👤 Igor Bibi

(STL) is an extensively used anti-depressant drug that has been reported to induce organ damage including cardiac impairments. Nepetin (NEP) is a naturally derived flavonoid which exhibits excellent biological as well as pharmacological properties. This research investigation explored the cardioprotective ability of NEP to counter STL induced cardiotoxicity in Sprague Dawley rats. Thirty-six male Sprague Dawley rats were categorized into control, STL (20 mg/kg), STL (20 mg/kg) + NEP (10 mg/kg), and NEP (10 mg/kg) alone treated group. NEP intoxication significantly suppressed the expression of Notch 1, JAG1, DDL4, HES1, and HEY2 while escalating the levels of ROS and MDA. Besides, STL administration increased intraventricular septal thickness during IVSd and IVSs, promoted the internal diameter of left ventricular as well as elevated ESV as while reducing PWs and PWd, LVEF, and LVFS in echocardiographic examination. The enzymatic activities of HO-1, SOD, GPx, GSR, GST, CAT, and contents of GSH were reduced while the levels of CPK, ProBNP, troponin-T, CK-MB, LDH, C-reactive protein, BNP, and troponin-I were promoted after STL intoxication. Moreover, the levels of COX-2, IL-6, TNF-α, NF- κB, and IL-1β were elevated after STL exposure. Histopathological analysis showed abnormal cardiac architecture following the administration of STL. Importantly, NEP therapy significantly conferred cardio-protection via regulating redox state, reactivating Notch signaling, suppressing inflammatory responses, and improving histopathological alterations. Moreover, echocardiographic parameters were also found normal after NEP supplementation. These findings highlight the cardioprotective role of NEP in mitigating anti-depressant drugs induced cardiotoxicity. NEP confers cardio-protection against STL-induced cardiotoxicity via regulating oxidative stress, notch signaling, inflammation and cardiac function markers. These findings suggest this compound a promising therapy to mitigate anti-depressant drug-induced cardiac damage. Show less

Cardiovascular diseases (CVDs) are the leading cause of death worldwide, and current predictors such as lipoprotein (a) [Lp(a)] and risk scores have limitations. Automated machine learning (AutoML) offers the potential to improve CVD risk prediction by processing large datasets and developing tailored models without the need for extensive data science expertise. Using clinical datasets from the LURIC (n = 3316) and UMC/M (n = 423) studies, we built AutoML models to predict Lp(a), specific CVDs and CVD-related mortality in three phases. Phase 1 identified key CVD determinants such as age, Lp(a), troponin T, BMI and cholesterol with good accuracy (AUC 0.6249 to 0.9101). Phase 2 validated models in the UMC/M dataset and showed robust performance (AUC 0.7224 to 0.8417), with SHAP analysis highlighting predictors like statin therapy, age and NTproBNP. Phase 3 focused on cardiovascular mortality prediction, achieving high AUC values (0.74 to 0.85) and showed data drift, highlighting the need for model adjustment. Show less

Alzheimer's disease (AD) is globally recognized as a prominent cause of dementia for which efficient treatment is still lacking. New candidate compounds that are biologically potent are regularly tested. We, therefore, hypothesized to study the neuroprotective potential of Zinc Ortho Methyl Carbonodithioate (thereafter called ZOMEC) against Scopolamine (SCOP) induced Alzheimer's disease (AD) model using adult albino mice. We post-administered ZOMEC (30 mg/Kg) into two group of mice for three weeks on daily basis that received either 0.9% saline or SCOP (1 mg/Kg) for initial two weeks. The other two groups of mice received 0.9% saline and SCOP (1 mg/Kg) respectively. After memory related behavioral analysis the brain homogenates were evaluated for the antioxidant potential of ZOMEC and multiple protein markers were examined through western blotting. Our results provide enough evidences that ZOMEC decrease oxidative stress by increasing catalase (CAT) and glutathione S transferase (GST) and decreasing the lipid peroxidation (LPO). The SIRT1 and pre and post synaptic marker proteins, synaptophysin (SYP) as well as post synaptic density protein (PSD-95) expression were also enhanced upon ZOMEC treatment. Furthermore, memory impairment was rescued and ZOMEC appreciably abrogated the Aβ accumulation, BACE1 expression C and the p-JNK pathway. The inflammatory protein markers, NF-kβ and IL-1β in ZOMEC treated mice were also comparable with control group. The predicted interaction of ZOMEC with SIRT1 was further confirmed by molecular docking. These findings thus provide initial reports on efficacy of ZOMEC in SCOP induced AD model. Show less

Cytokines play an important role in SARS-CoV-2 infection progression and severity. A number of inflammatory cytokines have been directly associated with disease severity including IL-6 (interleukin-6), IL-10, TNF-α (tumor necrosis factor alpha), IFN-γ (interferon-gamma). Here, in this study, the aim was to better understand the interplay between host immune response mediated by cytokines and severity of SARS-CoV-2 infection by assessing cytokine expression. Therefore, we measured expression levels of a total of 12 genes (IFNA-1, IFN-γ, IL-1α, IL-1β, IL-4, IL-6, IL-7, IL-10, IL-11, IL-13, IL-15, and IL-27) encoding inflammatory, anti-inflammatory and regulatory cytokines using QRT-PCR in hospitalized patients with severe infection compared to mildly infected. IFN-γ was identified as a potent marker of disease severity as indicated previously. Moreover, levels of IL-7 were also found to be partially reduced in patients compared to the healthy controls and linked negatively to disease severity. Identification of these cytokines may be helpful in not only understanding disease pathogenesis but also in better management of the patients after covid infection. Show less

Much of our knowledge on the function of proteins is deduced from their mature, folded states. However, it is unknown whether partially synthesized nascent protein segments can execute biological functions during translation and whether their premature folding states matter. A recent observation that a nascent chain performs a distinct function, co-translational targeting in vivo, has been made with the Escherichia coli signal recognition particle receptor FtsY, a major player in the conserved pathway of membrane protein biogenesis. FtsY functions as a membrane-associated entity, but very little is known about the mode of its targeting to the membrane. Here we investigated the underlying structural mechanism of the co-translational FtsY targeting to the membrane. Our results show that helices N Show less

Specific genetic anomalies or non-genetic factors could lead to epilepsy, but in various cases the underlying cause is unknown. Novel technologies, such as array comparative genomic hybridization, may reveal the copy number variants (CNVs), established as significant risk factor for epilepsy. This study carried out a high-density whole genome array- comparative genomic hybridization analysis with blood DNA samples from a cohort of twenty epilepsy patients to search for CNVs associated with epilepsy. Microdeletion of 14q31.1 was observed in four patients including two from the same family with loss of the NRXN3 gene; microdeletion of 15q12 in one patient with loss of the GABRG3 gene, and microduplication of 20q13.33 in three patients with loss of the gene group CHRNA4, KCNQ2, EEF1A2 and PPDPF were also found. These CNV findings were confirmed by real-time quantitative polymerase chain reaction. We have described, for the first time, numerous potential CNVs/genes implicated in epilepsy in the Saudi population. The study presents a better description of the genetic variations in epilepsy, and would eventually enable us to provide a foundation for understanding the critical genome regions which might be involved in the development of epilepsy. Show less