Schistosoma japonicum peptide SJMHE1 suppresses airway inflammation of allergic asthma in mice

Helminths and their products can shape immune responses by modulating immune cells, which are dysfunctional in inflammatory diseases such as asthma. We previously identified SJMHE1, a small molecule peptide from the HSP60 protein of Schistosoma japonicum. SJMHE1 can inhibit delayed‐type hypersensitivity and collagen‐induced arthritis in mice. In the present study, we evaluated this peptide's potential intervention effect and mechanism on ovalbumin‐induced asthma in mice. SJMHE1 treatment suppressed airway inflammation in allergic mice, decreased the infiltrating inflammatory cells in the lungs and bronchoalveolar lavage fluid, modulated the production of pro‐inflammatory and anti‐inflammatory cytokines in the splenocytes and lungs of allergic mice, reduced the percentage of Th2 cells and increased the proportion of Th1 and regulatory T cells (Tregs). At the same time, Foxp3 and T‐bet expression increased, and GATA3 and RORγt decreased in the lungs of allergic mice. We proved that SJMHE1 can interrupt the development of asthma by diminishing airway inflammation in mice. The down‐regulation of Th2 response and the up‐regulation of Th1 and Tregs response may contribute to the protection induced by SJMHE1 in allergic mice. SJMHE1 can serve as a novel therapy for asthma and other allergic or inflammatory diseases.     

Extracellular vesicles from human umbilical cord mesenchymal stem cells improve nerve regeneration after sciatic nerve transection in rats

Peripheral nerve injury results in limited nerve regeneration and severe functional impairment. Mesenchymal stem cells (MSCs) are a remarkable tool for peripheral nerve regeneration. The involvement of human umbilical cord MSC‐derived extracellular vesicles (hUCMSC‐EVs) in peripheral nerve regeneration, however, remains unknown. In this study, we evaluated functional recovery and nerve regeneration in rats that received hUCMSC‐EV treatment after nerve transection. We observed that hUCMSC‐EV treatment promoted the recovery of motor function and the regeneration of axons; increased the sciatic functional index; resulted in the generation of numerous axons and of several Schwann cells that surrounded individual axons; and attenuated the atrophy of the gastrocnemius muscle. hUCMSC‐EVs aggregated to rat nerve defects, down‐regulated interleukin (IL)‐6 and IL‐1β, up‐regulated IL‐10 and modulated inflammation in the injured nerve. These effects likely contributed to the promotion of nerve regeneration. Our findings indicate that hUCMSC‐EVs can improve functional recovery and nerve regeneration by providing a favourable microenvironment for nerve regeneration. Thus, hUCMSC‐EVs have considerable potential for application in the treatment of peripheral nerve injury.     

间颅鼠兔的种群遗传结构和历史演化动态

本研究基于多个线粒体基因（包括COI、Cyt b、tRNA-Thr、tRNA-Pro、D-loop控制区部分序列共计2417bp）对间颅鼠兔（Ochotona cansus）的种群遗传结构和历史演化动态进行了研究。基于线粒体基因联合数据构建的贝叶斯树显示,间颅鼠兔分为两大支系：来自岷山山系东部的甘肃白水江和四川唐家河的种群组成了支系一;其余采样点的种群组成了支系二。基于以上基因所构建的单倍型网络图显示的遗传结构与贝叶斯树一致。贝叶斯聚类分析（BAPS）将间颅鼠兔分为4个地理种群。A种群包括甘肃白水江（BSJ）和四川唐家河（TJH）的样本;B种群仅包括四川卧龙（WL）的样本;C种群包括青海北部种群（GC、MY、QL）、青海南部-四川北部种群（JW、JZ、ZK、RE）、四川康定（KD）和陕西太白山（TB）的样本;D种群包括山西娄烦（LF）以及陕西吴起（WQ）的样本。基于线粒体基因构建的物种树进行支系分化时间的推测,结果显示4个地理种群的分化时间约为0.72 Ma、0.32 Ma、0.12 Ma, 这与造成青藏高原剧烈隆起的昆黄运动（1.10-0.60Ma）和共和运动（0.15Ma）发生时间基本吻合。采用中性检验、错配分布、扩展贝叶斯天际线（EBSPs）3种方法对间颅鼠兔的种群历史动态进行预测,分析结果显示间颅鼠兔在历史上并没有经历过显著的种群扩张,而且在末次盛冰期后开始衰减。生态位模型（ENM）预测结果表明：末次盛冰期时间颅鼠兔的潜在分布区比其现今分布区小,末次盛冰期比末次间冰期潜在分布区略大,表明间颅鼠兔受末次盛冰期影响较大。气候因子分析显示降水比温度对间颅鼠兔种群影响更大,推测降水对植被的演化影响显著,从而影响间颅鼠兔的食物来源和栖息环境。     

三峡库区次生柏木林中物种分布格局的分形特征

应用非线性科学中的分形几何理论,以三峡库区一移民安置示范区次生柏木林为对象,研究该群落中物种在中、小尺度上水平分布格局的分形特征,主要应用计盒维数计算群落中一些重要物种分布格局的分维值,如柏木为1.588,地枇杷为1.617,莎草为1.627.得到的结果与用经典群落分析方法所得结果相符,表明分维计算在本研究中是一种有效的手段;对一些物种分布分维值的进一步分析还能说明人类活动对物种分布格局或空间占有程度的影响.     

Diesterified Nitrone Rescues Nitroso-Redox Levels and Increases Myocyte Contraction Via Increased SR Ca2+ Handling

Nitric oxide (NO) and superoxide (O₂ ⁻) are important cardiac signaling molecules that regulate myocyte contraction. For appropriate regulation, NO and O₂ ^.− must exist at defined levels. Unfortunately, the NO and O₂ ^.− levels are altered in many cardiomyopathies (heart failure, ischemia, hypertrophy, etc.) leading to contractile dysfunction and adverse remodeling. Hence, rescuing the nitroso-redox levels is a potential therapeutic strategy. Nitrone spin traps have been shown to scavenge O₂ ^.− while releasing NO as a reaction byproduct; and we synthesized a novel, cell permeable nitrone, 2–2–3,4-dihydro-2H-pyrrole 1-oxide (EMEPO). We hypothesized that EMEPO would improve contractile function in myocytes with altered nitroso-redox levels. Ventricular myocytes were isolated from wildtype (C57Bl/6) and NOS1 knockout (NOS1^−/−) mice, a known model of NO/O₂ ^.− imbalance, and incubated with EMEPO. EMEPO significantly reduced O₂ ^.− (lucigenin-enhanced chemiluminescence) and elevated NO (DAF-FM diacetate) levels in NOS1^−/− myocytes. Furthermore, EMEPO increased NOS1^−/− myocyte basal contraction (Ca²⁺ transients, Fluo-4AM; shortening, video-edge detection), the force-frequency response and the contractile response to β-adrenergic stimulation. EMEPO had no effect in wildtype myocytes. EMEPO also increased ryanodine receptor activity (sarcoplasmic reticulum Ca²⁺ leak/load relationship) and phospholamban Serine16 phosphorylation (Western blot). We also repeated our functional experiments in a canine post-myocardial infarction model and observed similar results to those seen in NOS1^−/− myocytes. In conclusion, EMEPO improved contractile function in myocytes experiencing an imbalance of their nitroso-redox levels. The concurrent restoration of NO and O₂ ^.− levels may have therapeutic potential in the treatment of various cardiomyopathies.     

Characterization of an Arabidopsis cadmium-resistant mutant <Emphasis Type="Italic">cdr3</Emphasis>-<Emphasis Type="Italic">1D</Emphasis> reveals a link between heavy metal resistance as well as seed development and flowering

A lot of studies have identified many key genes involved in heavy metal detoxification and tolerance in plants; however, our understanding of its molecular mechanisms is far from complete. To gain insight into the regulatory mechanisms for heavy metal detoxification and tolerance, we performed a mutant screen for identifying Arabidopsis (Arabidopsis thaliana) cadmium (Cd)-resistant mutants. A Cd-resistant mutant cdr3-1D (c a d mium-r esistant) was isolated because of its increased root growth and fresh weight in Cd stress, and genetic analysis showed that cdr3-1D is a single dominant nuclear mutation. Compared with the wild type, the cdr3-1D mutant was more resistant to heavy metals Cd, Pb, and copper as well as hydrogen peroxide. Moreover, we also observed that seeds of the cdr3-1D mutant were larger than those of wild type, and that cdr3-1D displayed early flowering compared with wild type. A lower Cd/Pb content was detected in cdr3-1D plants than in wild-type plants when subjected to Cd/Pb treatment, which was associated, at least in part, with increase of expression of AtPDR8/AtPDR12, a pump excluding Cd/Pb and/or Cd/Pb-containing toxic compounds from the cytoplasm, respectively. In addition, enhanced Cd/Pb resistance of the cdr3-1D mutant was partially glutathione (GSH) dependent, which was related to increase of expression of GSH1 gene involved in GSH synthesis and consequently increased GSH content. Taken together, our results provide genetic evidence indicating that CDR3 is involved in the regulation of heavy metal resistance as well as seed development and flowering.     

雾化吸入金葡素诱导主动性免疫防护降低兔金黄色葡萄球菌的感染效应

目的探索雾化吸入金葡素(staphylococcin)是否诱导主动性免疫防护以降低兔金黄色葡萄球菌(Staphylococcus aureus)的感染效应。方法将金黄色葡萄球菌感染的新西兰大白兔模型30只(雌雄各半,平均体质量2.45 kg)随机分为对照组、雾化组,每组15只。对照组采用生理盐水进行雾化吸入,雾化组采用生理盐水+金葡素雾化吸入,每天1次,共20 d。ELISA法检测各组兔模型采用干预因素处理前后血清IgG抗体滴度,碱性磷酸酶-抗碱性磷酸酶桥联酶染色法(APAAP法)检测T细胞亚群CD4^+、CD8^+T淋巴细胞比例和CD4^+/CD8^+比值的变化。结果雾化组处理后兔血清IgG抗体滴度显著高于对照组,差异有统计学意义(χ^2=18.9451,P<0.01)。同时,雾化组CD4^+T淋巴细胞比例显著高于对照组(t=2.1340,P<0.01),CD4^+/CD8^+比值也明显高于对照组(t=5.2983,P<0.05)。结论雾化吸入金葡素能有效诱导金黄色葡萄球菌感染的兔产生主动性免疫防护,降低金黄色葡萄球菌感染的效应。     

Low Frequency Magnetic Fields Enhance Antitumor Immune Response against Mouse H22 Hepatocellular Carcinoma

Objective

Many studies have shown that magnetic fields (MF) inhibit tumor growth and influence the function of immune system. However, the effect of MF on mechanism of immunological function in tumor-bearing mice is still unclear.

Methods

In this study, tumor-bearing mice were prepared by subcutaneously inoculating Balb/c mice with hepatocarcinoma cell line H22. The mice were then exposed to a low frequency MF (0.4 T, 7.5 Hz) for 30 days. Survival rate, tumor growth and the innate and adaptive immune parameters were measured.

Results

MF treatment could prolong survival time (n = 28, p<0.05) and inhibit tumor growth (n = 9, p<0.01) in tumor-bearing mice. Moreover, this MF suppressed tumor-induced production of cytokines including interleukin-6 (IL-6), granulocyte colony- stimulating factor (G-CSF) and keratinocyte-derived chemokine (KC) (n = 9–10, p<0.05 or 0.01). Furthermore, MF exposure was associated with activation of macrophages and dendritic cells, enhanced profiles of CD4⁺ T and CD8⁺ T lymphocytes, the balance of Th17/Treg and reduced inhibitory function of Treg cells (n = 9–10, p<0.05 or 0.01) in the mice model.

Conclusion

The inhibitory effect of MF on tumor growth was related to the improvement of immune function in the tumor-bearing mice.