Low HDL concentration in rs2048327-G carriers can predispose men to develop coronary heart disease: Tehran Cardiometabolic genetic study (TCGS).

Recent genome-wide association studies (GWAS) highlighted the importance of genetic variations on SLC22A3 and MIA3 genes in developing coronary heart disease (CHD) among different ethnicities. However, the influence of these variations is not recognized within the Iranian population. Hence, in the present study, we aim to investigate two key single nucleotide polymorphisms (SNPs) on CHD incidence in this population. For this purpose, from Tehran Cardiometabolic Genetic Study (TCGS), 453 individuals with CHD were selected as a case and 453 individuals as a control that matched their age and gender. After quality control of two selected SNPs, rs2048327 (SLC22A3) and rs17465637 (MIA3), we used genotyps resulted from chip-typing technology and conducted the logistic regression analysis adjusted for non-genetic risk factors to detect the possible association of these SNPs with the CHD development. Our findings demonstrated the rs2048327-G and rs17465637-C can significantly increase the risk of CHD development about two times in only males and females, respectively. Interestingly, in the male carriers of the risk allele (G) of rs2048327, the low high-density lipoprotein (HDL) level can significantly predispose them to develop coronary heart disease in the future. According to our results, paying more attention to gender and genetic markers can help more efficient coronary heart disease screening and diagnosis.

A Rare Mutation in the MARVELD2 Gene Can Cause Nonsyndromic Hearing Loss.

The MARVELD2 gene which is located on the 5q13.2 may cause nonsyndromic hearing loss (NSHL) with autosomal recessive inherited pattern. So far c.1331+1G>A (IVS4+1G>A); NM_001038603.3, variant in deafness, has only reported previously in one Pakistani family in 2008 and it is reported for the first time in Iran and second time in the world. The case is a 21-year-old Iranian woman who has NSHL referred for genetic consultation, and her parents had a consanguineous marriage. To study the responsible genes for the mentioned disorder, whole exome sequencing (WES) was performed for the case. The result of WES analysis revealed a transition at the splice donor variant site of the MARVELD2 gene. The NGS result was confirmed by Sanger sequencing.

Anti-biofilm activity of Chlorella-mediated light activated disinfection: Ex vivo inhibition of intracanal mature Enterococcus faecalis biofilms via application of natural product.

BACKGROUND: This study aimed to evaluate the effects of light-activated disinfection (LAD) as a strategy for optimizing root canal disinfection using Chlorella (Chlo) as a natural photosensitizer against Enterococcus faecalis biofilms ex vivo. MATERIALS AND METHODS: The physical and chemical stability and absorption spectra of Chlo were determined. The mature microbial biofilm of E. faecalis was formed in root canals of 70 freshly extracted single-rooted premolars. After determining the minimum inhibitory concentration (MIC) of Chlo using the agar dilution testing, E. faecalis biofilms were exposed in the following groups (n = 10): 1- Chlo at a concentration of 2× MIC, 1- Chlo at a concentration of 4× MIC, 3- Diode laser, 4-2× MIC dose of Chlo-mediated LAD, 5-4× MIC dose of Chlo-mediated LAD, 6-0.2 % chlorohexidine (CHX), and 7- control group (E. faecalis biofilms without exposure to any photosensitizer and light source). The quantitative and qualitative evaluations of E. faecalis biofilms were done using counts of colony forming units (CFUs) and scanning electron microscope (SEM) and fluorescence microscope analysis, respectively. RESULTS: According to the results, the MIC of Chlo was 125 µg/mL, which inhibited the growth of E. faecalis. To evaluate the anti-biofilm effects of Chlo, the 2× and 4× MICs of Chlo (250 and 500 µg/mL, respectively) were used in the current study. The 4× MIC dose (500 µg/mL) of Chlo-mediated LAD was significantly more effective compared to other groups (P < 0.05), while the lowest percentage of dead cells was detected in the diode laser irradiation group. In addition, there was no significant difference in the log10 CFU of E. faecalis between the biofilm treated with 500 µg/mL Chlo-mediated LAD (1.27 ±â€¯0.05) versus 0.2 % CHX (1.10 ±â€¯0.06) (P < 0.05). As Moreover, SEM and fluorescence microscope images of the microbial biofilms showed that the highest percentage of dead bacteria was found in the 500 µg/mL Chlo-mediated LAD group. CONCLUSIONS: The results of this study suggest that Chlo-mediated LAD can be used as an adjuvant therapy to eliminate the E. faecalis biofilms in the root canal system.

Valproic acid may exerts its cytotoxic effect through rassf1a expression induction in acute myeloid leukemia.

In acute myeloid leukemia (AML), despite the acceptance of standard intensive chemotherapy as an optimal induction regimen for all age groups, in the elderly patients, the best treatment should meet the challenge of multiple factors like age, comorbidities, and cytogenetics, making them ineligible for standard induction chemotherapy. Using the current low-intensity therapies like decitabine, azacitidine, and low-dose cytarabine as a single arm, outcomes for these patients remain poor. As a histone deacetylase inhibitor valproic acid (VPA) exhibit anticancer activity by triggering apoptosis, the mechanism of which is not yet completely clarified. To explore the possible connection between VPA treatment and the Hippo pathway as an apoptosis stimulating route, we also explore the expression of major components of this pathway and for the first time we postulate a relationship between VPA treatment and cell death induction through RASSF1A expression induction. Furthermore, we demonstrate that autophagy inhibition by chloroquine (CQ) significantly augmented the cytotoxic effect of VPA on AML cells, especially in those with unfavorable and normal karyotype. Regarding that VPA and CQ are well-tolerated drugs and our presumptive results of usefulness of VPA + CQ in three cytogenetic risk groups of AML, this combinatorial therapy could represent an attractive treatment option for older AML patients unfit for intensive therapy.