Prostate cancer remains one of the leading causes of cancer-related morbidity and mortality among men worldwide. Despite considerable progress in early detection and androgen receptor-targeted therapies, the management of advanced and castration-resistant prostate cancer continues to present major clinical challenges. Nimbolide, a bioactive limonoid derived from Azadirachta indica (neem), has emerged as a promising natural compound with potent anticancer potential. This phytochemical exerts pleiotropic effects on multiple cellular processes, including proliferation, apoptosis, migration, invasion, angiogenesis, and oxidative stress. Mechanistically, nimbolide regulates both intrinsic and extrinsic apoptotic pathways through modulation of PI3K/Akt/mTOR, STAT3, NF-κB, and Bcl-2 signaling. It further inhibits metastasis and angiogenesis via HDAC6 inhibition and stabilization of cytoskeletal dynamics. In vivo studies using xenograft and transgenic mouse models confirm its ability to suppress tumor growth and metastasis with minimal systemic toxicity. This review summarizes the recent in vitro and in vivo evidence supporting nimbolide's anticancer potential in prostate cancer and discusses its molecular targets, pharmacokinetic limitations, and translational prospects.

Background: Clinical trials on drugs for cardiac diseases becomes essential as coronary artery disease is the most common cause of death globally. This study observes if COVID-19 has influenced the number and pattern of cardiac trials conducted prior to and during COVID-19 from clinical trial registry of India web portal. Methods: The CTRI website was searched for the key words “myocardial infarction”, “heart failure”, “cardiac arrhythmia”, “myocarditis” and “pulmonary embolism” and the trials registered were reviewed. Data was collected for every trial registered from 1st January 2019 to 16th April 2021. Results: 156 Clinical trials were registered in the specified period. Of which 104 were on myocardial infarction, 24 on pulmonary embolism, 13 on cardiac arrhythmia, 9 on cardiac failure and 6 on myocarditis. Among the 156 trials, 98 were observational, 53 were interventional and 5 Post marketing surveillance type. 83% of the interventional studies were randomized controlled trials. Karnataka had the maximum number of trials registered 57, followed by Delhi 37 trials. 135 trials were done in India alone and 21 trials involved other countries as well. Among the interventions, 25 were drugs, 19 medical devices, 2 cardiac rehabilitations, 2 based on Yoga, 95 trials mentioned their intervention as NA and remaining 13 were adjuvant, standard treatment, physiotherapy, homeopathy and others. Conclusions: It was observed that COVID-19 pandemic did not have an influence on the conduct and pattern of cardiac trials in India.

Objectives: To evaluate the anti-rheumatoid activity of Sesamin Complex in Freund's Complete Adjuvant (FCA) induced arthritis in Wistar albino rats. Methodology: A total of 36 female Wistar albino rats weighing 150-200 g were selected and allocated to 6 groups with 6 rats in each. Group 1 served as normal control (NC). The animals in group 2 to 6 were injected with single dose of 0.1 ml of FCA intradermally into the left hind paw on day 0. All the animals developed arthritis by day 7. From day 7 to 28, the animals were treated with the following. Group 1 & 2 normal saline 10 ml/kg, Group 3, Diclofenac 25 mg/kg, Group 4, Metho trexate 50 μg/kg/week, Group 5, Sesamin complex (SC) 15 mg/kg and Group 6, SC 30 mg/kg per oral once daily. Body weight, temperature, spontaneous activity and paw volume (PV) were measured once in 7 days for all the groups. Erythrocyte sedimentation rate (ESR), Creactive protein (CRP), Hemoglobin (Hb%), White blood cell (WBC) count, Red blood cell (RBC) count, Interleukin-6 (IL-6) and Tumor necrosis factor alpha (TNFα) were estimated on day 7 and 28. Radiological and histopathological examinations of the ankle joint were done on day 28. The results were analyzed using One-way Analysis of Variance (ANOVA) followed by post hoc (Tukey’s) test. Results: All the animals injected with FCA developed arthritis. Animals treated with SC, diclofenac and methotrexate showed a significant decrease in PV, body temperature, WBC count, ESR, CRP, IL-6 and TNF-α and a significant increase in body weight, spontaneous activity, Hb%, RBC count when compared with RA control (P < 0.01). Histopathological and radiological examination showed improvement in joint space and reduction in joint swelling in SC treated as well as the groups treated with diclofenac and methotrexate. Both SC 15 mg/kg and 30 mg/kg produced significant anti-inflammatory effect. SC 30 mg/kg produced an effect equivalent to diclofenac and methotrexate. Conclusion: Sesamin complex had anti-rheumatoid activity. The effect of 30 mg/kg of Sesamin complex was comparable to diclofenac and methotrexate.

Many clinical trials are ongoing in India to evaluate the efficacy and safety of various interventions in COVID-19. It is mandatory that the clinical trials be registered in the Clinical Trials Registry-India (CTRI) before enrollment of study participants. The present study was carried out with the objective of collecting, compiling and analyzing various types of trial data such as study design, interventions, outcomes and study sites. The clinical trial data were collected from the CTRI web portal using the key word “COVID-19” on 14 July 2020. The CTRI data output of every study registered till 14 July 2020 was stored as PDF document and the data were transcribed into a validated excel sheet based on the pre-defined methods and categories and analyzed. A total of 293 clinical studies have been registered in CTRI as on 14 July 2020. Among them, 188 (64.16%) are interventional and 105 (35.83%) are observational studies. The interventions being evaluated are modern medications including drugs and biologicals, AYUSH formulations, Nutraceuticals, Yoga and Naturopathy. Most of the interventions are already in clinical use for non-COVID indications and undergoing repurposing evaluations for COVID-19 in the clinical studies. Trials with AYUSH formulations constitute more than half of the interventional studies (51.06%) while modern medications in 31.09% of the studies. 119 trials (63.3%) of the interventional studies are randomized studies. Large numbers of trials are conducted in the states where the incidence of COVID-19 is high. 146 interventional studies out of 188 are expected to be completed within 6 months and the outcomes of these studies may provide valid information on the potential treatments in COVID-19.

Introduction: Increasing infertility rate worldwide raises research to investigate plausible reason health community. To find out the characteristics of semen and spermatozoa in alcohol users and compare these characteristics with that of non-users of alcohol. Methodology: The data on alcohol use and semen analysis were obtained from case records of patients reported to the Department of Andrology & Reproductive Medicine of a tertiary care hospital for a period of one year from January 2018 to December 2018. The semen volume, sperm concentration, motility and morphology in alcohol users were compared with non-users. Results: A total of 231 patients had reported to the Department of Andrology & Reproductive Medicine during the study period. Among them 81 (35.06%) were alcohol users and 150 (64.94%) alcohol non-users. Analysis of their semen reports revealed that the difference in semen volume and sperm morphology was not found to be statistically significant, but the sperm concentration and progressive motility of spermatozoa showed significant reduction in alcohol users compared to non – users (p<0.05). Conclusion: The semen volume and sperm quality were found to be low in alcohol users. Among the spermatozoa characteristics, sperm concentration and motility were significantly reduced in alcohol users.

The objective is to find out whether the ethanolic extract of Jackfruit skin has anticancer activity against human melanoma and colon cancer cell lines. The ethanolic extract of Jackfruit skin (EEJS) was prepared by maceration and filtration technique. The human melanoma (A-431) and colon cancer(HT-29) cell lines were procured from NCCS (National Centre for Cell Science), Pune, India and grown in DMEM (Dulbecco’s Modified Eagle Medium). Anti-cancer activity of EEJS was evaluated in-vitro by MTT (3-(4,5-dimethylthiazolyl-2)-2,5diphenyltetrazolium bromide)and LDH (Lactate dehydrogenase) assays in six different concentrations 0.5, 1, 2, 4, 8 and 12mg/ml against these two cell lines. The yield of the extract was 3.08%. EEJS exhibited cytotoxicityin all the doses and a maximum of 93% and 90% was observed at 12mg/ml againstA-431 cell lines in MTT and LDH assays respectively. The anti-colon cancer activity was 39% and 38% in both the assays. The anti-cancer activity was found to be higher for melanoma than colon cancer cell lines. EEJS showed cytotoxicity against human melanoma and colon cancer cell lines and the cytotoxicity was highly significant against melanoma than colon cancer cell lines.

Introduction: This cross-sectional survey was conducted to estimate the proportion of participants among health care workers and general population who are willing to get vaccinated against COVID-19 and those who are not, and to identify the reasons for vaccine hesitancy among the participants. Methods: Health care workers of a tertiary care hospital and the general population residing in the nearby areas of the tertiary care hospital were predominantly included in the study. A specific questionnaire was designed, validated, and administered to the participants after obtaining consent. Result: The responses were collected using Google Form and compiled in an excel sheet for analysis. The difference in opinion with regard to acceptance of the COVID-19 vaccine was statistically analysed using Chi-square test. The vaccine acceptance rate was high among the general population (70.2%) as compared to health care workers (56.7%) (p = 0.0006, highly significant). The remaining proportions of participants (43.3% of health care workers and 29.8% of general population) were hesitant to receive the COVID-19 vaccine. Conclusion: The reasons for vaccine hesitancy were fear of harmful effects, doubtful efficacy, lack of transparency in clinical trials, and fast track vaccine development.

Introduction Diabetes mellitus (DM) is a metabolic syndrome characterized by the presence of hyperglycemia that occurs due to reduction in insulin secretion or increase in insulin resistance in peripheral tissues. Sometimes both reduction in insulin secretion and increased insulin resistance can

Introduction: Proton pump inhibitors (PPI) are the drugs, most commonly used in the treatment of acid peptic diseases like gastric, duodenal ulcers, gastro-esophageal reflux disease, gastritis and Zollinger Ellison syndrome. Though they have good clinical safety profile, few adverse effects have been reported with chronic use of PPI. Hypomagnesemia is one of the adverse effects associated with long term PPI use.Hence, this study was conducted to identify the implication of long term PPI therapy on serum magnesium (Mg).Methods: It was a cross sectional, clinical study involving 60 participants in three groups. Group I included 20 subjects who were on PPI for 45 to 60 days. Group II had 20 subjects on PPI for more than 1 year. Group III (Control) had 20 subjects not on PPI. Results: Demographic data, height, weight, BMI, pulse rate and blood pressure were recorded and serum magnesium was estimated.The mean serum Mg level was found to be 2.28±0.32mg/dL in control group, 1.82±0.12mg/dl in Group I and 1.63±0.24mg/dl in Group II. One way ANOVA followed by Tukey post-hoc test was used to evaluate the difference in serum Mg levels between the groups. The difference noted in Groups I and II in comparison with Control group was statistically significant. Conclusion: This study Saradha et al (2020): Clinical assessment of the effect of chronic PPI therapy Oct 2020 Vol. 23 Issue 15 Annals of Tropical Medicine & Public Health http://doi.org/10.36295/ASRO.2020.231507 demonstrated that chronic PPI use is associated with reduced serum Mg levels and the reduction is proportionate to the duration of PPI therapy.

Introduction Tuberculosis (TB) is one of the most common diseases causing mortality worldwide. Nearly one quarter of the world’s population is having latent TB infection and 5 to 15% of the people with latent TB infection have the chance of developing active TB1. According to World Health Organ

Objective: To assess the reproductive toxicity of concoction of Andrographis paniculata in male Wistar albino rats. Methods: 18 male Wistar albino rats were divided into 3 groups with 6 animals in each group. Group 1 served as control and received distilled water. Group 2 and 3 received 0.5 ml of a concoction of Andrographis paniculata and Nilavembu kudineer (a concoction of 9 herbs) respectively for 30 days. Serum testosterone levels were measured at the baseline and at the end of the study. Animals were sacrificed at the end of the study, and histopathological examination of testes and sperm analysis were carried out. Results: There were no significant changes in the body weight and general behavior of the animals within the groups and between the groups. The differences noted in mean sperm count, as well as the qualitative characteristics such as progressive & non-progressive sperms and percentage of immotile sperms among the 3 groups, were not significant. Histopathology of testes did not show any difference between the control and treated groups. Similarly, serum testosterone levels also did not show significant changes. Conclusion: This study shows that concoction of Andrographis paniculata and Nilavembu kudineer in male Wistar albino rats, administered for 30 days, did not produce any significant adverse reproductive effects in terms of sperm count, sperm quality and testicular histology.

Objective: The objective of the study was to estimate the effects of Non-caloric Artificial Sweeteners (NAS) on glycaemic status in male Swiss albino mice. Methods: 36 male Swiss albino mice were selected and divided into six groups of 6 animals each. Group 1 served as control and received a normal pellet diet with drinking water. Groups 2, 3, 4. 5 and 6 received normal pellet diet and drinking water along with oral administration of Glucose, Saccharin, Sucralose, Aspartame, and commercial Aspartame, respectively for 8 weeks. Bodyweight of the animals was measured every week from baseline until the end of the experiment. Fasting blood glucose, serum glycated hemoglobin (HbA1c). serum insulin. Homeostatic Model Assessment of Insulin Resistance (HOMA-IR), renal function tests, liver enzymes, fecal culture, and lipid profile were assessed during baseline and end of the study. Results: The bodyweight of the animals was increased in all groups. Fasting blood glucose and HbA1c were significantly increased in NAS groups. Saccharin group showed increase in serum insulin, HOMA-IR, liver enzymes, urea, and creatinine. Aspartame group had dyslipidemic changes with deranged renal function tests. The fecal microbial culture showed Escherichia coli and Citrobacter koseri during baseline and Escherichia coli at the end of experiment. Conclusion: This study provides evidence that long term consumption of NAS can lead to significant increase in fasting blood glucose and HbA1c. The treating physicians, diabetic patients, and the general population may have to consider the metabolic problems associated with NAS before advising and/or choosing NAS for regular consumption.

Objectives: The objectives of the study were to investigate the neurological, hematological, and histological effects of chronic exposure to nitrous oxide (N2O) in male Wistar albino rats. Methodology: 12 adults, male, Wistar albino rats (150-200g) were divided into 2 groups of 6 animals each. Group 1 served as control. Group 2 received N2O + O-2 (70:30 mixture) for 1 h every day for 60 days. Neurological assessments were done by forced swim test, tail suspension test, actophotometer, rotarod, and elevated plus maze models at baseline and every 2 weeks, after that for 60 days. Complete blood count, liver function tests, renal function tests, and serum methemoglobin levels were assessed at baseline and on day 60. Rats were sacrificed on the 60th day, and histopathological examination of liver, kidney, spleen, and brain was done. Results: On comparing the results with the control group, the following changes were observed in nitrous oxide exposed rats. A: The duration of immobility was significantly reduced in forced swim test and tail suspension test, implying antidepressant-like activity. B: The activity of the animals was significantly reduced in actophotometer model, implying a reduction in the locomotor activity. C: No significant changes were observed in rotarod and elevated plus maze. D: Serum methemoglobin was significantly elevated. E: Histopathological examination showed hepatitis and interstitial nephritis. Conclusion: Chronic nitrous oxide exposure resulted in significant neurological changes, methemoglobinemia, hepatitis and interstitial nephritis. Hence healthcare workers such as dentists, doctors and paramedical staff need to take necessary precautions to prevent chronic occupational exposure of nitrous oxide.

Sesamum indicum, one of the first recorded plants used for its seeds, is reported to have analgesic, antioxidant, anticancer, anti-obesity as well as hepato and nephro protective activities. The current study evaluated the effects of two doses (400 and 800 mg/kg) of ethanolic extract of S. indicum seeds in Freund's complete adjuvant induced arthritis in rats in comparison with diclofenac and methotrexate by the changes produced in body weight, body temperature, paw volume and spontaneous activity, hemoglobin, erythrocyte sedimentation rate, total white blood cells, red blood cells, Interleukin-6 and Tumor necrosis factor-α as well as joint changes in X-ray and histological changes in joint tissue. Unlike the untreated group, the groups treated with S. indicum showed significant decrease in paw volume, body weight, white blood cell count, erythrocyte sedimentation rate, Interleukin-6 and Tumor necrosis factor-α and an increase in body weight, spontaneous activity, hemoglobin level, and red blood cell count. Histopathological examination showed gross reduction in synovial inflammation and cartilage damage. X-ray revealed significant improvement in joint space. The effect of ethanolic extract of S. indicum was found to be equivalent to methotrexate and greater than diclofenac.

Prostate cancer is most common malignancy among men in the world. PI3K-Akt signaling appears to be critical to prostate cancer cell proliferation and survival. Our earlier study reveals that nimbolide (2 µM) prevents cell survival via IGF signaling pathway through PI3K/Akt and induces apoptosis in PC-3 cell line. Akt mediates the phosphorylation and activation of mTOR that plays a critical role in the regulation of protein translation and synthesis, angiogenesis, and cell cycle progression. The present study was aimed to investigate the effect of nimbolide on tPI3K, tAkt, pAkt, tmTOR, GSK3β, pGSK3β, PCNA, c-Myc, Cyclin D1, and Survivin protein levels by western blot analysis. Apoptosis was visualized by Ao/EtBr dual staining (20×), and protein expression of PCNA by immunocytochemistry was performed. Molecular docking was performed to understand the possible interaction between nimbolide and Akt, PCNA, and Cyclin D1. Nimbolide altered the PI3K-Akt-mediated cell survival and proliferative molecules. Thus, nimbolide exerted anticancer effects in vitro by representing the PI3K-Akt-mTOR pathway in PC-3 cells. Thereby, it acts as a potent anticancer drug for prostate cancer.

Background: Prostate cancer is the most prominent cancer in men, experiencing a relapse in disease often express high serum TNF-alpha levels. It has been correlated with increased cell survival and proliferation of prostate cancer cells. Previous studies reported that nimbolide, a terpenoid derived from the leaves and flowers of neem tree inhibits cancer growth through selective modulation of cell signaling pathways linked to inflammation, survival, proliferation, angiogenesis and metastasis.Methods: The present study aimed to examine the effect of nimbolide at 1 and 2 mu M concentrations on TNF-alpha/TNFR1 mediated signaling molecules involved in cell survival and proliferation in PC-3 cell line via NF-kB and MAPK pathways by real time PCR and western blot. Protein and compound interaction were performed by Molecular docking analysis.Results: Our results indicate that nimbolide treatment suppressed expression of TNF-alpha, SODD, Grb2, SOS mRNA and modulated TNF-alpha/TNFR1 regulated NF-kB and MAPK signaling molecules in PC-3 cells. Additional molecular dynamics simulation studies confirmed the stability of nimbolide and signaling molecules binding interactions. Binding pose analysis revealed the significance of hydrogen bond interactions for effective stabilization of virtual ligand protein complexes.Conclusion: Nimbolide inhibited prostate cancer cell survival and proliferation via NF-kB and MAPK pathways. (C) 2016 Elsevier Masson SAS. All rights reserved.

Introduction: Prostate cancer is a major public health cancer worldwide, since it represents one in 10 cases of cancer in men and is of the highest incidence than any other cancers in India. Garlic has been extensively used as dietary supplements and as natural pharmaceutical in the treatment of various diseases including cancer. Methods: In-vitro Migration and Invasion assay used to assess the invasion and migration potential of cancer cells, upon treatment with DADS. In addition, using zebrafish embryo model anti-angiogenic potential of DADS was observed by RBC staining. Signaling molecules involved were analyzed using RT–PCR and Western bolt method respectively. Results: The result was found that DADS down-regulated PI3K/Akt and Ras/Raf signaling leading to down-regulation of MMPs and some pro-inflammatory/pro-angiogenic molecules especially VEGF expression at transcriptional level through hypoxia-inducible factor-1 (HIF-1). Thereby, it clearly demonstrates that the anti-invasive and anti-metastatic activity of DADS is mainly mediated through the inhibition of various pro-inflammatory and pro-angiogenic factors which regulated by this PI3K/Akt and Ras/Raf signaling. Furthermore, abrogation of blood vessel formation reversed by DADS studied using zebrafish model supports the anti-angiogenic effect of DADS. Conclusion: These findings emphasize the potential use of DADS against pathological situations where angiogenesis is stimulated during tumor progression and metastasis of prostate cancer.

Background: The objective was to study the prevalence of human leukocyte antigen (HLA)-A*3101 allele among epileptic patients and to assess the safety and efficacy of antiepileptic therapy.Methods: 295 subjects were selected and divided into two groups, Group I had 192 epileptic patients and Group II had 103 normal healthy controls. After written informed consent, 30 ml of mouthwash sample was collected from each subject and DNA was extracted by standard salting-out technique and used for HLA-A*3101 genotyping by two-step nested allele-specific polymerase chain reaction amplification and agarose gel electrophoresis.Results: In Group I, 12 (6.25%) of the 192 patients were tested positive for HLA-A*3101 allele and all were taking carbamazepine (CBZ). Among them, 56 (30%) subjects had developed less severe adverse effects such as headache and giddiness, skin rashes and memory disturbances, and HLA-A*3101 was present in 8 of them while 136 had no adverse effects in which 4 of them were tested positive for the allele. In Group II, 3 (2.9%) of the 103 healthy controls were tested positive for the allele. No difference was found in response to antiepileptic therapy between allele positive and negative patients.Conclusion: The present study had shown that HLA-A*3101 is prevalent in 6.25% of the Indian epileptic population under study. The presence of this allele has a significant association with the development of mild cutaneous reactions like skin rashes. However, no difference was observed in allele positive patients in response to antiepileptic therapy in comparison with allele negative patients.

Background & aim Prostate cancer is one of the frequently diagnosed cancers in men. Increased Growth factor IGF-1/IGF-1R axis activation mediated by both PI3K/Akt or RAF/MEK/ERK system and AR expression remains important in the development and progression of prostate cancer. Targeting such system by dietary agents quercetin in vivo model could aid its application in both treatment as well as prevention of prostate cancer. Methods In our study the rats were divided into four groups; Group I: control (propylene glycol-vehicle), Group II: cancer-induced (MNU and Testosterone treated) rats, Group III: cancer-induced + Quercetin (200 mg/kg body wt/orally) and Group IV: Quercetin (200 mg/kg body wt) thrice a week. After the treatment period rats were sacrificed and the ventral and dorsolateral prostate lobes were dissected. Results Antioxidant enzymes and apoptotic proteins were significantly decreased in cancer-induced animal and upon quercetin supplement its level was increased. The IGFIR, AKT, AR, cell proliferative and anti-apoptotic proteins were increased in cancer-induced group whereas supplement of quercetin decreased its expression. Conclusions Quercetin down regulates the cell survival, proliferative and anti-apoptotic proteins thereby prevents prostate cancer, by acting as a chemopreventive agent in preclinical model.