Heme oxygenase-1 (HO-1) has anti-inflammatory effects in asthma. CD4+CD25high regulatory T cells (Treg) are a potent immunoregulator that suppresses the immune response. We studied the effects of HO-1-mediated CD4+CD25high Treg on suppression of allergic airway inflammation by comparing mice treated with hemin, OVA, Sn-protoporphyrin (SnPP), and hemin plus SnPP. Airway responsiveness, airway eosinophil infiltration, the level of OVA-specific IgE, and the numbers of cells in general and eosinophils in particular in bronchial alveolar lavage fluid were lower in the hemin group than in the OVA, SnPP, and hemin plus SnPP groups. The expressions of HO-1 mRNA and protein in the lung were increased by repeated administrations of hemin and SnPP. However, the activity of HO-1 was highest in hemin mice. The percentage and suppressive function of CD4+CD25high Treg and the expression of Foxp3 mRNA were obviously enhanced after treatment with hemin. This increase was diminished by the administration of SnPP. The concentration of serum IL-10 was higher in the hemin group than in the other groups, whereas the level of serum TGF-β did not significantly differ across groups. Furthermore, the ratio of IFN-γ/IL-4 mRNA in the lung was higher in hemin-treated mice than in OVA and SnPP mice. The suppressive capacity of CD4+CD25high Treg was not enhanced in the IL-10-deficient mice treated with hemin. In conclusion, our experiments in the animal model demonstrated that HO-1 has anti-inflammatory effects, probably via enhancement of the secretion of IL-10 and promotion of the percentage of CD4+CD25high Treg.

Asthma is an airway disease characterized by recurrent inflammation. It occurs in all age groups and is ranked as one of the most prevalent noninfectious diseases. It is estimated that 160 million people worldwide suffer with asthma. Despite 20 years of effort, the morbidity and mortality rates of asthma have been rising all throughout the world. As a result, our society bears significant health and economic burdens for the disease. Therefore, it is imperative to understand fully the pathogenesis of asthma and develop novel preventive/therapeutic strategy. Heme oxygenase (HO) is a rate-limiting enzyme for heme metabolism. It catalyzes heme into equivalent amounts of biliverdin, carbon monoxide (CO), and free iron. At present, there are three known isoenzymes of HO: inducible HO-1, constitutive HO-2, and a newly found isomer HO-3.

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Uveitis is a major and common cause of visual disability.Recent studies have shown that Th17 cells are implicated in the pathogenesis of this serious intraocular disorder. Activated T cells express an inducible costimulatory molecule called OX40, and OX40 in turn promotes the activation and proliferation of these lymphocytes. Nevertheless, it is unclear whether OX40 plays a vital role in enhancing the effector function of Th17 cells as well as the severity of uveitis. In this study, we demonstrated an increase of OX40 transcription in ovalbumin-induced uveitis, whereas anti-OX40L antibody substantially inhibited the antigen-specific ocular inflammation. Next , results from flow cytometry showed that activated Th17 cells expressed OX40, and OX40-activating antibody significantly augmented the production of Th17 cytokines in vitro. To validate the impact of OX40 in vivo, we stimulated ovalbumin-specific T cells with the OX40-activating antibody. Compared to donor cells without OX40 activation, adoptive transfer of OX40-stimulated lymphocytes elicited more severe ocular inflammation. Furthermore, an interleukin-17-neutralizing antibody attenuated OX40-mediated uveitis. In conclusion, our findings suggest that activation of OX40 augments Th17 cell function and thereby contributes to ocular inflammation. This study thus enhances our knowledge of costimulatory molecule-mediated immunopathological mechanisms of uveitis and suggests a future therapeutic strategy to treat uveitis by the targeting of OX40. (Am J

ObjectiveTo investigate the effect of surgical decompression on painful diabetic peripheral neuropathy (DPN) patients and discuss the role which pain distribution and characterization play in the management of painful DPN as well as the underlying mechanism involved.MethodsA total of 306 patients with painful diabetic lower-extremity neuropathy were treated with Dellon surgical nerve decompression in our department. Clinical evaluation including Visual analogue scale (VAS), Brief Pain Inventory Short Form for diabetic peripheral neuropathy (BPI-DPN) questionnaire, two-point discrimination (2-PD), nerve conduction velocity (NCV) and high-resolution ultrasonography (cross-sectional area, CSA) were performed in all cases preoperatively, and at 6 month intervals for 2 years post-decompression. The patients who underwent surgery were retrospectively assigned into two subgroups (focal and diffuse pain) according to the distribution of the diabetic neuropathic pain. The control group included 92 painful DPN patients without surgery.ResultsThe levels of VAS, scores in BPI-DPN, 2-PD, NCV results and CSA were all improved in surgical group when compared to the control group (P<0.05). More improvement of VAS, scores in BPI-DPN and CSA was observed in focal pain group than that in diffuse group (P<0.05).ConclusionsEfficacy of decompression of multiple lower-extremity peripheral nerves in patients with painful diabetic neuropathy was confirmed in this study. While both focal and diffuse group could benefit from surgical decompression, pain relief and morphological restoration could be better achieved in focal group.

There is some evidence which shows that higher levels of serum leptin and lower levels of serum adiponectin are associated with the diagnosis of asthma. This meta-analysis evaluated the association of serum leptin and adiponectin levels with the diagnosis of asthma. We searched the MEDLINE, Cochrane, EMBASE and CINAHL Plus databases up to July 2015. Eligible studies were randomized controlled trials, prospective studies, retrospective studies, case-control studies and cohort studies. 13 studies with 3642 patients were included in the study. The meta-analysis found that in the overall study population, the diagnosis of asthma was associated with higher levels of leptin (pooled standardized difference in means=0.867, 95% CI 0.416 to 1.318, p<0.001) and lower levels of adiponectin (pooled standardized difference in means=-0.371, 95% CI -0.728 to -0.014, p=0.042) in patients with asthma compared with controls. Subgroup analysis found that higher leptin levels were associated with asthma both in adults (standardized difference in means=1.374, 95% CI 0.621 to 2.126, p<0.001) and children (standardized difference in means=0.302, 95% CI 0.010 to 0.594, p=0.042). However, borderline association of adiponectin with asthma was seen in adults (p=0.05), but not in children (p=0.509). Sensitivity analysis indicated that the findings for leptin were robust. Our findings are consistent with higher levels of serum leptin being associated with asthma regardless of age, and low adiponectin levels being associated with asthma in adults only.

The aim of this study is to examine the burden of family caregivers of patients with retinoblastoma in China and the relationships between depression, caregiver burden and social support. A descriptive and correlational survey was conducted with 117 Chinese family caregivers of outpatient patients with retinoblastoma from the Department of Ophthalmology of a tertiary hospital in Shanghai, China. Family caregivers of outpatient patients with retinoblastoma were asked to respond to four questionnaires including sociodemographic questionnaire, Becker Depression Inventory, Caregiver Burden Inventory and Social Support Rating Scale. The incidence of depression in this study was 51.3%; the average score for social support indicated moderate social support available to the caregivers, although their level of caregiver burden was heavy. Depression scores were significantly positively correlated with caregiver burden scores and significantly negatively correlated with the social support scores. Heavy caregiver burden was associated with lower monthly income, low subjective social support and less use of social support.

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