Traumatic brain injury (TBI) is a global health challenge; however, penetrating brain injury (PBI) remains under-represented in evidence-based knowledge and research efforts. This study utilized data from the Trauma Quality Improvement Program (TQIP) of the National Trauma Data Bank (NTDB) to investigate outcomes of PBI as compared with clinical-severity-matched non-penetrating or blunt TBI. A total of 1765 patients with PBI were 1:1 propensity score-matched for clinical severity with blunt TBI patients. The intent of PBI was self-inflicted in 34.1% of the cases, and the mechanism was firearm-inflicted in 89.1%. Mortality was found to be significantly more common in PBI than in the severity- matched TBI cohort (33.9% vs. 14.3 %, p < 0.001) as was unfavorable outcome. Mortality was mediated by withdrawal of life-sustaining therapies (WOLST) 30% of the time, and WOLST occurred earlier (median 3 days vs. 6 days, p < 0.001) in PBI. Increased rate of mortality was observed with a Glasgow Coma Scale (GCS) of <11 in PBI as compared with <7 in blunt TBI. In conclusion, PBI patients exhibited higher mortality rates and unfavorable outcomes; one third of excess mortality was mediated by WOLST. The study also brings into question the applicability of the conventional TBI classification, based on GCS, in PBI. We emphasize the need to address the observed disparities and better understand the distinctive characteristics and mechanisms underlying PBI outcomes to improve patient care and reduce mortality.

Alzheimer’s disease (AD) is a severe, varied, and complex brain condition that gradually impairs memory and cognitive function. Epidemiological studies have shown that patients who have a history of long-term NSAID use have a decreased risk of developing AD. The objective of this study is to conduct the structural analysis of a novel ibuprofen prodrug and test its anti-Alzheimer’s properties. Computational and docking studies were conducted using AMBER 18 package. The in-vivo studies were performed using aluminum chloride-induced experimental AD in rats. Adult Wistar rats of either sex were used and treated with aluminum chloride (32.5 mg/kg, p.o) and ibuprofen prodrug (50 mg/kg, p.o) daily for 30 days. The hole-board test and elevated plus maze were conducted on 10th, 20th and 30th day. Further, on 31st day, animals were euthanized and the brain tissue was used for histopathology. The results obtained were subjected to statistical analysis by one-way ANOVA and Dunnet’s test, p < 0.05 was considered to indicate the significance. The structural configuration of the novel compound indicated the presence of several structures such as aliphatic, aromatic, and asymmetry in the compound. The geometrical analysis indicated that the ibuprofen conjugate has dreiding energy of 51.22 kcal/mol with a van der waals radius of 62.56 A. The Huckel analysis confirmed the presence of aromatic rings in the compound. The molecular docking studies suggested affinity towards beta-secretase and acetylcholinesterase, besides indicating that the compound has ideal characteristics for the oral route (Log P = 2.33), cellular absorption (TPSA = 95.50), and oral bioavailability (number of rotatable bonds = 10). The toxicity profile indicated devoid of major systemic toxicity with mild possibility of cytotoxicity. The in-vivo analysis showed that the Ibu-prodrug significantly (P < 0.001) reversed the changes induced by aluminum chloride and restored histomorphological features in brain tissue. The findings suggested that the ibuprofen conjugate might possess the potential to manage the complications of AD. The action appears to be mediated through inhibition of beta-secretase and acetylcholinesterase activities. More studies might aid in identifying a specific therapeutic intervention that is still lacking in the treatment of AD.

Background: The development of novel anti-microbial drugs for multidrug-resistant (MDR) is a significant challenge. This study aimed to synthesize various derivatives of (Z)-4-(2-aminothiazol-5-yl)-N-benzohydrazide (DT01-DT10) that are effective against a wide variety of anti-bacterial and antifungal pathogens. Results: The binding energy of the compounds ranged from − 9.0 to − 10.0 kcal/mol. Molecular simulations produced a major result in improving the representation of the real biological conditions with an average RMSD of 0.110 nm. The derivatives DT03, DT04, and DT06 showed overall good anti-microbial activity at lower concentrations of 1.8 µg/ml. Compound DT03 showed significant activity against Gram-positive, Gram-negative bacteria and fungal strains, with inhibition zone diameters of 17, 19 and 16 mm, respectively. Compound DT04 showed promising anti-bacterial effects against S.mutans and C.albicans, with inhibition zone diameters of 18 and 17 mm, and moderate activity against B. cereus. Compound DT06 showed enhanced activity against P.aeruginosa. Conclusion: The derivative 4-(2-amino-1,3-thiazol-5-yl)-N′-(Z)-(2-nitrophenyl) methylidene benzohydrazide (DT06), which contained a nitro group displayed potent activity at 1.8 µg/ml with an IC₅₀ of 50.31 and a selectivity index of 61.33. Graphical

Mangiferin is obtained naturally from Mangifera indica which is used in treating various diseases including gastrointestinal tract diseases. Ulcer means the damage of the mucosal membrane which commonly occurs in the stomach and upper duodenum. In the study, an antiulcer activity was conducted and the interactivity of human carbonic anhydrase 1 was studied. The human carbonic anhydrase 1 enzyme belonging proteins were taken in the study for the molecular docking. It was observed that mangiferin showed better activity in treating ulcers. The human carbonic anhydrase enzyme also mentioned as CA1 is one of the major reasons for an increase in gastric acid which leads to ulcers. In this study, mangiferin was able to inhibit the action of the CA1 enzyme which was increasing the levels of hydrochloric acid and preventing the formation of ulcers. A protein of CA1 (PDB ID: 6G3V) was docked with mangiferin which showed good interaction with the mangiferin. Further albino rats were used for the study of ulcer activity. ADMET studies were performed for mangiferin which showed a low toxic effect. A detailed study has been depicted for ulceration and its prevention using mangiferin.

Objective: One of the declining medicinal plant species is Coptis teeta Wall, found solely in eastern parts ofIndia and China. The major chemical constituents present in the plant are berberine, pentadecanoic acid,copisine, palmatine, columbamine, epiberberineand jateorrhizine. The aim of present study is screening thephytoconstitutes in methanolic extract of roots by GC-MS analysis and isolating the pentadecanoic acid,aligned with DNA gyrase subunit B protein target involved in bacterial infection by carrying out moleculardocking.Methods: Each concentrate of Coptis teeta was evaluated for antibacterial action by plate disseminationtechnique against gram-positive and gram-negative microorganisms.GC-MS was performed for theidentification of various phytochemical constituents present in methanolic extracts of Coptis teeta.Out ofvarious chemical constituents,pentadecanoic acid was isolated and characterised by IR, 1HNMR and MASSspectroscopy.The isolated pentadecanoic acid was screened against bacterial strains such as Staphylococcusaureus, Staphylococcus epidermidis, Pseudomonas aeruginosa and Escherichia colihave shown good antibacterialactivity.Results: Column chromatography was performed for separation andGC-MS showed the presence ofpentadecanoic acid by a significant spot on methanolic extract, characterized by IR, NMR and MASS. Themethanolic extract and isolated compoundhas shown good antibacterial activity.Protein-ligand dockingwas achieved between the protein PDBID: 1KZM and pentadecanoic acid which showed a good affinityindicating its potent inhibiting action.Conclusion:In binding studies, ligand showed an interaction with amino acids residue His 170, Ala 140 andSer 246 of 1KZM which indicated the inhibition of bacterial growth.