IL-22 regulates endometrial regeneration by enhancing tight junctions and orchestrating extracellular matrix.

The uterine endometrium uniquely regenerates after menses, postpartum, or after breaks in the uterine layer integrity throughout women's lives. Direct cell-cell contacts ensured by tight and adherens junctions play an important role in endometrial integrity. Any changes in these junctions can alter the endometrial permeability of the uterus and have an impact on the regeneration of uterine layers. Interleukin 22 (IL-22) is a cytokine that is recognized for its role in epithelial regeneration. Moreover, it is crucial in controlling the inflammatory response in mucosal tissues. Here, we studied the role of IL-22 in endometrial recovery after inflammation-triggered abortion. Fecundity of mice was studied in consecutive matings of the same animals after lipopolysaccharide (LPS) (10 µg per mouse)-triggered abortion. The fecundity rate after the second mating was substantially different between IL-22 knockout (IL-22-/-) (9.1%) and wild-type (WT) (71.4%) mice (p < 0.05), while there was no difference between the groups in the initial mating, suggesting that IL-22 deficiency might be associated with secondary infertility. A considerable difference was observed between IL-22-/- and WT mice in the uterine clearance following LPS-triggered abortion. Gross examination of the uteri of IL-22-/- mice revealed non-viable fetuses retained inside the horns (delayed clearance). In contrast, all WT mice had completed abortion with total clearance after LPS exposure. We also discovered that IL-22 deficiency is associated with a decreased expression of tight junctions (claudin-2 and claudin-10) and cell surface pathogen protectors (mucin-1). Moreover, IL-22 has a role in the remodeling of the uterine tissue in the inflammatory environment by regulating epithelial-mesenchymal transition markers called E- and N-cadherin. Therefore, IL-22 contributes to the proper regeneration of endometrial layers after inflammation-triggered abortion. Thus, it might have a practical significance to be utilized as a treatment option postpartum (enhanced regeneration function) and in secondary infertility caused by inflammation (enhanced barrier/protector function).

The role of immunologic tests for subfertility in the clinical environment.

Unexplained subfertility and implantation failures not only are emotionally and physically distressing but also become a significant obstacle to reproductive-age couples who wish to build their family. Often, the currently recommended evaluation for these couples is significantly limited, and many of causes remain unexplained. To obtain an accurate diagnosis and treatment, proper evidence-based laboratory evaluation should be performed. Immune tests for women with subfertility and implantation failures are essential to recognize the immune etiology and appropriate therapeutic strategies. This review focuses on currently used immune tests for subfertile women.

Involvement of Transcription Factor 21 in the Pathogenesis of Fibrosis in Endometriosis.

Repeated tissue injury and repair and fibrosis play a pivotal role in endometriosis. Fibrotic tissue consists of extracellular matrix proteins, regulated by transcriptional factors promoting cell proliferation and survival. Periostin is one of the putative key extracellular matrix proteins. This study aimed to determine whether transcription factor 21 (TCF21) is involved in the development of endometriosis as an upstream regulatory gene of periostin. Formalin-fixed, paraffin-embedded tissue samples [normal endometrium of women without endometriosis; eutopic endometrium of women with endometriosis; ovarian endometriosis (OE); and deep infiltrating endometriosis (DIE)] and respective cells were analyzed. Basal, transiently stimulated, and knocked down periostin and TCF21 concentrations in stromal cells of women with or without endometriosis were examined. Periostin and TCF21 expressions were undetected in normal endometrium of women without endometriosis, weakly positive in eutopic endometrium of women with endometriosis, moderately positive in OE, and strongly positive in DIE. Type 2 helper T-cell cytokines (IL-4, IL-13, and transforming growth factor-ß1) increased the mRNA expression of periostin and TCF21. These cytokines, periostin, and TCF21 colocalized in the stroma of OE and DIE. siRNA against human TCF21 gene suppressed periostin expression. Transfection of TCF21 plasmid vector into stromal cells of women without endometriosis, which originally expressed neither periostin nor TCF21, resulted in TCF21 and periostin expression. TCF21 and periostin are involved in the regulation of fibrosis in endometriosis. TCF21 may be a promising therapeutic target and biomarker in endometriosis.

Drug use in children hospitalized with cardio-rheumatologic diseases in Andijan, Uzbekistan: a cross-sectional descriptive study.

BACKGROUND: No studies have been conducted on rational drug use among children in Uzbekistan. This study aimed to analyze drug uses based on pharmaco-epidemiologic (PE) data from Regional Children's Multi-Profile Medical Centre (RCMPMC) in Andijan, Uzbekistan. Our study assessed drug usage in children with cardiovascular (CV) diseases, without intervening in the treatment processes or in the course of the diseases. METHODS: Subjects were 853 children aged 0 to 180 months (median age, 60 months; inter-quartile range, 24-108 months) who were hospitalized in the department of Cardiology and Rheumatology in RCMPMC from January to December, 2013 and were prescribed one or more drugs during hospitalization. Drugs used for a different disease or medical condition, given in a different way and/or given in a different dose were analyzed and considered to be irrational drugs. RESULTS: The most commonly used medications among 10 drug groups prescribed by the doctors of RCMPMC were as follows: anti-arrhythmic (aspartic acid - 54.0 %), glycosides (digoxin - 44.0 %), diuretics (furosemide - 34.0 %), vitamins (ascorbic acid - 25.0 %), steroid anti-inflammatory drugs (prednisolone - 19.0 %), non-steroid anti-inflammatory drugs (diclofenac - 17.0 %), antibiotics (amoxicillin - 16.0 %), non-steroid anabolic drugs (potassium orotas - 14.0 %) and angiotensin-converting enzyme inhibitors (captopril - 11.0 %). CONCLUSIONS: The study found that irrational drug schemes were quite frequent among pediatric CV patients and they are most frequent in children aged 2-3 years and younger.