We found four microRNAs that could participate in the pathogenesis of male pattern baldness. Regarding the strong therapeutic potential of microRNAs and the easy accessibility of hair follicles for gene therapy, microRNAs are possible candidates for a new generation of revolutionary treatments.

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.

Previous studies have shown controversial results about the role of androgens in coronary artery disease (CAD). We performed this study to examine and compare the relationship between androgenic hormones and CAD using conventional linear statistical techniques as well as novel non-linear approaches. The study was conducted on 502 consecutive men who were referred for selective coronary angiography at Tehran Heart Center due to different indications. We studied the relationship between androgenic hormones and CAD by using the generalized linear models, generalized additive models, and neural networks. Free testosterone (fT), total testosterone (tT) and dehydroepiandrosterone sulfate levels in patients with significant CAD versus normal individuals were 6.69 +/- 3.20 pg/ml, 16.60 +/- 6.66 nm/l, and 113.38 +/- 72.9 microg/dl versus 7.12 +/- 3.58 pg/ml, 15.82 +/- 7.26 nm/l, and 109.03 +/- 68.19 microg/dl, respectively (P > 0.05). The Generalized linear models was unable to show any significant relationship between androgenic hormones and CAD, while generalized additive model and neural networks supported the significant effect of androgenic hormones on CAD. This finding suggests a nonlinear association of tT levels with CAD: lower levels have a preventive effect on CAD, whereas higher values increase the risk of CAD. Emphasizing the non-linearity of the variables may provide new insight into the possible explanation of the effect of androgenic hormones on CAD.

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Viper venom contains antibacterial and cytotoxic components. The aim of this study was to identify and evaluate the antimicrobial and cytotoxic properties of the crude venom of Vipera latifii (V. latifii). Lyophilized venom of V. latifii was quantified by Bradford method and its antibacterial activity (6.25-400 μg/ml) was assessed using the MTT, MIC, Disc diffusion, and Well diffusion assays. Also, its cytotoxic activity was investigated using MTT reduction, Neutral uptake, and Comet assay on human liver cancer (HepG2) cell line. Crude venom showed antibacterial effects against Bacillus subtilis and Staphylococcus aureus, but was not effective on Escherichia coli. Also, the crude venom showed apoptotic and necrotic effects on human liver cancer cells. The venom of V. latifii can inhibit the growth of bacteria and cancer cells. These findings suggest that this may be a potential source of molecules with antibacterial and anticancer characteristics.

Our findings show a relationship between the AGT-TT genotype and hypertension in patients with both hypertension and simple renal cysts. This finding suggests an additive role for the AGT gene of the renin-angiotensin system in the process of hypertension and simple renal cysts formation. Future studies are needed to elucidate the mechanisms through which this association is mediated.

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.

IntroductionCoronary artery diseases (CAD) are the most common causes of death. Myocardial infarction (MI) is a complex multifactorial and the most severe type of CAD. Early onset MI in a first-degree relative could be defined as an independent risk factor for CAD. This study was performed to investigate the genetic cause of early onset familial CAD.Material and methodsIn this study, the genetic cause of familial CAD was investigated in patients with a family history of CAD who underwent angiography before the age of 50 years. The patients did not have any diagnostic criteria for familial hypercholesterolemia, diabetes, or obesity, and also they were not opium or alcohol users. Whole exome sequencing in probands was performed and mutation was confirmed by PCR and Sanger sequencing.ResultsIn our studied population, the c.501G>C (p.K167N) mutation in the OLR1 gene was identified in a family. Mutation was confirmed by PCR and Sanger sequencing in the homozygous state (GG) in patients. Healthy individuals in this family were heterozygous (GC) and homozygous (CC).ConclusionsThis finding suggests that the OLR1 gene could be a possible cause of early onset familial MI. Considering that parents of all affected individuals had a consanguineous marriage, it is important to perform carrier screening and genetic counseling in this family and their close relatives as a prevention strategy in populations at risk.