Applied Biosciences

The present study aims to evaluate the interaction of gliclazide with proteins related to inflammation—{inhibitor of nuclear factor kappa-B kinase subunit beta (IKKα) and NF-kappa-B-inducing kinase (NIK)}; oxidative stress—{kelch domain of Kelch-like ECH-associated protein 1 (KKeap1)} and ER stress—{inositol-requiring enzyme-1alpha (IRE1α)}. X-ray crystal structure of IKKα, (PDB ID: 5EBZ), KKeap1 (PDB ID: 4L7B), NIK (PDB ID: 8YHW) and IRE1α (PDB ID: 4YZ9) were obtained from Protein Data Bank and Open Babel 3.1.1 was used to prepare the ligands. Prior to docking, protein structures were prepared by removing water molecules, adding hydrogen atoms, and optimizing side chain conformations using Maestro (Schrödinger Suite, version 2024-2) along with the OPLS4 force field. Ligand docking was performed using the Glide application. Molecular dynamics simulation was performed with Desmond (Schrödinger Suite) within the Maestro interface for 100 ns for the NPT ensemble at 300 K and 1 atm pressure. Physicochemical and pharmacokinetics properties were analyzed using ADMETlab 3.0 and SwissADME. The binding energies of gliclazide with IKKα, NIK, KKeap1 and IRE1α were −8.3, −7.9, −8.4 and −8.8, respectively. Root mean square displacement (RMSD), root mean square fluctuation (RMSF) and radius of gyration analyses predicted relatively strong and stable interactions between gliclazide and the proteins, with favourable pharmacokinetic properties. It was also observed that CYP3A4 metabolizes gliclazide, in addition to CYP2C9 and CYP2C19. The activity of gliclazide against inflammation, oxidative stress and endoplasmic reticulum stress might be via interaction with these proteins.

Despite significant advances in neurosurgical and critical care, traumatic brain injury (TBI) remains a major cause of morbidity and mortality. Surgical treatment of intracranial hemorrhagic lesions can only target the primary mechanical injuries and their immediate consequences but fails to address the biochemical pathological cascade that unfolds during the second injury. This review synthesizes current knowledge regarding the use of several biomarkers in diagnosis and prognosis assessment. A structured literature search was conducted by querying the PubMed database. Articles evaluating diagnostic and prognostic biomarkers in adult TBI were screened according to Prisma guidelines, and data regarding biomarkers type, cut-off values, and correlations with the outcome were extracted and summarized. Among Central Nervous System (CNS)-Specific markers, S100 calcium-binding protein (S100B) emerged as a remarkably strong negative predictor for Computed Tomography (CT)-visible intracranial lesions (NPV = 97.3–100%), whereas glial fibrillary acidic protein (GFAP) yielded both high NPV and brain specificity. Coagulation parameters such as the international normalized ratio (INR) and fibrinogen were independently correlated with mortality and unfavorable outcomes. Fibrinogen displayed a bidirectional relationship with increased mortality risk at both low (<2 g/L) and high (>4.5 g/L) values. In conclusion, biomarkers quantify the otherwise invisible progression of secondary traumatic brain injury that persists even after successful surgery.

Background: Caveolin-1 (Cav-1) is a protein found in various forms and locations within cells and tissues throughout the body. Studying its structure and function provides valuable insights into key cellular processes such as growth, death, and cell signaling. This review synthesizes evidence from human studies and animal models to elucidate the complex role of Caveolin-1 (Cav-1) in regulating nitric oxide (NO) synthesis within the vasculature and perivascular adipose tissue (PVAT) during atherosclerosis. Cav-1 is a master regulator of endothelial NO synthase (eNOS), a relationship well-defined in rodent endothelial cells and cell lines. In humans, loss-of-function CAV1 mutations are linked to pulmonary arterial hypertension, suggesting a protective vascular role. Paradoxically, Cav-1 is upregulated in atherosclerotic plaques. Whether this represents a pathological process reducing NO bioavailability or a compensatory response remains unclear. Furthermore, the direct translation of the Cav-1/eNOS axis to PVAT—a metabolically active tissue expressing Cav-1—is not fully established outside of preclinical models. PVAT influences vascular tone and inflammation, potentially contributing to the paradoxical, stage-specific roles of Cav-1 in disease. Resolving these questions requires integrating human observational data with mechanistic insights from animal models to evaluate Cav-1 as a therapeutic target in vascular disease.