Aim: Background: Voluminous of the anti-tumor drugs in practice known to yield adverse side effects for instance hepatotoxicity. Objective: This preliminary was carried out to ascertain the histological change after treatment with Sorafenib (SOR) before execution the B17 coadministration and detection of the histochemical change in Ascites Carcinoma mice model (EAC). Methods: In total 12 Swiss albino mice received intraperitoneal injections of Sorafenib (30 mg/ kg mouse) after tumor cells were injected, semi quantifiable scoring of the architectural disparities validated by histopathological inspection of mice tissues. Results: Upsurge of Liver enzymes, Kidney functions and significant reduction after SOR treatment of Hb, RBCs, and Platelets. Membrane integrity, separation of muscle fiber, Intrusion of inflammatory cells, Edematous intramuscular space were evaluated in addition, liver tissue revealed large focal area and diffuse pleomorphic darkly basophilic cells in the perivascular area around the dilated central vein (CV) besides the mild dilation of some blood sinusoids. Improvement in the histological pictures of hepatic tissues in comparison to EAC bearing positive control group were enhanced Conclusion: Sorafenib showed alterations in histological mice tissues, however improvements in biochemical parameters were noted; that's why the Coadministration of B17 will be applied to alleviate the side effects of Sorafenib on the next perspective study.
The burden of cancer diseases is increasing every year, therefore, the demands to figure out novel drugs that can retain antitumor properties have been raised. This study aimed to investigate the anti-tumor properties of amygdalin (Amy) against Ehrlich ascites carcinoma (EAC) bearing mice and its protective properties against liver damage. Amy and the standard anticancer drug Sorafenib (Sor) were given alone or in combination to Swiss albino female mice that had been injected with EAC cells. Biochemical parameters of liver function (AST, ALT, GGT, total protein, albumin), tumor volume, oxidative stress [malondialdehyde, (MDA)] and antioxidative [superoxide dismutase (SOD), and reduced glutathione (GSH)] markers were measured. The hepatic expression of the antioxidant-related gene [nuclear factor erythroid-2-related factor 2 (Nrf2)], the migration-related gene [matrix metalloprotease 9 (MMP9)], and the angiogenesis-related gene [vascular endothelial growth factor (VEGF)] were evaluated by qPCR. The results revealed that EAC-bearing mice treated with Amy and/or Sor showed a decrease in the tumor burden and hepatic damage as evidenced by (1) decreased tumor volume, number of viable tumor cells; (2) increased number of dead tumor cells; (3) restored the liver function parameters; (4) reduced hepatic MDA levels; (5) enhanced hepatic GSH and SOD levels; (6) upregulated expression of Nrf2; (7) downregulated expression of MMP9 and VEGF, and (8) improved hepatic structure. Among all treatments, mice co-treated with Amy (orally) and Sor (intraperitoneally) showed the best effect. With these results, we concluded that the Amy improved the antitumor effect of Sor and had a protective role on liver damage induced by EAC in mice.
Background: Nowadays, the new coronavirus-induced severe acute respiratory syndrome (COVID-19) outbreak was primarily stated in December 2019. Three months later, the Director-General of the World Health Organization, avowed the COVID-19 a global pandemic. Gathered evidence discloses that coagulation syndrome is repeatedly seen in COVID-19, and the incidence is higher in severe cases. The worsening lung functions and coagulopathy are some of the most significant poor prognostic criteria in the outcome of COVID-19. The pragmatic coagulopathy in patients hospitalized with COVID-19 (COVID-19 associated coagulopathy) is categorized by the increased level of D-dimer and fibrinogen/fibrin degradation products. They are interrelated with the severity of COVID-19. This elevation will aid the arrangement of the patients consistent with the disease severity and management. These coagulation parameters elevation can point to a poor prognosis. Coagulopathy in COVID-19 mainly affects immobilized patients, those in critical care units, and those who have extra risk factors that predispose to coagulopathy, for instance, acute inflammatory conditions and hypoxia. The exact pathogenesis of hypercoagulability in COVID-19 is unwell understood. The signs suggest that the COVID-19 coagulopathy is an evolving phenomenon in which endothelial damage, platelet aggregation, augmented innate immune response, and other measures as systemic inflammation favoring coagulation would divide up the severity of this disease. Understanding the pathophysiology of COVID-19 related coagulopathy is crucial for suitable treatment and monitoring of these patients. Encouraging interest in the potential uses of anticoagulation in COVID-19 particularly is the use of heparin that has a potential benefit over other anticoagulants due to its anticoagulant role, anti-inflammatory, and potentially anti-viral properties. The incidence of thrombotic phenomena associated with COVID-19. Importantly, laboratory and imaging studies found an increased risk of thrombotic complications in patients with SARS-CoV-2 infection. Klok et al assessed the incidence of thrombotic complications in COVID-19 patients admitted to the ICU. They found that 31% of these patients had thrombotic complications, even in patients who were already getting standard doses of prophylactic
Cancer remains one of the most common diseases worldwide. Unlimited efforts were executed to find new therapies to treat cancer. Eliminating tumours by surgery, chemotherapy, radiotherapy, immunotherapy, and gene therapy is currently in use (Olga et al., 2021). Even though, conventional chemotherapy is considered one of the best choices for cancer therapy, upon treatment with chemotherapeutic agents, drug resistance and side effects on vital organs were existed (El-Naggar et al., 2017). To overcome the chemo-resistance and to decrease chemotherapeutic agents' side effects different protocols have been modified for treatment with different chemotherapeutic agents (
Background Traditional herbal medicine has been used for centuries to cure many pathological disorders, including cancer. Thymoquinone (TQ) and piperine (PIP) are major bioactive constituents of the black seed (Nigella sativa) and black pepper (Piper nigrum), respectively. The current study aimed to explore the potential chemo-modulatory effects, mechanisms of action, molecular targets, and binding interactions after TQ and PIP treatments and their combination with sorafenib (SOR) against human triple-negative breast cancer (MDA-MB-231) and liver cancer (HepG2) cells. Methods We determined drug cytotoxicity by MTT assay, cell cycle, and death mechanism by flow cytometry. Besides, the potential effect of TQ, PIP, and SOR treatment on genome methylation and acetylation by determination of DNA methyltransferase (DNMT3B), histone deacetylase (HDAC3) and miRNA-29c expression levels. Finally, a molecular docking study was performed to propose potential mechanisms of action and binding affinity of TQ, PIP, and SOR with DNMT3B and HDAC3. Results Collectively, our data show that combinations of TQ and/or PIP with SOR have significantly enhanced the SOR anti-proliferative and cytotoxic effects depending on the dose and cell line by enhancing G2/M phase arrest, inducing apoptosis, downregulation of DNMT3B and HDAC3 expression and upregulation of the tumor suppressor, miRNA-29c. Finally, the molecular docking study has identified strong interactions between SOR, PIP, and TQ with DNMT3B and HDAC3, inhibiting their normal oncogenic activities and leading to growth arrest and cell death. Conclusion This study reported TQ and PIP as enhancers of the antiproliferative and cytotoxic effects of SOR and addressed the mechanisms, and identified molecular targets involved in their action.
Aniseeds (Pimpinella anisum) have gained increasing attention for their nutritional and health benefits. Aniseed extracts are known to contain a range of compounds, including flavonoids, terpenes, and essential oils. These compounds have antimicrobial properties, meaning they can help inhibit the growth of nasty bacteria and other microbes. The purpose of this study was to determine if aniseed extracts have potential antioxidant, phytochemical, and antimicrobial properties against multidrug-resistant (MDR) bacteria. A disc diffusion test was conducted in vitro to test the aniseed methanolic extract’s antibacterial activity. The MIC, MBC, and inhibition zone diameters measure the minimum inhibitory concentration, minimum bactericidal concentration, and size of the zone developed when the extract is placed on a bacterial culture, respectively. HPLC and GC/MS are analytical techniques used for identifying the phenolics and chemical constituents in the extract. DPPH, ABTS, and iron-reducing power assays were performed to evaluate the total antioxidant capacity of the extract. Using HPLC, oxygenated monoterpenes represented the majority of the aniseed content, mainly estragole, cis-anethole, and trans-anethole at 4422.39, 3150.11, and 2312.11 (g/g), respectively. All of the examined bacteria are very sensitive to aniseed’s antibacterial effects. It is thought that aniseed’s antibacterial activity could be attributed to the presence of phenolic compounds which include catechins, methyl gallates, caffeic acid, and syringic acids. According to the GC analysis, several flavonoids were detected, including catechin, isochiapin, and trans-ferulic acid, as well as quercitin rhamnose, kaempferol-O-rutinoside, gibberellic acid, and hexadecadienoic acid. Upon quantification of the most abundant estragole, we found that estragole recovery was sufficient for proving its antimicrobial activity against MDR bacteria. Utilizing three methods, the extract demonstrated strong antioxidant activity. Aniseed extract clearly inhibited MDR bacterial isolates, indicating its potential use as an anti-virulence strategy. It is assumed that polyphenolic acids and flavonoids are responsible for this activity. Trans-anethole and estragole were aniseed chemotypes. Aniseed extracts showed higher antioxidant activity than vitamin C. Future investigations into the compatibility and synergism of aniseed phenolic compounds with commercial antibacterial treatments may also show them to be promising options.
Background: Although sensitive screening assays for hepatitis B virus surface antigen (HBsAg) are available, special cases of post-transfusion hepatitis B virus infection still occur. The present study was conducted to evaluate the prevalence of anti-hepatitis B core (anti-HBc) positivity and the presence of HBV-DNA in serum samples of healthy blood donors negative for both HBsAg and anti-HCV antibodies in Benha, Egypt. Materials and methods: The study included a screening of 450 selected blood donors. The distribution of blood donors was 288 males (64%) and 162 females (36%). The recruited blood donors who met the criteria for blood donation were routinely screened for HBsAg, HIV I/2-Ab, and syphilisantibodies. The blood units for donations were further analyzed for the presence of HBc-IgM and HBV-DNA levels by PCR method. Results: Testing of the accepted units for the donation was about 12 (2.7%) HBc-IgM positive, and 9 (2%) HBV-DNA positive units. The standard screening of blood unit failed to recognize early acute or window HBV infection where HBsAg is missing. Conclusions: Our investigations proposed that sensitive methods for the detection of HBV by PCR might be recommended in the screening of donated blood. Furthermore, anti-HBc antibodies should be tested regularly on all blood donation units.
Introduction Hematological complications such as neutropenia, thrombocytopenia, and anemia of DAAs/ribavirin in HCV can result in suboptimal outcomes. This study was aimed to investigate the frequency of hematological variations and their impact on the response to DAA therapy. Patients were defined as having hematological abnormalities if they had the presence of either/or a combination of the following hematological parameters at least once during the first month of treatment: drop in (Hb) level, TLC, and PLT count. Pretreatment, Hb, WBC count, and PLT count were not statistically related to the treatment response. However, lower count of all parameters was associated with moderate or advanced hepatic fibrosis stages according to the METAVIR scoring (P < .001). Static analysis showed that drop in Hb, TLC, and PLT count was significantly associated with response to treatment; P < .001, .21, and .41, respectively. Methods Fifty-eight patients for treatment of chronic hepatitis were studied. Their hematological parameters including TLC, Hb, and platelet counts were recorded before starting antiviral therapy and then at 3 monthly intervals. All the patients were given DAAS/ribavirin as antiviral therapy. Data were collected over a period of 3 months. Results Fifty-eight patients with mean (SD) age of 54.38 (12.67) years were studied. There was a mean hemoglobin (Hb) fall of 1.5 g/dL at the first 4 weeks of antiviral therapy. Mean TLC fell to 1.03 × 10⁹/L in the first month. A similar downward trend was noted in platelet values with a mean fall of 12.3 × 10⁹/mm in the first month of the antiviral therapy. Of the cases, 41.4% developed clinically significant anemia as evidenced by hemoglobin 11 g/dL after 4 weeks of antiviral therapy; this fall was noted only in first 4 weeks of treatment. Conclusion Significant hematological abnormalities occurred within the first 4 weeks of antiretroviral therapy. There was significant decrease in hemoglobin level.
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