The Janus kinase (JAK)-signal transducer and activator of transcription (STAT) pathway plays critical roles in orchestrating of immune system, especially cytokine receptors and they can modulate the polarization of T helper cells. This pathway is regulated by an array of regulator proteins, including Suppressors of Cytokine Signaling (SOCS), Protein Inhibitors of Activated STATs (PIAS) and Protein Tyrosine Phosphatases (PTPs) determining the initiation, duration and termination of the signaling cascades. Dysregulation of the JAK-STAT pathway in T helper cells may result in various immune disorders. In this review, we represent how the JAK-STAT pathway is generally regulated and then in Th cell subsets in more detail. Finally, we introduce novel targeted strategies as promising therapeutic approaches in the treatment of immune disorders. Studies are ongoing for identifying the other regulators of the JAK-STAT pathway and designing innovative therapeutic strategies. Therefore, further investigation is needed.

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How the intracellular parasite Toxoplasma gondii causes placental inflammation and infects the fetus is unknown. By use of a culture model of primary human trophoblasts, we examined the consequences of infection by a virulent strain of T. gondii. Infection fractions (parasitophorous vacuoles per trophoblast nuclei) < or =0.9 were observed 1 day after challenge at an inoculum ratio of T. gondii to nuclei of 10. The culture content of infectious T. gondii increased 45-fold in 48 h. Two days after infection, almost 30% of trophoblast nuclei became apoptotic, and 30%-35% of nuclei were lost. Almost 90% of apoptotic nuclei were not adjacent to a parasitophorous vacuole, suggesting infection protected against apoptosis. However, there was no T. gondii-dependent accumulation of putative cytotoxic factors, such as tumor necrosis factor-alpha, that could mediate paracrine killing. Both mature and immature trophoblasts can be productively infected, and uninfected, but not infected, cells undergo apoptosis.

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The objective of study was to determine the normative values of anterior and posterior best fit sphere (A-BFS and P-BFS) measured with Orbscan II Topography System. In this cross-sectional study, patients (age range: 18-40 years) referred to the Khatam Eye Hospital (Mashhad, Iran) were put in an observational cross-sectional study. The A-BFS and P-BFS were measured with the Orbscan II. The differences between genders, between right and left eyes, and age-related changes were evaluated. A total of 977 healthy participants consisted of 614 female and 363 male subjects aged 18-35 years participated. The average A-BFS in our study population was recorded as 43.060 ± 1.541 D (median: 43.00 D, mode: 43.10 D, range: 38.80-55.80 D). The average P-BFS in our study population was recorded as 52.702 ± 2.190 D (median: 52.60 D, mode: 53.10 D range: 46.9-62.20 D). The A-BFS and P-BFS were respectively 42.753 ± 1.629 and 52.327 ± 2.376 D in males and 43.242 ± 1.457 and 52.924 ± 2.041 D in females, which were statistically different between the genders (P < 0.001). However, A-BFS and P-BFS were not statistically different between right and left eyes (P = 0.649 and P = 0.688 respectively). In addition, A-BFS and P-BFS were not correlated with the age (r = 0.038, P = 0.096 and r = -0.142, P = 0.178 respectively). Considering 95 % confidence interval, A-BFS less than 43.13 D and greater than 42.99 D and P-BFS less than 52.80 D and greater than 52.60 D would be considered abnormal. Detailed description and analysis of A-BFS and P-BFS with Orbscan demonstrated that the obtained average value of BFS were higher in male than female and did not change with increasing age.

Background: The role of IL-33, a member of the IL-1 family, in airway hyperresponsiveness and asthma has still to be fully understood. Objectives: This study is aimed at investigating serum IL-33 in children with asthma and its association with asthma severity. Methods: This age- and sex-matched case-control study comprised 61 children with asthma and 63 healthy controls. The mean age of the participants was 9.21 years (range: 6-14). Serum IL-33 was measured using ELISA and was compared between children with asthma and controls. In addition, the association of serum IL-33 with asthma severity was investigated. Results: The level of serum IL-33 was significantly higher in children with asthma than in controls (15.17 ± 32.3 vs. 0.61 ± 2.16 pg/ml; p = 0.028). It was significantly increased proportionately to asthma severity, namely 9.92 ± 30.26 pg/ml in children with mild asthma, 13.68 ± 29.27 pg/ml in children with moderate asthma and 31.92 ± 41.45 pg/ml in children with severe asthma (p = 0.026). Conclusion: Serum IL-33 is increased in children with asthma and is associated with disease severity.

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The mechanism of in vivo activation of transforming growth factor-beta1 (TGF-beta1), which is critical to its role in many physiological and pathological conditions, is not fully understood. To explore the mechanism by which dermal fibroblasts respond to latent TGF-beta1 directly, the efficacy of either latent TGF-beta1 (LTGF-beta1) alone or LTGF-beta1 plus cell membranes isolated from fibroblasts, mink lung, and one skin-related (Sk23) and two skin-unrelated (U251 and D54MG) transformed cell lines was examined using the mink lung epithelial cell (Mv1Lu) inhibition assay. As a source of LTGF-beta1, PA317 cells were transfected with previously constructed pLin-TGF-beta1 or pLin vectors with no TGF-beta1 insert. LTGF-beta1 expressing PA317 cells were then enriched by growth in the presence of 0.5 mg G-418 for 6-10 days. Eight out of 53 colonies of cells expressing high levels of LTGF-beta1 were selected and their conditioned media were removed after 3 days and used to evaluate the latency and bioactivity of TGF-beta1 using ELISA and Mv1Lu growth inhibition assay, respectively. The level of TGF-beta1 was 19-fold greater (21.4 +/- 0.4 vs. 1.1 +/- 0.2 ng/ml) in conditioned medium derived from pLin-TGF-beta1 transfected cells than that of control. These conditioned media were then used for the subsequent cell proliferating experiments. The results showed that latent TGF-beta1, which proved to be inactive in an Mv1Lu inhibition assay, significantly stimulates fibroblast cell proliferation compared to that of control in a dose-dependent fashion. In another set of experiments, cells were treated with either active (acidified/neutralized) or latent TGF-beta1 and the results showed a significant increase in cell proliferation in response to low concentrations of active TGF-beta1. However, high concentrations of active TGF-beta1 markedly suppressed fibroblast proliferation. These dual effects were in contrast to a steady increase in fibroblast proliferation found in response to latent TGF-beta1. To explore why LTGF-beta1 has a differential proliferating effect on epithelial and fibroblast cell proliferation, cell membranes from these cells were isolated and incubated with PA317-conditioned medium containing LTGF-beta1 and then added to mink lung cells. Only isolated fibroblast cell membranes incubated with LTGF-beta1 inhibited Mv1Lu cells. To examine whether the LTGF-beta1 cell proliferating activity is unique to dermal fibroblasts or is a general phenomenon, in similar experimental conditions cell membranes from several cell lines, U251, D54MG, and SK23, were isolated, incubated with LTGF-beta1, and then added to an Mv1Lu inhibition assay. The proliferation of Mv1Lu epithelial cells was significantly (1547 +/- 269 vs. 3568 +/- 23) inhibited with SK23, but not U251 cell membranes plus LTGF-beta1 relative to that of control. The inhibitory effect of SK23 plus LTGF-beta1 was cell membrane dose-dependent. In conclusion, the result of this study shows that LTGF-beta1 may directly modulate cell proliferation of those cells that p...