The combined effect of dichloroacetate and 3-bromopyruvate on glucose metabolism in colorectal cancer cell line, HT-29; the mitochondrial pathway apoptosis.

BACKGROUND: 5-Fluorouracil (5-FU) is regarded as the first line treatment for colorectal cancer; however, its effectiveness is limited by drug resistance. The ultimate goal of cancer therapy is induction of cancer cell death to achieve an effective outcome with minimal side effects. The present work aimed to assess the anti-cancer activities of mitocans which can be considered as an effective anticancer drug due to high specificity in targeting cancer cells. METHODS: MTT (3-4,5-dimethylthiazol-2-yl-2,5-diphenyltetrazolium bromide) assay was performed to determine the effects of our mitocans on cell viability and cell death. Apoptosis and necrosis, caspase 3 activity, mitochondrial membrane potential and ROS production in HT29 cell lines were analyzed by ApopNexin™ FITC/PI Kit, Caspase- 3 Assay Kit, MitoTracker Green and DCFH-DA, respectively. Moreover, quantitative real-time polymerase chain reaction (qRT-PCR) was performed to detect the expression level of pro-apoptotic (Bax) and anti-apoptotic (Bcl-2) genes in HT29 cell lines. RESULTS: Treatment with mitocans (3Br-P + DCA) inhibited the growth of HT29. Moreover, 3Br-P + DCA significantly induced apoptosis and necrosis, activation of caspase 3 activity, depolarize the mitochondrial membrane potential, and ROS production. At a molecular level, 3Br-P + DCA treatment remarkably down-regulated the expression of Bcl-2, while up-regulated the expression of Bax. CONCLUSION: Mitocans, in particular the combined drug, 3Br-P + DCA, could be regarded and more evaluated as a safe and effective compound for CRC treatment. Targeting hexokinase and pyruvate dehydrogenase kinase enzymes may be an option to overcome 5-FU -mediated chemo-resistant in colorectal cancer.

Investigating the diagnostic and prognostic value of anti-SARS-CoV-2 Spike IgG/IgM ELISA tests in patients infected with coronavirus Delta variant.

Aim: This study aimed to investigate the diagnostic and prognostic value of anti-severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) Spike IgG/IgM antibodies in patients infected with coronavirus Delta variant. Methods: This analytical observational study included 270 unvaccinated patients (aged ≥18 years) diagnosed with coronavirus disease 2019 (COVID-19) Delta variant who referred to Emergency Department of our hospital. The serum levels of anti-SARS-CoV-2 Spike IgG and IgM were measured by indirect ELISA. Main measured outcomes included anti-SARS-CoV-2 Spike IgG and IgM, chest computed tomography (CT) severity score, clinical and laboratory findings which were prospectively evaluated throughout the study period. Results: The IgM levels in critical patients were significantly higher than non-critical patients (p<0.05). But the mean level of IgG in critical patients was not significantly different from its level in non-critical patients (p>0.05). However, a significant positive correlation was observed between the levels of both antibodies and chest CT severity score (p<0.0001); this implies that their levels may reflect the degree of lung involvement. The IgM level on 15th-16th days after symptoms onset was significantly associated with the hazard of death even after adjusting for all other factors (adjusted HR (95%CI):1.28(1.014_1.63), p=0.03), whereas IgG was not (p>0.05). The survival probability among patients with IgM level ≥8.67 RU/ml (34.2%) was significantly lower than those with IgM level <8.67 RU/ml (99.5%, p=0.0001). Conclusions: Anti-SARS-CoV-2 Spike IgM antibody was significantly associated with the disease severity and risk of death in unvaccinated patients infected with coronavirus Delta variant. However, further large-scale investigations on diverse infected populations are required to precisely determine the diagnostic/prognostic value of these antibodies.