Plasminogen Activator Inhibitor-1 Polymorphisms and Risk of Coronary Artery Disease: Evidence From Meta-Analysis and Trial Sequential Analysis.

A systematic review and meta-analysis were conducted to find out if there was association between Plasminogen Activator Inhibitor-1 (PAI-1) gene polymorphisms (- 844 G > A and - 675 4G > 5G) and susceptibility to coronary artery disease (CAD). Search of electronic databases was performed and the pooled odds ratio (OR) and 95% confidence interval (CI) were exerted to evaluate the pooled association between the single-nucleotide polymorphisms (SNPs) and risk of CAD. For - 675 4G > 5G SNP, dominant (OR = 0.90), recessive (OR = 0.90), allelic (OR = 0.91), homozygous (OR = 0.84), and heterozygous (OR = 0.96) models were significantly associated with decreased risk of CAD. Moreover, all five genetic models were associated significantly with decreased CAD risk in the Causation and Arab populations. The results in Asians were marginally significant in recessive, allelic, and homozygote models. The male gender was found to be a risk factor in individuals with PAI-1 4G > 5G SNP in the dominant model (OR = 0.89), recessive model (OR = 0.91), allelic model (OR = 0.92), homozygous model (OR = 0.86), and heterozygous model (OR = 0.91). The results of pooled ORs for overall populations and subgroup analysis by ethnicity reject any association between PAI-1 gene - 844 G > A polymorphism and CAD risk under all genetic comparisons. The results of this meta-analysis indicated that PAI-1 4G > 5G SNP was associated with decreased risk of CAD in the overall population as well as in the Asians, Caucasians, and Arab populations. However, the PAI-1 gene - 844 G > A polymorphism had no significant association with susceptibility to CAD.

Systematic review and meta-analytic findings on the association between killer-cell immunoglobulin-like receptor genes and susceptibility to pulmonary tuberculosis.

Several studies have evaluated the association between killer-cell immunoglobulin-like receptors (KIR) genes and susceptibility risk to tuberculosis (TB) infection. Nonetheless, their outcomes have not been conclusive and consistent. Here we implemented a systematic review and meta-analysis of KIR genes association to susceptibility risk of pulmonary TB (PTB) infection to attain a clear understanding of the involvement of these genes in susceptibility to PTB infection. A systematic search was conducted in the MEDLINE/PubMed and Scopus databases to find case-control studies published before November 2020. Pooled odds ratio (OR) and 95% confidence interval (95% CI) were calculated to determine the association between KIR genes and risk of PTB infection. After comprehensive searching and implementing the inclusion and exclusion criteria, 10 case-control studies were included in the meta-analysis. Four KIR genes were found to have significant positive association with PTB susceptibility risk of infection, including 2DL3 (OR = 1.454, 95% CI = 1.157-1.827; P = 0.001), 2DS1 (OR = 1.481, 95% CI = 1.334-1.837; P < 0.001), 2DS4 (OR = 1.782, 95% CI = 1.273-2.495; P = 0.001) and 3DL1 (OR = 1.726, 95% CI = 1.277-2.333; P < 0.001). However, the results showed that the remaining KIR genes (2DS2-4, 2DL1, 2, 4, 3DL1-2) and two pseudogenes (2DP1 and 3DP1) did not have significant associations with risk of PTB infection. This meta-analysis provides reliable evidence that the KIR genes 2DL3, 2DS1, 2DS4, and 3DL1 may be associated with an increased risk of PTB infection.

Association between IL7 Receptor Alpha (Il7ra) gene rs6897932 polymorphism and the risk of Multiple Sclerosis: A meta-regression and meta-analysis.

BACKGROUND: In this systematic review and meta-analysis, we aimed to find a consistent conclusion for the association between the interleukin 7 receptor alpha (IL7RA) gene rs6897932 single nucleotide polymorphism (SNP) and multiple sclerosis (MS) risk. METHODS: Here, we performed a comprehensive systematic search in PubMed, Scopus, and Web of Science to find relevant studies published before November 2020 investigating the association between rs6897932 SNP and MS risk. In the pooled analysis, we determined the odds ratio (OR) and the corresponding 95% confidence interval (CI) for the association level between rs6897932 SNP and the risk of MS. RESULTS: In the current meta-analysis 33 case-control studies (30 articles) containing 19351 patients and 21005 healthy controls certify the inclusion criteria. According to the pooled analysis, a statistically significant association of IL7RA gene rs6897932 SNP with MS risk was found across recessive model (OR= 0.84, 95% CI= 0.77-0.92, P< 0.001, FEM), allelic model (OR= 0.91, 95% CI= 0.85-0.99, P= 0. 02, REM), TT vs. CC model (OR= 0.79, 95% CI= 0.67-0.93, P= 0.005, REM). Moreover, the subgroup analysis based on the ethnicity indicated a negative significant association in Europeans; dominant model (OR= 0.88, 95% CI= 0.78-1.01, P= 0.06, REM), recessive model (OR= 0.79, 95% CI= 0.71-0.88, P< 0.001, REM), allelic model (OR= 0.88, 95% CI= 0.81-0.96, P= 0.003, REM), TT vs. CC model (OR= 0.74, 95% CI= 0.61-0.88, P<0.001, REM) models. Nonetheless, no significant association was detected in Asians and Americans. CONCLUSIONS: IL7RA gene rs6897932 SNP decreases MS susceptibility in overall population and Europeans.

Frequency and Correlation of Common Genes Copy Number Alterations in Childhood Acute Lymphoblastic Leukemia with Prognosis.

OBJECTIVE: It was shown by genomic profiling that despite no detectable chromosomal abnormalities a proportion of children with pre-B acute lymphoblastic leukemia harbors copy number alterations (CNA) of genes playing role in B-cell development and function. The aim of the study was to determine the frequency of CNA in pediatric acute lymphoblastic leukemia and correlate these findings with clinical outcome. METHODS: DNA extracted from peripheral blood or bone marrow at diagnosis/relapse of fifty newly diagnosed children with precursor B-cell acute lymphoblastic leukemia was analyzed for CNA with multiplex ligation-dependent probe amplification. RESULTS: The analysis revealed 76 CNA in 24 patients most frequently found in PAR1 (17%), CDKN2A/B (15.7%) and PAX5 (14.4%) genes. There were significant CNA co-occurrences between PAX5, CDKN2A/B, BTG1, ETV6, PAR1 or XP22 genes, (p <0.020) and the high-risk group. There was a significant correlation between EBF1, RB1, and IKZF1 alterations and bone marrow relapse. Patients with CNA in screened genes are more likely to succumb to their disease except for those with PAR1 or XP22 genes (p <0.050). CONCLUSION: The multiplex ligation-dependent probe amplification could be considered as an independent diagnostic tool allowing prompt identification of patients at high risk of treatment failure and, subsequently, a more adequate treatment approach.

The Effects of Evening Primrose/Hemp Seed Oil Compared to Rapamycin on the Gene Expression of Immunological Parameters in Experimental Autoimmune Encephalomyelitis Splenocytes.

Mouse model of multiple sclerosis (MS) is used for the inflammatory demyelinating disease. Rapamycin (RAPA) may contribute to the reduction of inflammatory responses to experimental autoimmune encephalomyelitis (EAE). Due to its adverse side effects, identifying new therapeutic agents is important. We investigated the transcriptional effects of evening primrose/hemp seed oil (EP/HS oil) compared to RAPA on the expression of immunological factors genes in spleen cells of EAE mouse models. We firstly induced EAE mice by injection of myelin oligodendrocyte glycoprotein (MOG). Then, the EAE mice treated and untreated with EP/HS oil were evaluated and compared with naïve mice. The spinal cords were examined histologically. The immunological factors including genes expression of the regulatory-associated protein of mammalian target of rapamycin (RAPTOR), regulatory-associated companion of mammalian target of rapamycin (RICTOR), interferon (IFN)-γ, interleukin (IL)-10, signal transducer and activator of transcription factors (STAT3), forkhead box P3 (FOXP3), and IL-17 of splenocytes were evaluated by real time-polymerase chain reaction (RT-PCR). The data showed that EP/HS oil was able to reduce the severity of EAE and inhibited the development of the disease. EP/HS oil treatment significantly inhibited the expression of RAPTOR, IFN-γ, IL-17, and STAT3 genes and promoted the expression of RICTOR, IL-10, and FOXP3 genes. In conclusion, the EP/HS oil is likely to be involved in transcription of factors in favor of EAE improvement as well as participating in remyelination in the EAE spinal cord and that it suggests to be effective in therapeutic approaches for MS.

Electrochemical Nano-biosensors as Novel Approach for the Detection of Lung Cancer-related MicroRNAs.

In both men and women around the world, lung cancer accounts as the principal cause of cancer-related death after breast cancer. Therefore, early detection of the disease is a cardinal step in improving prognosis and survival of patients. Today, the newly-defined microRNAs regulate about 30 to 60 percent of the gene expression. Changes in microRNA Profiles are linked to numerous health conditions, making them sophisticated biomarkers for timely, if not early, detection of cancer. Though evaluation of microRNAs in real samples has proved to be rather challenging, which is largely attributable to the unique characteristics of these molecules. Short length, sequence similarity, and low concentration stand among the factors that define microRNAs. Recently, diagnostic technologies with a focus on wide-scale point of care have recently garnered attention as great candidates for early diagnosis of cancer. Electrochemical nano-biosensors have recently garnered much attention as a molecular method, showing great potential in terms of sensitivity, specificity and reproducibility, and last but not least, adaptability to point-of-care testing. Application of nanoscale materials in electrochemical devices as promising as it is, brings multiplexing potential for conducting simultaneous evaluations on multiple cancer biomarkers. Thanks to their enthralling properties, these materials can be used to improve the efficiency of cancer diagnostics, offer more accurate predictions of prognosis, and monitor response to therapy in a more efficacious way. This article presents a concise overview of recent advances in the expeditiously evolving area of electrochemical biosensors for microRNA detection in lung cancer.

The use of stromal vascular fraction (SVF), platelet-rich plasma (PRP) and stem cells in the treatment of osteoarthritis: an overview of clinical trials.

Osteoarthritis (OA) is a major cause of disability across the world, which its prevalence is relatively high in elder population. Current accepted therapies such as exercise, anti-inflammatory drugs and intra-articular inoculation of corticosteroids are aimed at controlling symptoms in the affected patients. Surgical options including arthroplasty, osteotomy and joint replacement are other choices of treatment, which are invasive and can be applied in case of failure of conventional therapies. In the last few decades, efforts to treat musculoskeletal diseases are being increasingly focused on regenerative cellular therapies. Stromal vascular fraction (SVF), which obtained from adipose tissue, contains a variety of cells include mesenchymal stem cells (MSCs) and has shown to be effective in cartilage repair. Autologous blood products such as platelet-rich plasma (PRP) act as an adjuvant of surgical treatment and its intra-articular delivery has shown beneficial effects for OA treatment. Given the efficacy of such treatment approaches in OA, this paper discusses both preclinical and clinical evidence with major focus on clinical trials.

Myeloid-derived suppressor cells and tumor: Current knowledge and future perspectives.

The immunosuppressive features of tumor lesions participate not only as one of the major players inducing cancer progression but also a big challenge for effective immunotherapy. It has been found that immunosuppression associated with chronic inflammatory factors, such as growth factors, cytokines, and chemokines is generated by stroma and tumor cells. Chronic and exhaustive secretion of these mediators triggers the generation of myeloid-derived suppressor cells (MDSCs) demonstrating one of the key players engaged in tumor immunosuppression. In point of fact, direct cell-to-cell contact is a prerequisite for immunosuppressive functions of MDSCs. From the clinical perspective, the frequency of peripheral blood MDSCs is correlated with clinical stage and therapeutic response in various cancers. Furthermore, MDSCs are involved in chemoresistant settings. Altogether, it is a rational therapeutic approach to block the fierce cycle in which MDSCs are developed and infiltrated to favor cancer progression. In this review, we will summarize recent findings of MDSCs in tumor progression and discuss potential therapeutic strategies that could be evaluated in future clinical trials.