Altered Expression of the HLA-G and IL10RB Genes in Placental Tissue of Women with Recurrent Pregnancy Loss.

BACKGROUND: Several lines of evidence strongly suggest that the contribution of human leukocyte antigen-G (HLA-G) and interleukin 10 receptor (IL10R) to maternal immunological tolerance toward paternal alloantigens of the embryo limits the activation and function of the maternal immune system. This study is aimed to assess the varia-tion of the mRNA expression levels of HLA-G and IL10RB genes in placental tissue of women with recurrent pregnancy loss (RPL). METHODS: Placental tissue samples were collected from 78 women with a history of at least two consecutive miscarriages and 40 healthy women with no history of pregnancy loss. The expression of HLA-G and IL10RB in placental tissue specimens was evaluated by the quantitative real-time PCR (qPCR) method. Moreover, the correlation be-tween the expression levels of these genes and clinicopathological parameters was analyzed. RESULTS: The results showed that the expression of HLA-G was down-regulated in placental tissues samples of RPL patients compared to healthy subjects, while the expression of IL10RB was up-regulated, but none of them was statistically significant (p-value > 0.05). The mRNA expression levels of HLA-G and IL10RB in placental tissue of RPL patients were negatively correlated with age and number of miscarriages (p-value > 0.05). A significant positive correlation was observed between the expression levels of HLA-G and IL10RB in women with RPL (p-value < 0.05). CONCLUSIONS: The altered expression of HLA-G and IL10RB in placental tissue may contribute to the pathogenesis of RPL and therefore serve as potential therapeutic targets for its prevention.

The effect of platelet-rich plasma on the improvement of pregnancy results in repeated implantation failure: A randomized controlled trial.

Background: The success rate of infertility treatment depends on many different factors. Objective: This study aimed to determine the effect of platelet-rich plasma (PRP) on the improvement of pregnancy outcomes in participants with repeated implantation failure. Materials and Methods: The study is a randomized triple-blind clinical trial. The study population was 118 women with repeated implantation failure during assisted reproductive technology treatment at Tabriz Jihad-e Daneshgahi ART Center from May 2017 to December 2019. Intervention: Intrauterine injection of autologous PRP. Standard treatment of fetal transfer to the uterine cavity was performed without intrauterine PRP injection in the control group: After 4 wk, the level of ß-human chorionic gonadotropin hormone in participants' blood was measured. Results: Comparing the effect of intrauterine injection of PRP in 2 groups showed the level of ß-human chorionic gonadotropin positive in the intervention group was 21 (43.8%), in the control group was 12 (26.1%), odds ratio = 2.20 (0.92-5.26) and p = 0.073. Conclusion: The therapeutic effect in the intervention group compared to the control regarding the outcome of a successful pregnancy showed that intrauterine injection of PRP can be effective in improving pregnancy outcomes, although this improvement is not significant.

Down-Regulation of circulating miR-23a-3p, miR-101-3p, and miR-let-7c in Women with Idiopathic Recurrent Pregnancy Loss.

BACKGROUND: Recently, circulating microRNAs have attracted much attention because they can serve as reliable, non-invasive diagnostic biomarkers for human diseases. This study aimed to quantify miR-23a-3p, miR-101-3p, and miR-let-7c expression levels in plasma samples of patients with idiopathic recurrent pregnancy loss (iRPL) and healthy subjects and to evaluate their potential diagnostic value in diagnosis of iRPL. METHODS: A total of 120 plasma samples were obtained from sixty women with a history of iRPL and sixty healthy fertile women to evaluate the expression levels of the circulating miR-23a-3p, miR-101-3p, and miR-let-7c by quantitative real-time polymerase chain reaction (qPCR) technique. The correlation between miR-23a-3p, miR-101-3p, and miR-let-7c and clinicopathological parameters was also assessed. Receiver operating characteristic (ROC) curve was plotted to determine the diagnostic accuracy of studied miRNAs in iRPL. RESULTS: Our results showed that the miR-23a-3p expression level in plasma of iRPL patients was lower than those in healthy controls but without a statistically significant difference (p = 0.113). The expression levels of miR-101-3p and miR-let-7c were significantly downregulated in iRPL patients compared with healthy subjects (p < 0.05). The plasma levels of miR-23a-3p and miR-let-7c were negatively correlated with number of abortions in iRPL patients. We observed statistically significant positive correlation between miR-23a-3p and miR-101-3p (r = 0.478, p = 0.001), miR-23a-3p and miR-let-7c (r = 0.561, p = 0.0001), and miR-101-3p and miR-let-7c (r = 0.533, p = 0.0001) in patients with iRPL. CONCLUSIONS: The current study provides evidence indicating that downregulation of miR-23a-3p, miR-101-3p, and miR-let-7c may be associated with iRPL.

Immunomodulatory role of Nanocurcumin in COVID-19 patients with dropped natural killer cells frequency and function.

The ongoing COVID-19 pandemic is still a challenging problem in the case of infection treatment. The immunomodulatory effect of Nanocurcumin was investigated in the present study in an attempt to counterbalance the immune response and improve the patients' clinical symptoms. 60 confirmed COVID-19 patients and 60 healthy controls enrolled in the study. COVID-19 patients were divided into Nanocurcumin and placebo received groups. Due to the importance of the role of NK cells in this disease, the frequency, cytotoxicity, receptor gene expression of NK cells, and serum secretion levels of inflammatory cytokines IL-1ß, IL-6, TNF-α, as well as circulating C5a as a chemotactic factor an inflammatory mediator was evaluated by flow cytometry, real-time PCR and enzyme-linked immunosorbent assay in both experimental groups before and after the intervention. Given the role of measured factors in the progression and pathogenesis of COVID-19 disease, the results can help find appropriate treatments. The results of this study indicated that the Nanocurcumin could significantly increase the frequency and function of NK cells compared to the placebo-treated group. As an immunomodulatory agent, Nanocurcumin may be a helpful choice to improve NK cell function in COVID-19 patients and improve the clinical outcome of patients.

Erratum to: Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as a potential of tumor marker.

[This corrects the article on p. 69 in vol. 50, PMID: 28417057.].

Evaluation of sHLA-G levels in serum of patients with prostate cancer identify as a potential of tumor marker.

Prostate cancer is the most common cancer type in men and is the second cause of death, due to cancer, in patients over 50, after lung cancer. Prostate specific antigen (PSA) is a widely used tumor marker for prostate cancer. Recently, PSA is discovered in non-prostatic cancer tissues in men and women raising doubts about its specificity for prostatic tissues. PSA exists in low serum level in healthy men and in higher levels in many prostate disorders, including prostatitis and prostate cancer. Thus, a supplementary tumor marker is needed to accurately diagnose the cancer and to observe the patient after treatment. Recently, soluble human leukocyte antigen-G (sHLA-G) has been introduced as a new tumor marker for different cancer types, including colorectal, breast, lung, and ovary. The present descriptive-experimental study was carried out including patients with malignant prostate tumor, patients with benign prostate tumor, and a group of health men as the control group, as judged by an oncologist as well as a pathologist. After sterile blood sampling, sHLA-G was measured by enzyme-linked immunosorbent assay in each group. The data was then analyzed using one-way ANOVA. P≤0.05 was considered as statistically significant. The results showed that the mean of sHLA-G level was high in patients. Also, it was found that there was a significant difference in sHLA serum level between the three groups. The data revealed that sHLA-G can be a novel supplementary tumor marker in addition to PSA to diagnose prostate cancer.

Transcript, methylation and molecular docking analyses of the effects of HDAC inhibitors, SAHA and Dacinostat, on SMN2 expression in fibroblasts of SMA patients.

Several histone deacetylase inhibitors (HDACis) are known to increase Survival Motor Neuron 2 (SMN2) expression for the therapy of spinal muscular atrophy (SMA). We aimed to compare the effects of suberoylanilide hydroxamic acid (SAHA) and Dacinostat, a novel HDACi, on SMN2 expression and to elucidate their acetylation effects on the methylation of the SMN2. Cell-based assays using type I and type II SMA fibroblasts examined changes in transcript expressions, methylation levels and protein expressions. In silico methods analyzed the intermolecular interactions between each compound and HDAC2/HDAC7. SMN2 mRNA transcript levels and SMN protein levels showed notable increases in both cell types, except for Dacinostat exposure on type II cells. However, combined compound exposures showed less pronounced increase in SMN2 transcript and SMN protein level. Acetylation effects of SAHA and Dacinostat promoted demethylation of the SMN2 promoter. The in silico analyses revealed identical binding sites for both compounds in HDACs, which could explain the limited effects of the combined exposure. With the exception on the effect of Dacinostat in Type II cells, we have shown that SAHA and Dacinostat increased SMN2 transcript and protein levels and promoted demethylation of the SMN2 gene.

Two novel gross deletions of TSC2 in Malaysian patients with tuberous sclerosis complex and TSC2/PKD1 contiguous deletion syndrome.

Tuberous sclerosis complex is an autosomal dominant neurocutaneous disorder affecting multiple organs. Tuberous sclerosis complex is caused by mutation in either one of the two disease-causing genes, TSC1 or TSC2, encoding for hamartin and tuberin, respectively. TSC2/PKD1 contiguous gene deletion syndrome is a very rare condition due to deletion involving both TSC2 and PKD1 genes. Tuberous sclerosis complex cannot be easily diagnosed since there is no pathognomonic feature, although there are consensus diagnostic criteria for that. Mutation analysis is useful and plays important roles. We report here two novel gross deletions of TSC2 gene in Malay patients with tuberous sclerosis complex and TSC2/PKD1 contiguous gene deletion syndrome, respectively.

Novel complex re-arrangement of ARG1 commonly shared by unrelated patients with hyperargininemia.

BACKGROUND: Hyperargininemia is a very rare progressive neurometabolic disorder caused by deficiency of hepatic cytosolic arginase I, resulting from mutations in the ARG1 gene. Until now, some mutations were reported worldwide and none of them were of Southeast Asian origins. Furthermore, most reported mutations were point mutations and a few others deletions or insertions. OBJECTIVE: This study aims at identifying the disease-causing mutation in the ARG1 gene of Malaysian patients with hyperargininemia. METHODOLOGY: We employed a series of PCR amplifications and direct sequencing in order to identify the mutation. We subsequently used quantitative real-time PCR to determine the copy number of the exons flanking the mutation. We blasted our sequencing data with that of the reference sequence in the NCBI in order to obtain positional insights of the mutation. RESULTS: We found a novel complex re-arrangement involving insertion, inversion and gross deletion of ARG1 (designated g.insIVS1+1899GTTTTATCAT;g.invIVS1+1933_+1953;g.delIVS1+1954_IVS2+914;c.del116_188;p.Pro20SerfsX4) commonly shared by 5 patients with hyperargininemia, each originating from different family. None of the affected families share known relationship with each other, although four of the five patients were known to have first-cousin consanguineous parents. CONCLUSION: This is the first report of complex re-arrangement in the ARG1. Further analyses showing that the patients have shared the same geographic origin within the northeastern part of Malaysia prompted us to suggest a simple molecular screening of hyperargininemia within related ethnicities using a long-range PCR.

The effect of high level natural ionizing radiation on expression of PSA, CA19-9 and CEA tumor markers in blood serum of inhabitants of Ramsar, Iran.

Since several high level natural radiation areas (HLNRAs) exist on our planet, considerable attention has been drawn to health issues that may develop as the result of visiting or living in such places. City of Ramsar in Iran is an HNLRA, and is a tourist attraction mainly due to its hot spas. However, the growing awareness over its natural radiation sources has prompted widespread scientific investigation at national level. In this study, using an ELISA method, the level of expression of three tumor markers known as carcinoembryonic antigen (CEA), prostate-specific antigen (PSA) and carcino antigen 19-9 (CA19-9) in blood serum of 40 local men of Ramsar (subject group) was investigated and compared to 40 men from the city of Noshahr (control group). Noshahr was previously identified as a normal level natural radiation area (NLNRA) that is some 85 km far from Ramsar. According to statistical analysis, there was a significant difference in the levels of PSA and CA19-9 markers between the two groups (p < 0.001) with those of Ramsar being considerably higher. CEA level did not show any difference. Although some of the volunteers tested positive to the markers, they were in good health as confirmed by the physician. Moreover, the high number of positive markers in Noshahr was considerable. Therefore, future study is needed to further validate this result and to determine the level of positivity to tumor markers in both cities.

Histone deacetylase inhibitors as potential treatment for spinal muscular atrophy.

Histone acetylation plays an important role in regulation of transcription in eukaryotic cells by promoting a more relaxed chromatin structure necessary for transcriptional activation. Histone deacetylases (HDACs) remove acetyl groups and suppress gene expression. HDAC inhibitors (HDACIs) are a group of small molecules that promote gene transcription by chromatin remodeling and have been extensively studied as potential drugs for treating of spinal muscular atrophy. Various drugs in this class have been studied with regard to their efficacy in increasing the expression of survival of motor neuron (SMN) protein. In this review, we discuss the current literature on this topic and summarize the findings of the main studies in this field.