Acidic pH derived from cancer cells as a double-edged knife modulates wound healing through DNA repair genes and autophagy

Wound healing is a sequester program that involves diverse cell signalling cascades. Notwithstanding, complete signal transduction pathways underpinning acidic milieu derived from cancer cells is not clear, yet. MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) assay, fluorescein diacetate/propidium iodide staining, and cell cycle flow cytometry revealed that acidic media decreased cell viability and cell number along with enhanced dead cells and S-phase arrest in normal fibroblasts. Notably, the trends of intracellular reactive oxygen species production and lactate dehydrogenase release significantly increased with time. It seems the downregulation of Klf4 is in part due to acidosis-induced DNA damage. It promoted cells towards S-phase arrest and diminished cell proliferation. Klf4 downregulation had a direct correlation with the P53 level while acidic microenvironment promotes cells towards cell death mechanisms including apoptosis and autophagy. Noteworthily, the unchanged levels of Rb and Mlh1 indicated in those genes had no dominant role in the repairing of DNA damage in fibroblasts treated with the acidic microenvironment. Therefore, cells owing to not entering to mitosis and accumulation of DNA damage were undergone cell death to preserve cell homeostasis. Since acidic media decreased the level of tumour suppressor and DNA repair genes and altered the normal survival pathways in fibroblasts, caution should be exercised to not lead to cancer rather than wound healing. © 2019 Medicalhelplines.com Inc and John Wiley & Sons Lt

Exploring the Effects of Vitamin D Supplementation on Cognitive Functions and Mental Health Status in Subjects under Methadone Maintenance Treatment

Objectives:Vitamin D deficiency may be linked to several mental complications including cognitive deficits, depression, and anxiety in patients under methadone maintenance treatment (MMT). This study was designed to explore the effect of vitamin D supplementation on cognitive functions and mental health parameters in subjects under MMT.Methods:This randomized, double-blinded, placebo-controlled clinical trial was carried out among 64 patients under MMT. Participants were randomly allocated to receive either 50,000 IU vitamin D supplements (n=32) or placebo (n=32) every 2 weeks for 24 weeks. Cognitive functions and mental health parameters were taken at baseline and posttreatment to evaluate relevant variables.Results:After the 24-week intervention, compared with the placebo, serum 25(OH) vitamin D levels significantly increased in participants who received vitamin D supplements (β 14.50; 95 confidence interval CI, 13.17-15.83; P<0.001). In addition, compared with the placebo, subjects who received vitamin D had a significant reduction in Iowa Gambling Task (β-6.25; 95% CI,-8.60 to-3.90; P<0.001), and significant increases in Verbal Fluency Test (β 2.82; 95% CI, 0.78-4.86; P=0.007), Immediate Logic Memory (β 1. 32; 95% CI, 0.27-2.37; P=0.01), Reverse Digit Span (β 2.06; 95% CI, 1.18-2.94; P<0.001) and visual working memory (β 0.75; 95% CI, 0.33-1.16; P=0.001). Also, vitamin D supplementation significantly improved BDI (β-2.76; 95% CI,-3.97 to-1.55; P<0.001) compared with the placebo. When we applied Bonferroni correction, LM-Immediate (P=0.07) became nonsignificant, and other mental health parameters did not alter.Conclusions:Overall, taking 50,000 IU vitamin D supplements every 2 weeks for 24 weeks by patients under MMT had beneficial effects on cognitive functions and some mental health parameters. Further studies are needed to confirm our findings. Copyright © 2020 Wolters Kluwer Health, Inc. All rights reserved

The effects of melatonin supplementation on mental health, metabolic and genetic profiles in patients under methadone maintenance treatment

This investigation was designed to determine the effect of melatonin supplementation on mental health parameters, metabolic and genetic profiles in patients under methadone maintenance treatment (MMT). This randomized, double-blind, placebo-controlled, clinical trial was conducted among 54 patients under MMT. Participants were randomly allocated to receive either 10 mg melatonin (2 melatonin capsules, 5 mg each) (n = 26) or placebo (n = 28) once a day, 1 hour before bedtime for 12 weeks. Melatonin supplementation significantly decreased Pittsburgh Sleep Quality Index (β �4.08; 95 percent CI, �5.51, �2.65; P < 0.001), Beck Depression Inventory index (β �5.46; 95 CI, �8.92, �2.00; P = 0.003) and Beck Anxiety Inventory index (β �3.87; 95 CI, �5.96, �1.77; P = 0.001) and significantly increased International Index of Erectile Functions (β 5.59; 95 CI, 1.76, 9.42; P = 0.005) compared with the placebo. Subjects who received melatonin supplements had significantly lower serum insulin levels (β �2.53; 95 CI, �4.48, �0.59; P = 0.01), homeostasis model of assessment-insulin resistance (β �0.56; 95 CI, �1.03, �0.09; P = 0.01) and higher quantitative insulin sensitivity check index (β 0.01; 95 CI, 0.004, 0.02; P = 0.009) and HDL-cholesterol levels (β 3.71; 95 CI, 1.77, 5.64; P = 0.002) compared to placebo. Additionally, melatonin intake resulted in a significant reduction in serum high sensitivity C-reactive protein (β �0.15; 95 CI, �0.27, �0.02; P = 0.02), malondialdehyde (β �0.31; 95 CI, �0.57, �0.05; P = 0.02) and protein carbonyl (β �0.06; 95 CI, �0.09, �0.04; P < 0.001). This trial indicated that taking melatonin supplements for 12 weeks by patients under MMT had beneficial effects on their mental health metabolic profiles. © 2018 Society for the Study of Addictio