Coronavirus disease 2019 or COVID-19, starting from Wuhan, China, in December 2019, is a pandemic situation affecting millions worldwide and has exerted a huge burden on healthcare infrastructure. Therefore, there is an urgent need to understand the molecular mechanisms underlying severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection and design novel effective therapeutic strategies for combating this pandemic. In this regard, special attention has been paid to the exosomes. These nanoparticles are extracellular vesicles with critical function in the pathogenesis of several diseases including viral sepsis. Therefore, they may be involved in the pathogenesis of COVID-19 infection and also may be a way for transferring viral components and infecting other neighbor cells. Exosomes also can be considered as a therapeutic strategy for treating COVID-19 patients or used as a carrier for delivering effective therapeutic agents. Therefore, in this review, we discussed the biogenesis and contents of exosomes, their function in viral infection, and their potential as a therapeutic candidate in treating COVID-19.
The use of heat shock protein 90 inhibitors like 17-allylamino-17-demethoxy-geldanamycin (17-AAG) has been recently introduced as an attractive anticancer therapy. It has been shown that 17-AAG may potentiate the inhibitory effects of some classical anticolorectal cancer (CRC) agents. In this study, two panels of colorectal carcinoma cell lines were used to evaluate the effects of 17-AAG in combination with capecitabine and oxaliplatin as double and triple combination therapies on the proliferation of CRC cell lines. HT-29 and all HCT-116 cell lines were seeded in culture media in the presence of different doses of the mentioned drugs in single, double, and triple combinations. Water-soluble tetrazolium-1 (WST-1) assay was used to investigate cell proliferation 24 h after treatments. Then, dose-response curves were plotted using WST-1outputs, and IC50 values were determined. For double and triple combinations respectively 0.5 × IC50 and 0.25 × IC50 were used. Data was analyzed with the software CompuSyn. Drug interactions were analyzed using Chou-Talalay method to calculate the combination index (CI).The data revealed that 17-AAG shows a potent synergistic interaction (CI < 1) with oxaliplatin and capecitabine in double combinations (0.5 × IC50) in both cell lines. In the case of triple combinations, the findings showed an antagonistic interaction (CI > 1) in HT-29 and a synergistic effect (CI < 1) in HCT-116 (0.25 × IC50) cell lines. It was concluded that double combinations of 17-AAG with oxaliplatin or capecitabine might be effective against HCT-116 and HT-29 cell lines. However, in triple combinations, positive results were seen only against HCT-116. Further investigation is suggested to confirm the effectiveness of these combinations in clinical trials.
Purpose: Dihydropyrimidine dehydrogenase (DPD) is the principal enzyme in the catabolism of fluoropyrimidine drugs including capecitabine. A recent report has suggested that oxaliplatin chemotherapy is associated with elevated DPD levels and chemoresistance pattern. As a newly developed chemotherapeutic agent, 17-allyloamino-17-demethoxy-geldanamycin (17-AAG) can be effective in combination therapy with oxaliplatin and capecitabine in colorectal cancer (CRC). DPD expression level can be a predictive factor in oxaliplatin and capecitabine-based chemotherapy. We evaluated DPD in mRNA and protein levels with new treatments: 17-AAG in combination with oxaliplatin and capecitabine in HT-29 and HCT-116 cell lines. Methods: Drug sensitivity was determined by the water-soluble tetrazolium-1 assay in a previous survey. Then, we evaluated the expression levels of DPD and its relationship with the chemotherapy response in capecitabine, oxaliplatin, and 17-AAG treated cases in single and combination cases in two panels of CRC cell lines. DPD gene and protein expression levels were determined by real-time polymerase chain reaction and western blotting assay, respectively. Results: DPD gene expression levels insignificantly increased in single-treated cases versus untreated controls in both cell lines versus controls. Then, the capecitabine and oxaliplatin were added in double combinations, where DPD gene and protein expression increased in combination cases compared to pre-chemotherapy and single drug treatments. Conclusion: The elevated levels of cytotoxicity in more effective combinations could be related to a different mechanism apart from DPD mediating effects or high DPD level in the remaining resistance cells (drug-insensitive cells), which should be investigated in subsequent studies.
Background
Myocardial infarction is one of the most common life threatening diseases that may lead to renal disorders via oxidative stress and inflammation. Betaine is a safe and well‐tolerated compound exhibiting beneficial antioxidant and anti‐inflammatory properties. Previous studies have demonstrated protective effects of betaine against myocardial infarction and renal injury. This study aimed to investigate the protective effect of betaine on tissue structure and renal function after isoprenaline‐induced myocardial infarction in rats.
Methods
Fifty Wistar strain male albino rats, weighing 200 ± 10, were selected for the study. The animals were housed individually under standard environmental conditions (Light–dark cycle, temperature and constant humidity) for 1 week. After acclimatization, they were randomly divided into five groups. G1, G2, and G3 groups received betaine at doses of 50, 150, and 250 mg/kg body weight/day via gavage for a period of 60 days. After 60 days, isoprenaline is injected subcutaneously (200 mg/kg body weight). In the isoprenaline group (G4), the rats were injected with isoprenaline (200 mg/kg body weight) and the control group (G5) received a standard diet (Without isoprenaline). Then, isoproterenol solution was used for induction of myocardial infarction. At the end, the expression of nitric oxide synthase (iNOS) protein was detected using immunohistochemical analysis and kidney tissues were assessed via histopathological analysis. In addition, serum level of TNF‐α and creatinine level were measured via ELISA test and colorimetric methods, respectively.
Results
The results of our study indicate that isoproterenol‐induced renal histopathological injury without changing creatinine level. Betaine has protective effects against renal injuries induced by isoprenaline and the expression of nitric oxide synthase (nNOS) protein showed no significant difference in all groups. Further, betaine reduced TNF‐α level significantly.
Conclusion
According to our results, betaine has protective effects on isoprenaline‐induced renal failure via a decrease in TNF‐α level and nitric oxide synthase.
Background:A large number of psychotropic drugs can interfere with the thyroid physiology, function and autoimmunity.Objective:The aim of the present study was to investigate the effects of alprazolam and haloperidol on thyroglobulin, antithyroglobulin (aTg), antithyroid peroxidase, and thyroid stimulating hormone levels on rats.Materials and Methods:First group of adult male Wistar rats was the control, second group received 0.5 mg kgResults:We have investigated a decrease in aTg amounts of control group (5.461±0.718) compared with drug treated rats with alprazolam (1.433±0.225) and haloperidol (1.21±0.228). (PConclusion:We found that these two drugs may interfere with the thyroid physiology and metabolism.
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