Possible Mechanisms of the Neuroprotective Actions of Date Palm Fruits Aqueous Extracts against Valproic Acid-Induced Autism in Rats.

The current study aimed to determine how palm date aqueous fruit extracts (AFE) affected the autistic-like behaviors brought on by valproic acid (VPA) injection, as well as any potential contributions from Sirt-1, oxidative stress, apoptosis, and autophagy. The pregnant Sprague Dawley females were treated with VPA at 12.5th gestation day and pregnant females and their offspring were treated with AFE orally at doses of 4 mg/Kg by gastric gavage for 45 days after birth. The elevated plus-T maze, water maze, and rotarod tests were used to examine autism-like behaviors. At the end of the study, the expression of Nrf2, heme oxygenase (HO-1), Sirt-1, caspase-3 (a marker of apoptosis), LC3 (a marker of autophagy), and NFκB (inflammatory cytokines) were evaluated along with the oxidative stress in brain tissues and the histological changes in the cerebellum and hippocampus. The neurobehavioral assessments significantly declined due to VPA, which also significantly increased oxidative stress in the brain tissues and significantly decreased Nrf2 and HO-1 expression. Additionally, VPA administration caused significant increase in the expression of caspase-3 in the cerebellar cortex, not in the hippocampus; LC3 and NFκB in the hippocampus, not in the cerebellar cortex; and significant reduction in the expression of Sirt-1 in the hippocampus, not in the cerebellum. On the other hand, AFE treatment significantly improved the neurobehavioral changes as well as it improved significantly the oxidative stress and the expression of LC3, NFκB, NrF2, HO-1, and Sirt-1 in the cerebellum and hippocampus. Conclusions: AFE administration might improve the autistic-like symptoms induced by VPA in rats via attenuation of the oxidative stress, upregulation of Nrf2 and HO-1, Sirt-1 and LC3 expression with downregulation of caspase-3, and NFκB expression in the cerebellum and hippocampus.

Enhancement of Cisplatin Cytotoxicity by Cu(II)-Mn(II) Schiff Base Tetradentate Complex in Human Oral Squamous Cell Carcinoma.

Oral squamous cell carcinoma (SCC) is one of the most predominant tumors worldwide and the present treatment policies are not enough to provide a specific solution. We aimed to assess the cytotoxic effect of Cu(II)-Mn(II) Schiff base tetradentate complex alone or in combination with cisplatin against squamous cell carcinoma cell line (SCCs) in vitro. Oral-derived gingival mesenchymal stem cells (GMSCs) were used as control. The cell viability was assessed by MTT assay. IC50 values were calculated. Evaluation of apoptosis and DNA damage were performed. In addition, the expression of pro-apoptotic and anti-apoptotic genes and proteins were tested. IC50 values indicated less toxicity of the Schiff base complex on GMSCs compared to cisplatin. Schiff base complex treatment resulted in up-regulation of p53 and Bax genes expression and down-regulation of Bcl2 gene expression in SCCs paralleled with increased protein expression of caspase-3 and Bax and down-regulation of Bcl-2 protein. Annexin V-FITC apoptosis kit showed a higher apoptotic effect induced by a Schiff base complex compared to the cisplatin-treated group. These effects were markedly increased on the combination of Schiff base and cisplatin. The present study established that Cu(II)-Mn(II) Schiff base tetradentate complex might induce a cytotoxic effect on SCCs cells via induction of the apoptotic pathway. Moreover, this Schiff base complex augments the anticancer effect of cisplatin.

Hepatoprotective Effects of Hyaluronic Acid-Preconditioned Bone Marrow Mesenchymal Stem Cells against Liver Toxicity via the Inhibition of Apoptosis and the Wnt/ß-Catenin Signaling Pathway.

BACKGROUND: Doxorubicin (DOX) is widely used to treat a variety of malignancies in both adults and children, including those of the bladder, breast, stomach, and ovaries. Despite this, it has been reported to cause hepatotoxicity. The recent discovery of bone marrow-derived mesenchymal stem cells' (BMSCs) therapeutic effects in the context of liver diseases suggests that their administration plays a part in the mitigation and rehabilitation of drug-induced toxicities. OBJECTIVES: This study investigated whether bone BMSCs could reduce DOX-induced liver damage by blocking the Wnt/ß-catenin pathway that causes fibrotic liver. MATERIALS AND METHODS: BMSCs were isolated and treated with hyaluronic acid (HA) for 14 days before injection. Thirty-five mature male SD rats were categorized into four groups; group one (control) rats were supplemented with saline 0.9% for 28 days, group two (DOX) rats were injected with DOX (20 mg/kg), group three (DOX + BMSCs) rats were injected with 2 × 106 BMSCs after 4 days of DOX injection, group four (DOX + BMSCs + HA) rats were injected with 0.1 mL BMSCs pretreated with HA after 4 days of DOX. After 28 days the rats were sacrificed, and blood and liver tissue samples were subjected to biochemical and molecular analysis. Morphological and immunohistochemical observations were also carried out. RESULTS: In terms of liver function and antioxidant findings, cells treated with HA showed considerable improvement compared to the DOX group (p < 0.05). Moreover, the expression of inflammatory markers (TGFß1, iNos), apoptotic markers (Bax, Bcl2), cell tracking markers (SDF1α), fibrotic markers (ß-catenin, Wnt7b, FN1, VEGF, and Col-1), and ROS markers (Nrf2, HO-1) was improved in BMSCs conditioned with HA in contrast to BMSCs alone (p < 0.05). CONCLUSION: Our findings proved that BMSCs treated with HA exert their paracrine therapeutic effects via their secretome, suggesting that cell-based regenerative therapies conditioned with HA may be a viable alternative to reduce hepatotoxicity.

The effect of high oral loading dose of cholecalciferol in non-alcoholic fatty liver disease patients. A randomized placebo controlled trial.

Background and Aim: Non-alcoholic fatty liver (NAFLD) is one of the most common progressive metabolic disorders worldwide. There are increasing scientific interests nowadays for the association between vitamin D status and Non-alcoholic fatty liver. Earlier studies have revealed that vitamin D deficiency is highly prevalent in Non-alcoholic fatty liver patients that contributes to poor outcomes. Hence, the present study aimed to assess the efficacy and safety of oral cholecalciferol on Non-alcoholic fatty liver patients. Subjects and Methods: This study was conducted on 140 patients that were randomized either to group 1 that received the standard conventional therapy in addition to placebo or group 2 that received the standard conventional therapy in addition to cholecalciferol during the 4 months study period. Results: At the end of the study group 2 revealed significant decrease (p < 0.05) in the mean serum level of TG, LDL-C, TC, hsCRP as compared to their baseline results and group 1 results. Additionally, a significant improvement in the serum levels of ALT (p = 0.001) was seen in group 2 at the end of the study when compared to group 1. Whereas group 1 did not show any change in these parameters when compared to group 2 and their baseline results. Conclusion: Cholecalciferol was shown to have beneficial effects on serum ALT levels, hsCRP levels and lipid profile of NAFLD patients. Clinical Trial Registration: https://prsinfo.clinicaltrials.gov/prs-users-guide.html, identifier NCT05613192.

NAFLD mark: an accurate model based on microRNA-34 for diagnosis of non-alcoholic fatty liver disease patients.

BACKGROUND: It remains essential for non-alcoholic fatty liver (NAFLD) patients, to develop a sensitive and specific diagnostic model. Data regarding the use of micro (mi)RNA-34 for NAFLD diagnosis are few. Routine clinical assessment, laboratory tests were done for Egyptian individuals (n = 314) were included (100 healthy individuals and 214 NAFLD patients). Quantification of miRNA-34 was done using real-time PCR. Extremely significant variables were entered into stepwise logistic regression. The diagnostic power of variables was estimated by the area under the ROC (AUC). RESULTS: MiRNA-34 levels were higher in NAFLD patients than healthy individuals with a significant difference (P< 0.0001). The multivariate analysis was used to evaluate the NAFLD-associated variables (CRP, cholesterol, body mass index (BMI), ALT had p< 0.0001 while mRNA-34 had (p=0.0004). The AUCs (CI) of candidate NAFLD markers were in the order of miRNA-34 0.72 (0.66-0.77) < ALT 0.73 (0.67-0.79) < BMI 0.81 (0.76-0.86) < cholesterol < 0.85 (0.79-0.90) < CRP 0.88 (0.84-0.92). We developed a novel index for discriminating patients with NAFLD named NAFLD Mark. AUC was jumped to 0.98 (0.93-0.99) when five markers were combined. The AUC of NAFLD mark for NAFLD detection was higher than the AUCs of seven common NAFLD indexes (0.44-0.86). CONCLUSIONS: The NAFLD mark is a non-invasive and highly sensitive and specific model for NAFLD diagnosis.

Hepatitis C Virus: Efficacy of New DAAs Regimens.

BACKGROUND: HCV treatment showed dramatical change due to the introduction of potent, strong, direct antiviral drugs. Before the appearance of Direct-acting antivirals, multiple therapeutic interventions were used for hepatitis C, but none of these interventions were effective on patient-centered outcomes. Direct-acting antivirals cause disruption of viral replication because they target specific nonstructural viral proteins. AIM: To review the advantages of efficient HCV therapy and its long term drawbacks. METHODS: A search of the literature published in indexed databases (PubMed, Medline In-Process, and Embase) within the last 5 years was conducted. Any duplicated citations were excluded before first-pass screening. Citations (titles and abstracts) were screened for eligibility by a single reviewer. Full texts (including congress abstracts, posters and other congress communications) of citations deemed relevant during title and abstract screening were retrieved for second-pass review. RESULTS: Studies on the clinical effects of DAAs for hepatitis C show better tolerance, improved survival and fewer complications when compared to previous interferon therapy. CONCLUSION: HCV treatment has improved dramatically. Since that time, there are multiple approved oral therapies all with high efficacy. The most important factor which should be considered during choosing appropriate therapy is to ensure that it covers the viral genotype of the infected patients.

Single Nucleotide Polymorphism in Adiponectin Gene and Risk of Pancreatic Adenocarcinoma

Introduction: Adiponectin is anti-inflammatory and anti-tumor cytokine secreted exclusively from adipocytes. There is a growing evidence of association between adiponectin gene polymorphism and development of pancreatic cancer. The current study aimed at evaluation of the possible association between selected adiponectin gene polymorphism and the risk of pancreatic cancer. Methods: Prospective case-control study included 77 patients (29 women and 48 men) with biopsy-proven pancreatic adenocarcinoma and 97 healthy control. Blood samples from all included participants were genotyped for 3 single nucleotide polymorphism (SNPs) of adiponectin genes (rs1501299C>A, rs266729C>G and rs2241766G>T) by PCR. Clinical, biochemical, and radiological data analyzed. Results: We demonstrated a significant association between the three studied SNPs (rs1501299, rs266729, and rs2241766) and increased risk of pancreatic adenocarcinoma (p<0.001). Furthermore, in clinical correlation analysis, Patients with rs2241766 polymorphism have a lower frequency of lymph node involvement (p 0.05). Smoking and older age were independent predictors of pancreatic adenocarcinoma. Conclusion: We provided evidence that variants in adiponectin gene might influence the development and progression of pancreatic cancer.

Attenuation of metabolic dysfunctions in the skeletal muscles of type 1 diabetic rats by Stevia rebaudiana extracts, via AMPK upregulation and antioxidant activities.

BACKGROUND: Stevia rebaudiana Bertoni leaves are well-known for their sweetness and have been used as a non-caloric sweetener in several countries. It has numerous therapeutic properties which have been proven safe and effective over hundreds of years. In the present study, we aimed to evaluate the possible antioxidant effects of stevia extracts and their role in regulating AMPK in type-1 diabetic rats. METHODS: Fifty male Sprague Dawely rats were divided into: (1) normal control (NC) group; normal rats receiving 0.5 ml normal saline, (2) DM group; diabetic rats receiving 0.5 ml normal saline, (3) DM + MSE group; DM rats receiving 200 mg/kg of methanolic extract of stevia, (4) DM + S group; DM rats receiving 2 mg/kg of pure stevioside, and (5) DM + CGA group; DM rats receiving 10 mg/kg of pure chlorogenic acid. Four weeks after treatment, AMPK activity, GLUT4 mRNA and oxidative stress markers were measured in frozen muscles. Also, fasting blood glucose in serum, insulin and HbA1c were measured at the end of experiment. RESULTS: DM caused a significant increase in serum fasting glucose, HbA1c and muscle MDA with significant reduction in serum insulin, muscle SOD, catalase, GPx, AMPK activity and GLUT4 expression (p < 0.05). Treatment with stevia extract, pure stevioside and chlorogenic acid caused significant improvements in the studied parameters (p < 0.05). CONCLUSIONS: We concluded that stevia extracts and derivatives may improve metabolic dysfunction in skel- etal muscles via upregulation of AMPK and GLUT4 and suppression of oxidative stress.

Calibration of the 4pi gamma-ray spectrometer using a new numerical simulation approach.

The 4pi gamma-counting system is well suited for analysis of small environmental samples of low activity because it combines advantages of the low background and the high detection efficiency due to the 4pi solid angle. A new numerical simulation approach is proposed for the HPGe well-type detector geometry to calculate the full-energy peak and the total efficiencies, as well as to correct for the coincidence summing effect. This method depends on a calculation of the solid angle subtended by the source to the detector at the point of entrance, (Abbas, 2006a). The calculations are carried out for non-axial point and cylindrical sources inside the detector cavity. Attenuation of photons within the source itself (self-attenuation), the source container, the detector's end-cap and the detector's dead layer materials is also taken into account. In the Belgium Nuclear Research Center, low-activity aqueous solutions of (60)Co and (88)Y in small vials are routinely used to calibrate a gamma-ray p-type well HPGe detector in the 60-1836keV energy range. Efficiency values measured under such conditions are in good agreement with those obtained by the numerical simulation.