Antibacterial Potential of Bacopa monnieri (L.) Wettst. and Its Bioactive Molecules against Uropathogens-An In Silico Study to Identify Potential Lead Molecule(s) for the Development of New Drugs to Treat Urinary Tract Infections.

Urinary tract infections (UTIs) are becoming more common, requiring extensive protection from antimicrobials. The global expansion of multi-drug resistance uropathogens in the past decade emphasizes the necessity of newer antibiotic treatments and prevention strategies for UTIs. Medicinal plants have wide therapeutic applications in both the prevention and management of many ailments. Bacopa monnieri is a medicinal plant that is found in the warmer and wetlands regions of the world. It has been used in Ayurvedic systems for centuries. The present study aimed to investigate the antibacterial potential of the extract of B. monnieri leaves and its bioactive molecules against UTIs that are caused by Klebsiella pneumoniae and Proteus mirabilis. This in vitro experimental study was conducted by an agar well diffusion method to evaluate the antimicrobial effect of 80% methanol, 96% ethanol, and aqueous extracts of B. monnieri leaves on uropathogens. Then, further screening of their phytochemicals was carried out using standard methods. To validate the bioactive molecules and the microbe interactions, AutoDock Vina software was used for molecular docking with the Klebsiella pneumoniae fosfomycin resistance protein (5WEW) and the Zn-dependent receptor-binding domain of Proteus mirabilis MR/P fimbrial adhesin MrpH (6Y4F). Toxicity prediction and drug likeness were predicted using ProTox-II and Molinspiration, respectively. A molecular dynamics (MD) simulation was carried out to study the protein ligand complexes. The methanolic leaves extract of B. monnieri revealed a 22.3 mm ± 0.6 mm to 25.0 mm ± 0.5 mm inhibition zone, while ethanolic extract seemed to produce 19.3 mm ± 0.8 mm to 23.0 mm ± 0.4 mm inhibition zones against K. pneumoniae with the use of increasing concentrations. In the case of P. mirabilis activity, the methanolic extracts showed a 21.0 mm ± 0.8 mm to 24.0 mm ± 0.6 mm zone of inhibition and the ethanol extract produced a 17.0 mm ± 0.9 mm to 23.0 mm ± 0.7 mm inhibition zone with increasing concentrations. Carbohydrates, flavonoids, saponin, phenolic, and terpenoid were common phytoconstituents identified in B. monnieri extracts. Oroxindin showed the best interactions with the binding energies with 5WEW and 6Y4F, -7.5 kcal/mol and -7.4 kcal/mol, respectively. Oroxindin, a bioactive molecule, followed Lipinski's rule of five and exhibited stability in the MD simulation. The overall results suggest that Oroxindin from B. monnieri can be a potent inhibitor for the effective killing of K. pneumoniae and P. mirabilis. Additionally, its safety has been established, indicating its potential for future drug discovery and development in the treatment for UTIs.

Effects of Tenofovir Disoproxil Fumarate on Bone Quality beyond Bone Density-A Scoping Review of the Literature.

Tenofovir disoproxil fumarate (TDF) is a widely used pharmacological agent for the treatment of human immunodeficiency virus infection. While prolonged exposure to TDF has been associated with a decrease in bone mineral density (BMD) and increased fracture risk, limited discussion exists on its effects on various aspects of bone quality. This scoping review aims to provide a comprehensive overview of the impact of TDF on bone quality beyond BMD. A literature search was conducted using the PubMed and Scopus databases to identify studies investigating the effects of TDF on bone quality. Original research articles written in English, irrespective of study type or publication year, were included in the review. Seven articles met the inclusion criteria. Findings indicate that prolonged exposure to TDF adversely affects bone microarchitecture and strength, impeding fracture healing and skeletal microdamage repair. The observed effects suggest a complex interplay involving bone cell signalling, cytokines and bone remodelling processes as potential mechanisms underlying TDF's impact on bone quality. As a conclusion, TDF impairs bone remodelling and microarchitecture by influencing dynamic bone cell behaviour and signalling pathways. Future studies should delve deeper into understanding the intricate negative effects of TDF on bone and explore strategies for reversing these effects.

Navigating Adherence: Unraveling Factors Shaping Opioid Substitution Therapy Compliance.

Background and objective In drug-deaddiction programs, dropout is a major problem in any drug de-addiction program, as dependence is a chronic illness known to relapse frequently. Understanding factors that predict dropout can help design targeted interventions to promote follow-up. This study aimed to assess the various sociodemographic characteristics of opioid-dependent subjects on buprenorphine maintenance treatment and dropping out at or before the three-month follow-up period. Method In this study, the sociodemographic characteristics and quality of life (QOL) of 34 opioid-dependent subjects (males, 32, 94%; females, 2, 6%) on the day of their enrolment in an opioid substitution therapy (OST) center were assessed, and a comparison of sociodemographic and drug use pattern was made between those who followed up and those who dropped out by the end of three months. Results Statistical analysis of the various sociodemographic characteristics using appropriate tests yielded that predictors of good follow-up are younger age (F = 4.57907, P = 0.04008), better education (F = 5.07221, P = 0.031305), and being part of a nuclear family. Longer follow-up was associated with shorter opioid intake duration (F = 8.58908, P = 0.006195). Better social relationships, as evidenced by the social relationship domain score of QOL, predicted longer follow-up (F = 8.58908, P = 0.006195). Other characteristics analyzed did not yield significant associations. Conclusions The study unveils the complexity of opioid addiction recovery, revealing the interplay of age, education, family, addiction duration, and support, shaping one's resilience in recovery.

Gene-editing, immunological and iPSCs based therapeutics for muscular dystrophy.

Muscular dystrophy is a well-known genetically heterogeneous group of rare muscle disorders. This progressive disease causes the breakdown of skeletal muscles over time and leads to grave weakness. This breakdown is caused by a diverse pattern of mutations in dystrophin and dystrophin associated protein complex. These mutations lead to the production of altered proteins in response to which, the body stimulates production of various cytokines and immune cells, particularly reactive oxygen species and NFκB. Immune cells display/exhibit a dual role by inducing muscle damage and muscle repair. Various anti-oxidants, anti-inflammatory and glucocorticoid drugs serve as potent therapeutics for muscular dystrophy. Along with the above mentioned therapeutics, induced pluripotent stem cells also serve as a novel approach paving a way for personalized treatment. These pluripotent stem cells allow regeneration of large numbers of regenerative myogenic progenitors that can be administered in muscular dystrophy patients which assist in the recovery of lost muscle fibers. In this review, we have summarized gene-editing, immunological and induced pluripotent stem cell based therapeutics for muscular dystrophy treatment.

Examining the glacial lake dynamics in a warming climate and GLOF modelling in parts of Chandra basin, Himachal Pradesh, India.

The presented study reports applicability of Lake Detection Algorithm (LDA) for an automated extraction of glacial lakes over a large geographical region and dynamics of Samudra Tapu and Gepang Gath glacial lakes. The areal extent of lake boundary extracted through LDA and areal extent of manually interpreted lake boundary exhibit a remarkable agreement (R2~0.99). Glacial lake dynamics is assessed in terms of areal and volumetric expansion for two selected glacial lakes from 1979 to 2017, i.e. Samudra Tapu (0.95 km2), and Gepang Gath (0.67 km2). They show volumetric expansion from 8.52 × 106 m3 (1979) to 80.34 × 106 m3 (2017) and 2.04 × 106 m3 (1979) to 32.44 × 106 m3 (2017) respectively. Statistical analysis (Mann-Kendall and Sen's slope) of climate data indicates rise in mean annual temperature (0.021 °C yr-1; 1961-2015) and fall in annual precipitation (-2.74 mm yr-1; 1951-2015) at different confidence intervals. Further Glacial Lake Outburst Flood (GLOF) is modelled using empirical relationship and Simplified Dam Breach Model (SMPDBK). The SMPDBK demonstrates discharge of 3866.52 and 2100.90 m3 s-1 reaching Chhatru and Sissu village posing threat to life and property. The study also exhibits that glacial shrinkage under the influence of climate change causes expansion of glacial lakes. This expansion is expected to intensify catastrophic GLOF and resultant fatalities and destruction in the downstream region.

Effect of proteolytic enzyme bromelain on pain and swelling after removal of third molars.

AIMS AND OBJECTIVES: To evaluate the effect of bromelain on pain and swelling after surgical removal of third molars. MATERIALS AND METHODS: A prospective randomized clinical study was conducted among 40 patients requiring surgical removal of impacted mandibular third molars. All the impacted molars were surgically removed, and the patients were administered bromelain along with amoxicillin. Patients were recalled on day 1, day 3, and day 7 for postoperative pain assessment using visual analogue scale (VAS) and postoperative swelling assessment using facial reference points tragus and pogonion. VAS score was statistically analyzed using repeated analysis of variance with post-hoc Bonferroni test postoperatively on day 1, day 3, and day 7 using the Statistical Package for the Social Sciences software version 14. RESULTS: Out of the total 40 patients, bromelain was effective in 28 (70%) patients. In these patients, there was reduction in swelling and pain after taking bromelain. CONCLUSION: Bromelain can be used as a successful oral enzyme therapy for oral surgery patients, especially after removal of impacted third molars.