Background Pain-associated depression is a symptom of many diseases such as cancer, and postoperative and myocardial infarction. Tramadol (TRM) is a centrally acting synthetic opioid, similar to an analgesic, used worldwide to treat severe pain with an anti-depressant-like effect. TRM is more popular abused among adults in most countries to relive pain and increase sexual activities. Thymoquinone (TQ), a volatile oil, is one of the main constituents of Nigella sativa seeds. It has anti-inflammatory, antioxidant, anticonvulsant, antitussive, and anti-tumor effects. The aim of work The present study was designed to evaluate the effects of TRM on the structure of cerebral cortex of the adult male albino rats and the possible impact of using TQ to improve these changes and to test the analgesic, anti-depressant, and antioxidant effects of TRM and/or TQ. Materials and methods Forty-eight male albino rats weighting 180–200 g were used in the present study. The rats were divided into four groups: control group (GI): 12 rats received food and water. TQ group (GII): 12 rats received an oral dose of TQ (20 mg/kg) for 4 weeks. TRM group (GIII): 12 rats received an oral dose of TRM HCl (50 mg/kg) for 4 weeks. Combined group (GIV): 12 rats received both TRM (50 mg/kg) and TQ (20 mg/kg) for 4 weeks. Results TQ supplementation significantly increased the analgesic effect of TRM after acute and chronic treatment by the thermal and chemical methods and attenuated the development of tolerance. TQ also significantly improved the anti-depressant effect of TRM. Furthermore, TQ significantly increased the suppressed levels of glutathione content and activities of superoxide dismutase, catalase, and glutathione peroxidase induced by TRM. It also significantly reduced the elevated levels of malondialdehyde and nitric oxide caused by TRM. Histological examination of TRM-treated cerebral cortex showed distortion of its layers, increased vascularity, and cellularity, with a significantly increased number of apoptotic cells. TRM also induced a significant increase in the mean area percentage of both apoptotic index and the optical density of BAX immune-stain compared with the control group. These changes were improved in TQ-treated rats. Conclusion TQ supplementation improved the analgesic, anti-depressant effects of TRM, with an improvement in the cerebral cortex structure and antioxidant markers and amelioration of oxidative stress markers. Furthermore, it attenuated TRM tolerance and neurotoxic effects.

Diabetic retinopathy (DR) is a typical microvascular complication of diabetes mellitus (DM) and it remains one of the leading causes of vision loss worldwide. Studies postulated that a distinct metabolic signature of DR exists and can be resolved from that of diabetes alone. Serum Semaphorin3A (Sema3A) levels have also been found to be correlated with the phenotypes of diabetic retinopathy. We aimed to analyze and identify serum metabolites and serum Sema3A levels that could be useful biomarkers of DR progression. This cross-sectional study included 45 type 2 diabetes (T2D) patients. Diabetic patients were divided into three groups based on the status of their complications: non-DR (NDR, n=15), non-proliferative DR (NPDR, n=15), and proliferative DR (PDR, n=15) groups. Serum metabolomic profiles of these patients were determined by using high-performance liquid chromatography-mass spectrometry (HPLC-MS), and serum Sema3A levels measured by ELISA. Metabolomics analysis revealed a set of metabolites that were altered in the serum of PDR patients as compared with NPDR and NDR groups. Among these metabolites total asymmetric dimethylarginine (ADMA) and Kynurenine were potential predictors of PDR patients. Significantly higher serum levels of Sema3A in PDR patients as compared with NPDR and NDR groups (p<0.001), their serum levels were positively correlated with the central macular thickness (r= 0.952, p<0.001) and negatively correlated with the superficial macular density (r=-0.952, p<0.001). In conclusion, the metabolite signatures identified in this study and serum Sema3A levels could be proposed as biomarkers for DR development and progression in T2D patients. However, Sema3A was superior to metabolomics in the prediction of the severity of DR.

Preeclampsia (PE) is a pregnancy disorder characterized by hypertension and end-organ damage. Reliable biochemical markers for diagnosis and prediction of PE severity can improve maternal health, and several of these markers have been suggested till now. The goal of our study was to evaluate maternal serum levels of Perlecan and Ischemia modified albumin (IMA) in PE patients, and to investigate their relationship with the severity. This study included 45 pregnant women, who were divided into three groups: mild PE (n=15), severe PE (n=10), and normal pregnant females (n=20) as a control group. Maternal serum levels of Perlecan and IMA were determined by the enzyme linked immunosorbent assay (ELISA). Preeclamptic women with severe features have significantly higher serum Perlecan and IMA levels than women with mild PE and control (P<0.001 for both). Serum levels of Perlecan and IMA were significantly increased in patients with mild PE as compared with control (P<0.001 for both). Serum Perlecan levels were positively correlated with systolic blood pressure (SBP), diastolic blood pressure (DBP), ALT, AST, creatinine, urea, uric acid, and proteinuria, but negatively correlated with platelet count and fetal birth weight. Serum IMA level was positively correlated with SBP, DBP, but negatively correlated with Albumin, and fetal birth weight. The receiver operating characteristic (ROC) curve analysis was performed to evaluate the diagnostic performance of Perlecan and IMA in the prediction of PE severity. Serum Perlecan had greater sensitivity and lower specificity for severe PE than for mild PE. Serum IMA had greater sensitivity and lower specificity for severe PE than for mild PE. In conclusion, maternal serum Perlecan and IMA levels were biomarkers for monitoring PE and the increase in serum Perlecan levels was in accordance with the severity of PE. Also, Perlecan was superior to IMA as a predictor for PE severity.

Background: Zingerone is one of the active components of ginger that possesses multiple biological activities and anti-inflammatory properties against either radiation effect or cisplatin toxicity. Purpose: to examine the protective effect of zingerone against gamma radiation (IR) or cisplatin-induced immunotoxicity. Material and Methods: 48 rats were divided into six groups as follows: (group-1); normal control group received distilled water; (group-2); rats received Zingerone orally at a dose of 25 mg/kg b.wt. Once / day for 14 consecutive days (Zing.). (group-3); Rats were given a single injection of Cisplatin at a dose of 7.5 mg/kg b.wt. intraperitoneally (Cispl.). (group-4); Rats exposed to a single dose of 6 Gy whole-body gamma irradiation using 137Cesium source in a Gamma cell 40 (Rad.). (group-5); rats received same dose of Zingerone then they were exposed to gamma radiation as in group 4 (Zing+Rad.). (group-6); rats received Zingerone followed by single injection of Cisplatin at the dose of 7.5 mg/kg b.wt. Intraperitoneally (Zing+Cisp.). Results: Exhibited a significant increase in expression of NF-κB, IL-10, caspase-3, and gene expression of TNF-α as well as oxidative stress biomarkers (MDA and NO) levels accompanied with a reduced level of SOD in either whole body-irradiated or cisplatin-received group. Conversely, pro-inflammatory cytokines levels were significantly decreased with an improvement of oxidative stress in groups that received zingerone. Conclusion: It could be concluded that zingerone exerts its antioxidative activity and immunomodulatory effects through inhibition of pro-inflammatory mediators induced by whole body-gamma irradiation or cisplatin administration at two time interval early and late stage of radiation exposure (after 2 h and one week).Therefore, further studies are required to elucidate the molecular signaling pathway concerning zingerone.

Background: Metabolic syndrome (MS) increases the risk of developing cardiovascular diseases (CVDs) which are the leading cause of death worldwide.Objective: This study is aiming to investigate the curative effects of dipeptidyl peptidase-4 inhibitors and the prophylactic effects of curcumin on diet induced metabolic syndrome which is associated with cardiac dysfunction in rats.Methodology: sixty adult male albino rats were divided into six groups: Group I: (control). Group II: (MS induced). Group III: (Vildagliptin only). Group IV: (Curcumin only). Group V (therapeutic): Vildagliptin treated rats after 8 weeks of MS to the end of 12 weeks. Group VI (prophylactic): Curcumin is administered with MS induction concomitantly for 12 weeks. Transthoracic echocardiogram was done while rats were alive. At the end of the experiment, blood was collected and biochemical analysis (blood glucose, serum insulin, lipid profile and cardiac enzymes) was done. Heart tissues were used for oxidative stress parameters (cardiac mitochondrial reactive oxygen species (ROS) and cardiac mitochondrial complex I and complex II) beside histopathological examination.Results: High fat diet (HFD) administration resulted in a significant increase in blood glucose, serum insulin, homeostasis model assessment of IR (HOMA-IR) index with disturbed lipid profile. Significant increase in serum cardiac enzymes and oxidative stress tissue markers were also noticed. Echocardiography revealed structural and functional cardiomyopathy. Histopathological examination showed cellular infiltrations with fat cells and collagen fibers accumulation. DPP-4 inhibitors and curcumin resulted in a significant decrease in glucose, insulin, and HOMA-IR index, partial amelioration of lipid profile, cardiac enzymes, and cardiac oxidative stress markers. Echocardiography revealed alleviation of cardiomyopathy. Histopathological examination also revealed highly manifested structural improvement. Conclusion:The current study revealed that both DPP-4 inhibitors and curcumin improve cardiomyopathy resulted from HFD administration with a diversity of mechanisms including anti-inflammatory, anti-apoptotic and anti-oxidative ways.