TNF-α -308 G/A variant and susceptibility to chronic obstructive pulmonary disease: A systematic review and meta-analysis.

BACKGROUND AND OBJECTIVE: TNF-α -308 G/A variant is recognized to play an important role in the pathogenesis of chronic obstructive pulmonary disease (COPD). Although many studies have investigated the association of TNF-α-308 and COPD risk, a deep understanding of this association is lacking due to small subjects sizes and insufficiently study designs among different investigations. In this study, a systematic review and meta-analysis was performed based on published reports on the association of TNF-α and COPD. METHOD: The published studies concerned the association between TNF-α and COPD were identified using a systematic research in Scopus, Google Scholar, and PubMed up to April 2018. A total of 46 different papers studying the rs1800629 variant in TNF-α gene were included. Then, human studies were selected to further analysis regardless of papers language. RESULTS: Based on the results, the major outcome of this meta-analysis can be represented as follows: individuals with GG and GA genotypes possess less risk of developing COPD (OR = 0.58, 95%CI: (0.44-0.79), P < 0.00) compared to AA genotype carriers. In contrast, the AA genotype carriers of the TNF-α rs1800629 has a significantly higher risk of developing COPD (OR = 1.83, 95%CI: (1.34-2.51), P < 0.00) compared to GG carrier. Despite the previous meta-analysis results which reported significantly decreasing of heterogeneity with ethnicity, we found that the source of controls has a significant contribution to observed heterogeneity. CONCLUSIONS: Thanks to the global burden of COPD studies, proving TNF-α 308 gene variant as an independent factor in its pathogenesis opens new insights to diagnosis and management of COPD.

Whole Exome Sequencing to Find Candidate Variants for the Prediction of Kidney Transplantation Efficacy.

INTRODUCTION: Kidney transplantation is the optimal treatment strategy for some end-stage renal disease (ESRD); however, graft survival and the success of the transplantation depend on several elements, including the genetics of recipients. In this study, we evaluated exon loci variants based on a high-resolution Next Generation Sequencing (NGS) method. METHODS: We evaluated whole-exome sequencing (WES) of transplanted kidney recipients in a prospective study. The study involved a total of 10 patients (5 without a history of rejection and 5 with). About five milliliters of blood were collected for DNA extraction, followed by whole-exome sequencing based on molecular inversion probes (MIPs). RESULTS: Sequencing and variant filtering identified nine pathogenic variants in rejecting patients (low survival). Interestingly, in five patients with successful kidney transplantation, we found 86 SNPs in 63 genes 61 were variants of uncertain significance (VUS), 5 were likely pathogenic, and five were likely benign/benign. The only overlap between rejecting and non-rejecting patients was SNPs rs529922492 in rejecting and rs773542127 in non-rejecting patients' MUC4 gene. CONCLUSIONS: Nine variants of rs779232502, rs3831942, rs564955632, rs529922492, rs762675930, rs569593251, rs192347509, rs548514380, and rs72648913 have roles in short graft survival.

A novel biallelic LMNB2 variant in a patient with progressive myoclonus epilepsy and ataxia: A case of laminopathy.

The report of LMNB2-related progressive myoclonus epilepsy and ataxia due to missense homozygous c.473G>T variant.

Trimethyl Chitosan Improves Anti-HIV Effects of Atripla as a New Nanoformulated Drug.

BACKGROUND: Highly active antiretroviral therapy (HAART) has been commonly used for HIV treatment. Its main drawbacks like drug resistance and side effects raised researcher's interest to find new approaches for its treatment. Trimethyl chitosan is one of the drug carriers which has been introduced recently. MATERIALS AND METHODS: the conjugated atripla-trimethyl chitosan was designed and characterized by zetasizer, AFM and FTIR techniques. The drug conjugation with trimethyl chitosan and cellular uptake of nano-conjugate were determined by spectrophotometry. XTT test was used to measure the cytotoxicity. Anti-retroviral efficiency was studied by ELISA test. RESULTS: Zetasizer Results proved that the average size of nano-conjugate particles agglomeration was 493.4±24.6 nm but the size of the majority of the particles was 177.2±7.8 nm with the intensity of 87.9%. AFM technique revealed that the sizes of nano-conjugate and trimethyl chitosan were 129 nm and 59.78 nm, respectively. Zeta potential was -1.35±0.04 mv for nano-conjugate and -7.69±0.3 mv for drug. Conjugation efficiency of atripla with trimethyl chitosan was 5.27%. Measured cellular uptake with spectrophotometry for nano-conjugate was about twice of the free drug in examined concentrations (P=0.007). Compared to atripla, the nano-conjugate showed a higher inhibitory effect on HIV replication (P=0.0001). CONCLUSION: The result showed that atripla-TMC conjugate does not have a significant cytotoxicity effect. Due to the higher inhibitory effect of nano-conjugate on viral replication, it can be used in lower concentration for antiviral treatment, which resulted in reduction of drug resistance and other side effects.

Up-regulation of miR-21 and 146a expression and increased DNA damage frequency in a mouse model of polycystic ovary syndrome (PCOS).

INTRODUCTION: Polycystic ovary syndrome (PCOS), a multigenic endocrine disorder, is highly associated with low-grade chronic inflammation, however its etiology remains unclear. In this study, we employed dehydroepiandrosterone (DHEA)-treated mice to reveal the molecular mechanism of inflammation and its correlation with oxidative stress in PCOS patients. METHODS: miR-21 and miR-146a expression levels were measured using quantitative real-time polymerase chain reaction (qRT-PCR). DNA strand breakage frequency was measured using the single cell gel electrophoresis (SCGE) assay (comet assay) and micronucleus test (MN). CRP levels were measured by ELISA method and ESR values were measured by means of Micro-Dispette (Fisher No: 02-675-256) tubes according to the manufacturer's instructions. Data were analyzed using one-way ANOVA in SPSS 21.0 software. RESULTS: Our results showed that miR-21 and miR-146a as inflammation markers were upregulated in the sample group in comparison with control group. Erythrocyte sedimentation rate (ESR) and C- reactive protein (CRP) levels were also increased in mouse models of PCOS (p < 0.000). Micronucleated polychromatic erythrocyte (MNPCE) rates per 1000 polychromatic erythrocyte (PCE) significantly increased in DHEA treated mice (6.22 ± 3.28) in comparison with the controls (2.33 ± 2.23, p < 0.000). Moreover, mean arbitrary unit in DHEA treated animals (277 ± 92) was significantly higher than that in controls (184 ± 76, p = 0.005). CONCLUSION: To conclude, increased DNA strand breakage frequency and increased expression levels of miR-21 and miR-146a in DHEA administrated animals suggest that low grade chronic inflammation and oxidative stress can act as the main etiologies of PCOS.