Restoration of miR-152 expression suppresses cell proliferation, survival, and migration through inhibition of AKT-ERK pathway in colorectal cancer.

BACKGROUND: MiR-152 has been reported as a tumor suppressor microRNA that is downregulated in a number of cancers, including colorectal cancer (CRC). A recent study suggested that miR-152 could be one of the key regulators of CRC. The aim of this study is to investigate the role of miR-152 in CRC and its mechanisms. METHODS: The pCMV-GPF-miR-152 vector was transfected into SW-480 and HCT-116 CRC cells via JetPEI transfection reagent. The stable miR-152-expressed cells were selected for the further experiment. To evaluate the effect of miR-152 on cell proliferation, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay was performed. Also, the effect of miR-152 on the survival of CRC cells was analyzed using terminal deoxynucleotidyl transferase dUTP nick-end labeling (TUNEL) assay. The inhibitory effect of miR-152 on migration was assessed by wound healing scratch assay. Then, the proteins expression levels of protein kinase B (AKT), phosphorylated AKT (p-AKT), extracellular signal-regulated kinase (ERK), and phosphorylated ERK (p-ERK) were measured by the western blot analysis method. RESULTS: The result of MTT assay represented miR-152 could inhibit cell proliferation. The TUNEL assay showed miR-152 could induce apoptosis in CRC cells. The wound healing scratch assay showed that miR-152 replacement repressed cell migration in CRC cell lines compared to control groups. The result of protein expression by western blot analysis demonstrated that miR-152 could reduce AKT-p-AKT, and ERK-p-ERK ratio compared to control cells. CONCLUSION: Our results show that miR-152 has new anticancer and antimetastatic effect in CRC tissue. The current study showed that miR-152 could be a novel therapeutic small molecule to suppress CRC cell proliferation, survival, and migration by suppressing AKT-ERK signaling pathways.

Long and Short-term Metformin Consumption as a Potential Therapy to Prevent Complications of COVID-19.

Purpose: The aim of the study is to evaluate the effect of metformin in complication improvement of hospitalized patients with COVID-19. Methods: This was a randomized clinical trial that involved 189 patients with confirmed COVID-19 infection. Patients in the intervention group received metformin-500 mg twice daily. Patients who received metformin before admission were excluded from the control group. Patients who were discharged before taking at least 2000 mg of metformin were excluded from the study. Primary outcomes were vital signs, need for ICU admission, need for intubation, and mortality. Results: Data showed that patients with diabetes with previous metformin in their regimen had lower percentages of ICU admission and death in comparison with patients without diabetes (11.3% vs. 26.1% (P=0.014) and 4.9% vs. 23.9% (P≤0.001), respectively). Admission time characteristics were the same for both groups except for diabetes and hyperlipidemia, which were significantly different between the two groups. Observations of naproxen consumption on endpoints, duration of hospitalization, and the levels of spO2 did not show any significant differences between the intervention and the control group. The adjusted OR for intubation in the intervention group versus the control group was 0.21 [95% CI, 0.04-0.99 (P=0.047)]. Conclusion: In this trial, metformin consumption had no effect on mortality and ICU admission rates in non-diabetic patients. However, metformin improved COVID-19 complications in diabetic patients who had been receiving metformin prior to COVID-19 infection, and it significantly lowered the intubation rates.

Mannose-binding lectin gene and promoter polymorphism in visceral leishmaniasis caused by Leishmania infantum.

Visceral leishmaniasis is an infectious disease caused by various species of Leishmania and Leishmania infantum is known to be associated with VL in Iran. Different factors can consider risk factors for VL that some remain unknown. The aim of present study is to determine the distribution of the alleles ofmannose-binding lectin gene codon 52, 54, 57 and promoter variants H/L, X/Y, P and Q in confirmed VL patients while compares then with normal controls and seek correlation between these variants and confirmed VL patients. Fifty eight confirmed VL patients blood samples were compared with one hundred and twenty normal controls from Azarbaijan population of Iran. MBL genotypes were investigated by polymerase chain reaction and restriction fragment length polymorphism. Allelic and genotypic frequency of the polymorphism at promoters and genes didn't show statistical differences in patients and normal controls, but frequency of alleles with high MBL concentration in VL patients was higher than controls (p = 0.03). We can conclude that normal alleles with high MBL serum level are risk factor for VL and defective alleles have protective role in VL.