👤 Shaista Hayat

(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

Elaidic Acid (EA) is a major trans-fatty acid that has garnered significant attention due to its potential role in inducing systemic toxicity. The current investigation was conducted to assess the toxic effects of EA (50 mg/kg, 100 mg/kg, and 150 mg/kg) on testicular tissues of Sprague Dawley rats. EA intoxication disrupted Wnt/β-catenin via downregulating the expression of WNT3A and TCF7L2 while upregulating the expression of AXIN1 and GSK-3β. The activities of antioxidant enzymes were reduced while the levels of cellular oxidative stress were escalated following the EA exposure. EA administration disrupted the process of steroidogenesis as well as spermatogenesis through the downregulation of CYP11A1, 5α-reductase, 3β-HSD, CYP17A1, and StAR while elevating spermatogenic abnormalities in head, tail and neck of sperm cells. The levels of LH, androgen binding protein, FSH, inhibin B, plasma testosterone and estradiol were lowered after EA administration. Testicular tissues showed inflammatory responses after EA exposure that is evident by elevated levels of TNF-α, IL-1β, COX-2, IL-6 and NF-κB. The expressions of Bax and Caspase-3 were upsurged while expression of Bcl-2 was reduced following the EA intoxication. These findings showed EA exerted toxic effects on testicular tissues via elevating oxidative stress, inflammation and apoptosis. Show less

Identifying new genetic variants linked to plasma lipoprotein-lipid concentrations is of significant public health importance, as it can aid in developing genetic markers for CVD risk assessment, diagnosis, and prognosis. Our work aimed to investigate the relationship between lipoprotein lipase (LPL) genetic polymorphisms and hyperlipidemia in Pakistani population. To achieve this goal, 400 blood samples were obtained. DNA was extracted for the measurement of biochemical variables and genetic profiling. A lipid lowering agent, fibrate (200mg/day) is administered to the patients for two months. The online genetic epidemiology tool (http/www.oege.org) was used to determine the allelic and genomic frequencies. Odds ratio (OR) and 95% CI were calculated by chi-square. Single nucleotide polymorphism (SNP) in LPL gene, rs258 (T > C) and rs268 (A>G) were genotyped in 300 hypertriglyceridemia patients and 100 healthy/control individuals. The LPL gene showed a significant association with a high risk of hyperlipidemia diseases when differentiate the genotype evaluations between treated and untreated patients. Lipid levels were significantly (p<0.05) reduced after treatment. LPL SNP rs258 and rs268 were observed to be associated to hypertriglyceridemia in the Pakistani patients. Fibrate therapy showed a positive effect on the serum lipid levels after treating the patients with 200mg/day for two months. Show less

Acute pancreatitis results in high morbidity and mortality. Gallstones and alcoholism are considered leading causes of acute pancreatitis. However, increasing prevalence of obesity, diabetes and lifestyle choices has resulted in Hypertriglyceridaemia induced pancreatitis (HTAP) becoming more common. HTAP is said to be more severe than other causes. The treatment options available vary including intravenous (IV) insulin, heparin, plasma exchange, fibrates, niacin, omega three fatty acids and dietary restrictions. This is a case report of a patient presenting with HTAP and the dilemma treating physicians faced in trying to balance the need for urgent treatment with invasiveness of procedure and paucity of evidence. Show less

Extracellular signal-regulated kinase-1 and -2 (ERK1/2) are activated by dual threonine and tyrosine phosphorylation of a TEY motif. The highly related kinase ERK5 is also activated by phosphorylation at a TEY motif. Inactivation of ERK1/2 is achieved by distinct members of the dual-specificity protein phosphatase (DUSP) family, which are responsible for the specific, regulated de-phosphorylation of the TEY motif. These include both nuclear (DUSP5) and cytoplasmic (DUSP6) enzymes. DUSP6, a candidate tumour suppressor gene, is thought to be highly specific for inactivation of ERK1/2 but several reports have suggested that it may also inactivate ERK5. Here we have compared the ability of DUSP6 to regulate the ERK1/2 and ERK5 protein kinases. We find that DUSP6 binds to ERK1/2 in both yeast and human cells but fails to bind to ERK5. Recombinant ERK2 can induce catalytic activation of DUSP6 whereas ERK5 cannot. Ectopic expression of DUSP6 can de-phosphorylate a co-expressed ERK2 construct but does not de-phosphorylate ERK5. Finally, expression of DUSP6 blocks the MEK1-driven activation of GAL4-ELK1, an ERK1/2-regulated transcription factor, but fails to block the MEK5-driven activation of GAL4-MEF2D, an ERK5-regulated transcription factor. These results demonstrate that even upon over-expression DUSP6 fails to inactivate ERK5, confirming that it is indeed an ERK1/2-specific DUSP. Show less