Correlation of sPD1 with Procalcitonin and C-Reactive Protein Levels in Patients with Sepsis.

OBJECTIVE: Sepsis results from dysregulated host responses to infection, and it is a major cause of mortality in the world. Co-inhibitory molecules, such as PD-1, play a critical role in this process. Considering the lack of information on the relation between sPD1 and sepsis, the present study aimed to examine the sPD1 level in septic patients and evaluate its correlation with procalcitonin (PCT) and C-reactive protein (CRP) levels. MATERIALS AND METHODS: This descriptive cross-sectional study consisted of three groups, including septic patients (n=15), suspected of sepsis (n=15), and healthy subjects (n=15). White blood cells (WBCs) and platelet (PLT) counts are evaluated. The serum levels of CRP, PCT, and sPD1 were measured by immunoturbidimetric assay, electrochemiluminescence technology, and the enzyme-linked immunosorbent assay (ELISA), respectively. RESULTS: Our study indicated that there was a significant difference in WBC and PLT counts between the septic group compared to suspected and control groups (P<0.001, P<0.01, respectively). The CRP level was significantly higher in septic compared to suspected and control groups (P<0.001). There was also a significant difference between the PCT level in septic and suspected groups in comparison with the controls (P<0.001, P<0.01). The sPD1 level was significantly higher in septic patients compared to suspected and control groups (P< 0.001). In septic patients, sPD1 levels were correlated positively with the CRP and PCT levels. CONCLUSION: Overall, sPD1 correlation with inflammatory markers, might propose it as a potential biomarker to sepsis diagnosis. However, the clinical application of serum sPD-1 testing in patients with sepsis requires further investigation.

Gene expression analysis of membrane progesterone receptors in women with recurrent spontaneous abortion: a case control study.

OBJECTIVE: Recurrent spontaneous abortion (RSA) is a condition which is defined as three consecutive pregnancy losses prior to 20 weeks from the last menstrual period. Progesterone is a steroid hormone that has an essential role in the implantation and maintenance of pregnancy. The progesterone signaling is performed by nuclear progesterone receptors (NPRs) and membrane progesterone receptors (mPR). The aim of this study was to analyze gene expression of mPR-α, mPR-ß and NPR in the endometrium of patients with a history of RSA compared to normal fertile women. RESULTS: In this study, endometrial samples were obtained from 10 women with a history of RSA and 10 fertile women during days 10-14 of menstrual cycle. Relative expression of mPR-α, mPR-ß and NPR genes were studied by a quantitative real time polymerase chain reaction (qRT-PCR) and compared between the two groups. The mean relative expression of mPR-ß gene was significantly lower in the case group compared to the fertile women (p < 0.05). However, the gene expression of mPR-α and NPR showed no significant difference between two groups. The findings suggest a reduction of endometrial gene expression of mPR-ß in RSA patients may play an important role in pathogenesis of RSA.

MicroRNA-29b variants and MxA expression change during interferon beta therapy in patients with relapsing-remitting multiple sclerosis.

BACKGROUND: Multiple sclerosis is a chronic inflammatory demyelinating disease of the central nervous system (CNS) characterized by immune-mediated demyelination and axonal injury. Myelin-reactive IFN-γ-producing Th1 cells has been shown to play an important role in the development of MS. MicroRNAs (miRNAs) are a new class of small non-coding RNA molecules about 22 nucleotides long which regulate gene expression post-transcriptionally by binding to 3' UTR of their mRNA targets, and resulting in degradation or transcriptional repression of the targeted mRNA. Accumulating evidence supports that miRNA dysregulation is linked to the pathogenesis of autoimmune diseases that include MS. miR-29b expression has been shown to be upregulated in memory CD4+T cells from relapsing-remitting MS (RR-MS) patients, which may reflect chronic Th1 inflammation. Interferon beta (IFN-ß) benefits patients with MS and reduces symptoms of the RR-MS. MxA is induced by type I interferon and predicts IFN-ß response in MS patients. The aim of this study was to evaluate miR-29b variants and MxA expression and serum IFN-γ level in responders and non-responders to IFN-ß treatment. METHODS: A total of 70 IFN-ß treated RR-MS patients including 35 responders and 35 non-responders were enrolled. We analyzed the expression level of miR-29b variants and MxA using the peripheral blood of MS patients treated with IFN-ß for more than one year. Real-time RT-PCR was performed to analyze miR-29b variants and MxA expression one year after initiation of IFN-ß therapy. Serum cytokine level was measured by ELISA. RESULTS: The results indicated that the expression level of miR-29b-3p changed related to IFN-ß response. Moreover, miR-29b-5p was downregulated under IFN-ß treatment in responders versus non-responders. MxA level was significantly decreased in the responders. There was no change in IFN-γ level following treatment with IFN-ß in the MS patients. CONCLUSIONS: Our results might provide fundamentals for the development of new markers of the biological effects of IFN-ß therapy.

Serum IL-33 Level and IL-33, IL1RL1 Gene Polymorphisms in Asthma and Multiple Sclerosis Patients.

BACKGROUND: Asthma is a chronic and complex inflammatory disease of the respiratory tract. Also, multiple sclerosis (MS) is a chronic inflammatory demyelinating disease of the central nervous system. Against this background, IL-33 and IL1RL1 play a critical role in autoimmune and inflammatory disorders. Here, we explored the IL-33 serum level and two potential genetic variants in the IL33 gene and its receptor in Iranian asthma and MS patients. METHODS: This study consisted of asthma (n=140) and MS patients (n=140), and healthy subjects (n=72). Genotyping was carried out in two genetic polymorphisms, rs1342326 variant of IL-33 and rs10204137SNP variant of IL-33 receptor genes, using High- Resolution Melt Real- Time PCR based method. The level of serum IL-33 was also measured using enzyme-linked immunosorbent assay method. RESULTS: The level of IL33 was significantly higher in asthma and MS patients compared to the control group (P< 0.001- P<0.001).The frequency distribution of the genotype in rs1342326 variant of IL-33 gene in patients with asthma, MS and healthy subjects was not significantly different (P>0.05). The frequency distribution of the genotype in rs10204137 variant of IL-33 gene in MS patients and healthy subjects was significantly different (p = 0.013). CONCLUSION: Our findings demonstrated that asthma and MS patients had a higher level of IL-33, and IL-33 receptor genetic polymorphism was associated with MS. Further studies in a larger multicenter setting are needed to explore the value of this marker as a risk stratification biomarker.

The Review of in Vitro and in Vivo Studies over the Glycyrrhizic Acid as Natural Remedy Option for Treatment of Allergic Asthma.

Allergic asthma is the most common type of allergy which have become increasingly prevalent in all around the world. Airway eosinophilic inflammation is a major feature of allergic asthma. Glycyrrhiza uralensis (licorice) is one of the regular herbs in traditional Chinese medicine (TCM) as it has many effects on the immune system such as anti-inflammatory and immune regulatory activity; antiviral and antitumor effects. This review focuses on the "licorice" components, mainly glycyrrhizic acid (GA) and derivatives structure that evaluate its effects on the allergic asthma. We performed searching articles in Pubmed, Web of Science, and Scopus data bank from 1990 to 2017. The search syntax were: "glycyrrhizin" OR " glycyrrhizic acid" OR " glycyrrhizinic acid" OR" glycyrrhiza glabra" OR " liquorice root" OR "G. glabra" OR "glycyrrhizic Acid" AND "allergic asthma" OR "bronchial asthma" OR "asthma, bronchial" OR "airway hyper-responsiveness" OR "airway inflammation". Several molecular mechanisms and inflammatory mediators may possibly be responsible for efficacy of glycyrrhizin. Some in vitro studies indicated to the fact that possible mechanisms of anti-inflammatory effects could be through reduction of pro-inflammatory mediator's synthesis that motivates eosinophil, basophils and mast cells to release cytokines for the differentiation of T helper cells into Th2 cells to secrete interleukins. Furthermore, some transcription factors such as NF-κB, STAT6 and HDAC2 go between modulations of anti-asthmatic effects. The last but not the least it can be said that glycyrrhizin is potentially a good herbal drug with the lower most adverse effects for asthma treatment.

The In Vitro Impact of Glycyrrhizic Acid on CD4+ T Lymphocytes through OX40 Receptor in the Patients with Allergic Rhinitis.

Glycyrrhizic acid (GA), the major bioactive component of glycyrrhiza, possesses anti-inflammatory, anti-allergic, and immunomodulatory activities. This study aimed to investigate the in vitro anti-allergic effect of GA through the OX40 receptor in patients with allergic rhinitis. Purified naive CD4+ T cells of patients with allergic rhinitis (n = 12) were activated with anti-CD3/anti-CD28 with and without anti-OX40 agonist mAbs and then treated with 50, 100, and 200 µM GA and 0.1 µM dexamethasone. Cells were incubated (72 h) to measure cell proliferation. Expression of OX40 in anti-OX40 mAb stimulated CD4+ T cells was evaluated by flow cytometry. mRNA expression of the OX40 receptor and T-bet, GATA-3, and forkhead box P3 (FoxP3) transcriptional factors were measured by a quantitative polymerase chain reaction. The levels of interleukin (IL)-4, IL-10, and interferon-γ (IFN-γ) were also measured. GA inhibited significantly the augmented T cell proliferation induced with anti-OX40 mAb. Protein and gene expression of OX40 was also decreased significantly. Dexamethasone and GA inhibited T-bet and GATA-3 genes expression, but this inhibition was only significant for GATA-3. In contrast, enhanced gene expression of FoxP3 was seen using 200 µM GA and dexamethasone. The levels of IL-4, IL-10, and IFN-γ decreased after treatment with both dexamethasone and GA, but the ratio of IFN-γ/IL-4 (Th1/Th2 balance) increased significantly due to 200 µM GA treatment. This study suggests that GA may have a therapeutic effect on allergic rhinitis, partly by modulation of the Th1/Th2 balance through suppression of OX40 and increasing the activity of regulatory T cells.