The tumor suppressor effect of miRNA 200-c-3p on A549 non-small cell lung cancer cell line is associated with down-regulation of programmed cell death ligand 1; an immune-check point mechanism.

MiRNA 200-c-3p has varying functions in different tumor types, whether tumor suppression or promotion. Comprehensive assessment of its function in non-small cell lung cancer (NSCLC) together with its effect on antitumor immune response have not been declared before. We aimed to explore the effect of replacement and suppression of miRNA 200-c-3p on non-small cell lung cancer and its impact on immune checkpoint function and subsequently antitumor immunity. MiRNA 200-c-3p mimic/inhibitor was transfected into the A549 cells. A 549 non-small cell lung cancer cells viability was done by trypan blue staining and 3-(4, 5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Flowcytometric analysis was done for apoptosis detection. Real-time reverse transcription-quantitative polymerase chain reaction (RT-qPCR) and western blot analysis were used to study its effect on relative gene expression and relative protein level of programmed cell death ligand 1 (PD-L1). Finally, co-culture with isolated and activated T cells was performed. Multiple comparisons were performed using one-way analysis of variance (ANOVA) followed by Tukey's multiple-comparison test. Decreased cell viability, increased apoptosis, reduced PD-L1 relative gene expression and its relative protein level, together with enhanced T cell cytotoxicity towards tumor cells were detected after miRNA 200-c-3p mimic transfection of A549 NSCLC cell line.  However, these results were reversed in miRNA 200-c-3p suppression. MiRNA 200-c-3p had a tumor suppressive effect in non-small cell lung cancer cells which might be through down regulation of PD-L1 relative gene expression, and it may be used as a new target to improve immune checkpoint dysfunction.

Musculoskeletal Symptoms in Hemodialysis Patients and their Effect on Health-Related Quality of Life.

BACKGROUND/AIMS: Hemodialysis (HD) represents one of the most commonly used modalities as a renal replacement therapy. Health-related quality of life (HRQoL) is much lower in HD patients than general population. Musculoskeletal (MSK) symptoms are one of the most important health problems that affect patients on maintenance HD. The main purpose of this study was to investigate the association between MSK symptoms and HRQoL among HD patients. METHODS: The study was carried out on 200 patients with chronic renal failure on chronic HD at different nephrology units in Egypt. They completed the Arabic version of the Kidney Disease and Quality of Life-Short Form 1.3 Questionnaire and answered the questions of MSK discomfort form based on the Nordic MSK Questionnaire. RESULTS: The mean age of the patients was 50.6 years, 61% were males. Of the 200 HD patients, 180 patients (90%) had MSK manifestations. The most commonly affected part was knee joint (51.5%). Regarding HRQoL, patients with MSK symptoms had significantly lower scores than did patients without on the physical role (p = 0.035), pain domain (p = 0.003), general health (p = 0.017), quality of social interaction (p = 0.046), and sleep domain (p = 0.022). CONCLUSION: MSK manifestations have a negative impact on HRQoL in HD patients. So, early identification and treatment are highly recommended.

Transforming Growth Factor Beta-1 in Human Breast Milk and Its Correlation with Infants' Parameters.

Background: Breastfeeding provides optimal nutrition and health protection for the infant; it contains many anti-inflammatory factors, including transforming growth factor beta-1 (TGF-ß1). Our study aimed to measure the level of TGF-ß1 in human milk and to find its correlation with some infant anthropometric characteristics. Subjects and Methods: A milk sample was collected from 84 mothers and the level of TGF-ß1 was measured using enzyme-linked immunosorbent assay. Results: TGF-ß1 was significantly higher in vegetarian mothers compared with nonvegetarian mothers (p = 0.044). Additionally, the mean value of breast milk TGF-ß1 was significantly higher in mothers using contraceptive pills compared with those who do not (p = 0.021). Also, the mean value of TGF-ß1 was significantly higher in infants 3-6 months than those <3 months (p = 0.010); also there was a significant difference regarding infants' weight and length with average weight and length (p = 0.042) and (p = 0.009), respectively. Conclusions: TGF-ß1 in human milk may play a role in infants' growth and development; mothers' diet is known to influence TGF-ß1 level and its relation to infants' age and weight. Contraceptive method could have an influence on TGF-ß1 levels during breastfeeding.

Autophagy in osteoporosis: Relation to oxidative stress.

Impaired autophagy and oxidative stress are implicated in the development of many diseases. This study aimed to investigate the involvement of autophagy represented by autophagy-related gene 7 (Atg7) and oxidative stress represented by superoxide dismutase 2 (SOD2) gene expression and enzyme activity in the pathogenesis of osteoporosis. Atg7 and SOD2 gene relative expression were evaluated by SYBR green quantitative real-time-polymerase chain reaction in the osteoporotic group (n = 26) versus the osteoporosis free group (n = 14). SOD2 enzyme activity was evaluated by colorimetric method in both study groups. Both Atg7 and SOD2 relative expression showed highly significant decrease (P < 0.01) between both groups. However, SOD2 enzyme activity showed no significant difference between the two groups. There was a significant direct correlation between Atg7 and SOD2 gene expression in both study groups. Atg7 relative expression showed significant ( P < 0.01) direct correlation with vitamin D serum levels and body mass index in osteoporotic group. In conclusion, both genes are involved in the pathogenesis of osteoporosis and this could be amenable to future therapeutic intervention.