Asthma is a chronic inflammatory airways disease in which respiratory viral infections frequently trigger exacerbations. Current treatment of asthma with combinations of inhaled corticosteroids and long acting beta2 agonists improves asthma control and reduces exacerbations but what impact this might have on innate anti-viral immunity is unclear. We investigated the in vitro effects of asthma drugs on innate anti-viral immunity. Peripheral blood mononuclear cells (PBMC) from healthy and asthmatic donors were cultured for 24 hours with the Toll-like receptor 7 agonist, imiquimod, or rhinovirus 16 (RV16) in the presence of budesonide and/or formoterol. Production of proinflammatory cytokines and expression of anti-viral intracellular signalling molecules were measured by ELISA and RT-PCR respectively. In PBMC from healthy donors, budesonide alone inhibited IP-10 and IL-6 production induced by imiquimod in a concentration-dependent manner and the degree of inhibition was amplified when budesonide and formoterol were used in combination. Formoterol alone had little effect on these parameters, except at high concentrations (10−6 M) when IL-6 production increased. In RV16 stimulated PBMC, the combination of budesonide and formoterol inhibited IFNα and IP-10 production in asthmatic as well as healthy donors. Combination of budesonide and formoterol also inhibited RV16-stimulated expression of the type I IFN induced genes myxovirus protein A and 2′, 5′ oligoadenylate synthetise. Notably, RV16 stimulated lower levels of type Myxovirus A and oligoadenylate synthase in PBMC of asthmatics than control donors. These in vitro studies demonstrate that combinations of drugs commonly used in asthma therapy inhibit both early pro-inflammatory cytokines and key aspects of the type I IFN pathway. These findings suggest that budesonide and formoterol curtail excessive inflammation induced by rhinovirus infections in patients with asthma, but whether this inhibits viral clearance in vivo remains to be determined.

BackgroundGrass pollen allergens are a major cause of allergic respiratory disease but traditionally prescribing practice for grass pollen allergen-specific immunotherapy has favoured pollen extracts of temperate grasses. Here we aim to compare allergy to subtropical and temperate grass pollens in patients with allergic rhinitis from a subtropical region of Australia.MethodsSensitization to pollen extracts of the subtropical Bahia grass (Paspalum notatum), Johnson grass (Sorghum halepense) and Bermuda grass (Cynodon dactylon) as well as the temperate Ryegrass (Lolium perenne) were measured by skin prick in 233 subjects from Brisbane. Grass pollen-specific IgE reactivity was tested by ELISA and cross-inhibition ELISA.ResultsPatients with grass pollen allergy from a subtropical region showed higher skin prick diameters with subtropical Bahia grass and Bermuda grass pollens than with Johnson grass and Ryegrass pollens. IgE reactivity was higher with pollen of Bahia grass than Bermuda grass, Johnson grass and Ryegrass. Patients showed asymmetric cross-inhibition of IgE reactivity with subtropical grass pollens that was not blocked by temperate grass pollen allergens indicating the presence of species-specific IgE binding sites of subtropical grass pollen allergens that are not represented in temperate grass pollens.ConclusionsSubtropical grass pollens are more important allergen sources than temperate grass pollens for patients from a subtropical region. Targeting allergen-specific immunotherapy to subtropical grass pollen allergens in patients with allergic rhinitis in subtropical regions could improve treatment efficacy thereby reducing the burden of allergic rhinitis and asthma.

miR-30a acts as a virulence MRA in OA, promoting ECM degradation by targeting Sox9 and by modulating activity of its downstream effectors Col II and proteoglycan aggrecan.

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Deletion of the melanocortin-4-receptor (Mc4r) gene in mice causes hyperphagia, followed by hyperinsulinemia, obesity and progressive infertility. Evidence shows that the number of developed corpora lutea is reduced in obese MC4R-knockout (MC4R KO) female mice, but the mechanism is unclear. The effect of hyperphagia and obesity by MC4R KO on pulsatile luteinizing hormone (LH) secretion and ovulation remains unknown. In MC4R KO mice and wild-type littermates (WT LM) during the diestrus period throughout different ages, we examined and monitored their metabolic status, pulsatile LH profiles, follicular morphology and the number of corpora lutea. MC4R KO mice were hyperphagic, obese, hyperglycemic, hyperinsulinemic and demonstrated insulin resistance and hepatic steatosis. Irregular estrous cycles and significant changes in the LH secretion profiles were observed in sexually matured 16- to 28-week MC4R KO mice, without any difference in testosterone levels. In addition, MC4R KO mice at 16 weeks of age had significantly fewer corpora lutea than same age WT LM mice. The ovary examinations of MC4R KO mice at 28 weeks of age showed predominantly antral and preovulatory follicles with no corpora lutea. These findings were consistent with the decrease in total, pulsatile, mass and basal LH releases in MC4R KO mice. The characteristics of hormone profiles in obese MC4R KO mice indicate that MC4R plays an important role in regulating LH release, ovulation and reproductive ability probably via hyperphagia-induced obesity. Further study of correlation between metabolic and reproductive regulatory hormones is warranted to dissect the pathological mechanism underlying obesity-induced infertility.Free Chinese abstract: A Chinese translation of this abstract is freely available at http://www.reproduction-online.org/content/153/3/267/suppl/DC1.

Background: Many diseases can be treated with metformin. People with serum thyrotropin (TSH) levels higher than 10 mIU/L are at a risk of cardiovascular events. Some studies have suggested that metformin can lower serum TSH levels to a subnormal level in patients with hyperthyrotropinaemia or hypothyroidism. Objective: The objective of this analysis is to evaluate the effect of metformin treatment on serum TSH, free triiodothyronine (FT3), and free thyroxine (FT4) levels and other associated physiological indices. Methods: A comprehensive search using the PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for controlled trials on the effect of metformin on serum TSH, FT3, and FT4 levels and associated physiological indices. The primary outcome measures were serum TSH, FT3 and FT4 levels, thyroid size, thyroid nodule size, blood pressure, heart rate, body weight, and body mass index (BMI). The final search was conducted in April 2019. Results: Six RCTs were included. A total of 494 patients met the inclusion criteria. Metformin treatment did not significantly lower the serum TSH levels at 3 or 6 months but did at 12 months. Moreover, forest plots also suggested that metformin can significantly lower the serum TSH levels in patients with normal thyroid function but cannot statistically change the serum TSH levels in patients with abnormal thyroid function. In addition, metformin treatment clearly lowered the serum FT3 levels and had no significant effect on serum FT4 levels. Lastly, metformin cannot significantly change the systolic blood pressure (SBP) or BMI but can clearly increase the diastolic blood pressure (DBP). Conclusion: Metformin treatment can significantly lower the serum TSH levels, and this effect was much clearer after a 12-month treatment duration and in people with normal thyroid function. However, metformin cannot significantly change the serum FT4 levels or lower serum FT3 levels in people with non-thyroid cancer diseases. In addition, metformin can significantly increase DBP, but it has no clear effect on SBP or BMI.

Background: Testosterone insufficiency may play a role in age-related decreases in bone mass density (BMD) and osteoporosis in aging men. Testosterone replacement therapy (T therapy) seems to be a simple and convenient way to increase BMD and improve the condition of osteoporosis. Objective: To evaluate the effects of T therapy in increasing BMD among older men with low serum testosterone concentrations. Methods: A comprehensive search in the PubMed, EMBASE, Web of Science and Cochrane Central databases was undertaken for randomized controlled trials (RCTs) on the effect of T therapy on osteoporosis in aging men. Primary outcome measures were the change in BMD, bone turnover markers, prostate symptoms, body composition, metabolic and endocrine system markers. The final search was performed in October 2018. Results: Seven RCTs were included. A total of 800 patients met the inclusion criteria. T therapy did not significantly reverse the trend toward decreasing BMD in the spine, femoral neck, Ward’s triangle and the whole body, with the exception of the trochanter and total hip. In addition, T therapy increased prostate size, lean mass, sex hormone levels; reduced HDL concentration; and had no statistical effect on prostate symptoms, body composition, serum hormones and metabolism. Conclusion: T therapy is not effective in increasing BMD in older men. In addition, it has limited effects on prostate-specific antigen (PSA), the International Prostate Symptom Score (IPSS), body mass index (BMI), fat mass, parathyroid hormone (PTH), 25-VitD and lipid metabolism, although it can increase prostate size, lean mass, and sex hormone levels, and reduce glucose levels and HDL concentrations.

Background Several studies have been performed to investigate association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis predisposition. However, the results were conflicting. So, we performed a meta-analysis designed to provide more reliable results for the association between IL-6 gene polymorphisms and osteoporosis. Methods Studies were searched using PubMed, EMBASE, the Cochrane Library and Wanfang electronic databases. The odds ratios (ORs) and 95% confidence intervals (CIs) were calculated to evaluate the association between IL-6 174G/C (rs1800795) and 572C/G (rs1800796) gene polymorphisms and osteoporosis risk. The false-positive report probabilities (FPRP) test and the venice criteria were used to assess the credibility of statistically significant associations. Results A total of 9 studies with 1891 osteoporosis patients and 2027 healthy controls were included in current meta-analysis. Overall, The IL-6 174G/C (rs1800795) gene polymorphism was insignificantly associated with osteoporosis vulnerability. For IL-6 572C/G (rs1800796), statistically significant elevated osteoporosis vulnerability was found in IL-6 572C/G additive model (OR = 2.25, 95% CI: 1.55–3.26), dominant model (OR = 1.42, 95% CI: 0.78–2.56) and recessive model (OR = 1.96, 95% CI: 1.36–2.83). However, the IL-6 572C/G C allele was found to be associated with reduced susceptibility to osteoporosis (OR = 0.76, 95% CI: 0.56–1.04). When excluding studies that did not conform to HWE, the results did not change significantly. Further, when we evaluated the credibility of the positive results of the current meta-analysis, we identified less credible positive results in IL-6 572C/G recessive and additive model. Conclusion In conclusion, IL-6 572C/G GG genotype may be associated with increased risk of osteoporosis.