Interleukin-22 drives the proliferation, migration and osteogenic differentiation of mesenchymal stem cells: a novel cytokine that could contribute to new bone formation in spondyloarthropathies.

OBJECTIVES.: The SpAs are genetically and therapeutically linked to IL-23, which in turn regulates IL-22, a cytokine that has been implicated in the regulation of new bone formation in experimental models. We hypothesize that IL-22, a master regulator of stem cells in other niches, might also regulate human mesenchymal stem cell (MSC) osteogenesis. METHODS.: The effects of IL-22 on in vitro MSC proliferation, migration and osteogenic differentiation were evaluated in the presence or absence of IFN-γ and TNF (to ascertain IL-22 activity in pro-inflammatory environments). Colorimetric XTT assay, trans-well migration assays, quantitative real-time PCR (qRT-PCR) for MSC lineage markers and osteogenesis assays were used. RESULTS.: Combined treatment of MSC with IL-22, IFN-γ and TNF resulted in increased MSC proliferation ( P = 0.008) and migration ( P = 0.04), an effect that was not seen in cells treated with IL-22 alone and untreated cells. Osteogenic and adipogenic, but not chondrogenic, transcription factors were upregulated by IL-22 alone ( P < 0.05). MSC osteogenesis was enhanced following IL-22 exposure ( P = 0.03, measured by calcium production). The combination of IFN-γ and TNF with or without IL-22 suppressed MSC osteogenesis ( P = 0.03). CONCLUSION.: This work shows that IL-22 is involved in human MSC proliferation/migration in inflammatory environments, with MSC osteogenesis occurring only in the absence of IFN-γ/TNF. These effects of IL-22 on MSC function is a novel pathway for exploring pathological, post-inflammation osteogenesis in human SpA.

Aromatase inhibitors or gonadotropin-releasing hormone agonists for the management of uterine adenomyosis: a randomized controlled trial.

OBJECTIVE: To compare the efficacy of aromatase inhibitor vs. gonadotrophin-releasing hormone agonists in treating premenopausal women with uterine adenomyosis. DESIGN: A prospective randomized controlled study. SETTING: A university hospital and a private practice setting. POPULATION: Thirty-two patients with uterine adenomyosis. METHODS: Patients were randomly allocated to receive oral letrozole (2.5 mg/day) or a subcutaneous gonadotropin-releasing hormone agonist (goserelin, 3.6 mg) for 12 weeks. Uterine and adenomyoma volumes were determined at baseline and during treatment at four, eight and 12 weeks. OUTCOME MEASURES: Measurements were performed at baseline and during treatment at four, eight 8 and 12 weeks, and mean values were calculated. Symptoms at the start and after 12 weeks were evaluated. RESULTS: No significant differences in the total uterine size between the post treatment uterine volumes in the two groups (20.1, 15.4 and 13.0 cm(3) vs. 21.7, 15.1 and 11.7 cm(3) , at four, eight and 12 weeks, respectively). Total adenomyoma volume decreased by 8.6, 29.7 and 40.9% vs. 5.7, 34.6 and 49.1% after four, eight and 12 weeks of treatment, in group A and B, respectively. Two patients became pregnant in group A during treatment. CONCLUSIONS: Aromatase inhibitors are as effective as gonadotropin-releasing hormone agonists in reducing adenomyoma volume and improving symptoms.

Synthesis and characterization of berberine-loaded chitosan nanoparticles for the protection of urethane-induced lung cancer.

Lung cancer is one of the most common types of malignant tumors of the respiratory system and has the highest rates of incidence and mortality of malignant tumors. This study aimed to synthesize and characterize berberine-loaded chitosan nanoparticles (BBR-COSNPs) and to evaluate their protective effects against urethane-induced lung cancer. Forty male albino mice were divided into four groups, with the first serving as a negative control and the other three groups were injected intraperitoneally with urethane (1 mg/kg b.w) each other day for 1 week then group 2 was served as a positive control, however, groups 3 and 4 were treated orally with a daily dose of BBR or BBR-COSNPs (75 mg/kg b.w) for 10 consecutive weeks. Blood and lung tissue samples are collected for laboratory assay. The BBR-COSNPs were spherical, with an average particle size of 45.56 nm and zeta potential of 39.82 1.82 mV. The in vivo data demonstrated that mice given urethane alone had a significant increase in MDA, NO, NF-κB level, HIF1-α, and COX-2-positive expression in the lung tissue and serum VEGFR2, ALT, AST, urea, and creatinine accompanied with a significant decrease in GSH, SOD, caspase 9 in the lung tissue and serum BAX. Co-treatment with BBR-COSNPs suppressed lung cancer growth and promoted apoptosis by modulating serum BAX and lung caspase 9 gene expressions. In addition, BBR-COSNPs inhibited tumor angiogenesis by reduction in levels of serum VEGFR2 and lung HIF 1 gene expression. It is possible to conclude that BBR-COSNPs can be used in oral administration formulations for lunganticancer therapy.

Anti-IL-6 receptor monoclonal antibody as a new treatment of endometriosis.

Many pro-inflammatory cytokines especially tumor necrotic factor alpha (TNFα), interleukin (IL)-1ß, and IL-6 have crucial role in the pathogenesis of endometriosis. In this study, we investigated the immune-modulatory role of humanized anti-IL-6 receptor monoclonal antibodies in the treatment of endometriosis. This is a prospective, randomized, controlled, blinded study in which Sprague Dawley rats were used as animal model of endometriosis. Animals were randomly divided into two groups, a test group which received tocilizumab (Actemra; Roche, Switzerland) and a control group which received saline. Afterwards, a comparison was done between the eutopic and ectopic endometrium that was excised from both groups, histopathologically and immune-histochemically. Histopathologic assessment and immune-histochemical staining were performed using antibodies against IL-6. Tocilizumab significantly suppressed the volume of endometriotic lesions compared with non-treated rats (P = 0.006) and atrophied the ectopic endometrial-like epithelium (in 42.8% of treated rats vs 0% in the control group). Tocilizumab also decreased the anti-IL-6 receptor immune-histochemical staining intensity in ectopic endometrium (from non to +++ in the test group vs ++ or more in the control group), with no apparent difference in the eutopic one reflecting the down-regulation of IL-6-producing cells in ectopic endometriotic lesions. In rats with induced endometriosis, anti-IL-6 receptor monoclonal antibodies could offer a new horizon of usage of this immune-modulatory biologic drug, used in other autoimmune diseases, in treatment of endometriosis.

Aromatase inhibitors for female infertility: a systematic review of the literature.

Ovulation induction remains a milestone in the treatment of women with anovulatory infertility. Clomiphene citrate (CC) is considered the first line treatment for induction of ovulation in women with polycystic ovary syndrome (PCOS), while it may be used for ovulation induction in unexplained infertility. Aromatase inhibitors (AI) have been introduced as a new treatment option that could challenge CC for ovulation induction. A systematic review of the literature was conducted in order to highlight the efficacy and safety of AI in female infertility. Current data from randomized and non-randomized trials suggest that AI may have a role in ovulation induction regimens in PCOS patients, as well as for ovarian stimulation, since they achieve comparable clinical pregnancy rates to CC. Furthermore, when combined with gonadotrophins, AI improve the ovarian response of poor responders and reduce the gonadotrophin dose required. However, the current review is based on small trials with a limited number of patients. If solid data from future large adequately powered randomized trials support current evidence regarding efficacy and safety, AI might offer a new treatment choice for infertile women.

Genital tract tuberculosis among infertile women: an old problem revisited.

OBJECTIVE: To estimate the prevalence of genital tract tuberculosis (TB) among infertile women during laparoscopic evaluation for infertility in a prospective observational study. METHODS: A total of 420 infertile women were included. All patients had laparoscopy and all suspicious lesions were biopsied and peritoneal fluids aspirated. Full endometrial curettage followed by histopathological examination was done for specimens. Polymerase chain reaction test (PCR) was performed for all peritoneal fluid samples and tissue biopsy. RESULTS: Genital tract tuberculosis was diagnosed with laparoscopy and confirmed by tissue biopsy in 24 patients (5.7%). Visual laparoscopic findings and direct tissue biopsy had the highest sensitivity and specificity (92-94%, respectively) followed by PCR (83-85%) and lastly endometrial biopsy (75-80%) for diagnosis of genital tuberculosis. The incidence of genital tuberculosis was higher among rural patients with low socioeconomic and educational levels. CONCLUSION: Genital tuberculosis has a role in the etio-pathogenesis of infertility. Laparoscopy and direct tissue biopsy are the gold standards for its diagnosis.

Can flowcytometric DNA studies forecast the prognosis of endometrial hyperplasia?

OBJECTIVES: The study is investigating the relation of the ploidy pattern and cell cycle kinetics to different types of endometrial hyperplasia to select the high-risk women who will need strict follow up surveillance. STUDY DESIGN: An observational study of 152 patients with endometrial hyperplasia. Endometrial samples were subjected to flowcytometric study of the nuclear DNA content to determine the ploidy pattern and cell cycle kinetics. RESULTS: The mean age of women was 46.3+/-3.6 years. 15.8% of women were nulliparae, 36.8% were diabetic and 43.6% were hypertensive. 48.7% of women were obese (BMI>30). Most of endometrial samples (88.2%) were simple endometrial hyperplasia without atypia. The cell cycle kinetics in different types of endometrial hyperplasia shows that there were significant statistical differences as regards the S-phase fraction and proliferative index (PI) between typical and atypical hyperplasia. CONCLUSION: The study of cell cycle kinetics by flowcytometry might help in picking up, among all women with endometrial hyperplasia, the group of patients who need further close and strict follow up by endometrial pathologic study. This is going to minimize the cost and invasiveness of surveillance of patients with various grades of endometrial hyperplasia.