The altered activity of complex III may contribute to the high penetrance of Leber's hereditary optic neuropathy in a Chinese family carrying the ND4 G11778A mutation

The ND4 G11778A mutation is the most common mitochondrial DNA mutation leading to Leber's hereditary optic neuropathy (LHON). Despite considerable clinical evidences, the modifier role of nuclear background and mitochondrial haplotypes in phenotypic manifestation of LHON remains poorly understood. We investigated the effect of these modifiers on bioenergetics in lymphoblastoid cell lines derived from five affected subjects of one Chinese family carrying the G11778A mutation and five Chinese controls. Significant reductions in the activities of complexes I and III were observed in mutant cell lines from the Chinese family, whereas the mutant cell lines from other families carrying the same mutation exhibited only reduced activity of complex I. The reduced activities of complexes I and III caused remarkably higher reductions of ATP synthesis in mutant cell lines from the Chinese family than those from other families. The deficient respiration increased generation of reactive oxygen species. The defect in complex III activity, likely resulting from the mitochondrial haplotype or nuclear gene alteration, worsens mitochondrial dysfunction caused by the G11778A mutation, thereby causing extremely high penetrance and expressivity of optic neuropathy in this Chinese family. Our data provide the first experimental evidence that altered activity of complex III modulates the phenotypic manifestation of LHON-associated G11778A mutation. Thus, our findings may provide new insights into the pathophysiology of LHON.     

A novel matrix derivatized from hydrophilic gigaporous polystyrene-based microspheres for high-speed immobilized-metal affinity chromatography

Agarose coated gigaporous polystyrene microspheres were evaluated as a novel matrix for immobilized-metal affinity chromatography (IMAC). With four steps, nickel ions were successfully immobilized on the microspheres. The gigaporous structure and chromatographic properties of IMAC medium were characterized. A column packed with the matrix showed low column backpressure and high column efficiency at high flow velocity. Furthermore, this matrix was used for purifying superoxide dismutase (SOD), which was expressed in Escherichia coli (E. coli) in submerged fermentation, on an Äkta purifier 100 system under different flow velocities. The purity of the SOD from this one-step purification was 79% and the recovery yield was about 89.6% under the superficial flow velocity of 3251 cm/h. In conclusion, all the results suggested that the gigaporous matrix has considerable advantages for high-speed immobilized-metal affinity chromatography.     

Comparative Effects of Hispidulin,Genistein, and Icariin with Estrogen on Bone Tissue in Ovariectomized Rats

Icariin, Genistein, and Hispidulin have been proven to have estrogen-like and antiosteoporotic activity and can be potentially used for the treatment of osteoporosis. The present study found that Icariin, Genistein, and Hispidulin treatments, emulating estrogen, significantly contributed to bone density. Comparative effects of Icariin, Genistein, and Hispidulin with estrogen on in ovariectomized rats were investigated. Our results showed that genistein was found to have superior bone protective effects against osteoporosis among genistein, Icariin, and Hispidulin.     

小RNA病毒和小DNA病毒的三维结构模型

本文综述了小RNA病毒和小DNA病毒的主要结构特征,绘制出了它们的三维结构模型,从中找出了两者间的共同点和差异,为进一步研究两种病毒提供了依据。     

Dorsal root ganglia P2X4 and P2X7 receptors contribute to diabetes-induced hyperalgesia and the downregulation of electroacupuncture on P2X4 and P2X7

Diabetic neuropathic pain (DNP) is highly common in diabetes patients. P2X receptors play critical roles in pain sensitization. We previously showed that elevated P2X3 expression in dorsal root ganglion (DRG) contributes to DNP. However, the role of other P2X receptors in DNP is unclear. Here, we established the DNP model using a single high-dose streptozotocin (STZ) injection and investigated the expression of P2X genes in the DRG. Our data revealed elevated P2X2, P2X4, and P2X7 mRNA levels in DRG of DNP rats. The protein levels of P2X4 and P2X7 in DNP rats increased, but the P2X2 did not change significantly. To study the role of P2X4 and P2X7 in diabetes-induced hyperalgesia, we treated the DNP rats with TNP-ATP (2’,3’-O-(2,4,6-trinitrophenyl)-adenosine 5’-triphosphate), a nonspecific P2X1–7 antagonist, and found that TNP-ATP alleviated thermal hyperalgesia in DNP rats. 2 Hz electroacupuncture is analgesic against DNP and could downregulate P2X4 and P2X7 expression in DRG. Our findings indicate that P2X4 and P2X7 in L4–L6 DRGs contribute to diabetes-induced hyperalgesia, and that EA reduces thermal hyperalgesia and the expression of P2X4 and P2X7.     

薰衣草叶片对低温胁迫的生理与分子响应机制

薰衣草(Lavandula angustifolia)作为名贵的芳香植物,其生长、繁育、品质和产量均受低温影响。前期研究已获得1个耐低温薰衣草品种。该研究将对其处理的温度从20℃降至0℃,揭示薰衣草响应冷胁迫的生理及分子调控机制,同时结合薰衣草的细胞质膜透性、可溶性糖和蛋白质含量及抗氧化酶活性等生理变化。采用转录组学和生物信息学方法挖掘分析相关耐寒基因,并探讨外施水杨酸缓解–10℃冻胁迫的可行性。研究发现7个编码脂肪酸去饱和酶和转移酶的基因(LaFADs)、3个参与合成可溶性糖的基因(LaBAM1和LaSS2)、19个编码胚胎晚期丰富蛋白的基因(LaLEAs)及7个编码过氧化物酶的基因(LaPODs),这些基因在低温胁迫下均上调表达,指导薰衣草合成并积累保护物质,维持膜稳定性以应对胁迫。此外, 150 mg·L^-1水杨酸预处理能有效缓解植株冻害,可作为低温保护剂。该研究丰富了薰衣草重要抗逆基因家族的遗传背景,为后续分子遗传学功能分析和定向品种改良奠定基础。     

Exosomal miR-146a-5p and miR-155-5p promote CXCL12/CXCR7-induced metastasis of colorectal cancer by crosstalk with cancer-associated fibroblasts

C-X-C motif chemokine receptor 7 (CXCR7) is a newly discovered atypical chemokine receptor that binds to C-X-C motif chemokine ligand 12 (CXCL12) with higher affinity than CXCR4 and is associated with the metastasis of colorectal cancer (CRC). Cancer-associated fibroblasts (CAFs) have been known to promote tumor progression. However, whether CAFs are involved in CXCR7-mediated metastasis of CRC remains elusive. We found a significant positive correlation between CXCR7 expression and CAF activation markers in colonic tissues from clinical specimens and in villin-CXCR7 transgenic mice. RNA sequencing revealed a coordinated increase in the levels of miR-146a-5p and miR-155-5p in CXCR7-overexpressing CRC cells and their exosomes. Importantly, these CRC cell-derived miR-146a-5p and miR-155-5p could be uptaken by CAFs via exosomes and promote the activation of CAFs through JAK2–STAT3/NF-κB signaling by targeting suppressor of cytokine signaling 1 (SOCS1) and zinc finger and BTB domain containing 2 (ZBTB2). Reciprocally, activated CAFs further potently enhanced the invasive capacity of CRC cells. Mechanistically, CAFs transfected with miR-146a-5p and miR-155-5p exhibited a robust increase in the levels of inflammatory cytokines interleukin-6, tumor necrosis factor-α, transforming growth factor-β, and CXCL12, which trigger the epithelial–mesenchymal transition and pro-metastatic switch of CRC cells. More importantly, the activation of CAFs by miR-146a-5p and miR-155-5p facilitated tumor formation and lung metastasis of CRC in vivo using tumor xenograft models. Our work provides novel insights into CXCR7-mediated CRC metastasis from tumor–stroma interaction and serum exosomal miR-146a-5p and miR-155-5p could serve as potential biomarkers and therapeutic targets for inhibiting CRC metastasis.Subject terms: Cancer microenvironment, Colon cancer     

土壤不同水分条件对长春花(Catharanthus roseus)生活史型的影响

为了研究土壤中不同水分条件对长春花生活史型形成及生理代谢的影响,设置对照、轻度干旱、中度干旱和重度干旱等土壤水分梯度,对长春花(Catharanthus roseus(L.)G.Don)幼苗进行处理。对长春花形态指标进行聚类分析发现选择的20个聚类实体被分为2组,第1组为对照(CK)和轻度干旱(LD)处理的植株,第2组为中度干旱(MD)和重度干旱(HD)处理的植株。运用主成分分析(Principal component analysis,PCA)方法对不同土壤水分条件下长春花营养生长(Vegetative growth,V)、有性生殖(Sexual reproduction,S)和无性繁殖(Clone reproduction,C)等3类15种性状进行统计。结果显示,长春花在对照条件下生活史型为V0.39S0.54C0.07,轻度干旱为V0.36S0.50C0.14,中度干旱为V0.53S0.27C0.20,重度干旱为V0.45S0.09C0.46,干旱程度加强显著提高了无性繁殖的比重,降低了有性生殖的比例。同时,对长春花中文朵灵、长春质碱和脱水长春碱等生物碱的含量进行了动态测定,发现重度干旱下的文朵灵、长春质碱和脱水长春碱的含量在16d时分别是对照水平的1.5倍、2.3倍和3.1倍,表明干旱胁迫诱导生物碱积累,为长春花高效栽培提供了理论依据。     

Caveolin-1 identified as a key mediator of acute lung injury using bioinformatics and functional research

Acute lung injury (ALI) is a potentially life-threatening, devastating disease with an extremely high rate of mortality. The underlying mechanism of ALI is currently unclear. In this study, we aimed to confirm the hub genes associated with ALI and explore their functions and molecular mechanisms using bioinformatics methods. Five microarray datasets available in GEO were used to perform Robust Rank Aggregation (RRA) to identify differentially expressed genes (DEGs) and the key genes were identified via the protein-protein interaction (PPI) network. Lipopolysaccharide intraperitoneal injection was administered to establish an ALI model. Overall, 40 robust DEGs, which are mainly involved in the inflammatory response, protein catabolic process, and NF-κB signaling pathway were identified. Among these DEGs, we identified two genes associated with ALI, of which the CAV-1/NF-κB axis was significantly upregulated in ALI, and was identified as one of the most effective targets for ALI prevention. Subsequently, the expression of CAV-1 was knocked down using AAV-shCAV-1 or CAV-1-siRNA to study its effect on the pathogenesis of ALI in vivo and in vitro. The results of this study indicated that CAV-1/NF-κB axis levels were elevated in vivo and in vitro, accompanied by an increase in lung inflammation and autophagy. The knockdown of CAV-1 may improve ALI. Mechanistically, inflammation was reduced mainly by decreasing the expression levels of CD3 and F4/80, and activating autophagy by inhibiting AKT/mTOR and promoting the AMPK signaling pathway. Taken together, this study provides crucial evidence that CAV-1 knockdown inhibits the occurrence of ALI, suggesting that the CAV-1/NF-κB axis may be a promising therapeutic target for ALI treatment.Subject terms: Cell signalling, Respiratory tract diseases