Association of vitamin D genetic pathway with asthma susceptibility in the Kurdish population.

BACKGROUND: Vitamin D (Vit D) function in asthma progression has been studied well. The effects of genetic variations in Vit D pathway molecules have been also studied, although the results are contradicted. In the present study, for the first time we examined the Vit D pathway molecules included serum Vit D and vitamin D-binding protein (VDBP) and also genetic variations in the vitamin D receptor (VDR) and VDBP in a Kurdish population with asthma. METHODS: An enzyme-linked immunosorbent assay (ELISA) method was used to measure the serum Vit D and VDBP. VDR rs1544410 and rs2228570 and VDBP rs7041 were assessed by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). RESULTS: The serum level of Vit D significantly decreased in asthmatic patients versus controls (16.26 ± 6.76 vs 23.05 ± 10.57 ng/mL, P value = .001). We observed an indirect correlation between Vit D and clinical findings. We also found an increased level of serum VDBP in patients as compared to the controls (1044.6 ± 310.82 vs 545.95 ± 121.73 µg/mL, P value < .0001). Besides, the risk of asthma progression was increased in patients with the VDR rs2228570 CC and VDBP rs7041 GG genotypes (OR = 3.56, P = .0382 and OR = 2.58, P = .01, respectively). CONCLUSION: In summary, our results explain the influence of the genetic variations in VDR and VDBP in addition to Vit D and VDBP serum concentrations on asthma susceptibility in the Kurdish population.

The role of histone deacetylase 3 in breast cancer.

It has been recently revealed that Histone Deacetylase (HDAC) 3, a unique member of the HDACs family, can trigger and progress cancers by alternation in genes expression and proteins activity. Epigenetic modifications by HDACs have been studied well in various cancer cells. Recent studies have focused on the HDAC enzymes as a possible target in cancer therapy. There are significant documents on upregulation of HDAC3 in breast cancer (BC) cells which suggest an oncogenic role for this enzyme. Interestingly, some studies showed that HDAC3 inhibition could be considered as a promising target in breast cancer therapy, and thus far, several inhibitors from different nature have been introduced. In this review, we discussed the function and highlight the existing inhibitors of HDAC3 in BC pathogenesis and therapy.

miR-589-5p Inhibits Cell Proliferation by Targeting Histone Deacetylase 3 in Triple Negative Breast Cancer.

BACKGROUND: Histone deacetylase 3 (HDAC3) is a potential oncogene that is significantly up-regulated in patients with breast cancer. MicroRNAs (miRs) are a group of small non-coding and regulatory RNAs which have recently been proposed as promising molecules for breast cancer target therapy. In the current study, we investigated the impact of miR-589-5p/ HDAC3 axis on cancer cell development in triple negative breast cancer (TNBC) cells. METHODS: In-silico analysis determined that miR-589-5p potentially targets HDAC3. We evaluated the HDAC3 and mir-589-5p expression levels in clinical samples and breast cancer cell lines including MDA-MB-231, MDA-MB-468, MCF-7 and MCF-10A. HDAC3 was knocked out to investigate its role on cancer cell progression. Anti-cancerous role of the miR-589-5p was assessed using an expression vector. We evaluated possible alteration in the cell cycle progression, cell viability and cell proliferation, after transient transfection. RESULTS: HDAC3 was over-expressed in TNBC clinical samples and breast cancer cell lines compared to non-cancerous controls while miR-589-5p was down regulated in cancer cells. Suppression of HDAC3 decreased the cell viability, cell proliferation and colony formation. Similar results were observed after over-expression of the miR-589-5p. Dual-Luciferase reporter assay confirmed the direct targeting of HDAC3 by miR-589-5p. CONCLUSION: Our results showed that miR-589-5p mediates its anti-proliferative effects on breast cancer cells via targeting HDAC3. These findings suggest that the miR-589-5p/ HDAC3 axis could be considered as a possible therapeutic strategy in TNBC.

rRT-PCR for SARS-CoV-2: Analytical considerations.

The COVID-19 pandemic remains a significant problem involving health systems worldwide. Accurate and early detection of Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection is critical for minimizing spread and initiating treatment. Among test methods, real-time reverse-transcriptase polymerase-chain-reaction (rRT-PCR) is considered the gold standard. Although this test has high specificity and relatively high sensitivity, the occurrence of falsely negative results in symptomatic patients and/or having a positive CT scan remains a challenge. Sources of error can be pre-analytical (sampling, storage and processing), analytical (RNA extraction, cDNA synthesis and amplification) and post-analytical (interpretation and analysis and test reporting). These potential sources of error and efforts to mitigate are reviewed in this article with an emphasis on the analytical phase.

Evaluation of adenosine deaminase (ADA) isoenzymes activity and tumor necrosis factor-α (TNFα) concentration in chronic heart failure.

INTRODUCTION: Chronic heart failure (CHF) has recently been considered as an inflammatory disease. Enhanced production of tumor necrosis factor-α (TNFα) in CHF patients has been proved. To compensate deleterious effects of TNα, the concentration of adenosine is increased in CHF. However, concurrent determination of serum TNFα and enzymatic activities of ADA and its ADA1 and ADA2 isoenzymes, as the main regulators of adenosine concentration, has not yet been carried out. MATERIALS AND METHODS: Blood samples were collected from 52 CHF patients and 55 healthy controls. Laboratory routine tests were performed, and after determining the concentration of TNFα, total ADA (tADA) as well as ADA1 and ADA2 isoenzyme activities were measured. RESULTS: Mean concentration of TNFα increased over 2 fold in CHF patients (12.54 ± 11.69 pg/ml compared with 6.0 ± 6.58 pg/ml in controls). The highest level of TNFα was observed in patients with the final stage of the disease (NHYA IV subgroup), according to the New York Heart Association classification. tADA activity was significantly lower in CHF patients compared with controls (19.29 ± 9.73 and 24.3 ± 6.01 U/L, respectively). ADA2 activity markedly decreased in CHF patients and showed a direct correlation with tADA (r = 0.641, P = 0001). In addition, the lowest levels of tADA and ADA2 activities were observed in patients from the 4(th) quartile of NYHA classification. CONCLUSION: Adenosine deaminase activity is reduced in CHF patients to give rise to the concentration of adenosine, thereby attenuating pathologic consequences of CHF. Therefore, it is concluded that ADA activity is of paramount importance in pathophysiology of heart failure and might be used for diagnostic purposes or treatment targets.

Analysis of serum adenosine deaminase (ADA) and ADA1 and ADA2 isoenzyme activities in HIV positive and HIV-HBV co-infected patients.

OBJECTIVES: To determine adenosine deaminase (ADA) activity as a possible diagnostic marker in HIV and HIV-HBV co-infected patients. DESIGN AND METHODS: Blood samples were collected from 72 healthy, 33 HIV positive and 30 HIV-HBV co-infected subjects. Blood CD4+ cell count was recorded and serum alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, total ADA, and ADA1 and ADA2 isoenzyme activities were determined. RESULTS: Serum ALT, AST, total ADA and ADA2 isoenzyme activities were significantly higher in HIV positive and HIV-HBV co-infected groups compare to the control (p<0.05), whereas serum ALP showed no differences between groups. CD4+ cell counts markedly decreased in all patients and showed a significant inverse correlation with ADA activities (R(2)=0.589, p<0.001). CONCLUSIONS: Serum ADA was significantly increased in HIV and HIV-HBV co-infections. Therefore, because of its low cost and simplicity to perform, ADA activity might be considered as a useful diagnostic tool among the other markers in these diseases.