Physiologic role of decidual beta1 integrin and focal adhesion kinase in embryonic implantation

Implantation refers to a series of interactions between embryo and endometrium including hatching, attachment, and outgrowth. We investigated the expression and function of beta1 integrin and focal adhesion kinase (FAK) in human decidual cells during implantation. Immunofluorescent staining localized beta1 integrin to surfaces of cultured decidual cells. Double staining for beta1 integrin and mediators of intracellular signaling involving beta1 integrin, such as FAK and vinculin, colocalized beta1 integrin with these substances, suggesting that human decidual cells express beta1 integrin in the focal adhesion region. We next investigated the actions of beta1 integrin and FAK in implantation by co-culturing mouse embryos and human decidual cells. Mouse blastocysts attached to cultured decidual cells after embryo hatching, usually within 24 h of culture initiation. Blastocysts attached to decidual cells exhibited extensive outgrowth at 48 h. Treatment of decidual cells with an antibody against beta1 integrin or with an antisense FAK oligonucleotide did not affect hatching or attachment of blastocysts, but either one could inhibit outgrowth. Thus, it was concluded that human decidual beta1 integrin and FAK participate in this final step of implantation.     

Effect of physical training on the proportion of slow‐twitch type I muscle fibers,a novel nonimmune‐mediated mechanism for muscle impairment in polymyositis or dermatomyositis

Objective

To compare muscle fiber type composition and muscle fiber area in patients with chronic polymyositis or dermatomyositis and healthy controls, and to determine whether physical training for 12 weeks could alter these muscle characteristics.

Methods

Muscle fiber type composition and muscle fiber area were investigated by biochemical and immunohistochemistry techniques in repeated muscle biopsy samples obtained from 9 patients with chronic myositis before and after a 12‐week exercise program and in healthy controls. Muscle performance was evaluated by the Functional Index (FI) in myositis and by the Short Form 36 (SF‐36) quality of life instrument.

Results

Before exercise, the proportion of type I fibers was lower (mean ± SD 32% ± 10%) and the proportion of type IIC fibers was higher (3% ± 3%) in patients compared with healthy controls. After exercise, percentage of type I fiber increased to 42% ± 13% (P < 0.05), and type IIC decreased to 1% ± 1%. An exercise‐induced 20% increase of the mean fiber area was also observed. The functional capacity measured by the FI in myositis and the physical functioning subscale of the SF‐36 increased significantly. Improved physical functioning was positively correlated with the proportion of type I fibers (r = 0.88, P < 0.01) and type II muscle fiber area (r = 0.70, P < 0.05).

Conclusion

Low muscle endurance in chronic polymyositis or dermatomyositis may be related to a low proportion of oxidative, slow‐twitch type I fibers. Change in fiber type composition and increased muscle fiber area may contribute to improved muscle endurance and decreased muscle fatigue after a moderate physical training program.     

Matched related donor hematopoietic stem cell transplantation results in a long‐term follow‐up of a pediatric acquired severe aplastic anemia subset: A stem cell source perspective

HSCT has substantially improved pediatric acquired SAA patients' outcomes. Retrospectively, we attempted to assess the outcome of MRD HSCT in 65 pediatric patients referred to a single center from 1992 to 2012. We were particularly interested to find out whether source of SC (PB, n = 40 and BM, n = 25) significantly impacts EFS and GVHD incidence. With a median follow‐up of 45 months, total EFS was 87.7%; EFS for PB and BM groups was 87.5% and 88%, respectively. Acute GVHD (grades 3–4) occurred in 13 patients (PB, n = 10 [25%] and BM, n = 3 [12%]), acute GVHD (grades 2–4) occurred in 24 (PB, n = 16 [40%] and BM, n = 8 [32%]). Extensive chronic GVHD occurred in five patients (PB, n = 3 [7.5%] and BM, n = 2 [8%]). Cox regression revealed that elapsed time of <10 months between diagnosis and HSCT is associated with improved survival (hazard ratio, 95% CI = 1.204, 1.010–1.434, p = 0.038). SC source did not significantly affect EFS, incidence of acute GVHD (grades 3–4), or extensive chronic GVHD (p = 0.938, 0.121, and 0.487, respectively). Based on our findings, pediatric acquired SAA patients are benefitted most if MRD‐HSCT is carried out early in disease process and SC source does not affect outcome of MRD‐HSCT in these patients.     

Anxiety and depression in rheumatoid arthritis: an epidemiologic survey and investigation of clinical correlates in Iranian population

Psychiatric disorders occur in a considerable proportion of patients with rheumatoid arthritis (RA). This study was conducted in order to evaluate the prevalence of anxiety and depression in Iranian RA patients. In the cross sectional study, 414 RA patients were enrolled prospectively during a period of 6 months from RA clinic of Rheumatology Research Center. Beck’s and Cattell’s inventories were applied to investigate depression and anxiety in RA patients. RA activity was measured by Disease Activity Score and patients’ disability was assessed by Health Assessment Questionnaire. Levels of pain perception were stratified based on Visual Analog Scale. The prevalence of depression was 63.6 % and anxiety was in 84.1 % among RA patients. Mixed anxiety and depression was detected in 60.2 % of the study population. Functional disability was significantly associated with severity of depressive and anxiety symptoms (p < 0.001); however there was no association between disease activity and depression or anxiety (p = 0.420). There was weak correlation between disease activity score and functional disability (Spearman’s rho = 0.33; p < 0.01). Severe levels of depression and anxiety were associated with higher levels of pain perception (p < 0.001). Our study stressed the impact of depressive and anxiety symptoms in functional disability and pain perception of RA patients. Our results point out the multidisciplinary management of RA.     

Thrombolytic Therapy for Right-Sided Mechanical Pulmonic and Tricuspid Valves: The Largest Survival Analysis to Date

Data regarding thrombolytic treatment of right-sided mechanical valve thrombosis are almost nonexistent, and all current guidelines arise from very small case series. We retrospectively studied the in-hospital and long-term outcome data of a larger series of patients who had received, from September 2005 through June 2012, thrombolytic therapy for right-sided mechanical pulmonary valve or tricuspid valve thrombosis.We identified 16 patients aged 8–67 years who had undergone thrombolytic therapy for definite thrombotic mechanical valve obstruction in the tricuspid or pulmonary valve position (8 in each position). All study patients except one had subtherapeutic international normalized ratios. The 8 patients with pulmonary mechanical valve thrombosis had a 100% response rate to thrombolytic therapy, and their in-hospital survival rate was also 100%. The 8 patients with tricuspid mechanical valve thrombosis had a 75% response rate to thrombolytic therapy, with an in-hospital survival rate of 87.5%. The one-year survival rate for mechanical valve thrombosis treated with thrombolytic therapy (whether pulmonary or tricuspid) was 87.5%.On the basis of our data, we recommend that thrombolytic therapy remain the first-line therapy for right-sided mechanical valve thrombosis in adults or children—including children with complex congenital heart disease and patients with mechanical pulmonary valve thrombosis. Surgery should be reserved for patients in whom this treatment fails.     

Th17/Treg immunoregulation and implications in treatment of sulfur mustard gas-induced lung diseases

Introduction: Sulfur mustard (SM) is an extremely toxic gas used in chemical warfare to cause massive lung injury and death. Victims exposed to SM gas acutely present with inhalational lung injury, but among those who survive, some develop obstructive airway diseases referred to as SM-lung syndrome. Pathophysiologically, SM-lung shares many characteristics with smoking-induced chronic obstructive pulmonary disease (COPD), including airway remodeling, goblet cell metaplasia, and obstructive ventilation defect. Some of the hallmarks of COPD pathogenesis, which include dysregulated lung inflammation, neutrophilia, recruitment of interleukin 17A (IL ?17A) expressing CD4⁺T cells (Th17), and the paucity of lung regulatory T cells (Tregs), have also been described in SM-lung.

Areas covered: A literature search was performed using the MEDLINE, EMBASE, and Web of Science databases inclusive of all literature prior to and including May 2017.

Expert commentary: Here we review some of the recent findings that suggest a role for Th17 cell-mediated inflammatory changes associated with pulmonary complications in SM-lung and suggest new therapeutic approaches that could potentially alter disease progression with immune modulating biologics that can restore the lung Th17/Treg balance.     

miR-17 and miR-20a Expression in IL-2 Signaling Pathway in Jurkat T Cells

Background: the miR-17-92 cluster is known as an oncogene (oncomiR-1) overexpressed in most cancers. However, recent studies have shown that these miRNAs were downregulated in some cancers. Thus, some or all members of miR-17-92 cluster may have dual activity: apoptosis induction or inhibition. Objectives: For a better understanding of miR-17-92 cluster activities, we focused on the function of mir-17 and mir-20a as two members of miR-17-92 cluster in Jurkat cells activated by phytohemagglutinin (PHA). Materials and Methods: Jurkat cells were stimulated by PHA for 24 h. P-lenti-mico-GFP plasmids containing miR-17 or miR-20a and an empty vector (blank) were transfected into activated Jurkat cells using Lipofectamine 2000 reagent. Cell viability was measured using XTT assay after transfection. Putative targets of these miRNAs were predicted by Targetscan and miRWalk algorithms in JAK/STAT and PI3K/AKT signaling pathways. Then the expression of several putative targets was evaluated by quantitative RT-PCR. Results: Transfection of mir-17 and mir-20a decreased the proliferation in activated Jurkat cells. In silico investigations revealed that mir-17 and mir-20a potentially target JAK1, AKT1 and AKT3. Q-RT-PCR analysis illustrated that these targets were downregulated in Jurkat cells after transfection with miR-17 and miR-20a. Conclusions: According to our findings, it seems that mir-17 and mir-20a expression, two members of miR-17-92 cluster, is dependent on cell condition and cell type; as a result, their ectopic expression in activated Jurkat cells may lead to cell death.     

Human T-Lymphotropic Virus Type I (HTLV-1) Infection among Iranian Blood Donors: First Case-Control Study on the Risk Factors

Human T-cell lymphotropic virus type 1 (HTLV-1) infection is an endemic condition in Northeast Iran and, as such, identification of risk factors associated with the infection in this region seems to be a necessity. All the possible risk factors for HTLV-1 seropositivity among first-time blood donors were evaluated in Mashhad, Iran, during the period of 2011–2012. Blood donation volunteers were interviewed for demographic data, medical history, and behavioral characteristics and the frequencies of risk factors were compared between HTLV-1 positive (case) and HTLV-1 negative (control) donors. The data was analyzed using Chi square and t-tests. Logistic regression analysis was performed to identify independent risk factors for the infection. Assessments were carried out on 246 cases aged 17–60 and 776 controls aged 17–59, who were matched based on their ages, gender, and date and center of donation. Logistic analysis showed low income (OR = 1.53, p = 0.035), low educational level (OR = 1.64, p = 0.049), being born in the cities of either Mashhad (OR = 2.47, p = 0.001) or Neyshabour (OR = 4.30, p < 0001), and a history of blood transfusion (OR = 3.17, p = 0.007) or non-IV drug abuse (OR = 3.77, p < 0.0001) were significant predictors for infection with HTLV-1. Lack of variability or small sample size could be reasons of failure to detect some well-known risk factors for HTLV-1 infection, such as prolonged breastfeeding and sexual promiscuity. Pre-donation screening of possible risk factors for transfusion-transmissible infections should also be considered as an important issue, however, a revision of the screening criteria such as a history of transfusion for more than one year prior to donation is strongly recommended.