Indole clubbed 2,4-thiazolidinedione linked 1,2,3-triazole as a potent antimalarial and antibacterial agent against drug-resistant strain and molecular modeling studies.

In the face of escalating challenges of microbial resistance strains, this study describes the design and synthesis of 5-({1-[(1H-1,2,3-triazol-4-yl)methyl]-1H-indol-3-yl}methylene)thiazolidine-2,4-dione derivatives, which have demonstrated significant antimicrobial properties. Compared with the minimum inhibitory concentrations (MIC) values of ciprofloxacin on the respective strains, compounds 5a, 5d, 5g, 5l, and 5m exhibited potent antibacterial activity with MIC values ranging from 16 to 25 µM. Almost all the synthesized compounds showed lower MIC compared to standards against vancomycin-resistant enterococcus and methicillin-resistant Staphylococcus aureus strains. Additionally, the majority of the synthesized compounds demonstrated remarkable antifungal activity, against Candida albicans and Aspergillus niger, as compared to nystatin, griseofulvin, and fluconazole. Furthermore, the majority of compounds exhibited notable inhibitory effects against the Plasmodium falciparum strain, having IC50 values ranging from 1.31 to 2.79 µM as compared to standard quinine (2.71 µM). Cytotoxicity evaluation of compounds 5a-q on SHSY-5Y cells at up to 100 µg/mL showed no adverse effects. Comparison with control groups highlights their noncytotoxic characteristics. Molecular docking confirmed compound binding to target active sites, with stable protein-ligand complexes displaying drug-like molecules. Molecular dynamics simulations revealed dynamic stability and interactions. Rigorous tests and molecular modeling unveil the effectiveness of the compounds against drug-resistant microbes, providing hope for new antimicrobial compounds with potential safety.

Analyzing the impact of remittance, FDI and inflation rate on GDP: A comparative study of Bangladesh, Pakistan and Sri-Lanka using VAR and BEKK-GARCH approach.

This study examines the impact, conditional correlation and volatility spillover effect of remittances, foreign direct investment and inflation rate on GDP in Bangladesh, Pakistan, and Sri-Lanka, three Asian nations that are particularly vulnerable. While numerous studies have examined the relationship between remittances, FDI and IR on GDP but this paper approaches advanced econometric techniques to capture spillover effect and the dynamic interactions between the variables. For estimation purposes the study employs different econometric techniques such as Augmented Dickey-Fuller (ADF) test, VAR model, Granger causality tests, Impulse Response function, Variance Decomposition and BEKK-GARCH model. Bangladesh and Sri Lanka's REM, FDI and IR have no significant effects on GDP according to the VAR model. BEKK-GARCH demonstrates that three countries have both unidirectional and bidirectional transmissions of volatility, with the exception of Pakistan's REM and Bangladesh's FDI. We find that VAR model may not be adequate in capturing the complex dynamics between variables, which can be better captured by BEKK-GARCH model. Our comparison research shows how these variables affect GDP differently and similarly in each of the three nations, giving policymakers information they can use to create customized policies that encourage economic growth.

Protostylid: Contributing and Aggravating Factor for Periodontitis.

Clinicians should be well-versed in the anatomy, variations, and teeth anomalies. Developmental disturbances of the teeth can lead to alterations in size, shape, number, structure, and eruption of the teeth. Developmental disturbances can lead to germination, fusion, concrescence, dilaceration, talons, cusps, dens in dente, etc. Protostylid, an additional cusp on the buccal aspect of the maxillary molar, which is a rare clinical finding, can lead to plaque accumulation, making oral hygiene maintenance difficult. This leads to clinical attachment loss and bone loss. This condition may often go undiagnosed. It should be diagnosed to prevent further complications. This case has been reported to make clinicians aware of the importance of diagnosing the case at the earliest possible time so that complications can be prevented and management is easier. From the perspective of forensic dentistry, this morphological feature, though uncommon, may be useful for the classification and identification of victims in mass causalities and bite marks on bodies or inanimate objects. This is one of the rarest cases of protostylids reported to date. This may not only pose a significant problem in endodontic therapy due to morphological alterations in root canals and periodontal therapy due to grove formation leading to an inability to maintain a plaque-free area (bone loss) but also be of very significant interest from the perspective of forensic dentistry.

D-Pinitol improves cognitive dysfunction and neuronal damage induced by isoproterenol via modulation of NF-κB/BDNF/GFAP signaling in Swiss albino mice.

Objectives: Neurological disorders are the world's most distressing problem. The adverse effects of current medications continue to compel scientists to seek safer, more effective, and economically affordable alternatives. In this vein, we explored the effect of D-Pinitol on isoproterenol-induced neurotoxicity in mice. Materials and Methods: Forty-two mice were randomly distributed into 7 groups each having 6 animals. Group I; received saline. Group II; received isoproterenol (ISO) 15 mg/kg/day, s.c. for 20 days. Group III, IV; received 50 and 100 mg/kg/day/oral of D-Pinitol, respectively along with ISO for 20 days. Group V; received D-Pinitol 100 mg/kg/day/oral for 20 days. Group VI; received propranolol 20 mg/kg/day/oral and ISO for 20 days. Group VII; received propranolol 20 mg/kg/day/oral for 20 days. On the 21st day after behavioral tests, blood was collected and mice were sacrificed for various biochemical, histopathological, and immunohistochemical analyses. Results: Chronic administration of isoproterenol caused neurotoxicity, cognitive dysfunction, and histopathological changes in the brain as evidenced by increase in GFAP, oxidative stress (via SOD, CAT, TBARS, and GSH), neuroinflammation (NF-kB, TNF-α, IL-6, and IL-10), and decrease in AchE and BDNF. Co-administration of D-Pinitol (100 mg/kg) significantly prevented these pathological alterations. The cognitive improvement was also observed through the forced swim test, elevated plus maze test, and rotarod test. Conclusion: Our findings on D-Pinitol thus clearly established its neuroprotective role in ISO-induced neurodegeneration in Swiss albino mice.

Efficacy of pegylated Graphene oxide quantum dots as a nanoconjugate sustained release metformin delivery system in in vitro insulin resistance model.

Metformin, the primary therapy for type 2 diabetes mellitus (T2DM), showed limitations such as varying absorption, rapid system clearance, required large amount, resistance, longstanding side effects. Use of Nano formulations for pharmaceuticals is emerging as a viable technique to reduce negative consequences of drug, while simultaneously attaining precise release and targeted distribution. This study developed a Polyethylene Glycol conjugated Graphene Oxide Quantum dots (GOQD-PEG) nanocomposite for the sustained release of metformin. Herein, we evaluated the effectiveness of metformin-loaded nanoconjugate in in vitro insulin resistance model. Results demonstrated drug loaded nanoconjugate successfully restored glucose uptake and reversed insulin resistance in in vitro conditions at reduced dosage compared to free metformin.