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The histone deacetylase 2 (HDAC2), an enzyme involved in gene regulation, is a potent drug target for the treatment of colon cancer. Phytocompounds having anticancer properties show the ability to interact with HDAC2 enzyme. Among the compounds, docking scores of caffeic acid (CA) and p-coumaric acid (pCA) with HDAC2 showed good binding efficacy of -5.46 kcal/mol and -5.16 kcal/mol, respectively, with small inhibition constants. The higher binding efficacy of CA compared to pCA can be credited to the presence of an extra oxygen atom in the CA molecule, which forms an additional hydrogen bond with Tyr297. The HDAC2 in complex with these molecules was found to be stable by analyzing RMSD, RMSF, Rg, and SASA values obtained through MD simulations. Furthermore, CA and pCA exhibited low MM/GBSA free energies of -16.32 ± 2.62 kcal/mol and -17.01 ± 2.87 kcal/mol, respectively. The HOMO and LUMO energy gaps, dipole moments, global reactivity descriptor values, and MEP surfaces showed the reactivity of the molecules. The favourable physicochemical and pharmacokinetic properties, along with absence of toxicity of the molecules determined using ADMET analysis, suggested both the acids to be regarded as effective drugs in the treatment of colon cancer. [ABSTRACT FROM AUTHOR]

Tuberculosis, one of the most ancient and formidable infectious diseases, primarily arises from the pathogenic bacterium Mycobacterium tuberculosis (Mtb). Phosphoenolpyruvate carboxykinase (Pck), a potential drug target, is essential for the growth of Mtb that involves in the pathway of gluconeogenesis at the centre of phosphoenolpyruvate-pyruvate-oxaloacetate node. This study aims to understand drug-like properties of the compounds derived from artemisinin, and to investigate their inhibitory roles against Mtb. Molecular docking was performed on a set of 56 artemisinin compounds to identify their binding efficacy to the Mtb protein target. Subsequently, the selected top three complexes were subjected to molecular dynamics simulations. By the trajectory analysis, root mean square deviation and radius of gyration indicated the compactness of the systems without much fluctuation. The principal component analysis revealed that the complexes were less dynamic and energetically more favourable, and Gibbs energy landscape revealed the favourable energetic transitions between conformations. The artemisinin dimer primary alcohol holding good bioavailability scores appears highly stable in complex with Pck (MM/GBSA of −37.67 kcal/mol) that stands as a potential inhibitor of the Mtb target. However, further preclinical experiments and investigations are necessary to evaluate the intrinsic properties and to confirm effectiveness of the drug candidate. [ABSTRACT FROM AUTHOR]

Most actions of daily life engage the two upper extremities (UEs) in a highly coordinated manner. While it is recognized that bimanual movements are impaired post-stroke, understanding how the paretic and non-paretic UE contributes to this impairment is important for future interventions. We investigated kinetic and kinematics at the shoulder, elbow, and wrist joints in the paretic and non-paretic UE in 8 individuals with chronic stroke and non-dominant UE in 8 healthy controls during unimanual and bimanual tasks. Kinematic analysis revealed little effect of stroke. However, kinetic analysis revealed that during unimanual movements, joint control was impaired during unimanual and bimanual movements in both UEs, although to a lesser extent in the non-paretic than paretic UE. During bimanual movements, joint control did not change in the paretic UE, and it further deteriorated in the non-paretic UE compared with the unimanual movements. Our findings suggest that a single session of bimanual task performance does not improve joint control of the paretic UE and it impairs control of the non-paretic UE, making it more like that of the paretic UE. [ABSTRACT FROM AUTHOR]

Retroperitoneal Tumors are relatively rare and usually present in locally advanced stage. They present special therapeutic challenges because of their location and frequent intimate association with major vessels in retroperitoneum. Herein, we present a case report of a patient with retropancreatic mass along with features of portal hypertension in CT scan. Intraoperatively tumor was adhered to portal vein, resection and anastomosis of Portal Vein with excision of tumor was done. Leiomysarcoma was diagnosed after histopathology and immunohistochemistry report. [ABSTRACT FROM AUTHOR]

Polyheterocyclic scaffolds were prepared by intramolec-ular aza-[4+3] cycloaddition reactions of aza-oxyallylic cations with cyclic dienes. The aza-oxyallylic cation was generated in situ by the dehydrohalogenation of a-halohydroxamates. The highly functionalized heterocyclic products undergo a variety of reactions that provide useful scaffolds for target-directed synthesis, including macrocyclic furans and polyhydroxylated azepanes. [ABSTRACT FROM AUTHOR]

The Omicron variant of SARS-CoV-2 spreads more rapidly than other variants and can affect even vaccinated individuals. The Omicron variant main protease (Mpro), crucial for viral replication and transcription, is an attractive target for antiviral drug discovery. This research aims to investigate non-toxic flavonoids that follow Lipinski's rule of five (RO5) and inhibit the Omicron variant Mpro. Molecular docking was performed on 35 flavonoids screened by analysing their medicinal values and adherence to RO5. Catechin (2-(3,4-dihydroxyphenol) chroman-3,5,7-triol), a non-toxic natural compound having predicted toxicity class 6 and LD50 value 10,000 mg/kg, exhibited a docking score of -7.1 kcal/mol with Mpro. The Mpro-catechin complex remained stable during 250 ns MD simulations. The post-MD free energy (MM/GBSA) calculations showed a binding energy of -20.5 kcal/mol, indicating strong interactions with the active amino acid residues. These findings suggest that catechin is a promising drug candidate against the Omicron variant.

Objectives: To identify the complex factors associated with anemia and overweight/obesity in pregnant Nepali women., Methods: This study was conducted with 609 pregnant women who visited the Western Regional Hospital in Pokhara, Nepal, for maternal health checkups. We assessed their nutritional status on the basis of their responses to a questionnaire (socio-economic, demographic and health information using the Nepali version of the 14-item Health Literacy Scale), hemoglobin levels and body mass index (BMI). Data were analyzed and adjusted for confounding factors by binomial logistic regression analysis; this aided in identifying factors associated with anemia and overweight/obesity., Results: The significant factor contributing to anemia is a low BMI (p=0.005, aOR=7.930, 95% CI=1.857, 33.870), followed by maternal age in the teens (p=0.000, aOR=3.018, 95% CI=1.852, 4.919). The significant factors contributing to overweight/obesity are household income, excluding the poorest (p=0.004, aOR=2.975, 95% CI=1.404, 6.303), followed by the presence of a nuclear family (p=0.000, aOR =2.156, 95% CI=1.493, 3.112). Functional literacy (p=0.005, aOR=1.045, 95% CI=1.013, 1.077) increases the risk of overweight/obesity, but critical literacy (p=0.009, aOR=0.819, 95% CI=0.705, 0.951) is a factor that buffers its onset., Conclusions: The association of malnutrition with anemia and overweight/obesity has been confirmed in pregnant Nepali women, indicating the urgent need for new supports and improvements to nutrition. Nutrition education should be designed to take into consideration reproductive generation, as well as families with low health literacy.