Disruption of Th17/Tregs homeostasis plays a crucial role in governing the immune response during myocardial fibrosis and its progression to heart failure. The present study aimed to assess for the first time the possible protection afforded by rupatadine against isoproterenol-induced heart failure in rats. It also explored the role of PI3k/Akt as a possible mechanistic pathway, through which rupatadine could modulate Th17/Tregs balance to display its effect. Isoproterenol (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively and rupatadine (4 mg/kg/day) was then given orally for 14 days with or without wortmannin (PI3K/Akt inhibitor). Rupatadine succeeded to completely ameliorate isoproterenol-induced cardiac dysfunction as demonstrated by improvements of electrocardiographic and echocardiographic measurements. Moreover, rupatadine prevented the marked elevation of PAF and oxidative stress in addition to Th17 promoting cytokines (IL-6, IL-23, and TGF-β). Accordingly, rupatadine prevented Th17 stimulation or expansion as indicated by increased Foxp3/RORγt ratio and decreased production of its pro-inflammatory cytokine (IL-17). Rupatadine treatment mitigated isoproterenol-induced activation of STAT-3 signaling and the imbalance in -Akt/total Akt ratio affording marked decrease in atrogin-1 and apoptotic biomarkers. Finally, this therapy was effective in averting cardiac troponin loss and reverting the histological alterations as assessed by myocardial fibrosis and hypertrophy grading. Contrariwise, co-administration of wortmannin mostly attenuated the protective effects of rupatadine affording more or less similar results to that of isoproterenol-untreated rats. In conclusion, rupatadine could be an effective therapy against the development of isoproterenol-induced heart failure where PI3K/Akt pathway seems to play a crucial role in its protective effect.

Disruption of Th17/Tregs homeostasis plays a crucial role in governing the immune response during myocardial fibrosis and its progression to heart failure. The present study aimed to assess for the first time the possible protection afforded by rupatadine against isoproterenol-induced heart failure in rats. It also explored the role of PI3k/Akt as a possible mechanistic pathway, through which rupatadine could modulate Th17/Tregs balance to display its effect. Isoproterenol (85 and 170 mg/kg/day) was injected subcutaneously for 2 successive days, respectively and rupatadine (4 mg/kg/day) was then given orally for 14 days with or without wortmannin (PI3K/Akt inhibitor). Rupatadine succeeded to completely ameliorate isoproterenol-induced cardiac dysfunction as demonstrated by improvements of electrocardiographic and echocardiographic measurements. Moreover, rupatadine prevented the marked elevation of PAF and oxidative stress in addition to Th17 promoting cytokines (IL-6, IL-23, and TGF-β). Accordingly, rupatadine prevented Th17 stimulation or expansion as indicated by increased Foxp3/RORγt ratio and decreased production of its pro-inflammatory cytokine (IL-17). Rupatadine treatment mitigated isoproterenol-induced activation of STAT-3 signaling and the imbalance in -Akt/total Akt ratio affording marked decrease in atrogin-1 and apoptotic biomarkers. Finally, this therapy was effective in averting cardiac troponin loss and reverting the histological alterations as assessed by myocardial fibrosis and hypertrophy grading. Contrariwise, co-administration of wortmannin mostly attenuated the protective effects of rupatadine affording more or less similar results to that of isoproterenol-untreated rats. In conclusion, rupatadine could be an effective therapy against the development of isoproterenol-induced heart failure where PI3K/Akt pathway seems to play a crucial role in its protective effect.

Global agricultural systems are under unprecedented pressures due to climate change. Advanced nano-engineering can help increase crop yields while ensuring sustainability. Nanotechnology improves agricultural productivity by boosting input efficiency and reducing waste. Alkaloids as one of the numerous secondary metabolites that serve variety of cellular functions essential for physiological processes. This study tests the competence of silver nanoparticles (AgNPs) in boosting alkaloids accumulation in Catharanthus roseus suspension cultures in relation to the expression of C. roseus Mitogen Activated Protein Kinase 3 (CrMPK3) and Strictosidine Synthase (STR) genes. Five concentrations (5, 10, 15, 20 and 25 mg·L−1) of AgNPs were utilized in addition to deionized water as control. Results reflected binary positive correlations among AgNPs concentration, oxidative stress indicated with increase in hydrogen peroxide and malondialdehyde contents, activities of ascorbate peroxidase and superoxide dismutase, expression of the regulatory gene CrMPK3 and the alkaloid biosynthetic gene STR as well as alkaloids accumulation. These correlations add to the growing evidence that AgNPs can trigger the accumulation of alkaloids in plant cells through a signaling pathway that involves hydrogen peroxide and MAPKs, leading to up-regulation of the biosynthetic genes, including STR gene.

Global agricultural systems are under unprecedented pressures due to climate change. Advanced nano-engineering can help increase crop yields while ensuring sustainability. Nanotechnology improves agricultural productivity by boosting input efficiency and reducing waste. Alkaloids as one of the numerous secondary metabolites that serve variety of cellular functions essential for physiological processes. This study tests the competence of silver nanoparticles (AgNPs) in boosting alkaloids accumulation in Catharanthus roseus suspension cultures in relation to the expression of C. roseus Mitogen Activated Protein Kinase 3 (CrMPK3) and Strictosidine Synthase (STR) genes. Five concentrations (5, 10, 15, 20 and 25 mg·L−1) of AgNPs were utilized in addition to deionized water as control. Results reflected binary positive correlations among AgNPs concentration, oxidative stress indicated with increase in hydrogen peroxide and malondialdehyde contents, activities of ascorbate peroxidase and superoxide dismutase, expression of the regulatory gene CrMPK3 and the alkaloid biosynthetic gene STR as well as alkaloids accumulation. These correlations add to the growing evidence that AgNPs can trigger the accumulation of alkaloids in plant cells through a signaling pathway that involves hydrogen peroxide and MAPKs, leading to up-regulation of the biosynthetic genes, including STR gene.

Although doxorubicin (Dox) is a backbone of chemotherapy, the search for an effective and safe therapy to revoke Dox-induced acute cardiotoxicity remains a critical matter in cardiology and oncology. The current study was the first to explore the probable protective effects of native and gamma-irradiated fractions with bradykinin-potentiating activity (BPA) isolated from scorpion (Leiurus quinquestriatus) venom against Dox-induced acute cardiotoxicity in rats. Native or irradiated fractions (1 μg/g) were administered intraperitoneally (i.p.) twice per week for 3 weeks, and Dox (15 mg/kg, i.p.) was administered on day 21 at 1 h after the last native or irradiated fraction treatment. Electrocardiographic (ECG) aberrations were ameliorated in the Dox-treated rats pretreated with the native fraction, and the irradiated fraction provided greater amelioration of ECG changes than that of the native fraction. The group pretreated with native protein with BPA also exhibited significant improvements in the levels of oxidative stress-related, inflammatory, angiogenic, fibrogenic, and apoptotic markers compared with those of the Dox group. Notably, the irradiated fraction restored these biomarkers to their normal levels. Additionally, the irradiated fraction ameliorated Dox-induced histological changes and alleviated the severity of cardiac injury to a greater extent than that of the native fraction. In conclusion, the gamma-irradiated detoxified fraction of scorpion venom elicited a better cardioprotective effect than that of the native fraction against Dox-induced acute cardiotoxicity in rats.

Chronic low back pain (CLBP) is often treated with opioid analgesics (OA), a class of medications associated with a significant risk of misuse. However, little is known about how treatment with OA affect the brain in chronic pain patients. Gaining this knowledge is a necessary first step towards understanding OA associated analgesia and elucidating long-term risk of OA misuse. Here we study CLBP patients chronically medicated with opioids without any evidence of misuse and compare them to CLBP patients not on opioids and to healthy controls using structural and functional brain imaging. CLBP patients medicated with OA showed loss of volume in the nucleus accumbens and thalamus, and an overall significant decrease in signal to noise ratio in their sub-cortical areas. Power spectral density analysis (PSD) of frequency content in the accumbens' resting state activity revealed that both medicated and unmedicated patients showed loss of PSD within the slow-5 frequency band (0.01-0.027 Hz) while only CLBP patients on OA showed additional density loss within the slow-4 frequency band (0.027-0.073 Hz). We conclude that chronic treatment with OA is associated with altered brain structure and function within sensory limbic areas.

Most of the published research studies for detecting induction motor broken bar faults (BBFs) use a time–frequency (t − f ) decomposition tool to characterize the fault-related components. However, the identification and the assessment of these components in (t − f ) domain require skilled user or powerful pattern recognition technique. Moreover, a relatively long starting duration is necessary. This article introduces an automated scheme to detect BBFs and distinguish fault severity in induction motors under startup conditions regardless of the user experience and even under short starting duration and in a noisy environment. This scheme is based on the analysis of the starting current using optimized Stockwell transform (ST). An active set algorithm is applied to maximize the energy concentration of the left-side harmonic (LSH) component. Then, an adaptive time–frequency filter is applied to extract the LSH component from the (t − f ) domain, where the energy of the right part of LSH (RLSH) is utilized as an effective index for BBFs detection and for discriminating BBFs severity. Both real experimental data and simulation-based tests on 0.746- and 11-kW motors are used to extensively verify the performance of the proposed scheme. The achieved results have ensured that the proposed scheme can achieve a high accuracy with the minimum data and shortest acquisition time in comparison with some recent methods in the literature.