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Abstract The widespread use of pesticides poses significant threats to both environmental and human health, primarily due to their potential toxic effects. The study investigated the cardiovascular toxicity of selected pesticides, focusing on their interactions with Toll-like receptor 4 (TLR4), an important part of the innate immune system. Using computational tools such as molecular docking, molecular dynamics (MD) simulations, principal component analysis (PCA), density functional theory (DFT) calculations, and ADME analysis, this study identified C160 as having the lowest binding affinity (-8.2 kcal/mol), followed by C107 and C165 (-8.0 kcal/mol). RMSD, RMSF, Rg, and hydrogen bond metrics indicated the formation of stable complexes between specific pesticides and TLR4. PCA revealed significant structural changes upon ligand binding, affecting stability and flexibility, while DFT calculations provided information about the stability, reactivity, and polarity of the compounds. ADME studies highlighted the solubility, permeability, and metabolic stability of C107, C160, and C165, suggesting their potential for bioavailability and impact on cardiovascular toxicity. C107 and C165 exhibit higher bioactivity scores, indicating favourable absorption, metabolism, and distribution properties. C165 also violated rule where molecular weight is greater than 500 g/mol. Further, DFT and NCI analysis of post MD conformations confirmed the binding of ligands at the binding pocket. The analysis shed light on the molecular mechanisms of pesticide-induced cardiovascular toxicity, aiding in the development of strategies to mitigate their harmful effects on human health.

In the title triangulo-triruthenium compound, [Ru3(C18H12Cl3P)(CO)11], one equatorial carbonyl group has been substituted by the monodentate phosphine ligand, leaving one equatorial and two axial carbonyl substituents on the Ru atom. The remaining two Ru atoms each carry two equatorial and two axial terminal carbonyl ligands. The three benzene rings make dihedral angles of 87.83 (17), 69.91 (17) and 68.26 (17)° with each other. In the crystal structure, molecules are linked into dimers by intermolecular C—H...O hydrogen bonds. The molecular structure is stabilized by an intramolecular C—H...O hydrogen bond.

The asymmetric unit of the title triangulo-triruthenium compound, [Ru3(C18H12Cl3P)2(CO)10]·H2O, consists of one triangulo-triruthenium complex and one disordered water solvent molecule. Two of the 3-chlorophenyl rings are disordered over two positions with refined site occupancies of 0.671 (3)/0.329 (3) and 0.628 (3)/0.372 (3). The water molecule is disordered over two positions with refined site occupancies of 0.523 (7) and 0.477 (7). Two equatorial carbonyl groups have been substituted by the two monodentate phosphine ligands, leaving one equatorial and two axial carbonyl substituents on the two Ru atoms. The remaining Ru atom carries two equatorial and two axial terminal carbonyl ligands. In the crystal structure, molecules are linked into columns along the a axis by intermolecular C—H...Cl and C—H...O hydrogen bonds. The molecular structure is stabilized by weak intramolecular C—H...O hydrogen bonds.

The asymmetric unit of the title triphenylphosphine compound, C19H17OP, consists of two crystallographically independent molecules with similar conformations. One of these two molecules has a whole-molecule disorder over two positions with refined occupancies of 0.753 (3) and 0.247 (3). The dihedral angles between the three benzene rings are 89.69 (7), 76.54 (7) and 86.02 (7)° in the non-disordered molecule and the corresponding angles are 88.3 (4), 83.2 (4) and 84.2 (3)° for the major component and 80.2 (11), 89.5 (11) and 74.4 (9)° for the minor component of the disordered molecule. This structure has been reported previously [Suomalainen et al. (2000). Eur. J. Inorg. Chem. pp. 2607–2613]; however, the disorder detailed here was not mentioned in that determination. In the crystal structure, the molecules are stacked down the b axis and stabilized by C—H...π interactions.

In the title compound, C21H21O3P, the whole molecule is disordered over two sets of positions with refined occupancies of 0.503 (1) and 0.497 (1). The dihedral angles between the three benzene rings are 72.9 (2)°, 82.9 (3)° and 70.0 (2)° in the major disorder component and the corresponding angles in the minor disorder component are 85.0 (2)°, 79.2 (2)° and 72.3 (2)°. The crystal structure is stabilized by C—H...π interactions.

In the title compound, C24H9F18OP, an intramolecular C—H...O short contact generates a five-membered ring, producing an S(5) ring motif. The dihedral angles between the benzene rings are 57.68 (10), 77.80 (11) and 79.48 (10)°. Each of the six trifluoromethyl substituents shows rotational disorder over two positions with refined site-occupany ratios of 0.64 (3)/0.36 (3), 0.649 (14)/0.351 (14), 0.52 (2)/0.48 (2), 0.545 (16)/0.455 (16), 0.774 (9)/0.226 (9) and 0.63 (5)/0.37 (5). The crystal structure is stabilized by intermolecular C—H...O and C—H...F interactions.

Naphthoquinones are secondary plant metabolites that are used to treat a variety of human ailments in traditional medicine. In light of this, the synthesis of derivatives of naphthoquinone has been investigated to include substances with potential biological processes. It has been claimed that adding chemical groups such as amines, amino acids, furan, pyran, pyrazole, triazole, and indole increases the pharmacological effects of naphthoquinones. Drugs based on 1,4 naphthoquinone ring-containing moieties have attracted a lot of interest lately because of their wide range of biological activity and possible therapeutic uses. This article offers a thorough overview of 1,4 naphthoquinone ring containing derivatives synthesizing methods and therapeutic uses. The creation of naphthoquinone scaffolds was accomplished using a variety of synthesis techniques, including both traditional chemical synthesis and contemporary green chemistry techniques. In addition, the pharmacological characteristics and therapeutic potential of medications based on 1,4 naphthoquinone ring-containing moieties are investigated in a number of disease states, including cancer, infectious illnesses, cardiovascular disorders, and neurological diseases.

AimTCF7L2 gene is believed to increase the risk of T2DM by its effects on insulin secretion. However, the exact mechanism of this enhanced risk is not clearly known. While TCF7L2 gene has been shown to affect lipid metabolism, these effects have remained largely unexplored in the context of diabetes risk.MethodsPostprandial lipid responses to a standardized fat challenge test were performed in 620 Asian Indian subjects (310 with NGT and 310 with T2DM/prediabetes) and compared between the risk and wild genotypes of the rs7903146 TCF7L2 gene. In 30 subjects scheduled to undergo abdominal surgery (10 each with NGT, Prediabetes and T2DM), adipocyte TCF7L2 gene expression was also performed by real time qPCR and confirmed by protein expression in western blot.ResultsT allele of rs7903146 TCF7L2 gene was confirmed as the risk allele for T2DM (OR=1.8(1.2-2.74), p=0.005). TT+CT genotypes of rs7903146 TCF7L2 gene showed significantly higher 4hrTg (p

Introduction: Buerger's disease, also known as thromboangiitis obliterans (TAO), is vasculitis of small- and medium-sized arteries and veins, which may involve both upper and lower extremities. It is strongly related to smoking and fairly common in the Indian subcontinent. Diagnosis is based on history, clinical examination, and angiography. The single most important modality of treatment is smoking cessation. As only few patients have suitable anatomy for surgical revascularization, the aim of this study is to evaluate the feasibility and outcome of surgical revascularization in TAO patients of North India. Methods: This is a prospective observational study involving 50 patients of TAO diagnosed by modified Shionoya criteria who underwent surgical revascularization. Computed tomographic angiography was done in all patients to see their suitability for surgical revascularization. Graft patency at 6 months postsurgery, pre- and post-operative ankle–brachial pressure index (ABPI), and visual analog scale (VAS) score for pain were calculated and compared. Results: All patients were male bidi smokers, with a mean age of 29.8 ± 9.5 years. Intermittent claudication was present in 42%, rest pain in 58%, and ulcer in 40%. Most common area of blockage was tibioperoneal trunk (62%) and tibial arteries (52%). The most frequent bypass procedure was popliteotibial done in 32 (64%) patients, followed by femoropopliteal bypass in 8 (16%) patients. Majority of our patients were symptom free at 6 months postsurgery. The mean VAS score for pain at the time of presentation was 6.08 ± 1.77, which decreased to 1.62 ± 1.23 at the end of 6 months. The mean preoperative ABPI was 0.45 ± 0.12 which improved to 0.73 ± 0.09 at 6 months postsurgery. A total of 46 (92%) limbs were salvaged while overall our graft patency rate was 70% at 6 months. Conclusion: We conclude that surgical revascularization is feasible in properly selected patients of TAO with acceptable results.

Nanoparticles (NPs) serve to reduce the toxicity, enhance bioactivity, improve targeting, and provide versatile means to control the release profile of the encapsulated moiety. Among different NPs, inorganic NPs of metals like Ag, Au, Ce, Fe, Se, Ti and Zn possess a significant place owing to their unique bioactivities in nanoforms. Selenium (Se) is an essential trace element. It is incorporated into selenoproteins as selenocysteine (Sec) representing the most important part of the active center of their enzymatic activities. Many selenoproteins have oxidoreductase activity and, thus, regulate the physiological redox balance. Se has a narrow therapeutic window and the toxicity margins are very delicate whereas the nanoparticles of Se (SeNPs) possess remarkably reduced toxicity. SeNPs have been explored in various oxidative stress and inflammation mediated disorders like arthritis, cancer, diabetes and nephropathy with potential therapeutic benefits. SeNPs constitute an attractive carrier platform to ferry various drugs to the site of action. Herein we have discussed the significance of nanosizing on the pharmacological activity of Se. The role of SeNPs in pharmacological protection against various inflammatory and oxidative stress mediated conditions is presented. However, it is largely unknown how SeNPs may affect the pharmacokinetics and pharmacodynamics of selenoproteins. Most of the available studies were poorly designed without any comparison to the other Se sources. In the future, detailed studies with inclusion of an appropriate source of Se should be carried out with emphasis on understanding the role of selenoproteins in the observed pharmacological activity.

Background: Apolipoprotein A-I (apoA-I) protects against atherosclerosis and participates in the removal of excess cellular cholesterol from peripheral organs. Several naturally occurring apoA-I mutations are associated with familial systemic amyloidosis, with deposition of amyloid aggregates in peripheral organs, resulting in multiple organ failure. Systematic studies on naturally occurring variants are needed to delineate their roles and involvement in pathogenesis. Methods: We performed a comparative structure–function analysis of five naturally occurring apoA-I variants and the wild-type protein. Circular dichroism, Fourier-transform infrared spectroscopy, thioflavin T and congo red fluorescence assays, thermal, chemical, and proteolytic stability assays, and 1,2-Dimyristoyl-sn-glycero-3-phosphocholine clearance analyses were used to assess the effects of mutations on the structure, function, stability, aggregation, and proteolytic susceptibility of the proteins to explore the mechanisms underlying amyloidosis and hypercholesterolemia. Results: We observed structural changes in the mutants independent of fibril formation, suggesting the influence of the surrounding environment. The mutants were involved in aggregate formation to varying degree; L170P, R173P, and V156E showed an increased propensity to aggregate under different physiological conditions. β sheet formation indicates that L170P and R173P participate in amyloid formation. Compared to WT, V156E and L170P exhibited higher capacity for lipid clearance. Conclusions: The selected point mutations, including those outside the hot spot regions of apoA-I structure, perturb the physiochemical and conformational behavior of the protein, influencing its function. General significance: The study provides insights into the structure–function relationships of naturally occurring apoA-I variants outside the hot spot mutation sites.