Plasma Levels and Gene Expression of RANK in Non-Alcoholic Fatty Liver Disease.

BACKGROUND: The pathobiology of initiation and progression of nonalcoholic fatty liver disease (NAFLD) has not been completely elucidated. It seems that the RANK/RANKL/OPG cytokine system play an etiologic role in pathogenesis of this disease. This study aimed to investigate the plasma content and gene expression of RANK in NAFLD patients as compared to healthy individuals. METHODS: This case-control work was performed on 63 patients with NAFLD and 25 healthy subjects. The plasma levels of RANK and biochemical parameters were measured using ELISA and colorimetric methods, respectively. Also, RANK mRNA content was evaluated by quantitative RT-PCR in peripheral blood mononuclear cells. RESULTS: RANK plasma contents were shown to be lower in NAFLD patients than in control subjects (1.02 ± 0.75 and 1.41 ± 1 ng/mL, respectively (p = 0.008)). The differences in gene expression of RANK between NAFLD patients and controls were significant (p = 0.001). In the NAFLD patients, RANK was inversely correlated with HDL. Logistic regression showed the association of RANK plasma content with the risk of NAFLD. Moreover, ROC curve analysis showed that RANK has a great ability to differentiate between NAFLD patients and controls. CONCLUSIONS: This study for the first time showed lower plasma and mRNA levels of RANK in NAFLD patients compared to control individuals. These results recommend a possible association between RANK and pathobiology of NAFLD.

EMAST status as a beneficial predictor of fluorouracil-based adjuvant chemotherapy for Stage II/III colorectal cancer.

BACKGROUND: Elevated microsatellite alteration at selected tetranucleotide repeats (EMAST) is a type of microsatellite instability that occurs in ∼60% of colorectal cancers (CRCs) and associated with MSH3 dysfunction. A 5-fluorouracil (5-FU)-related cytotoxicity is attenuated in MSH3-deficient colon cancer cells. Reported here is the predictive value of EMAST in CRCs with Stage II or III disease treated with 5-FU-based chemotherapy. METHODS: EMAST status was analyzed in 157 patients with CRC with Stage II or III disease and MSH3 expression was analyzed using immunohistochemistry. The patients treated with 5-FU-based chemotherapy were studied in terms of the links of EMAST status with MSH3 expression, clinicopathological features, and overall survival (OS). RESULTS: A total of 63 patients (40.1%) had EMAST positive (EMAST+ ) CRC and 77 patients (49.0%) had low MSH3 expression. EMAST+ tumors were associated with advanced TNM stage and poor and moderately differentiated tumor. EMAST CRC was more frequently observed in tumors with low expression of MSH3 in the nucleus (n = 53; 84.1%, p < .001). On multivariate analysis, patients with EMAST+ status had a worse OS (hazard ratio: 2.489, 95% confidence interval [1.149-5.394], and p = .021). Worse OS in EMAST+ patients who received 5-FU-based chemotherapy was significantly more common compared with EMAST- CRCs. CONCLUSION: There is a link between EMAST and reduced nuclear expression of MSH3. There is worse survival in patients with EMAST+ CRC after 5-FU-based chemotherapy. According to our findings, adjuvant 5-FU-based chemotherapy might not be advantageous in EMAST+ CRCs with Stage II or III disease.

Sex determination using free fetal DNA at early gestational ages: a comparison between a modified mini-STR genotyping method and real-time PCR.

OBJECTIVE: Recently the use of free fetal deoxyribonucleic acid (DNA) in maternal plasma and serum has been applicable for noninvasive prenatal genetic diagnosis. In this study, we applied a new algorithmic base conventional polymerase chain reaction (PCR) genotyping method and also real-time PCR for detecting fetal X and Y-chromosome sequences in maternal plasma to determine fetal sex in pregnant women in their early gestational ages (5-13 weeks). Finally, we compared the efficiency of each method in sex determination. STUDY DESIGN: DNA was extracted from 106 pregnant women and their husbands' blood samples. Fetus mini-short tandem repeat (STR) genotyping was accomplished through amplification of 19 mini-STRs and 3 non-STR markers using conventional PCR followed by polyacrylamide gel electrophoresis analysis. Simultaneously, TaqMan real-time PCR was done with the use of DYS14-specific primers and probe. RESULTS: In conventional PCR method, 47 cases were diagnosed to be male and 49 to be female. In comparison, real-time PCR amplified DYS14 (Y-marker) sequences in 45 pregnant women plasma samples. Sensitivity and specificity were calculated to be 95.9% and 98% for conventional PCR and 91.8% and 100% for real-time PCR method, respectively. CONCLUSION: According to our study, the conventional PCR method was more sensitive than real-time PCR and it could be employed in future clinical diagnostics singly or in combination with real-time PCR.

MicroRNAs take part in pathophysiology and pathogenesis of Male Pattern Baldness.

Male Pattern Baldness (MPB) or androgenetic alopecia is a common form of hair loss with androgens and genetics having etiological significance. Androgens are thought to pathophysiologically power on cascades of chronically dramatic alterations in genetically susceptible scalp dermal papillas, specialized cells in hair follicles in which androgens react, and finally resulting in a patterned alopecia. However, the exact mechanisms through which androgens, positive regulators of growth and anabolism in most body sites, paradoxically exert their effects on balding hair follicles, are not yet known. The role of microRNAs, a recently discovered class of non-coding RNAs, with a wide range of regulatory functions, has been documented in hair follicle formation and their deregulation in cancer of prostate, a target organ of androgens has also been delineated. Yet, there is a lack of knowledge in agreement with microRNAs' contribution in pathophysiology of MPB. To investigate the role of microRNAs in pathogenesis of MPB, we selected seven microRNAs, predicted bioinformatically on a reverse engineering basis, from previously published microarray gene expression data and analyzed their expression in balding relative to non-balding dermal papillas. We found for the first time upregulation of four microRNAs (miR-221, miR-125b, miR-106b and miR-410) that could participate in pathogenesis of MPB. Regarding microRNAs' therapeutic potential and accessibility of hair follicles for gene therapy, these microRNAs can be considered as good candidates for a new revolutionized generation of treatments.