Modulation of Skin Inflammatory Responses by Aluminum Adjuvant.

Aluminum salt (AS), one of the most commonly used vaccine adjuvants, has immuno-modulatory activity, but how the administration of AS alone may impact the activation of the skin immune system under inflammatory conditions has not been investigated. Here, we studied the therapeutic effect of AS injection on two distinct skin inflammatory mouse models: an imiquimod (IMQ)-induced psoriasis-like model and an MC903 (calcipotriol)-induced atopic dermatitis-like model. We found that injection of a high dose of AS not only suppressed the IMQ-mediated development of T-helper 1 (Th1) and T-helper 17 (Th17) immune responses but also inhibited the IMQ-mediated recruitment and/or activation of neutrophils and macrophages. In contrast, AS injection enhanced MC903-mediated development of the T-helper 2 (Th2) immune response and neutrophil recruitment. Using an in vitro approach, we found that AS treatment inhibited Th1 but promoted Th2 polarization of primary lymphocytes, and inhibited activation of peritoneal macrophages but not bone marrow derived neutrophils. Together, our results suggest that the injection of a high dose of AS may inhibit Th1 and Th17 immune response-driven skin inflammation but promote type 2 immune response-driven skin inflammation. These results may provide a better understanding of how vaccination with an aluminum adjuvant alters the skin immune response to external insults.

Emerging Roles of Adipose Tissue in the Pathogenesis of Psoriasis and Atopic Dermatitis in Obesity.

Obesity is a growing epidemic worldwide, and it is also considered a major environmental factor contributing to the pathogenesis of inflammatory skin diseases, including psoriasis (PSO) and atopic dermatitis (AD). Moreover, obesity worsens the course and impairs the treatment response of these inflammatory skin diseases. Emerging evidence highlights that hypertrophied adipocytes and infiltrated immune cells secrete a variety of molecules, including fatty acids and adipokines, such as leptin, adiponectin, and a panel of cytokines/chemokines that modulate our immune system. In this review, we describe how adipose hypertrophy leads to a chronic low-grade inflammatory state in obesity and how obesity-related inflammatory factors are involved in the pathogenesis of PSO and/or AD. Finally, we discuss the potential role of antimicrobial peptides, mechanical stress and impairment of epidermal barrier function mediated by fast expansion, and dermal fat in modulating skin inflammation. Together, this review summarizes the current literature on how obesity is associated with the pathogenesis of PSO and AD, highlighting the potentially important but overlooked immunomodulatory role of adipose tissue in the skin.

Angiotensin-(1-7) ameliorates high glucose-induced vascular endothelial injury through suppressing chloride channel 3.

Diabetes Mellitus (DM) is a significant risk factor for cardiovascular disease (CVD), which is leading cause of deaths in DM patients. However, there are limited effective medical therapies for diabetic CVD. Vascular endothelial injury caused by DM is a critical risk factor for diabetic CVD. Previous study has indicated that Angiotensin-(1-7) (Ang-(1-7)) may prevent diabetic CVD, whereas it is not clear that Ang-(1-7) whether attenuates diabetic CVD through suppressing vascular endothelial injury. In this study, we found that Ang-(1-7) alleviated high glucose (HG)-induced endothelial injury in bEnd3 cells. Moreover, Ang-(1-7) ameliorated HG-induced endothelial injury through downregulating chloride channel 3 (CIC-3) via Mas receptor. Furthermore, HG-induced CIC-3 enhanced reactive oxygen species (ROS) and cytokine production and reduced the level of nitric oxide (NO), while Ang-(1-7) preserved the impact of HG-induced CIC-3 on productions of ROS, cytokine and NO through inhibiting CIC-3 via Mas receptor. Summarily, the present study revealed that Ang-(1-7) alleviated HG-induced vascular endothelial injury through the inhibition of CIC-3, suggested that Ang-(1-7) may preserve diabetic CVD through suppressing HG-induced vascular endothelial injury.

Surgery Plus Chemotherapy Versus Surgery Alone for Limited-Stage Small-Cell Lung Cancer: A Population-Based Survival Outcome Analysis.

INTRODUCTION: For patients with limited-stage small-cell lung cancer (LS-SCLC), effective treatment methods still remain a clinical challenge. The aim of this study is to evaluate the survival outcome of surgery plus chemotherapy vs. surgery alone in patients with LS-SCLC. METHODS: LS-SCLC patients selected from the Surveillance, Epidemiology and End Results (SEER) database diagnosed between January 1, 2004, and December 31, 2015. Comparison of overall survival (OS) and cancer-specific survival (CSS) between two groups performed propensity score matching (PSM), inverse probability of treatment weight (IPTW), and overlap weighting analysis. RESULTS: Of the 477 LS-SCLC patients identified from the SEER database between 2004 and 2015, 262 (54.9%) received surgery-plus-chemotherapy treatment and the others received surgery-alone treatment. Univariate and multivariate analyses showed that treatment option (P< 0.001), tumor location (P= 0.02) and AJCC stage (P< 0.001) were independent prognostic predictors of OS in LS-SCLC patients. Median OS was 35 months in surgery-plus-chemotherapy group vs. 23 months in surgery-alone group. Survival analysis showed that surgery plus chemotherapy offered significantly improved OS as compared with surgery-alone treatment before and after IPTW, PSM and overlap weighting method (all P< 0.05). According to AJCC stage stratification, OS of the unmatched patients with stage I (P= 0.049) and II (P= 0.001) SCLC who received surgery-plus-chemotherapy treatment was significantly better than that of surgery-alone patients. CONCLUSIONS: This cohort study showed that surgery plus chemotherapy was associated with longer survival time than surgery alone in LS-SCLC patients, especially in those with stage I and II SCLC. Further prospective studies are required to confirm our conclusions.