Short hairpin RNAs against eotaxin or interleukin‐5 decrease airway eosinophilia and hyper‐responsiveness in a murine model of asthma

Background

Eosinophilia plays the major role in the pathogenesis of asthma and correlates with the up‐regulation of eotaxin, which, together with interleukin (IL)‐5, is important for differentiation, chemo‐attraction, degranulation, and survival of eosinophils in local tissue. In a previous study, we found that administration of lentivirus‐delivered short hairpin RNA (shRNA) to suppress the expression of IL‐5 inhibited airway inflammation. The present study aimed to investigate the role of eotaxin shRNA and the synergistic effect of eotaxin and IL‐5 shRNAs on airway inflammation in an ovalbumin (OVA)‐induced murine model of asthma.

Methods

Lentivirus‐delivered shRNAs were used to suppress the expression of eotaxin and/or IL‐5 in local tissue in an OVA‐induced murine asthma model.

Results

Intra‐tracheal administration of lentivirus containing eotaxin shRNA expressing cassette (eoSEC3.3) efficiently moderated the characteristics of asthma, including airway hyper‐responsiveness, cellular infiltration of lung tissues, and eotaxin and IL‐5 levels in bronchio‐alveolar lavage fluid. Administration of lentiviruses expressing IL‐5 or eotaxin shRNAs (IL5SEC4 + eoSEC3.3) also moderated the symptoms of asthma in a mouse model.

Conclusions

Local delivery of lentiviruses expressing IL‐5 and eotaxin shRNAs provides a potential tool in moderating airway inflammation and also has the potential for developing clinical therapy based on the application of shRNAs of chemokines and cytokines involved in T helper 2 cell inflammation and eosinophilia. Copyright © 2008 John Wiley & Sons, Ltd.     

Gut Microbiome Fermentation Determines the Efficacy of Exercise for Diabetes Prevention

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Evaluation of the role ofMicrovelia douglasi atrolineata (Bergroth) (Heteroptera: Veliidae) as predator of the brown planthopperNilaparvata lugens (Stål) (Homoptera: Delphacidae)

The biology of the veliid bug M. d. atrolineata, its predatory behavior, and the effects of plural hunting were studied to evaluate its role as a predator of the brown planthopper Nilaparvata lugens in the Philippines. The probability of planthoppers falling onto the water surface and provision of habitat continuity was measured by a sticky trap placed at the base of rice hills in a greenhouse and in paddy fields. The developmental period of immature stages combined was 21 days. If given prey, females laid 25 eggs on the average during an adult life span of 18 days. Starved adults could survive for only 3–5 days. The functional response to prey density was sigmoid, and the maximum number of prey killed was 7 per day. Prey feeding was completed in 12–36 min. The percentage of successful prey attacks averaged 5–8%, decreasing with higher (and larger) developmental. stages of prey, but adult prey were found the soonest. Plural hunting increased the probability of capturing prey by as much as 2.5 times that by individual hunting. Late-instar nymphs, which may be more active, fell from rice hills in a greenhouse more than early-instar nymphs, and the number falling increased with density. In the field the percentage of planthoppers falling to the water in 1 day varied considerably, from 1% for nymphs in one field to 67% for adults in another field. On the basis of work described above and given the high density of veliid predators in flooded paddy fields of tropical Asia, M. d. atrolineata is considered one of the most important natural enemies of the brown planthopper.     

Diallel analysis of androgenetic plant production in hexaploid Triticale (X. triticosecale,Wittmack)

Summary Studies were made on the genetic determination of androgenetic plant yield and its two components: embryo production and green plant regeneration. This involved the analysis of a complete 7×7 diallel cross of 4 androgenetic lines and 3 lines obtained by pedigree selection, one of them having the Triticum timopheevi cytoplasm. The three traits analysed are both heritable and environmentally influenced (by season and culture medium composition). The analysis of embryo production shows a mainly nuclear inheritance, with predominantly additive gene action, but also a favourable effect of Triticum timopheevi cytoplasm. Green plant regeneration has a more complex genetic determination, with additive as well as non-additive gene action and cytoplasmic influences. Hybrids appear superior to inbred lines for embryogenesis and green plant yield, but not for green plant regeneration. Androgenetic lines used as parents did not show superiority over other parents either in their own value or in the transmission of androgenetic abilities. Genetic improvement seems to be possible by recombination in progenies of hybrids between lines having complementary abilities.     

A proposed phylogenetic relationship between sea cucumber polian vesicles and the vertebrate lymphoreticular system

Evidence is presented that Polian vesicles of the sea cucumber, Holothuria cinerascens, a member of an echinoderm class considered close to the vertebrate evolutionary line, are organs of inflammatory (including immunologic) responsiveness. As such, they might represent a rudimentary beginning of what later evolved into the vertebrate lymphoreticular system.     

A stroma-related lncRNA panel for predicting recurrence and adjuvant chemotherapy benefit in patients with early-stage colon cancer

The heterogeneity in prognoses and chemotherapeutic responses of colon cancer patients with similar clinical features emphasized the necessity for new biomarkers that help to improve the survival prediction and tailor therapies more rationally and precisely. In the present study, we established a s troma-related l ncRNA s ignature (SLS) based on 52 lncRNAs to comprehensively predict clinical outcome. The SLS model could not only distinguish patients with different recurrence and mortality risks through univariate analysis, but also served as an independent factor for relapse-free and overall survival. Compared with the conventionally used TNM stage system, the SLS model clearly possessed higher predictive accuracy. Moreover, the SLS model also effectively screened chemotherapy-responsive patients, as only patients in the low-SLS group could benefit from adjuvant chemotherapy. The following cell infiltration and competing endogenous RNA (ceRNA) network functional analyses further confirmed the association between the SLS model and stromal activation-related biological processes. Additionally, this study also identified three phenotypically distinct colon cancer subtypes that varied in clinical outcome and chemotherapy benefits. In conclusion, our SLS model may be a significant determinant of survival and chemotherapeutic decision-making in colon cancer and may have a strong clinical transformation value.     

Basic concepts of fluid responsiveness

Predicting fluid responsiveness, the response of stroke volume to fluid loading, is a relatively novel concept that aims to optimise circulation, and as such organ perfusion, while avoiding futile and potentially deleterious fluid administrations in critically ill patients. Dynamic parameters have shown to be superior in predicting the response to fluid loading compared with static cardiac filling pressures. However, in routine clinical practice the conditions necessary for dynamic parameters to predict fluid responsiveness are frequently not met. Passive leg raising as a means to alter biventricular preload in combination with subsequent measurement of the change in stroke volume can provide a fast and accurate way to guide fluid management in a broad population of critically ill patients.     

Truck Drivers Sleep-Wake Time Arrangements

Irregular working hours, including night work, change sleep-wake time arrangements which in turn might affect the ability to drive safely. This study aims to compare the effects of an irregular and a fixed day shift system on the sleep-wake cycle of truck drivers. The investigation of sleep-wake cycle was carried-out with 37 truck drivers working on two transportation plants: 24 working on irregular working hours and 13 on fixed day shift. The truck drivers filled out sleep logs and wore actigraphs for 10 consecutive days to identify activity and rest episodes. The group working in irregular hours showed more sleep episodes per 24 h and they were shorter compared to the fixed shift group (p < 0.05). No differences were found between the two transportation plants. These results suggest an the influence of working hours on specific sleep-wake patterns. The polyphasic sleep pattern shown by irregular shift group could be a strategy to cope with sleep deprivation, which may account for their difficulty to resist falling asleep behind the wheel.     

床旁超声联合血乳酸对感染性休克患者容量反应性的预测价值分析

目的:研究床旁超声与血乳酸(LAC)联合应用于感染性休克患者容量反应性预测中的效能。方法:选取2015年10月~2017年10月于我院接受治疗的120例感染性休克患者进行研究。对所有患者均开展补液试验,并按照试验结果的差异将其分作反应组63例和无反应组57例。对两组人员均实施床旁超声检查以及LAC水平检测,并对比相关指标水平。通过Pearson相关性分析明确感染性休克患者床旁超声指标与LAC水平的关系。采用受试者工作特征(ROC)曲线分析床旁超声与LAC联合预测上述患者容量反应性的效能。结果:两组补液后平均动脉压(MAP)、中心静脉压(CVP)均高于补液前(P<0.05),反应组补液前下腔静脉呼吸变异率(△IVC)、主动脉峰值流速呼吸变异率(△VpeakAO)、肱动脉最大速度变异率(△VpeakBA)高于补液后及无反应组(P<0.05)。两组补液后LAC水平均低于补液前,且反应组低于无反应组(P<0.05)。经Pearson相关性分析可得:感染性休克患者LAC水平与△IVC、△VpeakAO、△VpeakBA均呈正相关(P<0.05)。经ROC曲线分析可知:床旁超声联合LAC预测感染性休克患者容量反应性的曲线下面积、灵敏度、特异度以及约登指数均高于床旁超声和LAC单独预测。结论:感染性休克患者补液后LAC水平降低,床旁超声联合LAC预测感染性休克患者容量反应性的效能较高,具有一定的临床应用价值。     

Aromatic trap analysis of free radicals production in experimental collagen-induced arthritis in the rat: protective effect of glycosaminoglycans treatment

Many findings demonstrated that Glycosaminoglycans (GAGs) and Proteoglycans (PGs) possess antioxidant activity. Collagen-induced arthritis (CIA) is an experimental animal model similar to human rheumatoid arthritis (RA) in which free radicals are involved. Sodium salicylate can be used as a chemical trap for hydroxyl radicals (OH •), the most damaging reactive oxygen species (ROS), yielding 2,5-dihydroxybenzoic acid), (2,5-DHBA) and 2,3-dihydroxybenzoic acid (2,3-DHBA). The measurement of these two acids in the plasma allows to indirectly assess the production of OH • radicals. The aim of the study was to investigate the effect of hyaluronic acid (HYA) (30 mg/kg i.p.) or chondroitin-4-sulphate (C4S) (30 mg/kg i.p.), on free radical production in Lewis rats subjected to CIA. After the immunization with bovine collagen type II in complete Freund's adjuvant, rats developed an erosive hind paw arthritis, that produced high plasma OH • levels assayed as 2,3-DHBA and 2,5-DHBA, primed lipid peroxidation, evaluated by analyzing conjugated dienes (CD) in the articular cartilage; decreased the concentration of endogenous vitamin E (VE) and catalase (CA) in the joint cartilage; enhanced macrophage inflammatory protein-2 (MIP-2) serum levels and increased elastase (ELA) evaluated as an index of activated leukocyte polymophonuclear (PMNs) accumulation in the articular joints. The administration of HYA and C4S starting at the onset of arthritis (day 11) for 20 days, limited inflammation and the clinical signs in the knee and paw, reduced OH • production, decreased CD levels, partially restored the endogenous antioxidants VE and CA, reduced MIP-2 serum levels and limited PMNs infiltration. The results indicate that the GAGs HYA and C4S significantly reduce free radical production in CIA and could be used as a tool to investigate the role of antioxidants in RA.