Effect of Thymoquinone on Hepatic Fibrosis Induced in BALB/C Mice: Is It Always Beneficial?

Thymoquinone (TQ) has a variety of beneficial properties including antioxidant and anti-inflammatory activities. In this study, the effect of TQ on biochemical changes and coagulopathy accompanying liver fibrosis in BALB/c mice was investigated. Fibrosis was induced by intraperitoneal injection of carbon tetrachloride (0.5 ml /kg) for 4 weeks. TQ was administrated at three dose levels (2, 4 and 8 mg/kg) in drinking water, starting 7 days before CCl4 injection and continuing during the CCl4 administration period (4 weeks). CCl4 raised serum alanine aminotransferase activity as well as hepatic malondialdehyde content and myeloperoxidase activity. This was accompanied by a significant decrease in superoxide dismutase, catalase activities and reduced glutathione level in liver. Treatment of mice with TQ ameliorated the hepatotoxicity induced by CCl4, as evidenced by disappearance of fibrosis. Serum alanine aminotransferase activity, hepatic malondialdehyde content and myeloperoxidase activity decreased significantly while antioxidant enzymes activities rose. Prothrombin time and activated partial thromboplastin time were significantly elevated after injection of CCl4 as compared to normal control group. TQ potentiated the effect of CCl4 on the coagulation parameters. Our results showed that TQ ameliorates hepatic fibrosis induced by CCl4. However, it did not improve the coagulopathy induced in this model. Consequently, the use of TQ may be not always beneficial in different stages of chronic liver disease

FORMULATION AND CHARACTERIZATION OF ODT USING DIFFERENT CO-PROCESS CONTAINNG DACLATSVIR: IN VITRO AND IN VIVO PHARMACOKINETICS STUDY ON HEALTHY VOLUNTEERS FOR HEPATITIS C TREATMENT

Objective: This study aimed to prepare and evaluate oral disintegrating tablets (ODTs) of Daclatasvir dihydrochloride (DCV) using different co-processed excipients to enhance drug dissolution and improve oral bioavailability for treatment of hepatitis C infection. Methods: Ten Daclatasvir-ODTs formulae were prepared using co-processed excipients via direct compression. The prepared formulae were evaluated according to taste masking, weight variation, thickness, friability, hardness, drug content, and wetting time. In-vitro disintegration time, in-vivo disintegration time, and in-vitro dissolution tests were also evaluated and taken as parameters for the selection of the best formula. The selected best formula was subjected to an in-vivo study on volunteers and compared to a marketed product. Results: All DCV-ODTs had acceptable physical properties in accordance with pharmacopeial standards. DCV-ODTs prepared with Pharmaburst® (F10) recorded the shortest wetting time (14±0.08s), fastest invitro disintegration time (46±0.16s), shortest in-vivo disintegration time (27±0.16s), and attained the fastest onset of dissolution (94.3±0.03 %) at 5 min to all other excipients and has been identified as the best formula. The in-vivo pharmacokinetic study showed that Pharmaburst-based formula has a significant Cmax increase of (2.17 ± 0.28 μg/ml) compared to (1.42±0.59) for the marketed product and a significant decrease of Tmax to 60 min instead of 110 min for the marketed product. Conclusion: The in-vivo pharmacokinetic study in humans showed that the ODTs was found to be appropriate for delivery of Daclatasvir with a faster drug absorption rate when compared to the marketed products with applicable taste related to the nature of dosage form

Thymoquinone Suppresses Angiogenesis in DEN-Induced Hepatocellular Carcinoma by Targeting miR-1-3p

Hepatocellular carcinoma (HCC) is characterized by its high vascularity and metastasis. Thymoquinone (TQ), the main bio-active constituent of Nigella sativa, has shown anticancer and hepatoprotective effects. TQ’s anticancer effect is mediated through miRNA regulation. miR-1-3p plays a significant role in various cancers but its role in HCC invasiveness remains poorly understood. Bio-informatics analysis predicted that the 3′-UTR of TIMP3 is a target for miR-1-3p; Rats were equally divided into four groups: Group 1, the negative control; Group 2 received TQ; Group 3 received DEN; and Group 4 received DEN after pretreatment with TQ. The expression of TIMP3, MMP2, MMP9, and VEGF in rats’ liver was determined immunohistochemically. RT-qPCR was used to measure the miR-1-3p level in rats’ liver, and TIMP3, MMP2, MMP9, and VEGF in the HepG2 cells after being transfected with miR-1-3p mimic or inhibitor; In rats pretreated with TQ, a decreased expression of MMP2, MMP9 and VEGF, and increased expression levels of TIMP3 and miR-1-3p were detected. Treating the HepG2 cells with miR-1-3p mimic led to the upregulation of TIMP3 and downregulation of MMP2, MMP9, and VEGF, and showed a significant delay in wound healing; These results suggested that the anti-angiogenic effect of TQ in HCC may be mediated through the regulation of miR-1-3p

Safety and Effectiveness of COVID-19 Vaccines: Results from a Cross-Sectional Survey among Staff, Workers and Students at an Egyptian University

Mass vaccination is the most effective strategy against the spread of the COVID-19 pandemic. However, concerns about the vaccine’s safety and effectiveness remain a huge obstacle to vaccine acceptance. The aim of the present study was to explore different COVID-19 vaccine outcomes, including the development of adverse events and/or COVID-19 infection following COVID-19 vaccination. A cross-sectional study was conducted by distributing an online survey targeting staff and students at the British university in Egypt. A total of 637 participants fully completed the survey. Of these, 609 (95.6%) participants received the COVID-19 vaccine. Only 12.6% of the total vaccinated participants reported COVID-19 infection after vaccination. Of these, only 2.8% reported having severe symptoms while 9.9% reported having no or mild symptoms. The most common side effects reported after the first vs. second dose were headache (36.3% vs. 14.6%), tiredness and fatigue (26.9% vs. 10.7), and fever (25.6% vs. 6.7%). In conclusion, the present study explored different COVID-19 vaccine outcomes where the overall incidence of side effects is higher after the first dose than after the second dose. There is a relationship between COVID-19 vaccines’ side effects and gastrointestinal disorders, gender, and the type of COVID-19 vaccine. Post-vaccination symptoms were more frequently reported in women compared to men and more frequent with viral vector vaccines compared to other types. The effectiveness of different types of COVID-19 vaccines was confirmed by the lower incidence rate of post-vaccination COVID-19 infection