Pre-treatment of recombinant mouse MFG-E8 downregulates LPS-induced TNF-α production in macrophages via STAT3-mediated SOCS3 activation

Milk fat globule-epidermal growth factor factor 8 (MFG-E8) regulates innate immune function by modulating cellular signaling, which is less understood. Herein, we aimed to investigate the direct anti-inflammatory role of MFG-E8 in macrophages by pre-treatment with recombinant murine MFG-E8 (rmMFG-E8) followed by stimulation with LPS in RAW264.7 cells and in peritoneal macrophages, isolated from wild-type (WT) or MFG-E8(-/-) mice. RAW264.7 cells and mouse peritoneal macrophages treated with rmMFG-E8 significantly downregulated LPS-induced TNF-α mRNA by 25% and 24%, and protein levels by 29% and 23%, respectively (P<0.05). Conversely, peritoneal macrophages isolated from MFG-E8(-/-) mice produced 28% higher levels of TNF-α, as compared to WT mice when treated with LPS. In in vivo, endotoxemia induced by intraperitoneal injection of LPS (5 mg/kg BW), at 4 h after induction, serum level of TNF-α was significantly higher in MFG-E8(-/-) mice (837 pg/mL) than that of WT (570 pg/mL, P<0.05). To elucidate the direct anti-inflammatory effect of MFG-E8, we examined STAT3 and its target gene, SOCS3. Treatment with rmMGF-E8 significantly induced pSTAT3 and SOCS3 in macrophages. Similar results were observed in in vivo treatment of rmMFG-E8 in peritoneal cells and splenic tissues. Pre-treatment with rmMFG-E8 significantly reduced LPS-induced NF-κB p65 contents. These data clearly indicated that rmMFG-E8 upregulated SOCS3 which in turn interacted with NF-κB p65, facilitating negative regulation of TLR4 signaling for LPS-induced TNF-α production. Our findings strongly suggest that MFG-E8 is a direct anti-inflammatory molecule, and that it could be developed as a therapy in attenuating inflammation and tissue injury.     

Gender differences and effect of air pollution on asthma in children with and without allergic predisposition: northeast Chinese children health study

Background

Males and females exhibit different health responses to air pollution, but little is known about how exposure to air pollution affects juvenile respiratory health after analysis stratified by allergic predisposition. The aim of the present study was to assess the relationship between air pollutants and asthmatic symptoms in Chinese children selected from multiple sites in a heavily industrialized province of China, and investigate whether allergic predisposition modifies this relationship.

Methodology/Principal Findings

30139 Chinese children aged 3-to-12 years were selected from 25 districts of seven cities in northeast China in 2009. Information on respiratory health was obtained using a standard questionnaire from the American Thoracic Society. Routine air-pollution monitoring data was used for particles with an aerodynamic diameter ≤10 µm (PM₁₀), sulfur dioxide (SO₂), nitrogen dioxides (NO₂), ozone (O₃) and carbon monoxide (CO). A two-stage regression approach was applied in data analyses. The effect estimates were presented as odds ratios (ORs) per interquartile changes for PM₁₀, SO₂, NO₂, O₃, and CO. The results showed that children with allergic predisposition were more susceptible to air pollutants than children without allergic predisposition. Amongst children without an allergic predisposition, air pollution effects on asthma were stronger in males compared to females; Current asthma prevalence was related to PM₁₀ (ORs = 1.36 per 31 µg/m³; 95% CI, 1.08–1.72), SO₂ (ORs = 1.38 per 21 µg/m³; 95%CI, 1.12–1.69) only among males. However, among children with allergic predisposition, more positively associations between air pollutants and respiratory symptoms and diseases were detected in females; An increased prevalence of doctor-diagnosed asthma was significantly associated with SO₂ (ORs = 1.48 per 21 µg/m³; 95%CI, 1.21–1.80), NO₂ (ORs = 1.26 per 10 µg/m³; 95%CI, 1.01–1.56), and current asthma with O₃ (ORs = 1.55 per 23 µg/m³; 95%CI, 1.18–2.04) only among females.

Conclusion/Significance

Ambient air pollutions were more evident in males without an allergic predisposition and more associations were detected in females with allergic predisposition.     

Direct activation of Transient Receptor Potential Vanilloid 1(TRPV1) by Diacylglycerol (DAG)

Voltage-gated sodium channels play important roles in modulating dorsal root ganglion (DRG) neuron hyperexcitability and hyperalgesia after peripheral nerve injury or inflammation. We report that chronic compression of DRG (CCD) produces profound effect on tetrodotoxin-resistant (TTX-R) and tetrodotoxin-sensitive (TTX-S) sodium currents, which are different from that by chronic constriction injury (CCI) of the sciatic nerve in small DRG neurons. Whole cell patch-clamp recordings were obtained in vitro from L₄ and/or L₅ dissociated, small DRG neurons following in vivo DRG compression or nerve injury. The small DRG neurons were classified into slow and fast subtype neurons based on expression of the slow-inactivating TTX-R and fast-inactivating TTX-S Na⁺ currents. CCD treatment significantly reduced TTX-R and TTX-S current densities in the slow and fast neurons, but CCI selectively reduced the TTX-R and TTX-S current densities in the slow neurons. Changes in half-maximal potential (V_1/2) and curve slope (k) of steady-state inactivation of Na⁺ currents were different in the slow and fast neurons after CCD and CCI treatment. The window current of TTX-R and TTX-S currents in fast neurons were enlarged by CCD and CCI, while only that of TTX-S currents in slow neurons was increased by CCI. The decay rate of TTX-S and both TTX-R and TTX-S currents in fast neurons were reduced by CCD and CCI, respectively. These findings provide a possible sodium channel mechanism underlying CCD-induced DRG neuron hyperexcitability and hyperalgesia and demonstrate a differential effect in the Na⁺ currents of small DRG neurons after somata compression and peripheral nerve injury. This study also points to a complexity of hyperexcitability mechanisms contributing to CCD and CCI hyperexcitability in small DRG neurons.     

石菖蒲提取物对四种储粮害虫的生物活性研究

研究了石菖蒲4种溶剂无水乙醇、丙酮、乙酸乙酯、石油醚提取物对玉米象、谷蠹、长角扁谷盗和锯谷盗4种储粮害虫的驱避作用和触杀作用。结果表明：石菖蒲4种溶剂提取物对4种试虫均有明显的驱避作用和触杀作用,处理60 h的平均驱避等级均达到Ⅲ级以上,对4种试虫的触杀死亡率均达到41.11%以上。     

Photosynthetic efficiency and nitrogen distribution under different nitrogen management and relationship with physiological N-use efficiency in three rice genotypes

Nitrogen fertilization strategies were widely adopted to enhance grain production and improve nitrogen utilization in rice all over the world. For fertilization timing strategy, ear fertilization was usually employed in recent years. For fertilization amount strategy, nitrogen fertilization would continually increase to meet the demands of increasing people for food. However, under heavy ear fertilization as well as great nitrogen amount (NA), physiological N-use efficiency (PE, defined as grain production per unit nitrogen uptake by plants) decreased. Under three NA and two ratios of fertilization given during ear development period to total NA (ear fertilization distribution ratio, EFDR), net photosynthetic rate (Pn), Pn to nitrogen content per unit area (photosynthetic N-use efficiency, Pn/N), nitrogen accumulation in plant tissues and PE of three rice (Oryza sativaL.) genotypes, Jinyou 253, Liangyoupeijiu and Baguixiang were screened in the first and second seasons in 2002 so as to understand the fluctuation patterns of Pn/N and nitrogen distribution in leaf blades under great NA & EFDR and relationship with PE in rice. Results showed that under greater NA & EFDR, Pn in flag leaves at heading and plant nitrogen accumulation at maturity always increased and PE & Pn/N always decreased in spite of increased grain production. Rice distributed more nitrogen in leaf blade under greater NA and EFDR. PE indicated significantly (P<0.05) positive relationship with Pn/N and negative relationship with nitrogen distribution ratio in leaf blades at heading and maturity, and no association with Pn in two growing seasons. Results suggested that low PE in rice under great NA and heavy ear fertilization is associated to more nitrogen distribution in leaf blades and decreases in photosynthetic efficiency.     

江苏沿海滩涂中华补血草的保护性研究

中华补血草是一种经济价值、生态价值较高的盐生植物,花朵细小艳丽,全草含各种黄酮体和杨梅树皮甙等有效成份,不仅可供观赏,还可药用.中华补血草可改善盐碱土的土壤结构,使盐土脱盐,被誉为盐碱地改造的"先锋植物".由于沿海滩涂开发速度加快,中华补血草的适生环境受到极大的威胁,导致种群数量越来越少.因此,加强对中华补血草的研究与迁地保护,势在必行.     

Characterization and crystallization of human DPY-30-like protein, an essential component of dosage compensation complex

Human DPY-30-like is a homolog of C. elegans DPY-30. DPY-30 is an essential component of dosage compensation machinery and loss of dpy-30 activity results in XX-specific lethality. In XO animals, DPY-30 is required for developmental processes other than dosage compensation. In yeast, the homolog of DPY-30, Saf19p, functions as a member of histone 3 lysine 4 methylation complex, which is the key part of epigenetic developmental control. In this report, human DPY-30-like protein was overexpressed and purified with the goal of structure determination. It was crystallized at 291 K in hanging drops by the vapour diffusion technique from a precipitant solution consisting of (NH4)2SO4 (1.5-2.0 M), Tris-HCl (0.1 M, pH 8.0). The crystal diffracted to 2.7 A resolution at 100 K in-house and belongs to the space group P4(1)2(1)2 or P4(3)2(1)2 with unit-cell parameters of a=b=74.5 A, c=87.0 A, alpha=beta=gamma=90.0 degrees. The asymmetric unit contains two molecules with 49% solvent content. We also analyzed its biochemical and biophysical characterizations. Efforts are now under way to determine the molecular structure of the DPY-30-like. These studies will open a new avenue towards the structure-based functional analysis of human DPY-30-like and dosage compensation machinery.