Effects of crystalline penicillin G sodium on human T-cells differentiation.

BACKGROUND: Although antibiotics are well-known for their anti-bacterial effects, their inaugurated immunomodulatory roles in chronic inflammatory diseases have not elucidated yet. Anecdotal reports support the beneficial effects of parenteral penicillin in arthritis suggesting an immunomodulatory other than antibacterial effects for penicillin. The present study was designed to address the possible effects of penicillin G sodium (PCN-G) on different T-helper cells differentiation. MATERIALS AND METHODS: In this experimental study, peripheral blood mononuclear cells (PBMCs) of 10 healthy donors were isolated using Ficoll density gradient. The stimulated PBMCs by anti-CD3, anti-CD28, and anti-CD69 were cultured in the presence of 120 µg/ml of PCN-G. Foxp3, T-bet, RORγT, GATA3 as well as interferon-gamma (IFN-γ) and interleukin (IL)-17A mRNA in stimulated cells were measured by the real-time polymerase chain reaction. Mann-Whitney U-test was used for determining differences between the medium of gene expression levels of stimulated cell population and unstimulated cells by PCN. Correlations between the related genes were determined using the Spearman test. RESULTS: Based on the results, T-bet gene expression levels were similar in stimulated cells by PCN G after 24 and 48 h while significant reduction was observed after 72 incubation with PCN G (difference = 3; 0.09-0.34; P = 0.031). Meanwhile, treated cells with PCN G expressed decreased levels of IFN-γ (difference = 8.0; 0.49-1.07; P = 0.001) and IL-17A (difference = 2.2; 0.05-0.75; P ≤ 0.05) genes comparing to unstimulated cell by PCN-G. GATA3 genes expression levels downregulated by PCN G after 72 h of incubation by PBMCs (difference = 1.1; 0.77-0.88; P = 0.035). CONCLUSION: Our results confirmed the immunomodulatory role of PCN G by affecting the expression of different cytokines genes in PBMCs.

Primary cutaneous secretory carcinoma: A previously overlooked low-grade sweat gland carcinoma.

INTRODUCTION: Twelve cases of primary cutaneous secretory carcinoma (PCSC) have been published, 9 showing ETV6-NTRK3 translocation, a characteristic finding shared with secretory breast carcinoma and mammary analogue secretory carcinoma. CASE REPORT: A 34-year-old female presented a solitary nodule on the right groin. Biopsy revealed a secretory carcinoma staining positive with CK7, CAM5.2, mammaglobulin and S100 and negative with GATA3, CK20, podoplanin, calponin and CDX2. ETV6-NTRK3 was demonstrated by Fluorescence in situ hybridization (FISH). DISCUSSION: PCSC is a rare neoplasm, described in the skin in 2009, that affects more frequently females with a mean age of 42.3 years and it is most commonly located in axilla. Histopathologically, these tumor cells are characterized by bubbly eosinophilic secretions diastase-resistant and bland nuclei and they are arranged in various growth patterns, including microcystic, tubular, solid and papillary. S100, mammoglobin and CK7 are usually positive. We review the main histopathological features to rule out histopathologic mimics such as breast metastasis, salivary tumors, cribriform carcinoma and primary cutaneous adenoid cystic carcinoma. GATA3 negative staining, as in our case, can help to rule out breast metastasis. Moreover, long-term benign follow up (144 months) in this case as well as follow-up data on outcomes from literature review support that PCSC is a low-grade sweat gland carcinoma.

Expression Pattern of Smad4/GATA3 as a Predictor of Survival in Invasive Ductal Carcinoma of the Breast.

BACKGROUND: Smad4 and GATA3 proteins are known prognostic markers in various cancers. Smad4 is a mediator linked to both tumour suppression and progression. GATA3 is a regulator of development and morphogenesis of the mammary gland. We assessed and compared the predictive performance of Smad4 and GATA3 for clinical outcomes in patients with breast cancer. METHODS: The combined expression pattern based on Smad4+/- and GATA3+/- was evaluated by immunostaining using breast cancer tissue microarray, and the relationships between protein expression and clinicopathological variables were analysed. RESULTS: Smad4 expression was only associated with an ill-defined tumour border, whereas GATA3 was associated with several good prognostic factors. On analysis of combined markers, there was a significant difference in the expression of fascin (an important factor for cancer invasiveness) between the Smad4+/GATA3- and Smad4-/GATA3+ groups. Smad4+/GATA3- was correlated with worse clinicopathological parameters, relapse-free survival (RFS), and overall survival (OS), compared to Smad4-/GATA3+. CONCLUSION: Combined markers of Smad4/GATA3 showed a superior performance compared to single markers for predicting RFS and OS in patients with breast cancer.

D-Pinitol Attenuated Ovalbumin-induced Allergic Rhinitis in Experimental Mice via Balancing Th1/Th2 Response.

Allergic rhinitis (AR) is a complex, chronic immunoinflammatory disorder of the membrane lining of the nasal mucosa. D-Pinitol is considered a cyclic polyol with a potential effect against various allergies. In the present study, we evaluated the anti-allergic effect of pinitol on ovalbumin (OVA)-induced AR model in mice. BALB/c mice were initially sensitized with an intraperitoneal injection of OVA and divided into 5 groups (n=18, in each group) for a treating schedule of distilled water (DW), montelukast (10 mg/kg), and pinitol (5, 10, and 20 mg/kg) through the mouth. Two saline-injected groups were considered as controls by orally administrating DW and pinitol 20. Thereafter, test and control groups were intranasally challenged by OVA and saline, respectively. Our results showed that the OVA challenge caused a marked elevation in AR symptoms like nasal rubbing, sneezing, and discharge which were remarkably diminished using pinitol (10 and 20 mg/kg) and the results were comparable with montelukast. Additionally, increased levels of total and OVA-specific serum Immunoglobulin (Ig) E and IgG1 were significantly attenuated by pinitol as compared to the control group but not the montelukast group. In AR-induced mice, pinitol had significant modulatory effects on representative markers of Th2 (GATA binding protein 3), signal transducer and activator of transcription-6, Interleukins (IL)-4, IL-5, IL-13, suppressors of cytokine signaling 1, Toll-like receptor 4, and myeloid differentiation factor 88), and Type 1 T helper (Th1) immune responses (T-box protein expressed in T cells and Interferon-gamma) as well as the histopathological aberrations induced in the nasal mucosa. In conclusion, Pinitol had potential effects on OVA-induced AR mice through amelioration of nasal symptoms and balancing the Th1/Th2 immune responses during the allergic rhinitis condition.

Negative association between GATA3 and fascin could predict relapse-free and overall survival in patients with breast cancer.

GATA3 and fascin proteins are known prognostic markers in several cancers. GATA3 is a key regulator of mammary gland morphogenesis and luminal cell differentiation, whereas fascin is a pro-metastatic actin-bundling protein. In this study, we analyzed and compared the predictive abilities of GATA3 and fascin for clinical outcomes of patients with breast cancer. The combined expression pattern based on GATA3-/+ and fascin-/+ was evaluated by immunostaining using a tissue microarray, and relationships between protein expression and several clinicopathological parameters were analyzed. GATA3 expression was associated with good prognostic parameters, but fascin was correlated with poor prognostic parameters. On comparing GATA3 and fascin, we found an inverse relationship between fascin and GATA3 expressions. On analysis of combined markers, GATA3+/fascin- was correlated with improved clinical outcomes compared to GATA3-/fascin+. Univariate and multivariate analyses revealed significant differences in relapse-free and overall survival between GATA3+/fascin- and GATA3-/fascin+. Combined marker analysis of GATA3/fascin showed an inverse association and improved prognostic information for patients with breast cancer.

Immune imbalance of regulatory T/type 2 helper cells in the pathogenesis of allergic rhinitis in children.

OBJECTIVES: To determine the role of regulatory T/type 2 helper cell-mediated immune imbalance in the pathogenesis of allergic rhinitis and examine the association between clinical severity and regulatory T/type 2 helper cell-mediated immune imbalance. METHODS: Levels of interleukins 4 and 5 and transforming growth factor ß1, and expression of FOXP3 and GATA3 (which are functionally related to regulatory T and type 2 helper cells, respectively), were evaluated in 46 allergic rhinitis patients and 42 healthy subjects. RESULTS: Compared to controls, allergic rhinitis patients showed significantly higher interleukin 4 and 5 levels, but lower transforming growth factor ß1 levels. Furthermore, FOXP3 messenger RNA expression was lower in allergic rhinitis patients, while GATA3 messenger RNA and protein expression was significantly higher. Regulatory T/type 2 helper cell ratio was inversely correlated with clinical symptom scores. CONCLUSION: Regulatory T/type 2 helper cell immune imbalance may contribute to allergic rhinitis development. These findings provide a new insight into disease pathogenesis and potential therapeutic approaches.