Epigallocatechin gallate and curcumin inhibit Bcl-2: a pharmacophore and docking based approach against cancer.

The protein Bcl-2, well-known for its anti-apoptotic properties, has been implicated in cancer pathogenesis. Identifying the primary gene responsible for promoting improved cell survival and development has provided compelling evidence for preventing cellular death in the progression of malignancies. Numerous research studies have provided evidence that the abundance of Bcl-2 is higher in malignant cells, suggesting that suppressing Bcl-2 expression could be a viable therapeutic approach for cancer treatment. In this study, we acquired a compound collection using a database that includes constituents from Traditional Chinese Medicine (TCM). Initially, we established a pharmacophore model and utilized it to search the TCM database for potential compounds. Compounds with a fitness score exceeding 0.75 were selected for further analysis. The Absorption, Distribution, Metabolism, Excretion, and Toxicity (ADMET) analysis identified six compounds with favorable therapeutic characteristics. The compounds that successfully passed the initial screening process based on the pharmacodynamic model were subjected to further evaluation. Extra-precision (XP) docking was employed to identify the compounds with the most favorable XP docking scores. Further analysis using the Molecular Mechanics Generalized Born Surface Area (MM-GBSA) method to calculate the overall free binding energy. The binding energy between the prospective ligand molecule and the target protein Bcl-2 was assessed by a 100 ns molecular dynamics simulation for curcumin and Epigallocatechin gallate (EGCG). The findings of this investigation demonstrate the identification of a molecular structure that effectively inhibits the functionality of the Bcl-2 when bound to the ligand EGCG. Consequently, this finding presents a novel avenue for the development of pharmaceuticals capable of effectively addressing both inflammatory and tumorous conditions.

A comparative absorption study of sucrosomial® orodispersible vitamin D3 supplementation vs. a reference chewable tablet and soft gel capsule vitamin D3 in improving circulatory 25(OH)D levels in healthy adults with vitamin D deficiency-Results from a prospective randomized clinical trial.

Background: Vitamin D (Vit D) deficiency (VDD), associated with diverse health conditions, is commonly treated with Vit D3 supplements. However, the gastrointestinal (GI) absorption of Vit D3 in different formulations has not been well studied. Objective: We aimed to compare the absorption of an innovative phospholipids-sucrester matrix biodelivery vehicle-based (sucrosomial®) orodispersible Vit D3 preparation against a reference chewable tablet and soft gel capsule (SGC) Vit D3 formulations in Vit D-deficient healthy adults. Methods: In study 1, 25 subjects were randomized to receive a weekly single dose of 200,000 IU of sucrosomial® Vit D3 (n = 12) or chewable tablet Vit D3 (n = 13) for 3 weeks. In study 2, 20 subjects were randomized to receive a single dose of 200,000 IU every other week of sucrosomial® Vit D3 (n = 10) or SGC Vit D3 (n = 10) for 6 weeks. Circulatory 25-hydroxyvitamin D3 [25(OH)D] levels were reassessed after 2, 3, and 6 weeks in study 1 and after 4 and 6 weeks in study 2. Results: In study 1, after 2 weeks, circulatory 25(OH)D levels increased significantly in both Vit D3 treatment groups (p < 0.0001) but improved markedly in the sucrosomial® Vit D3 group, with no further considerable change after 3 and 6 weeks in both groups. Overall, at all three follow-ups, sucrosomial® Vit D3 treatment achieved significantly higher and sustained 25(OH)D levels (p < 0.001). In study 2, after 4 weeks, both Vit D3 treatment groups showed significant improvement in circulatory 25(OH)D levels (p < 0.0001) but substantially higher in the sucrosomial® group with statistically significant differences between the two treatment groups (p = 0.02). At the 6-week follow-up, only subjects in the sucrosomial® Vit D3 group showed a further increase in circulatory 25(OH)D levels (p = 0.049), but no further significant changes in the levels of the SGC Vit D3 group (p = 0.062), showing a statistically significant difference between the two treatment groups (p = 0.002). The Vit D3 treatment was well tolerated by all participants, and no treatment-emergent effects or serious adverse events were reported. Conclusion: Our results suggest that the sucrosomial® Vit D3 preparation absorbs efficiently in the GI system, achieving adequately higher and sustained circulatory Vit D levels in VDD, and thus can effectively contribute to the body protection against VDD-associated health conditions. Clinical trial registration: clinicaltrials.gov, identifier: NCT05706259.

Seroepidemiology of dengue fever in Khyber Pakhtunkhawa, Pakistan.

BACKGROUND: Dengue is the most important vector-borne disease in many different parts of the world and is expanding into other areas of the globe without hindrance. The morbidity and mortality due to dengue complications are increasing globally at an alarming rate. Although transmission of the dengue virus has been documented in well-characterized areas of Pakistan, its incidence in Khyber Pakhtunkhawa has not been characterized. To address this issue we aimed to determine the seroprevalence of dengue (IgM and IgG) antibodies and the disease symptoms in the population of Khyber Pakhtunkhawa, and to investigate the incidence of dengue fever in different seasons and in urban as well as in rural areas. METHODS: From August to October 2011, data of suspected dengue patients were collected from different primary, secondary, and tertiary collection centers situated in Khyber Pakhtunkhawa in order to determine the actual seroprevalence of dengue antibodies (IgM and IgG) in Khyber Pakhtunkhawa. RESULTS: A total 612 subjects with a suspected infection were enrolled in our study. Of the 612 suspected cases, 319 were found positive for dengue IgG, IgM, or both IgG and IgM. The overall weighted prevalence of dengue-specific antibodies (IgM and/or IgG) was 52.12%. Overall, of the 52.12%, 31.86% (95% confidence interval (CI) 28.17-35.55) were positive for dengue IgM and 20.26% (95% CI 17.03-23.39) were positive for dengue IgG. Only 23 (3.75%) samples showed both IgG and IgM antibodies. A higher prevalence of IgM (39.35%, 95% CI 32.84-45.86) and IgG (22.42%, 95% CI 16.86-27.98) antibodies was found in the age group 21-30 years as compared to the children age group (≤10 years) and the oldest age group (≥51 years). The mean age of the febrile cohort was 53.16 ± 44.22 years, ranging from 4 to 85 years. Age group was not statistically associated with IgM (p=0.64) or IgG (p=0.49) positivity. A higher seroprevalence of IgM (37.24%, 95%CI 32.84-45.86) was observed in males as compared to females (IgM 17.88%, 95% CI 11.11-24.65) while higher seroprevalnce of IgG (22.76%, 95% CI 15.35-30.17) was seen in females as compared to males (IgG 17.58%, 95% CI 14.21-20.95). Gender was not significantly associated with IgM (p=0.06) or IgG (p=0.53) positivity. Dengue IgM (35.38%, 95% CI 38.61-62.91) and IgG (50.76%, 95% CI 38.61-62.91) were higher in patients who had a history of travel to a dengue endemic area as compared to those who did not (IgM 33%, 95% CI 29.06-36.94, and IgG 15%, 95% CI 12.01-17.99). History of travel to an endemic area was significantly associated with IgM (p=0.023) and IgG (p=0.041) positivity. A higher incidence of IgM (41.13%, 95% CI 35.55-46.71) and IgG (27.42%, 95% CI 22.36-32.48) was observed in urban areas than in rural areas (IgM 23%, 95% CI 18.34- 27.66, and IgG 13.41%, 95% CI 9.63-17.19). IgM (p=0.0005) and IgG (p=0.0007) positivity was significantly associated with area of residence. Symptoms including fever (p=0.007), headache (p=0.001), Skin rash (0.005), joint pain (0.004) and Fatigue were significantly linked to dengue fever. IgM and IgG antibodies were more frequently seen in the post-monsoon season (68.33%) than in the monsoon period (31.68%). The death ratio in the overall weighted prevalence was 2.19%. CONCLUSION: The results of the present cohort study of febrile subjects show that young people and males are more susceptible to dengue fever. Dengue infection was most prominent in the post-monsoon season, in urban areas, and in patients with a history of travel to an endemic locality. Furthermore seven deaths were found in our cohort study.