Inflammation and Stem Cell Stochasticity of HPV-induced Cervical Cancer: Epigenetics Based Biomarkers through Microbiome and Metabolome for Personalized Medicine: A Systematic Review.

BACKGROUND: Chemoresistance by stemness in HPV-induced cervical carcinogenesis has significant implications for the overall disease-specific survival of the patients. To date, there are no reports related to the implications of significant aspects of inflammation and microbiome-- mediated epigenetics in cervical cancers. OBJECTIVE: The current systematic review delineates the significant aspects of the inflammation-related pathophysiology, cervical cancer diagnosis based on the HPV-indued stemness, and microbiome- mediated epigenetic markers to develop personalized therapies to target the stemness-acquired indefinitely dividing cancer stem cells. METHODS: We performed a systematic review without a meta- analysis. We searched several public databases, such as Pubmed, ReleMed, National Library of Medicine, and Scopus, related to inflammation, metabolomics, microbiome-mediated epigenetic markers, and HPV-induced stemness. RESULTS AND CONCLUSION: The review significantly described the correlation between microbial inflammation and stem cell stochasticity of HPV-Induced cervical cancer and the expression of epigenetics- based biomarkers through microbiome and metabolome to foster the cervical cancer progression. These are major risk factors that can cause cervical dysplasia with substantial therapy resistance in cervical cancer patients. The qualitative and quantitative examination of the spatial transcriptomic expression of these stemness markers in the dividing cervical cancer stem cells has significant implications in the clinical sector to develop early personalized medicine to prevent cervical precancerous lesions depending on the prognosis of the cervical cancer patients. Mainly, the combinatorial regimen of current therapeutic modalities, along with microbiome-related therapies with future landscape of epigenetics-modulated therapies, may enhance overall disease-specific survival by modulating the stochastic dynamics of basal epithelial cells across the cervical region.

Influence of trazodone on the pharmacodynamics and pharmacokinetics of pioglitazone.

BACKGROUND: These days, poly pharmacy is very common for the treatment of multiple diseases and majority of drugs were metabolized with CYP 450 enzymes. Diabetes mellitus is such a disorder, which requires continuous therapy for the control of blood glucose concentration. Depression was quite common in diabetic patients. Therefore, multiple drugs required to treat diabetes mellitus and depression. Simultaneous administration of these drugs leads to drug interaction. Pioglitazone and trazodone metabolized by CYP3A4 enzymes which may lead to potential drug interaction. OBJECTIVES: This study aimed to find the influence of trazodone on the pharmacokinetics & pharmacodynamics of pioglitazone in normal & diabetic rats, also on rabbits and subsequently effectiveness and safety of the combination was evaluated. METHODS AND MATERIAL: Blood glucose concentration was determined by Glucose oxidase/peroxidase method in normal and diabetic rats. Diabetes was induced with Streptozotocin at a dose of 55 mg/kg body weight. Serum pioglitazone concentration was estimated by high performance liquid chromatography method for pharmacokinetic data. The values were expressed as Mean ± Standard Error Mean (SEM), GraphPad Prism 3.0 (San Diego, California, USA) software was used to express the data. Student's paired 't' test was used to determine the significance. RESULTS: Pioglitazone produces hypoglycaemia in normal rats with a maximum decrease of 36.78 % ± 0.81 at 3 hours interval and anti-hyperglycaemic activity in diabetic rats with maximum reduction of 45.13 % ± 1.52 at 2 hours interval. Trazodone altered the pharmacokinetics of pioglitazone and improved the pioglitazone hypoglycaemic effect. CONCLUSION: Trazodone apparently produced pharmacokinetic interaction with pioglitazone which might be by attenuating the metabolism of pioglitazone. Therefore, care should be taken in simultaneous therapy with pioglitazone and trazodone.

Predictors of acceptance and willingness to pay for the COVID-19 vaccine in the general public of India: A health belief model approach

Objective: To determine the predictors of acceptance and willingness to pay (WTP) for the COVID-19 vaccine among the Indian public and to provide insights for future demand forecasts and pricing considerations. Methods: A nationwide, web-based, self-administered, cross-sectional survey was conducted from 5 to 20 October 2020. The health belief model (HBM) approach was used as a theoretical framework to assess the predictors of acceptance of and WTP for the COVID-19 vaccine. Results: Of 2 480 respondents, 2 451 completed the online survey, yielding a response rate of 98.8%. Participants who participated in the survey had diverse demographics in terms of their location, educational level, occupation type, and family income. Among 2 451 respondents, the majority (89.3%) intended to receive the COVID-19 vaccine. Respondents with high perceived benefits of COVID-19 vaccination, such as reduction in worry (OR 5.87; 95% CI 4.39-7.96) and sickness (OR 4.31; 95% CI 3.31-5.62), showed higher intention to receive the vaccine. However, respondents with a high perception of the side effects and barriers to vaccination (OR 0.36; 95% CI 0.25-0.54) and vaccine shortage (OR 0.58; 95% CI 0.41-0.81) showed lower intention to receive the vaccine. The majority (2 162, 88.21%) of respondents were willing to pay an amount of INR: 500-1 000 or USD: 6.81-13.62 for a dose of COVID-19 vaccine, with a median (Q1, Q3) of INR: 500 (500, 1 000) or USD: 6.81 (6.81, 13.62). The higher marginal WTP for the COVID-19 vaccine was influenced by advanced age, marital status, female sex, intermediate educational background, high family income, fair or poor perceived health status, and no affordable barriers. Conclusions: The majority of respondents intended to receive the COVID-19 vaccine. Healthcare interventions focusing on HBM constructs and demographic predictors associated with low intention to receive the vaccine can be effective in enhancing the coverage of the COVID-19 vaccine. The findings of this study provide guidance for the future price considerations of the COVID-19 vaccine.

Knowledge, perception, and practices towards COVID-19 pandemic among general public of India: A cross-sectional online survey.

BACKGROUND: The success of battle against COVID-19 depends on public adherence towards infection control measures, which is greatly affected by their knowledge, perception, and practices towards this infection. AIM: To assess the knowledge, perception, and practice towards COVID-19 among the general public of India. MATERIALS AND METHODS: A cross-sectional, online survey was performed among Indian residents who were aged above 15 years. A pre-validated online questionnaire on COVID-19 was distributed through various messenger groups and social media in the author's network. The questionnaire comprised of four sections to collect data regarding demographics, knowledge, perception, and practices towards COVID-19 pandemic. Multiple linear regression analysis was used to correlate demographics with knowledge, perception and practice scores about COVID-19. RESULTS: A total of 2459 participants (Males = 1424; Females = 1035) completed the survey tool. The mean age of the study participants was 24.5 ± 7.2. The main sources for COVID-19 information were television (74.5%) and social media (71.0%). Majority of the respondents shown a correct rate of knowledge (74.7%), perception (57.6%), and practices (88.1%) towards COVID-19. Respondents aged more than 40 years; higher education level, living in urban areas, and pursuing healthcare profession were positively associated with high knowledge, perception, and practices scores towards COVID-19. CONCLUSION: The study concludes, majority of the respondents shown a good knowledge and right practices towards COVID-19 pandemic, still there was a gap in right perception towards underlying myths and facts about COVID-19. Providing educational programs and circulating WHO myth busters through media or social networks can resolve underlying misconceptions about COVID-19 and improves the knowledge, perception, and practices among public.

Effect of a polyherbal formulation in streptozotocin-induced diabetic nephropathy in wistar rats.

OBJECTIVES: Chronic kidney failure among people with diabetes mellitus (DM) is a burgeoning health problem that affects up to 25% of patients with type 2 DM. Current pharmacological treatment for diabetic nephropathy (DN) does not stop the attainment of renal complications. The intention of the current study was to explore the role of a polyherbal formulation (PHF) in diabetic-induced nephropathy in experimental animals. MATERIALS AND METHODS: Diabetic rats were grouped as follows and underwent the following treatment for about 16 weeks: Group I - normal rats - no treatment, Group II - DN rats - only vehicle (p.o), and Group III and IV - DN rats - PHF orally at 250 and 500 mg/kg, respectively. After the treatment, the animals were sacrificed, and lipid, renal function, and inflammatory markers were estimated. The observed microscopic changes in kidney were analyzed. RESULTS: Animals administered with PHF exhibited noteworthy decrease in triglycerides, total cholesterol, very low-density lipoprotein (LDL), LDL, serum creatinine, urinary protein, urinary albumin excretion rate, advanced glycation end products, type IV collagen excretion, interleukin-6, transforming growth factor-ß, and tumor necrosis factor-alpha and showed significant increase in high-density lipoprotein, urine volume, urinary urea, and urine creatinine. Histopathological examination established that administration of PHF prohibited kidney damage. CONCLUSION: Treatment with PHF showed beneficial effect on DN which may be due to the improvement of renal function parameters and hyperlipidemic and inflammatory mediators.

Evaluation of Antiulcer Activity of Peltophorum Pterocarpum.

INTRODUCTION: Peltophorum pterocarpum is a rich source for phenols and the wood, leaves, and flowers of the plant are used as medicinal agents in traditional medicine. Peptic ulcer is a major disease of gastrointestinal tract, affecting nearly 40 lac people each year worldwide and affects 10% of world population with different aetiologies. Peltophorum pterocarpum consists of phenols and flavonoids, tannins which have potential antioxidant and cytoprotective activity. AIM: To evaluate the antiulcer activity of methanolic extract of the leaves of Peltophorum pterocarpum (MEPP) on albino rats. MATERIALS AND METHODS: The rats were divided into four groups as control, standard, test 1 (extract: 100 mg/kg) and test 2 (extract: 200 mg/kg) with six rats in each group. Gastric lesions were induced by oral administration of indomethacin (20 mg/kg) followed by pylorus ligation. Standard group of animals were treated with misoprostol and test group of animals were treated with MEPP at doses of 100 and 200 mg/kg. To determine the antiulcer activity of extract, mean ulcer index, free acidity and total acidity were evaluated. RESULTS: Ulcer index was significantly decreased at p<0.01 in MEPP treated groups as compared to control group. Total and free acidity was significantly decreased at p<0.01 in MEPP treated groups as compared to control group. Histological analysis also supported the gastro protective effect of MEPP treated groups when compared with control groups. CONCLUSION: The study revealed that MEPP exhibited potential antiulcer activity and showed dose dependent antiulcer effect.