Erratum to: Exogenous Adipokine Peptide Resistin Protects Against Focal Cerebral Ischemia/Reperfusion Injury in Mice

Neurochemical Research -     

肺炎链球菌感染早期IFN-β通过调节巨噬细胞炎症反应保护宿主

该文旨在探讨干扰素-β(interferon-β,IFN-β)在肺炎链球菌(Streptococcus pneumoniae,S.pn)感染早期对宿主炎症免疫的影响。使用外源重组IFN-β蛋白(recombinant IFN-β,rIFN-β)预处理WT小鼠及其腹腔渗出巨噬细胞(peritoneal exudate macrophages,PEMs),以培养基处理组作为对照。同时应用内源干扰素α/β受体(interferonα/βreceptor,IFNAR)缺陷的小鼠以及PEMs,以WT组为对照。各组分别暴露于D39菌株后,通过RT-PCR和ELISA检测白细胞介素-1β(interleukin-1β,IL-1β)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的表达水平,并通过小鼠肺切片HE染色和肺干/湿重比评估其肺部炎症浸润和组织损伤,以分析IFN-β对宿主炎症反应的影响;为分析细菌清除率,对小鼠巨噬细胞系RAW264.7行吞噬实验、计数小鼠肺部细菌载量,最后通过小鼠生存率分析确认IFN-β对宿主抵抗S.pn的影响。结果表明,IFN-β抑制D39诱导的IL-1β和TNF-α的过度表达。与NC组比,rIFN-β预处理提高RAW264.7细胞对S.pn的吞噬能力(P<0.001),降低感染小鼠的肺部细菌负荷(P<0.01)和肺损伤评分(P<0.05)。而IFNAR–/–感染小鼠肺部菌载量相较于WT小鼠显著升高(P<0.001),持续更高水平的局部炎症反应导致其肺组织损伤加重且在9天内死亡率明显增加(P<0.05)。但各组小鼠体质量、肺干/湿重比和脾指数值差异无显著性(P>0.05)。可见,在S.pn感染早期,IFN-β通过调节巨噬细胞中促炎细胞因子的表达而维持适度的局部炎症反应,有助于宿主清除细菌,防止局部感染进展为致死性感染。     

Astragalus polysaccharides alleviates LPS-induced inflammation via the NF-κB/MAPK signaling pathway

Early weaning usually causes intestinal disorders, enteritis, and diarrhea in young animals and human infants. Astragalus polysaccharides (APS) possesses anti-inflammatory activity. To study the anti-inflammatory mechanisms of APS and its potential effects on intestinal health, we performed an RNA sequencing (RNA-seq) study in lipopolysaccharide (LPS)-stimulated porcine intestinal epithelial cells (IPEC-J2) in vitro. In addition, LPS-stimulated BALB/c mice were used to study the effects of APS on intestinal inflammation in vivo. The results from the RNA-seq analysis show that there were 107, 756, and 5 differentially expressed genes in the control versus LPS, LPS versus LPS+APS, and control versus LPS+APS comparison groups, respectively. The results of Kyoto Encyclopedia of Genes and Genomes enrichment analysis indicated that the mitogen-activated protein kinase (MAPK) and nuclear factor-κB (NF-κB) signaling pathways play significant roles in the regulation of inflammatory factors and chemokine expression by APS. Further verification of the above two pathways by using western blot and immunofluorescence analysis revealed that the gene expression levels of the phosphorylated p38 MAPK, ERK1/2, and NF-κB p65 were inhibited by APS, while the expression of IκB-α protein was significantly increased (p < .05), indicating that APS inhibits the production of inflammatory factors and chemokines by the inhibition of activation of the MAPK and NF-κB inflammatory pathways induced by LPS stimulation. Animal experiments further demonstrated that prefeeding APS in BALB/c mice can alleviate the expression of the jejunal inflammatory factors interleukin 6 (IL-6), IL-Iβ, and tumor necrosis factor-α induced by LPS stimulation and improve jejunal villus morphology.     

Activation and Proton Transport Mechanism in Influenza A M2 Channel

Molecular dynamics trajectories 2 μs in length have been generated for the pH-activated, tetrameric M2 proton channel of the influenza A virus in all protonation states of the pH sensor located at the His³⁷ tetrad. All simulated structures are in very good agreement with high-resolution structures. Changes in the channel caused by progressive protonation of His³⁷ provide insight into the mechanism of proton transport. The channel is closed at both His³⁷ and Trp⁴¹ sites in the singly and doubly protonated states, but it opens at Trp⁴¹ upon further protonation. Anions access the charged His³⁷ and by doing so stabilize the protonated states of the channel. The narrow opening at the His³⁷ site, further blocked by anions, is inconsistent with the water-wire mechanism of proton transport. Instead, conformational interconversions of His³⁷ correlated with hydrogen bonding to water molecules indicate that these residues shuttle protons in high-protonation states. Hydrogen bonds between charged and uncharged histidines are rare. The valve at Val²⁷ remains on average quite narrow in all protonation states but fluctuates sufficiently to support water and proton transport. A proton transport mechanism in which the channel, depending on pH, opens at either the histidine or valine gate is only partially supported by the simulations.     

粘性丝孢酵母的诱变及以玉米秸秆水解液为原料产油条件优化

对粘性丝胞酵母进行紫外诱变,获得一株产油率较高的菌株,较原菌株提高了1.53倍。将该菌株接种于用1%硫酸和酶水解处理并浓缩至还原糖浓度为5%的玉米秸秆水解液中培养,生长较好。通过四因素三水平正交实验,确定培养条件为初始pH值7.0、接种量1%、发酵温度30℃、发酵时间5 d时产油率最高。对最佳产油条件进行验证,测得油脂含量为21.3%。从而为利用农业废弃物大规模生产微生物油脂提供了试验数据。气相色谱-质谱联用分析仪显示油脂脂肪酸组成为棕榈酸28.36%,油酸55.86%,10-十八烯酸9.23%,硬脂酸6.70%,可以作为原料生产生物柴油。     

AIM2 promotes non-small-cell lung cancer cell growth through inflammasome-dependent pathway

The human absent in melanoma 2 (AIM2) is considered as a DNA recognizer. AIM2 has been described as a tumor suppressor gene in the early years. But recent studies suggested that it functions as an oncogene in several cancers. However, its roles in non-small-cell lung cancer (NSCLC) remain unclear. Here we reported that AIM2 highly expressed in NSCLC cells and exhibited a tumor-promoting property both in vitro and in vivo. Besides, AIM2 short hairpin RNA (shRNA)-mediated suppression of cell proliferation was triggered by the accumulation of cells at the G2/M phase. Knockdown of AIM2 reduced the inflammasome formation, while overexpression of AIM2 or stimulation by poly(dA:dT) induced the inflammasome formation. Interestingly, blockade of the inflammasome by caspase-1 inhibitor VX-765 or ASC small interfering RNA (siRNA) abolished the effects brought by AIM2 shRNA and AIM2 plasmid. In summary, our results revealed that AIM2 functioned as an oncogene in NSCLC in an inflammasome-dependent way.     

Decoding Diffusivity in Multiple Sclerosis: Analysis of Optic Radiation Lesional and Non-Lesional White Matter

Objectives

Diffusion tensor imaging (DTI) has been suggested as a new promising tool in MS that may provide greater pathological specificity than conventional MRI, helping, therefore, to elucidate disease pathogenesis and monitor therapeutic efficacy. However, the pathological substrates that underpin alterations in brain tissue diffusivity are not yet fully delineated. Tract-specific DTI analysis has previously been proposed in an attempt to alleviate this problem. Here, we extended this approach by segmenting a single tract into areas bound by seemingly similar pathological processes, which may better delineate the potential association between DTI metrics and underlying tissue damage.

Method

Several compartments were segmented in optic radiation (OR) of 50 relapsing-remitting MS patients including T2 lesions, proximal and distal parts of fibers transected by lesion and fibers with no discernable pathology throughout the entire length of the OR.

Results

Asymmetry analysis between lesional and non-lesional fibers demonstrated a marked increase in Radial Diffusivity (RD), which was topographically limited to focal T2 lesions and potentially relates to the lesional myelin loss. A relative elevation of Axial Diffusivity (AD) in the distal part of the lesional fibers was observed in a distribution consistent with Wallerian degeneration, while diffusivity in the proximal portion of transected axons remained normal. A moderate, but significant elevation of RD in OR non-lesional fibers was strongly associated with the global (but not local) T2 lesion burden and is probably related to microscopic demyelination undetected by conventional MRI.

Conclusion

This study highlights the utility of the compartmentalization approach in elucidating the pathological substrates of diffusivity and demonstrates the presence of tissue-specific patterns of altered diffusivity in MS, providing further evidence that DTI is a sensitive marker of tissue damage in both lesions and NAWM. Our results suggest that, at least within the OR, parallel and perpendicular diffusivities are affected by tissue restructuring related to distinct pathological processes.     

Screening of Non- Saccharomyces cerevisiae Strains for Tolerance to Formic Acid in Bioethanol Fermentation

Formic acid is one of the major inhibitory compounds present in hydrolysates derived from lignocellulosic materials, the presence of which can significantly hamper the efficiency of converting available sugars into bioethanol. This study investigated the potential for screening formic acid tolerance in non-Saccharomyces cerevisiae yeast strains, which could be used for the development of advanced generation bioethanol processes. Spot plate and phenotypic microarray methods were used to screen the formic acid tolerance of 7 non-Saccharomyces cerevisiae yeasts. S. kudriavzeii IFO1802 and S. arboricolus 2.3319 displayed a higher formic acid tolerance when compared to other strains in the study. Strain S. arboricolus 2.3319 was selected for further investigation due to its genetic variability among the Saccharomyces species as related to Saccharomyces cerevisiae and availability of two sibling strains: S. arboricolus 2.3317 and 2.3318 in the lab. The tolerance of S. arboricolus strains (2.3317, 2.3318 and 2.3319) to formic acid was further investigated by lab-scale fermentation analysis, and compared with S. cerevisiae NCYC2592. S. arboricolus 2.3319 demonstrated improved formic acid tolerance and a similar bioethanol synthesis capacity to S. cerevisiae NCYC2592, while S. arboricolus 2.3317 and 2.3318 exhibited an overall inferior performance. Metabolite analysis indicated that S. arboricolus strain 2.3319 accumulated comparatively high concentrations of glycerol and glycogen, which may have contributed to its ability to tolerate high levels of formic acid.