Thymol's modulation of cellular macromolecules, oxidative stress, DNA damage, and NF-kB/caspase-3 signaling in the liver of imidacloprid-exposed rats.

We evaluated whether thymol (THY) (30 mg/kg b.wt) could relieve the adverse effects of the neonicotinoid insecticide imidacloprid (IMD) (22.5 mg/kg b.wt) on the liver in a 56-day oral experiment and the probable underlying mechanisms. THY significantly suppressed the IMD-associated increase in hepatic enzyme leakage. Besides, the IMD-induced dyslipidemia was considerably corrected by THY. Moreover, THY significantly repressed the IMD-induced hepatic oxidative stress, lipid peroxidation, DNA damage, and inflammation. Of note, the Feulgen, mercuric bromophenol blue, and PAS-stained hepatic tissue sections analysis declared that treatment with THY largely rescued the IMD-induced depletion of the DNA, total proteins, and polysaccharides. Moreover, THY treatment did not affect the NF-kB p65 immunoexpression but markedly downregulated the Caspase-3 in the hepatocytes of the THY+IMD-treated group than the IMD-treated group. Conclusively, THY could efficiently protect against IMD-induced hepatotoxicity, probably through protecting cellular macromolecules and antioxidant, antiapoptotic, and anti-inflammatory activities.

Novel terpyridines as Staphylococcus aureus gyrase inhibitors: efficient synthesis and antibacterial assessment via solvent-drop grinding.

Aim: This study was designed to synthesize a novel series of terpyridines with potential antibacterial properties, targeting multidrug resistance. Materials & methods: Terpyridines (4a-h and 6a-c) were synthesized via a one-pot multicomponent reaction using 2,6-diacetylpyridines, benzaldehyde derivatives and malononitrile or ethyl 2-cyanoacetate. The reactions, conducted under grinding conditions with glacial acetic acid, produced high-yield compounds, confirmed by spectroscopic data. Results: The synthesized terpyridines exhibited potent antibacterial activity. Notably, compounds 4d and 4h demonstrated significant inhibition zones against Staphylococcus aureus and Bacillus subtilis, outperforming ciprofloxacin. Conclusion: Molecular docking studies highlighted compounds 4d, 4h and 6c as having strong binding affinity to DNA gyrase B, correlating with their robust antibacterial activity, suggesting their potential as effective agents against multidrug-resistant bacterial strains.

Cardioprotective Effect of Flibanserin against Isoproterenol-Induced Myocardial Infarction in Female Rats: Role of Cardiac 5-HT2A Receptor Gene/5-HT/Ca2+ Pathway.

Myocardial infarction (MI) is a life-threatening ischemic disease and is one of the leading causes of morbidity and mortality worldwide. Serotonin (5-HT) release during myocardial ischemia plays an important role in the progression of myocardial cellular injury. This study was conducted to investigate the possible cardioprotective effect of flibanserin (FLP) against isoproterenol (ISO)-induced MI in rats. Rats were randomly divided into five groups and were treated orally (p.o.) with FLP (15, 30, and 45 mg/kg) for 28 days. ISO was administered subcutaneously (S.C.) (85 mg/kg) on the 27th and 28th days to induce MI. ISO-induced myocardial infarcted rats exhibited a significant increase in cardiac markers, oxidative stress markers, cardiac and serum 5-HT levels, and total cardiac calcium (Ca2+) concentration. ISO-induced myocardial infarcted rats also revealed a remarkable alteration of electrocardiogram (ECG) pattern and significantly upregulated expression of the 5-Hydroxytryptamine 2A (5-HT2A) receptors gene. Moreover, ISO-induced myocardial infarcted rats showed significant histopathological findings of MI and hypertrophic signs. However, pretreatment with FLP significantly attenuated the ISO-induced MI in a dose-dependent manner, as the effect of FLP (45 mg/kg) was more pronounced than that of the other two doses, FLP (15 and 30 mg/kg). The present study provides evidence for the cardioprotective efficacy of FLP against ISO-induced MI in rats.

Insulin Resistance and Bone Metabolism Markers in Women with Polycystic Ovary Syndrome: A Cross-Sectional Study on Females from the Islamic University Medical Center.

Background and Objectives: polycystic ovarian syndrome (PCOS) prevails in females in the 18-40-year-old age group and varies from 5-20% depending on the demographic and diagnostic standards. It is unknown how long passes between the onset of a specific symptom and the appearance of the disease. The three most significant characteristics of PCOS include irregular menstruation, a polycystic ovarian shape found by pelvic ultrasound, and hyperandrogenism, which could possibly delay menarche. This study's objective was to assess insulin resistance and bone bio-markers' metabolism-involved characteristics of females with PCOS. Materials and Methods: We present a cross-sectional study carried out on 100 female patients suffering from PCOS and 100 healthy female subjects as a control living in Saudi Arabia in the Al-Madinah Al-Munawara Region between May 2021 and March 2022. The age of the studied groups ranges from 20-40 years, and patients were categorized into three groups; group I (control, n = 100), group IIa (overweight or obese females with PCOS, n = 70), and group IIb (non-obese females with PCOS, n = 30). The diagnosis of PCOS was carried out as per Rotterdam criteria as recommended for adolescent and adult subjects. All the groups were subjected to physical examination, and anthropometric measures, biochemical parameters, endocrine activity, and clinical parameters were determined. The data obtained were computerized and analyzed statistically using the SPSS program for range, mean, and standard deviation. ANOVA test with post hoc Tukey test was applied to assess the pattern and variation among the test and control groups. Results: In the present study, age, waist circumstances, systolic blood pressure, and diastolic blood pressure were reported enhanced in the PCOS over the control group. Additionally, anthropometric measures were reported slightly upregulated in group IIa over group IIb (p < 0.001). Biochemical parameters including glucose, insulin incidence, and lipids were reported higher in the PCOS over the control group, where group IIa showed slightly increased values compared to group IIb (p < 0.001). On the contrary, PTH, Ca+2, and 25(OH)D levels were reported lower in the PCOS over the control group. However, in the control groups, a slight variation was reported as higher in group IIa compared to group II. In the study, PTH and 25(OH)D were found associated with bone metabolism; a lower level of PTH and 25 (OH) D is linked with a decline in bone density. Conclusions: Lower serum levels of PINP and osteocalcin along with the 25(OH)D were associated with the PCOS compared to the control group, imposing a higher risk of the syndrome. On the contrary, an elevated level of NTx in groups IIa and IIb over the control group was associated with insulin resistance and bone metabolism.

Asian Pigeonwing Plants (Clitoria ternatea) Synergized Mesenchymal Stem Cells by Modulating the Inflammatory Response in Rats with Cisplatin-Induced Acute Kidney Injury.

Acute kidney injury is a heterogeneous set of disorders distinguished by a sudden decrease in the glomerular filtration rate, which is evidenced by an increase in the serum creatinine concentration or oliguria and categorized by stage and cause. It is an ever-growing health problem worldwide, with no reliable treatment. In the present study, we evaluated the role of Clitoria ternatea combined with mesenchymal stem cells in treating cisplatin-induced acute kidney injury in rats. Animals were challenged with cisplatin, followed by 400 mg/kg of Asian pigeonwing extract and/or mesenchymal stem cells (106 cells/150 g body weight). Kidney functions and enzymes were recorded, and histopathological sectioning was also performed. The expression profile of IL-1ß, IL-6, and caspase-3 was assessed using the quantitative polymerase chain reaction. The obtained data indicated that mesenchymal stem cells combined with the botanical extract modulated the creatinine uric acid and urea levels. Cisplatin increased the level of malondialdehyde and decreased the levels of both superoxide dismutase and glutathione; however, the dual treatment was capable of restoring the normal levels. Furthermore, all treatments modulated the IL-6, IL-1ß, and caspase-3 gene expression profiles. The obtained data shed some light on adjuvant therapy using C. ternatea and mesenchymal stem cells in treating acute kidney injury; however, further investigations are required to understand these agents' synergistic mechanisms fully. The total RNA was extracted from the control, the positive control, and all of the therapeutically treated animals. The expression profiles of the IL-6, IL-1ß, and caspase-3 genes were evaluated using the real-time polymerase chain reaction. Cisplatin treatment caused a significant upregulation in IL-6. All treatments could mitigate the IL-6-upregulating effect of cisplatin, with the mesenchymal stem cell treatment being the most effective. The same profile was observed in the IL-1ß and caspase-3 genes, except that the dual treatment (mesenchymal stem cells and the botanical extract) was the most effective in ameliorating the adverse effect of cisplatin; it downregulated caspase-3 expression better than the positive control.

Alhagi maurorum Ethanolic Extract Rescues Hepato-Neurotoxicity and Neurobehavioral Alterations Induced by Lead in Rats via Abrogating Oxidative Stress and the Caspase-3-Dependent Apoptotic Pathway.

This work investigated the probable protective effect of an Alhagi maurorum ethanolic extract on the hepatotoxicity and neurotoxicity accompanied by neurobehavioral deficits caused by lead in rats. Rats in four groups were orally administered distilled water, ethanolic extract of A. maurorum (300 mg/kg BW daily), lead (100 mg/kg BW daily for 3 months), and lead + A. maurorum extract. The results demonstrated that lead exposure resulted in elevated locomotor activities and sensorimotor deficits associated with a decrease in brain dopamine levels. Moreover, lead exposure significantly increased liver function markers. In addition, the lead-treated rats exhibited extensive liver and brain histological changes and apoptosis. The lead treatment also triggered oxidative stress, as demonstrated by the increase in malondialdehyde (MDA) concentrations with a remarkable reduction in the activities of antioxidant enzymes, reduced glutathione (GSH) levels, and transcriptional mRNA levels of antioxidant genes in the liver and brain. Nevertheless, co-treatment with the A. maurorum extract significantly ameliorated the lead-induced toxic effects. These findings indicate that the A. maurorum extract has the ability to protect hepatic and brain tissues against lead exposure in rats through the attenuation of apoptosis and oxidative stress.

Assessment of Pharmacological Potential of Novel Exopolysaccharide Isolated from Marine Kocuria sp. Strain AG5: Broad-Spectrum Biological Investigations.

With more than 17 clinically approved Drugs and over 20 prodrugs under clinical investigations, marine bacteria are believed to have a potential supply of innovative therapeutic bioactive compounds. In the current study, Kocuria sp. strain AG5 isolated from the Red Sea was identified and characterized by biochemical and physiological analysis, and examination of a phylogenetic 16S rRNA sequences. Innovative exopolysaccharide (EPS) was separated from the AG5 isolate as a major fraction of EPS (EPSR5, 6.84 g/L-1). The analysis of EPSR5 revealed that EPSR5 has a molecular weight (Mw) of 4.9 × 104 g/mol and number average molecular weight (Mn) of 5.4 × 104 g/mol and contains sulfate (25.6%) and uronic acid (21.77%). Analysis of the monosaccharide composition indicated that the EPSR5 fraction composes of glucose, galacturonic acid, arabinose, and xylose in a molar ratio of 2.0:0.5:0.25:1.0, respectively. Assessment of the pharmacological potency of EPSR5 was explored by examining its cytotoxicity, anti-inflammatory, antioxidant, and anti-acetylcholine esterase influences. The antioxidant effect of EPSR5 was dose- and time-dependently increased and the maximum antioxidant activity (98%) was observed at 2000 µg/mL after 120 min. Further, EPSR5 displayed a significant repressive effect regarding the proliferation of HepG-2, A-549, HCT-116, MCF7, HEP2, and PC3 cells with IC50 453.46 ± 21.8 µg/mL, 873.74 ± 15.4 µg/mL, 788.2 ± 32.6 µg/mL, 1691 ± 44.2 µg/mL, 913.1 ± 38.8 µg/mL, and 876.4 ± 39.8 µg/mL, respectively. Evaluation of the inhibitory activity of the anti-inflammatory activity of EPSR5 indicated that EPSR5 has a significant inhibitory activity toward lipoxygenase (5-LOX) and cyclooxygenase (COX-2) activities (IC50 15.39 ± 0.82 µg/mL and 28.06 ± 1.1 µg/mL, respectively). Finally, ESPR5 presented a substantial hemolysis suppressive action with an IC50 of 65.13 ± 0.89 µg /mL, and a considerable inhibitory activity toward acetylcholine esterase activity (IC50 797.02 µg/mL). Together, this study reveals that secondary metabolites produced by Kocuria sp. strain AG5 marine bacteria serve as an important source of pharmacologically active compounds, and their impact on human health is expected to grow with additional global work and research.

Thymol alleviates imidacloprid-induced testicular toxicity by modulating oxidative stress and expression of steroidogenesis and apoptosis-related genes in adult male rats.

The present work was designed to assess the potential ameliorative effect of thymol on the testicular toxicity caused by imidacloprid (IMI) in adult male rats. Forty adult male rats were allocated into four groups; control group was given corn oil, thymol-treated group (30 mg/kg b.wt), IMI-treated group (22.5 mg/kg b.wt), and IMI + thymol-treated group. All administrations were done by gavage every day for duration of 56 days. As a result, the IMI exposure caused a significant decline in the body weight change, reproductive organ weights, sperm functional parameters, and serum level of testosterone, widespread histological alterations, and apoptosis in the testis. Additionally, the IMI-treated rats exhibited a remarkable increment in the serum levels of follicle stimulating hormone and luteinizing hormone. Also, IMI induced testicular oxidative stress, as indicated by elevated malondialdehyde (MDA) levels and a marked decline in the activity of antioxidant enzymes and reduced glutathione (GSH), and total antioxidant capacity (TAC) levels. Moreover, IMI treatment significantly downregulated the mRNA expression of steroidogenic genes and proliferating cell nuclear antigen (PCNA) immunoexpression in the testicular tissue. However, thymol co-administration significantly mitigated the IMI-induced toxic effects. Our findings suggested that IMI acts as a male reproductive toxicant in rats and thymol could be a potential therapeutic option for IMI reprotoxic impacts.

Thyroid Function Assessment in Saudi Males with Metabolic Syndrome.

Background: Metabolic Syndrome (MetS) is a multifactor condition associated with cardiovascular risk. Thyroid hormones regulate MetS components via controlling energy homeostasis, lipids, and glucose metabolism. The risk ratio for MetS and related disorders changes between males and females. Aim and Objectives: Study aim to access thyroid functions in Saudi population with metabolic syndrome. Materials and Methods: The current study sought to evaluate the impact of thyroid stimulating hormone (TSH), free triiodothyronine (FT3), and free thyroxine (FT4) in predicting the risk of MetS. A total of 200 (MetS 100 and control 100) Saudi Arabian males were enrolled for the study, and after applying eligibility criteria, the eligible study size was examined for the physical test (chest, abdominal, and general examination with stress on blood pressure measurement) and anthropometric parameters (bodyweight, body mass index, and waist circumference). Results: In the present study, the biochemical parameters, such as TSH, FT3, FT4, total cholesterol (TC), triglyceride (TG), high-density lipoprotein (HDL), high-density lipoprotein (LDL), fasting glucose, and fasting insulin were measured in the study group, and statistical analysis was also performed. The results revealed that the MetS and control differ in terms of physical, anthropometric, and biochemical markers. The study showed that thyroid dysfunction (TD) and MetS are closely associated with the difference in physical, anthropometric, and metabolic characteristics. Conclusion: The result demonstrated hypothyroidism major risk factor due to TD in MetS. These findings provide a scientific basis for diagnosis and the management of TD, associated MetS, and cardiovascular disease (CVD).

Impact of Admission Glycosylated Hemoglobin A1c on Angiographic Characteristics and Short Term Clinical Outcomes of Nondiabetic Patients with Acute ST-Segment Elevation Myocardial Infarction.

We aimed to assess the predictive value of admission HbA1c level in nondiabetic patients presented by acute STEMI, on outcome of PCI and short term outcome of adverse cardiac events. Methods. 60 nondiabetic patients were admitted to Cardiology Department, Zagazig University Hospital, with acute STMI: 27 patients with HbA1c levels of 4.5% to 6.4% (group 1), 17 patients with HbA1c levels of 6.5% to 8.5% (group 2), and 16 patients with HbA1c levels higher than 8.5% (group 3). Either invasive intervention was done at admission by (pPCI) or coronary angiography was done within month (3-28 days) from taking thrombolytic. Participants were followed up for 6 months. Results. There was significant difference among different groups of HbA1c as regards the number of diseased vessels, severity of CAD lesions (p value < 0.01), and TIMI flow grades (p value < 0.05). There was significant difference among different groups as regards the adverse cardiac events on short term follow-up period (p value < 0.05). Conclusion. The present study showed that admission higher HbA1c level in patients presented by acute STEMI is associated with more severe CAD, lower rate of complete revascularization, and higher incidence of adverse cardiac events.