Isatin Counteracts Diethylnitrosamine/2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Male Wistar Rats by Upregulating Anti-Inflammatory, Antioxidant, and Detoxification Pathways

Hepatocellular carcinoma (HCC) represents around 85% of all known types of liver cancers and is estimated to be the fifth most common cause of cancer-related death worldwide. The current study assessed the preventive efficacy of isatin on diethylnitrosamine (DENA)/2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in male Wistar rats and investigated the underlying cellular and molecular mechanisms. HCC was initiated by intraperitoneal injection of DENA (150 mg/kg/week) for two weeks, followed by oral 2-AAF (20 mg/kg) every other day for three successive weeks. Oral isatin or vehicle (control) was administered at 25 mg/kg for 20 weeks during and following HCC induction. Isatin ameliorated the deleterious effects of DENA/2-AAF on liver function as evidenced by reduced serum levels of AST, ALT, total bilirubin, albumin, and liver tumor biomarkers (CA19.9 and AFP) compared to control DENA/2-AAF-treated rats. Histopathological evaluations demonstrated that isatin-mediated protection against hepatocarcinogenesis was accompanied by a decline in hepatic lipid peroxidation, a marker of oxidative stress, and enhanced antioxidant capacity, as evidenced by increased glutathione and superoxide dismutase expression. Isatin treatment also upregulated expression of the major stress-response transcription factor Nrf2 and the detoxifying enzymes NAD(P)H quinine oxidoreductase and glutathione-S-transferase alpha 2 and downregulated expression of the proliferation marker Ki67. Moreover, isatin significantly reduced the DENA/2-AAF-induced decrease in hepatic expression of anti-apoptotic Bcl2 and the DENA/2-AAF-induced increases in pro-inflammatory and pro-apoptotic factors (TNF-α, NF-κB p50, NF-κB p65, p53, and caspase 3). Thus, it can be concluded that isatin may protect against chemically induced hepatocarcinogenesis by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms, in part through upregulation of the Nrf2 signaling pathway

Isatin Counteracts Diethylnitrosamine/2-Acetylaminofluorene-Induced Hepatocarcinogenesis in Male Wistar Rats by Upregulating Anti-Inflammatory, Antioxidant, and Detoxification Pathways

Hepatocellular carcinoma (HCC) represents around 85% of all known types of liver cancers and is estimated to be the fifth most common cause of cancer-related death worldwide. The current study assessed the preventive efficacy of isatin on diethylnitrosamine (DENA)/2-acetylaminofluorene (2-AAF)-induced hepatocarcinogenesis in male Wistar rats and investigated the underlying cellular and molecular mechanisms. HCC was initiated by intraperitoneal injection of DENA (150 mg/kg/week) for two weeks, followed by oral 2-AAF (20 mg/kg) every other day for three successive weeks. Oral isatin or vehicle (control) was administered at 25 mg/kg for 20 weeks during and following HCC induction. Isatin ameliorated the deleterious effects of DENA/2-AAF on liver function as evidenced by reduced serum levels of AST, ALT, total bilirubin, albumin, and liver tumor biomarkers (CA19.9 and AFP) compared to control DENA/2-AAF-treated rats. Histopathological evaluations demonstrated that isatin-mediated protection against hepatocarcinogenesis was accompanied by a decline in hepatic lipid peroxidation, a marker of oxidative stress, and enhanced antioxidant capacity, as evidenced by increased glutathione and superoxide dismutase expression. Isatin treatment also upregulated expression of the major stress-response transcription factor Nrf2 and the detoxifying enzymes NAD(P)H quinine oxidoreductase and glutathione-S-transferase alpha 2 and downregulated expression of the proliferation marker Ki67. Moreover, isatin significantly reduced the DENA/2-AAF-induced decrease in hepatic expression of anti-apoptotic Bcl2 and the DENA/2-AAF-induced increases in pro-inflammatory and pro-apoptotic factors (TNF-α, NF-κB p50, NF-κB p65, p53, and caspase 3). Thus, it can be concluded that isatin may protect against chemically induced hepatocarcinogenesis by enhancing cellular antioxidant, anti-inflammatory, and detoxification mechanisms, in part through upregulation of the Nrf2 signaling pathway

The Outcomes of COVID-19 Patients with Spontaneous Intracerebral Hemorrhage Comorbidity and the Efficacy of Enoxaparin in Decreasing the Mortality Rate in Them: Single Egyptian Center Report

Patients with neurological comorbidities are more likely to develop severe COVID-19. We aimed to detect the outcomes of COVID-19 patients with spontaneous intracerebral hemorrhage comorbidity and the role of enoxaparin in decreasing the mortality rate in these cases, even though enoxaparin is a potential cause of intracerebral hemorrhage. The patients were checked on to detect surveillance outcomes, the relationship between mortality and patient characteristics, and the relationship between enoxaparin and study outcomes. Chest condition and GCS improved in 67.9% of participants. Hematoma course increased in 49.1%. Midline-shift, brain-edema, and COVID symptoms improved in 67.9%. There was a non-significant difference in mortality regarding age and gender. There was a significant difference in mortality regarding treatment with enoxaparin; 75% of the patients who did not receive enoxaparin died. 92.6% of the patients who showed decreases in hematoma course were administered enoxaparin. 76.9% of the patients who showed increases in hematoma-course were administered enoxaparin. Most of the patients who were admitted to the neurosurgical unit with spontaneous intracerebral hemorrhage acquired the COVID-19 infection. Most of the cases included in this study did not progress to severe cases. The dying patients showed deterioration in both neurological and COVID-19 symptoms. The anticoagulant properties of enoxaparin given earlier before and throughout the infection can considerably reduce mortality in COVID-19 individuals with spontaneous intracerebral hemorrhage. It is recommended to use enoxaparin for cases with spontaneous intracerebral hemorrhage and COVID-19 regardless of hematoma size because the rate of improvement was greater than the mortality rate after using enoxaparin in this study

Evaluation of CEP55, SERPINE1 and SMPD3 genes and proteins as diagnostic and prognostic biomarkers in gastric carcinoma in Egyptian patients

Abstract Background Gastric carcinoma (GC) is a fatal disease. Detection of new biomarkers that can be utilized in the early diagnosis of GC is a pressing need. This present study assessed centrosomal protein-55 (CEP55)’ serpin family E member 1 (SERPINE1) and sphingomyelin phosphodiesterase 3 (SMPD3) genes and proteins in gastric adenocarcinoma with different tumor progression features. Thirty surgically resected gastric tissue samples from thirty patients suffered from gastric cancers were obtained. The gastric tissue samples were divided into tumorous (with different stages and grades) and adjacent non-tumorous samples. CEP55, SERPINE1 and SMPD3 genes were assessed by quantitative qRT-PCR, and their proteins were assessed by ELISA in the gastric tissue samples. Results As regards SERPINE1, CEP55 genes and proteins, results revealed significant elevations in the GC samples (p < 0.0001). On the contrary, SMPD3 gene and protein revealed significant decreases as compared to non-tumorous samples. The studied genes and proteins showed highly significant specificity and sensitivity in the early detection of GC. SERPINE1 gene and protein revealed highly significant increases and positive correlations, while SMPD3 gene and protein revealed highly significant decreases and negative correlations as the tumor progresses. Conclusion CEP55, SERPINE1 and SMPD3 genes and proteins could be used as useful biomarkers for the early detection of GC. SERPINE1 and SMPD3 genes and proteins might be used as risk and protective prognostic factors in GC, respectively

SARS-CoV-2 Post Vaccinated Adverse Effects and Efficacy in the Egyptian Population

Vaccines are the solution to overcome SARS-CoV-2. This study aimed to determine the post-Sinopharm vaccine safety-profile and immunity through antibody titers. Data were collected using a structured questionnaire from Egyptian participants who received two doses of Sinopharm vaccine. Data were divided into three parts, the first and second parts were to detect participants' post-first and second dose symptoms and practices, and the third for the results of IgG anti spike protein antibodies test and laboratory tests. Pain, redness, swelling at the injection site, headache, fatigue, and lethargy were the most common post-vaccine symptoms for both first and second doses. Most of the participants felt mild or no symptoms after vaccination. The symptoms started mostly during the first day post-vaccination and lasted for no more than two days. Forty-nine percent of the participants resulted in positive antibodies tests on day 18 post-vaccination. The average antibody level for vaccinated participants with past SARS-CoV-2 infection was much higher than that for non-past infected participants. These vaccines' administration methods need to be reevaluated by changing the dose, dose interval, adding a third dose, or mixing it with other vaccines with different techniques to improve their protection rates. Further studies are required to validate this finding