Thymoquinone inhibits prostate cancer progression by modulating Cytochrome P450 (CYPs)

Background: Prostate cancer (PCa) incidence and mortality remain high in African American (AA) than Caucasian American (CA) men. Multiple factors contribute to this critical disease disparity, androgen receptors (AR), and differences among variants of the genes such as Cytochrome P450 (CYP) are involved in androgen biosynthesis and metabolism that may switch to gene regulation for prostate growth. However, inhibitors have been approved for CYP genes, the major pitfall, undesirable side effects, and quality of life in those patients. Therefore, targeting CYPs with a natural compound, Thymoquinone (TQ), a constituent of Nigella sativa (black seed), potentially safe and curative option for PCa patients. Methods: Cell viability assay (MTT) was performed to determine IC50 value in PCa cells (MDAPCa2b (AA) and LNCaP (CA) with varying concentrations of TQ for different time intervals. Further, Live/Dead cell assay, 3D invasion, migration, immunofluorescence (IF), qRT-PCR, and western blots were used to detect the role of TQ for the expression of CYPs gene. Results: Cell viability assay determines the optimal IC50 value of TQ in both cell lines. We showed overexpression of CYP3A4 and CYP17A1 stimulates proliferative, migratory, and invasive potential of PCa cells. However, treatment with TQ significantly downregulated the expression of these genes in PCa cells. Further, TQ exhibits high specificity for MDAPCa2b compared to LNCaP cells, confirmed by IF and immunoblots. Conclusions: These results demonstrate TQ could be the potent inhibitor of the active sites of the Cytochrome P450 enzymes and be used as potential therapeutics for men of African descent

IN VITRO ANALYSIS OF ANTICANCER POTENTIAL OF TRIGONELLA FOENUM-GRAECUM

Objective: The recent work was carried out to evaluate the presence of bioactive compounds and anticancer activities of selected plant Trigonella foenum-graecum extract. Methods: The crude extraction of whole plant was carried out using petroleum ether as a solvent by cold percolation as well as hot percolation method (Soxhlet method) both. The presence of phytochemicals was determined using standard protocols. The anticancer activities were evaluated by sulforhodamine B (SRB) dye assay method using Mitomycin-C (anticancer drug) as a positive control. Results: The qualitative analysis of plant extract showed the presence of bioactive compounds, namely, protein, alkaloids, steroids, phenolics, and flavonoids. The plant extract was tested for in vitro anticancer activity against human liver cancer (HEP-2) and colon cancer (HT-29) cell lines using SRB assay. The plant extract showed significant results against HT-29 and HEP-2 cancer cell lines. Conclusion: The study concluded that the extract of T. foenum-graecum can be further carefully used in herbal formulations for cancer therapy

Green Tea Catechins Reduce Invasive Potential of Human Melanoma Cells by Targeting COX-2, PGE2 Receptors and Epithelial-to-Mesenchymal Transition

Melanoma is the most serious type of skin disease and a leading cause of death from skin disease due to its highly metastatic ability. To develop more effective chemopreventive agents for the prevention of melanoma, we have determined the effect of green tea catechins on the invasive potential of human melanoma cells and the molecular mechanisms underlying these effects using A375 (BRAF-mutated) and Hs294t (Non-BRAF-mutated) melanoma cell lines as an in vitro model. Employing cell invasion assays, we found that the inhibitory effects of green tea catechins on the cell migration were in the order of (-)-epigallocatechin-3-gallate (EGCG)>(-)-epigallocatechin>(-)-epicatechin-3-gallate>(-)-gallocatechin>(-)-epicatechin. Treatment of A375 and Hs294t cells with EGCG resulted in a dose-dependent inhibition of cell migration or invasion of these cells, which was associated with a reduction in the levels of cyclooxygenase (COX)-2, prostaglandin (PG) E2 and PGE2 receptors (EP2 and EP4). Treatment of cells with celecoxib, a COX-2 inhibitor, also inhibited melanoma cell migration. EGCG inhibits 12-O-tetradecanoylphorbol-13-acetate-, an inducer of COX-2, and PGE2-induced cell migration of cells. EGCG decreased EP2 agonist (butaprost)- and EP4 agonist (Cay10580)-induced cell migration ability. Moreover, EGCG inhibited the activation of NF-κB/p65, an upstream regulator of COX-2, in A375 melanoma cells, and treatment of cells with caffeic acid phenethyl ester, an inhibitor of NF-κB, also inhibited cell migration. Inhibition of melanoma cell migration by EGCG was associated with transition of mesenchymal stage to epithelial stage, which resulted in an increase in the levels of epithelial biomarkers (E-cadherin, cytokeratin and desmoglein 2) and a reduction in the levels of mesenchymal biomarkers (vimentin, fibronectin and N-cadherin) in A375 melanoma cells. Together, these results indicate that EGCG, a major green tea catechin, has the ability to inhibit melanoma cell invasion/migration, an essential step of metastasis, by targeting the endogenous expression of COX-2, PGE2 receptors and epithelial-to-mesenchymal transition

Morbidity Pattern Among Out-Patients Attending Urban Health Training Centre in Srinagar

The current study was designed to identify the morbidity pattern of out-patients attending Urban Health Training Centre in an urban area of a medical college in Srinagar, Pauri Garhwal district, Uttarakhand, North India. The present study record-based retrospective study was conducted among the out-patients attending the regular clinic at the Urban Health Training Centre, of a medical college in Srinagar city of Uttarakhand State of North India during the study period of one year in 2014. Data was retrieved from the OPD registers maintained at the clinic. Data was collected pertaining to socio-demographic profile, morbidity details and treatment pattern. Diseases were identified using the International Classification of Diseases (ICD-10) code. Descriptive analysis was done. During the study period, a total of 9343 subjects attended the OPD. Among them, majority of them (60%) were females. More than half (56 %) belonged to the age group of 35-65 year age-group. The association of disease classification was found to be statistically significant with respect to gender. The leading morbidity of communicable disease was found to be certain infectious and parasitic diseases especially Typhoid whereas musculoskeletal system and connective tissue disorders were the most common cause among morbidity due to NCDs. Out of all, typhoid was found to cause maximum of morbidity among the subjects. The present study highlights the morbidity pattern of communicable and NCDs among the population of hilly areas of Garhwal, Uttarakhand India. Priority should be preferred for the regular tracking of diseases in terms of preventive and promotive aspects. Morbidity in the out- door clinics reflects the emerging trend of mixed disease spectrum burden comprising communicable and non-communicable diseases

Methods, potentials, and limitations of gene delivery to regenerate central nervous system cells

This review evaluates methods, success and limitations of transgenes delivery in central nervous system (CNS). Both viral and nonviral (such as liposome mediated) methods, expression and stability of transgenes have been discussed. The controlled expression and delivery techniques of transgene at the injured or diseased sites have also been discussed. Mifepristone (RU486) and tetracycline-based switch system for controlled expression could be a very useful tool for clinical purposes. Here we emphasized the importance and consequences of viral- and nonviral-mediated transgenes transfer and therapeutic ability along with advantages of controlled expressions

Phenomenology and diagnoses associated with psychogenic non-epileptic seizures

Introduction: Psychogenic non-epileptic seizures (PNES) are seizure resembling behavior without electrical correlates insidethe brain, often having a psychogenic etiology. However, there is a paucity of research into the phenomenology, and hence,there is frequent diagnostic dilemma. The phenomenology appears to be spread across multiple diagnostic categories in nonspecificmanner. The study aimed at finding the phenomenology and the other diagnoses associated with PNES. Materials andMethods: 50 consecutive patients presenting to the tertiary psychiatric center of Eastern India were enquired on semi-structuredproforma to assess the phenomenology (including the antecedent events or stressors, ictal details, and the post-ictal stage) andassociated diagnosis. Appropriate diagnostic tools were used to verify the associated diagnoses. Results: The patients of thissample mostly belonged mostly to low socioeconomic group, females from second decade who were unemployed and had poorsocioeconomic support. They mostly had ongoing stressors, were mute during spells showed non-stereotyped movements of bodyparts. Most of them also had other Axis I and Axis II diagnosis of which depression, anxiety, and personality disorder were common.Conclusion: PNES is a non-specific expression of various underlying psychopathologies, because it is seen most often with otherindependently diagnosable psychiatric conditions