Curcumin nanocapsules effect in apoptotic processes, gene expression, and cell cycle on Hep-G2 cell lines.

OBJECTIVES: Curcumin has antioxidant and antiproliferative properties, and its therapeutic effect must be considered. Nanocurcumin capsules showed a potential increase against in vitro biological cancer. This study sought to determine how curcumin nanoparticles and nanocapsules affected the expression of p53, Bcl-2, Bax, and Bax in a liver cancer cell line (Hep-G2). Mechanisms of apoptosis were also examined in this cell line. METHODS: This study used quantitative real-time polymerase chain reaction (qRT-PCR) to analyze the p53, Bcl-2, Bax, and Caspase-3 gene pathways and to evaluate the molecular mechanisms responsible for the efficacy of curcumin nanoparticles (CNPs) and curcumin nanocapsules (CNCs) against liver cell lines. Flow cytometry was used to check for signs of apoptosis and the cell cycle. RESULTS: Curcumin nanocapsules produced by the ball milling process at 90 min significantly boosted the populations of apoptotic cells in a dose- and time-dependent manner. The mRNA expression analysis revealed that the proapoptotic Bax, Caspase-3, and the tumor suppressor gene p53 were upregulated throughout the process started by curcumin nanocapsules and decreased in the Bcl-2/Bax ratio. CONCLUSION: This research provides a fresh understanding of the molecular mechanisms behind the liver cancer-fighting abilities of curcumin nanoparticles. Curcumin nanocapsules produced through a unique mechanical technique can be used as an anticancer agent.

Dose-dependent effects of taurine against testicular damage in a streptozotocin-induced type 1 diabetes mellitus rat model.

OBJECTIVES: Testicular dysfunction has been associated with chronic hyperglycemia in diabetes mellitus patients. We investigated taurine's possible mechanisms and protective effects against testicular damage using a rat model of streptozotocin-induced diabetes. METHODS: Wistar rats (N = 56) were divided into seven equal groups. Untreated control rats received saline, and treated control rats received taurine 50 mg/kg orally. To induce diabetes, rats received a single dose of streptozotocin. Metformin-treated diabetic rats received metformin at a dose of 300 mg/kg. Taurine-treated groups received 10, 25, or 50 mg/kg. All treatments were provided orally once a day for 9 weeks following the streptozotocin injection. Levels of blood glucose, serum insulin, cholesterol, testicular tumour necrosis factor-alpha (TNF-α), interleukin-6 (IL-6), interleukin-1beta (IL-1ß), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx), glutathione (GSH), and catalase (CAT) were examined. Sperm count, progressive sperm motility, and sperm abnormalities were examined. Body and relative reproductive gland weights were assessed. Histopathological examinations of the testes and epididymis were performed. RESULTS: Metformin as well as taurine (in a dose-dependent manner) resulted in significant improvements in body and relative reproductive gland weights, blood glucose, serum cholesterol, and insulin levels, as well as cytokine and oxidative parameters. These findings were associated with significant improvement in sperm count, progressive sperm motility, sperm abnormalities, and histopathological lesions in the testes and epididymis. CONCLUSION: Taurine can potentially improve hyperglycemia, hypercholesterolemia, and testicular damage associated with diabetes mellitus, possibly by controlling inflammation and oxidative stress.

Study of the possible effect of sacubitril/valsartan combination versus valsartan on the cognitive function in Alzheimer's disease model in rats.

Objectives: Alzheimer's disease (AD) is an irreversible, progressive neurodegenerative disorder. The proportion of elderly individuals at risk for AD and cardiovascular problems increases by raising life expectancy. The present study was designed to investigate the effect of the sacubitril/valsartan combination compared to that of valsartan alone in a rat model of AD. Methods: 72 male adult Wistar rats were divided into seven groups; control untreated rats received saline, control valsartan-treated rats received valsartan orally, control sacubitril/valsartan treated rats received sacubitril/valsartan orally, model rats received aluminum chloride i.p., model valsartan treated rats received aluminum chloride i.p. and valsartan orally and model sacubitril/valsartan treated rats received aluminum chloride i.p. and sacubitril/valsartan combination orally. All previous treatments continued on a daily basis for 6 weeks. At the second, fourth, and sixth weeks of the experiment, behavioral changes were evaluated using the Morris water maze and novel object recognition tests, and systolic blood pressure was measured. In the end, rat brain malondialdehyde and amyloid-beta 1-42 levels were measured, and the isolated hippocampus was evaluated histopathologically. Results: Valsartan improved AD symptoms in the aluminum-induced rat model, while the sacubitril/valsartan combination significantly worsened all tested parameters in both control and model rats compared with untreated and valsartan-treated animals. Conclusion: Based on the current study's findings, valsartan did not increase the risk for AD development in control rats and improved AD symptoms in a rat model, while sacubitril/valsartan combination increased the risk of AD in control rats and worsened the condition in a rat model.

Comparison of Different Antiviral Regimens in the Treatment of Patients with Severe COVID-19: A Retrospective Cohort.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) causes respiratory disorders, with disease severity ranging from asymptomatic to critical manifestations. The current retrospective study compared the efficacies of different antiviral regimens used in patients suffering from severe COVID-19 disease from 19 January 2020 to December 2021 in a single center in Saudi Arabia. In total, 188 patients were enrolled in the current study, including 158 patients treated with different antiviral regimens, and 30 who did not receive any antiviral treatment. Different antiviral regimens, including favipiravir, remdesivir, oseltamivir, favipiravir/remdesivir, and favipiravir/oseltamivir were adopted. The effects of using different antivirals and antibiotics on the survival rate were evaluated, as well as the presence of comorbidities. Among all severely affected patients, 39/188 (20.7%) survived. Both age and comorbidities, including diabetes and hypertension, were significantly correlated with high case fatality following SARS-CoV-2 infection. Remdesivir alone and the combination of favipiravir and remdesivir increased the survival rate. Surprisingly, both imipenem and linezolid helped in the deterioration of disease outcome in the patients. A negative correlation was detected between increased mortality and the use of favipiravir and the use of either imipenem or linezolid. Among the compared antiviral regimens used in the treatment of severe COVID-19, remdesivir was found to be an effective antiviral that reduces COVID-19 case fatality. Antibiotic treatment using imipenem and/or linezolid should be carefully re-evaluated.

Fluoropyrimdine therapy induced alterations in interleukins expression in colorectal cancer patients.

This study monitored the changes in the expression of inflammatory IL-6 and IL-1ß during the treatment period of Fluoropyrimidine (FP) based therapy. RNA was extracted from the peripheral blood of 102 CRC patients before treatment with FP therapy, and from 48 and 32 patients after 3 and 6 months of treatment, respectively. The genetic transcription of IL-6 and IL-1ß was determined by real time PCR. Patients were stratified according to their levels of IL-6 and IL-1ß genes expression for subgroup and survival analyses. Baseline CRC patients showed overexpression of IL-6 and IL-1ß compared to healthy control. FP therapy significantly induced IL-6 and IL-1ß expression. Subgroup analysis showed that patients with right colon tumors had significant elevation in both IL-6 and IL-1ß with FP therapy. FP therapy significantly induced IL-1ß expression in patients ⩽45 years, smokers, with high baseline level of CA19.9, right colon tumors, low grade pathology, T3 tumors and positive lymph nodes. Survival analysis showed that baseline levels of interleukins expression had insignificant effect on overall survival and event free survival. FP therapy has an impact on the level of interleukins expression declared in certain clinicopathological subgroups of CRC patients, but without a prognostic significance on patients' survival.

Study of the protective effect of ischemic and pharmacological preconditioning on hepatic ischemic reperfusion injury induced in rats.

BACKGROUND AND AIM: Hepatic ischemia reperfusion injury is the main cause of liver failure following liver surgery, so an effective method is needed to prevent or reduce this hepatic injury. The aim of the present study is to investigate the potential effect of ischemic preconditioning versus pharmacological preconditioning with lisinopril or verapamil for protection against hepatic ischemia reperfusion injury induced in rats. METHODS: Rats were divided into six groups. Group I served as control untreated. Rats of group II were subjected to laparotomy without induction of ischemia reperfusion. Ischemia reperfusion by ligation of the portal trait for 30 min, followed by reperfusion for 2 h, was performed in rats of groups III-VI. Ischemic preconditioning was performed for rats of group IV before induction of ischemia reperfusion. Lisinopril and verapamil was given daily for 3 days before induction of ischemia reperfusion in groups V and VI, respectively. Serum level of liver transaminases and liver malondialdehyde content were measured, and hepatic histopathological examination was assessed. RESULTS: Induction of ischemia reperfusion resulted in significant elevation of liver transaminases and liver malondialdehyde content associated with significant hepatic histopathological injury that were significantly improved by ischemic preconditioning, lisinopril, or verapamil treatment. Verapamil showed the most significant improvement compared with ischemic preconditioning or lisinopril treatment. CONCLUSION: Ischemic preconditioning and pharmacological preconditioning by lisinopril or verapamil can protect against hepatic ischemia reperfusion probably through inhibition of oxidative stress and neutrophil infiltration. The most potent protection is demonstrated by verapamil treatment.