and the funds are used to provide genetic diagnosis (detect SNVs and CNVs) in suspected LSD patients using the smMIP-based NGS technology and to develop a national Bio-bank for LSD patients. B.J. co-ordinated the work carried out by the national centers in the DHR-ICMR-NTF LSD project. A.N. is a PhD student working on the development, validation and application smMIP based NGS technology for detecting SNVs and CNVs in suspected LSD patients. There was no funding involved in preparing the current manuscript. The authors declare that the work was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (© 2022 The Author(s).)

For coronaviruses, RNA-dependent RNA polymerase (RdRp) is an essential enzyme that catalyses the replication from RNA template and therefore remains an attractive therapeutic target for anti-COVID drug discovery. In the present study, we performed a comprehensive in silico screening for 16,776 potential molecules from recently established drug libraries based on two important pharmacophores (3-amino-4-phenylbutan-2-ol and piperazine). Based on initial assessment, 4042 molecules were obtained suitable as drug candidates, which were following Lipinski's rule. Molecular docking implemented for the analysis of molecular interactions narrowed this number of compounds down to 19. Subsequent to screening filtering criteria and considering the critical parameters viz. docking score and MM-GBSA binding free energy, 1-(4-((2 S ,3 S )-3-amino-2-hydroxy-4-phenylbutyl)piperazin-1-yl)-3-phenylurea (compound 1 ) was accomplished to score highest in comparison to the remaining 18 shortlisted drug candidates. Notably, compound 1 displayed higher docking score (-8.069 kcal/mol) and MM-GBSA binding free energy (-49.56 kcal/mol) than the control drug, remdesivir triphosphate, the active form of remdesivir as well as adenosine triphosphate. Furthermore, a molecular dynamics simulation was carried out (100 ns), which substantiated the candidacy of compound 1 as better inhibitor. Overall, our systematic in silico study predicts the potential of compound 1 to exhibit a more favourable specific activity than remdesivir triphosphate. Hence, we suggest compound 1 as a novel potential drug candidate, which should be considered for further exploration and validation of its potential against SARS-CoV-2 in wet lab experimental studies.Communicated by Ramasawamy H. Sarma.