Ameliorative potential of rosmarinic acid in a rat model of polycystic ovary syndrome: Targeting MCP-1 and VEGF: A histological, immunohistochemical, and biochemical study.

Polycystic ovary syndrome (PCOS) is a multidisciplinary endocrinopathy that affects women of reproductive age. It is characterized by menstrual complications, hyperandrogenism, insulin resistance, and cardiovascular issues. The current research investigated the efficacy of rosmarinic acid in letrozole-induced PCOS in adult female rats as well as the potential underlying molecular mechanisms. Forty female rats were divided into the control group, the rosmarinic acid group (50 mg/kg per orally, po) for 21 days, PCOS group; PCOS was induced by administration of letrozole (1 mg/kg po) for 21 days, and rosmarinic acid-PCOS group, received rosmarinic acid after PCOS induction. PCOS resulted in a marked elevation in both serum luteinizing hormone (LH) and testosterone levels and LH/follicle-stimulating hormone ratio with a marked reduction in serum estradiol and progesterone levels. A marked rise in tumor necrosis factor-α (TNF-α), interleukin-1ß, monocyte chemotactic protein-1, and vascular endothelial growth factor (messenger RNA) in the ovarian tissue was reported. The histological analysis displayed multiple cystic follicles in the ovarian cortex with markedly thin granulosa cell layer, vacuolated granulosa and theca cell layers, and desquamated granulosa cells. Upregulation in the immune expression of TNF-α and caspase-3 was demonstrated in the ovarian cortex. Interestingly, rosmarinic acid ameliorated the biochemical and histopathological changes. In conclusion, rosmarinic acid ameliorates letrozole-induced PCOS through its anti-inflammatory and antiangiogenesis effects.

Dynamic changes in the levels of sCD62L and SPARC in chronic myeloid leukaemia patients during imatinib treatment.

WHAT IS KNOWN AND OBJECTIVE: Chronic myeloid leukaemia (CML) microenvironment is responsible for resistance of leukaemic cells to tyrosine kinase inhibitor, altered adhesion, increased proliferation and leukaemic cells growth and survival through the secretion of many soluble molecules. We aimed at monitoring soluble L-selectin (sCD62L) and secreted protein acidic and rich in cysteine (SPARC) levels in chronic phase chronic myeloid leukaemia (CP-CML) patients and assessing the impact of imatinib on these parameters. METHODS: This prospective controlled clinical trial enrolled 35 subjects classified into two groups: control group included 10 healthy volunteers and CP-CML patients group included 25 newly diagnosed CP-CML patients received imatinib 400 mg once daily. sCD62L plasma levels, SPARC serum levels, breakpoint cluster region-Abelson1 (BCR-ABL1) %, complete blood count with differential, liver and kidney functions parameters were assessed at baseline and after 3 and 6 months of treatment. RESULTS AND DISCUSSION: At baseline, sCD62L and SPARC were significantly elevated in CP-CML patients (p < 0.05) compared to control group. After 3 months of treatment, sCD62L was non-significantly decreased (p > 0.05), while surprisingly SPARC was significantly increased (p < 0.05) compared to baseline. Moreover, after 6 months of treatment, sCD62L was significantly decreased (p < 0.05) and SPARC was non-significantly decreased (p > 0.05) compared to baseline. In addition, sCD62L was significantly correlated with WBCs and neutrophils counts, while SPARC was significantly correlated with lymphocytes count at baseline and after 3 and 6 months of imatinib treatment. WHAT IS NEW AND CONCLUSION: The elevated levels of sCD62L and SPARC at diagnosis in CP-CML patients could reflect their roles in CML pathogenesis and the dynamic changes in their levels during imatinib therapy might suppose additional mechanisms of action of imatinib beside inhibition of BCR-ABL. Furthermore, imatinib showed a significant impact on sCD62L and SPARC levels during treatment period.

Betahistine Attenuates Seizures, Neurodegeneration, Apoptosis, and Gliosis in the Cerebral Cortex and Hippocampus in a Mouse Model of Epilepsy: A Histological, Immunohistochemical, and Biochemical Study.

Epilepsy is a prevalent and chronic neurological disorder marked by recurring, uncontrollable seizures of the brain. Chronic or repeated seizures produce memory problems and induce damage to different brain regions. Histamine has been reported to have neuroprotective effects. Betahistine is a histamine analogue. The current research investigated the effects of convulsions on the cerebral cortex and hippocampus of adult male albino mice and assessed the possible protective effect of betahistine. Four groups of 40 adult male mice were organized: control, betahistine (10 mg/kg/day), pentylenetetrazole (PTZ) (40 mg/kg/ on alternate days), and Betahistine-PTZ group received betahistine 1 h before PTZ. PTZ induced a substantial rise in glutamate level and a considerable decrease in histamine level. Structural changes in the cerebral cortex and cornu ammonis (CA1) of the hippocampus were detected in the pattern of neuron degeneration. Some neurons were shrunken with dark nuclei, and others had faintly stained ones. Focal accumulation of neuroglial cells and ballooned nerve cells of the cerebral cortex were also detected. Cleaved caspase-3, glial fibrillary acidic protein, and ionized calcium-binding adaptor molecule 1 showed substantial increases, while synaptophysin expression was significantly reduced. Interestingly, these changes were less prominent in mice pretreated with betahistine. In conclusion, betahistine had shown neuroprotective properties against brain damage induced by convulsions.

Methotrexate enhances oxidative stress, apoptosis, and ultrastructural alterations in the placenta of rat.

The chemotherapeutic drug methotrexate (MTX) is utilized to treat various malignancies. MTX exposure during pregnancy causes miscarriages, abnormalities in newborns, and developmental delays. The current study examined the placenta's sequential histopathological alterations following exposure to the MTX in pregnant rats. Twenty-four pregnant rats were assigned into; the control group and MTX group (0.2 mg/kg). MTX was given intraperitoneally on gestational days 11-12. Oxidative stress parameters were measured in placental homogenates. The placental specimens were evaluated by light, immunohistochemical (caspase-3 and vascular endothelial growth factor (VEGF)), and electron microscopic study. Malondialdehyde levels were significantly elevated by MTX, whereas glutathione peroxidase and superoxide dismutase levels were significantly reduced. The MTX group showed a marked reduction in the thickness of both the basal and labyrinth zones. Degeneration of the labyrinth zone was demonstrated. Also, giant trophoblast cells and the spongiotrophoblasts of the basal zone showed vacuolations with dark nuclei. Up-regulation of caspase-3 and down-regulation of VEGF immunoexpression were demonstrated. Ultrastructurally, disintegration of the interhemal membrane, spongiotrophoblasts with vacuolated cytoplasm and small condensed nuclei, and the giant trophoblasts with irregular nuclear outlines and vacuolated cytoplasm were demonstrated. In conclusion, MTX has profoundly altered the structure of the placenta.

Optimal low voltage ride through of wind turbine doubly fed induction generator based on bonobo optimization algorithm.

The large-scale wind energy conversion system (WECS) based on a doubly fed induction generator (DFIG) has gained popularity in recent years because of its various economic and technical merits. The fast integration of WECS with existing power grids has caused negative influence on the stability and reliability of power systems. Grid voltage sags produce a high overcurrent in the DFIG rotor circuit. Such these challenges emphasise the necessity of the low voltage ride through (LVRT) capability of a DFIG for ensuring power grid stability during voltage dips. To deal with these issues simultaneously, this paper aims to obtain the optimal values of injected rotor phase voltage for DFIG and wind turbine pitch angles for all operating wind speeds in order to achieve LVRT capability. Bonobo optimizer (BO) is a new optimization algorithm that is applied to crop the optimum values of injected rotor phase voltage for DFIG and wind turbine pitch angles. These optimal values provide the maximum possible DFIG mechanical power to guarantee rotor and stator currents do not exceed the rated values and also deliver the maximum reactive power for supporting grid voltage during faults. The ideal power curve of a 2.4 MW wind turbine has been estimated to get the allowable maximum wind power for all wind speeds. To validate the results accuracy, the BO results are compared to two other optimization algorithms: particle swarm optimizer and driving training optimizer. Adaptive neuro fuzzy inference system is employed as an adaptive controller for the prediction of the values of rotor voltage and wind turbine pitch angle for any stator voltage dip and any wind speed.

Accurate emulation of steady-state and dynamic performances of PEM fuel cells using simplified models.

The current effort addresses a novel attempt to extract the seven ungiven parameters of PEMFCs stack. The sum of squared deviations (SSDs) among the measured and the relevant model-based calculated datasets is adopted to define the cost function. A Kepler Optimization Algorithm (KOA) is employed to decide the best values of these parameters within viable ranges. Initially, the KOA-based methodology is applied to assess the steady-state performance for four practical study cases under several operating conditions. The results of the KOA are appraised against four newly challenging algorithms and the other recently reported optimizers in the literature under fair comparisons, to prove its superiority. Particularly, the minimum values of the SSDs for Ballard Mark, BCS 0.5 kW, NedStack PS6, and Temasek 1 kW PEMFCs stacks are 0.810578 V2, 0.0116952 V2, 2.10847 V2, and 0.590467 V2, respectively. Furthermore, the performance measures are evaluated on various metrics. Lastly, a simplified trial to upgrade Amphlett's model to include the PEMFCs' electrical dynamic response is introduced. The KOA appears to be viable and may be extended in real-time conditions according to the presented scenarios (steady-state and transient conditions).

Delayed vs. early enteral feeding after repair of congenital recto-vestibular fistula: The effect on perineal wound healing.

Introduction: congenital Recto vestibular fistula represents the commonest type of anorectal malformation in females. The treatment of this anomaly is mainly approached either through anterior or posterior sagittal ano-rectoplasty approach. Several perioperative factors may affect the outcome. One of major postoperative complications is the occurrence of wound infection. We aimed to study the effect of delayed vs. early enteral feeding on the occurrence of perineal wound infection (PWI) after repair of congenital recto vestibular fistula. Patients and methods: Fifty-five infants with recto-vestibular fistula were included. They were managed by single stage anterior sagittal anorectoplasty (ASARP) at an age ≥3 months. Groups A and B included infants who started oral intake on the 6th and 2nd postoperative days respectively. Group A infants were kept on peripheral parenteral nutrition (PPN) during the fasting period. Results: Superficial wound infection occurred in three cases in group A while it developed in seven cases in group B. Deep perineal infection occurred in two and five cases in group A and group B respectively. The mean hospital stay was 8 days in group A vs. 13 days in group B when PWI developed. Conclusion: Delayed enteral feeding with PPN keeps the perineal wound less contaminated with stool. This promoted proper and fast healing with lower incidence of PWI. Also, PPN compensates the catabolic effects of both surgical trauma and fasting during the postoperative period and ensures maintenance of normal levels of essential nutrients that allow for proper healing.

The immune modulatory role of marjoram extract on imidacloprid induced toxic effects in thymus and spleen of adult rats.

Imidacloprid (IMID), one of environmental persistent neonicotinoid insecticides, has been used a long time ago and categorized from insecticide induced moderate toxicity by World Health Organization (WHO). Marjoram, is one of the most worldwide used herbs in Egypt due to its antioxidant, anti-inflammatory, anti-genotoxic, anti-mutagenic, anticoagulant, and beneficial effects. This study aimed to evaluate the protective role of marjoram extract on the immunotoxic response and oxidative stress induced by IMID in the immune lymphoid organs (thymus and spleen) of rats. Fifty adult male albino rats were divided randomly into five groups; negative and positive (distilled water) control, marjoram extract (200 mg/kg/day), IMID (22.5 mg/kg/day), marjoram extract + IMID (200 mg/kg +22.5 mg/kg) orally for 8 weeks. Marjoram pretreatment reversed reduced animals body, thymus and spleen weights attributed to IMID. It amended the significantly elevated total leukocytes, neutrophils percentage, increased immunoglobulin G and the significantly reduction of lymphocytes percentage, phagocytic activity, phagocytic index and lysozyme activity induced by IMID. Moreover, marjoram administration significantly reduced thymic and splenic gene expression of interleukin-1ß, interleukin-6, tumor necrosis factor-α and increased interleukin-10, in addition, it decreased thymic and splenic contents of malondialdehyde and restored the reduced antioxidant enzymes' activities following IMID exposure. Marjoram ameliorated IMID induced histopathological alterations in thymus and spleen and adjusted IMID immunomodulatory effects by increased the downregulation of CD4 and CD8 immune reactive cell expression. Conclusion, Marjoram has a protective role to reverse IMID immune toxic effects in thymus and spleen tissues of rats by its antioxidant, anti-inflammatory and immunomodulatory defense mechanisms.