Dexamethasone turns tumor antigen-presenting cells into tolerogenic dendritic cells with T cell inhibitory functions

BackgroundDendritic cells (DCs) are usually immunogenic, but they are also capable of inducing tolerance under anti-inflammatory conditions. Immunotherapy based on autologous DCs loaded with an allogeneic melanoma cell lysate (TRIMEL/DCs) induces immunological responses and increases melanoma patient survival. Glucocorticoids can suppress DC maturation and function, leading to a DC-mediated inhibition of T cell responses.MethodsThe effect of dexamethasone, a glucocorticoid extensively used in cancer therapies, on TRIMEL/DCs phenotype and immunogenicity was examined.ResultsDexamethasone induced a semi-mature phenotype on TRIMEL/DC with low maturation surface marker expressions, decreased pro-inflammatory cytokine induction (IL-1β and IL-12) and increased release of regulatory cytokines (IL-10 and TGF-β). Dexamethasone-treated TRIMEL/DCs inhibited allogeneic CD4⁺ T cell proliferation and cytokine release (IFNγ, TNF-α and IL-17). Co-culturing melanoma-specific memory tumor-infiltrating lymphocytes with dexamethasone-treated TRIMEL/DC inhibited proliferation and effector T cell activities, including cytokine secretion and anti-melanoma cytotoxicity.ConclusionsThese findings suggest that dexamethasone repressed melanoma cell lysate-mediated DC maturation, generating a potent tolerogenic-like DC phenotype that inhibited melanoma-specific effector T cell activities. These results suggest that dexamethasone-induced immunosuppression may interfere with the clinical efficacy of DC-based melanoma vaccines, and must be taken into account for optimal design of cellular therapy against cancer.     

Cecal coccidiosis in turkeys: Comparative biology of Eimeria species in the lower intestinal tract of turkeys using genetically typed,single oocyst–derived lines

Parasitology Research - Differentiating the Eimeria species causing cecal coccidiosis in turkeys is challenging. To obtain benchmark biological data for Eimeria gallopavonis Hawkins 1952 and...     

血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性研究

目的探讨血糖、血脂水平与糖尿病视网膜病变患者视力损害的相关性。方法选取2016年1月至2018年1月我院内分泌科收治的250例DR患者进行研究。根据视力分级标准分为三个组:盲组(n=28),低视力组(n=80),低视力以上组(n=142)。比较各组患者FPG、HbAlC、TC、TG、LDL-C、HDL-C、LDL-C/HDL-C、ApoB、ApoA1、ApoB/ApoA1水平,对FPG、HbA1C、LDL-C/HDL-C及ApoB/ApoA1与DR患者视力损害进行Pearman相关性分析和Logistic回归分析。结果三组患者的TC、TG差异均无统计学意义(P>0.05);与低视力以上组相比,盲组和低视力组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoA1更高,HDL-C、ApoA1更低(P<0.05);盲组FPG、HbAlC、LDL-C、LDL-C/HDL-C、ApoB、ApoB/ApoAl显著高于低视力组,HDL-C、ApoA1显著低于低视力组(P<0. 05)。经Spearman相关性分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1比值与DR患者视力损害均呈正相关。经Logistic回归分析,FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1均是DR患者视力损害的独立危险因素。结论 FPG、HbAlC、LDL-C/HDL-C、ApoB/ApoA1与DR患者的视力损害有密切关系,通过监测这些指标有利于DR患者视力损害的预测,及时采取治疗措施。     

120例临床真菌感染的分析

目的分析真菌感染的危险因素,为临床预防和减少真菌感染提供参考.方法对2003年1～12月间真菌感染的120份病例进行回顾性调查,同时随机抽取87例同期非真菌感染住院病例作为对照组.结果调查的真菌感染病例中,真菌感染标本来源最多者为呼吸道分泌物,原发基础病也以呼吸系统的疾病为多,占41.7%;患者年龄构成60岁以上者占70%;感染前广谱抗菌素使用超过7 d者占52.5%;各种插管占15%,均明显高于对照组(P＜0.05).结论年龄超过60岁,严重基础疾病、高效广谱抗菌素的应用、插管等侵袭性操作均为临床真菌感染的危险因素.临床应针对上述因素有重点地加以预防.     

Eucalyptol-based green extraction of brown alga Zonaria tournefortii

A green extraction method, based on the use of 1,8-cineole (eucalyptol) as biosolvent, has been developed to prepare crude extracts from the brown alga Zonaria tournefortii characterized by chemical composition, particularly dominated by phenolic compounds derived from phloroglucinol. The main advantage of the developed technique are the recovery of eucalyptol, based on multistep liquid-liquid extraction with distilled water, followed by centrifugation and elimination of the aqueous phase, and the complete recycling of biosolvent by steam distillation. A comparative study between the proposed green extract and the conventional extract, prepared by solvent maceration using the mixture CH₂Cl₂/MeOH (1/1:v/v), was performed in terms of qualitative and quantitative determination of several parameters as:(i) the total phenolic content determined by the Folin-Ciocalteu assay, (ii) the presence of phenols determined by high performance liquid chromatography (HPLC), and (iii) the antioxidant activity assessed by the DPPH (2,2-diphenyl-1-picrylhydrazyl) radical scavenging assay. In short, eucalyptol provides a safe and selective extraction of phenolic compounds from Zonaria tournefortii with no environmental side effects and a good recovery of the solvent.     

Comparing the spatial attractiveness of hospitals using zero-inflated spatial models

Policy makers increasingly rely on hospital competition to incentivize patients to choose high-value care. Amongst all possible drivers, the travel distance without any doubt is one of the most important. In this paper we propose the use of a spatial Bayesian hierarchical model to assess the impact of distance on the number of patient admissions in hospitals, and thereby, compare hospital attractiveness. To this aim a MCMC sampler has been designed. We apply our methodology to patient admissions for asthma in four hospitals located in the Hérault department of France. Results indicate that the most attractive hospital is the CHU Montpellier.     

Childhood polybrominated diphenyl ether (PBDE) exposure and executive function in children in the HOME Study

Prenatal exposure to polybrominated diphenyl ethers (PBDEs) have been reported to impair executive function in children, but little is known whether childhood PBDE exposures play a role. Using the Health Outcomes and Measures of the Environment (HOME) Study, a prospective birth cohort in the greater Cincinnati area, we investigated the association between repeated measures of PBDEs during childhood and executive function at 8 years in 208 children and whether effect modification by child sex was present. We used child serum collected at 1, 2, 3, 5, and 8 years to measure PBDEs. The Behavior Rating Inventory of Executive Function was completed by parents to assess executive function at 8 years. We used multiple informant models to examine childhood PBDEs during several exposure windows. Null associations were observed between early childhood PBDEs and executive function. However, we observed significant adverse associations between a 10-fold increase in concurrent concentrations of BDE-28 (β = 4.6, 95% CI 0.5, 8.7) and BDE-153 (β = 4.8, 95% CI 0.8, 8.8) with behavioral regulation. In addition, PBDEs at 8 years were significantly associated with poorer emotional and impulse control. No associations were noted between childhood PBDEs and metacognition or global executive function. However, child sex significantly modified the associations, with significantly poorer executive function among males with higher concurrent BDE-153, and null associations in females. Our study findings suggest that concurrent PBDE exposures during childhood may be associated with poorer executive function, specifically behavior regulation. Males may also be more sensitive to adverse associations of concurrent PBDEs on executive function.