Malignant B cells induce the conversion of CD4+CD25- T cells to regulatory T cells in B-cell non-Hodgkin lymphoma

Recent evidence has demonstrated that regulatory T cells (Treg) were enriched in the tumor sites of patients with B-cell non-Hodgkin lymphoma (NHL). However, the causes of enrichment and suppressive mechanisms need to be further elucidated. Here we demonstrated that CD4(+)CD25(+)FoxP3(+)CD127(lo) Treg were markedly increased and their phenotypes were different in peripheral blood (PB) as well as bone marrow (BM) from newly diagnosed patients with B-cell NHL compared with those from healthy volunteers (HVs). Involved lymphatic tissues also showed higher frequencies of Treg than benign lymph nodes. Moreover, the frequencies of Treg were significantly higher in involved lymphatic tissues than those from PB as well as BM in the same patients. Suppression mediated by CD4(+)CD25(+) Treg co-cultured with allogeneic CFSE-labeled CD4(+)CD25(-) responder cells was also higher in involved lymphatic tissues from B-cell NHL than that mediated by Treg from HVs. In addition, we found that malignant B cells significantly induced FoxP3 expression and regulatory function in CD4(+)CD25(-) T cells in vitro. In contrast, normal B cells could not induce the conversion of CD4(+)CD25(-) T cells to Treg. We also showed that the PD-1/B7-H1 pathway might play an important role in Treg induction. Taken together, our results suggest that malignant B cells induce the conversion of CD4(+)CD25(-) T cells to Treg, which may play a role in the pathogenesis of B-cell NHL and represent a promising therapeutic target.     

BB染色体组野生种花生LTR反转录转座子RT基因的多样性分析

利用简并PCR技术从野生花生种(Arachis ipaensis Krapov. et W. C. Greg.)的基因组中扩增分离Ty1-copia类(1类)和Ty3-gypsy类(2类)反转录转座子RT基因,并对其序列特征、多样性、系统进化关系及转录活性进行分析。结果显示:对于1和2类RT基因,目的条带分别约为260和430 bp;分离获得了23和32条序列,长度范围分别为262～266、395～435 bp;AT所占比例分别为61.60%～69.17%和55.79%～61.34%;核苷酸序列间相似性分别为52.5%～98.9%和45.0%～98.8%,氨基酸序列间相似性分别为39.8%～100%和9.0%～97.2%。其中2类基因的异质性高于1类;1类和2类基因分别有3条和15条发生了无义突变,2类的无义突变发生率远高于1类。1类基因的保守基序保守性较高,2类的保守基序呈一定程度的变异。代表序列的蛋白质三级结构基本类似。聚类分析结果显示,1类和2类基因可被分为5个和6个家族。1类和2类基因都有部分序列与其他物种的RT基因序列亲缘关系较近,表明它们之间可能存在两类反转录转座子的横向传...     

LRP6 downregulation promotes cardiomyocyte proliferation and heart regeneration

The adult mammalian heart is thought to be a terminally differentiated organ given the postmitotic nature of cardiomyocytes. Consequently, the potential for cardiac repair through cardiomyocyte proliferation is extremely limited. Low-density lipoprotein receptor-related protein 6 (LRP6) is a Wnt co-receptor that is required for embryonic heart development. In this study we investigated the role of LRP6 in heart repair through regulation of cardiomyocyte proliferation. Lrp6 deficiency increased cardiomyocyte cell cycle activity in neonatal, juvenile and adult mice. Cardiomyocyte-specific deletion of Lrp6 in the mouse heart induced a robust regenerative response after myocardial infarction (MI), led to reduced MI area and improvement in left ventricular systolic function. In vivo genetic lineage tracing revealed that the newly formed cardiomyocytes in Lrp6-deficient mouse hearts after MI were mainly derived from resident cardiomyocytes. Furthermore, we found that the pro-proliferative effect of Lrp6 deficiency was mediated by the ING5/P21 signaling pathway. Gene therapy using the adeno-associated virus (AAV)9 miRNAi-Lrp6 construct promoted the repair of heart injury in mice. Lrp6 deficiency also induced the proliferation of human induced pluripotent stem cell-derived cardiomyocytes (iPSC-CMs). Our study identifies LRP6 as a critical regulator of cardiomyocyte proliferation, which may lead to the development of a novel molecular strategy to promote myocardial regeneration and repair.Subject terms: Cell-cycle exit, Cytokinesis     

极耐盐碱固氮菌的分离鉴定及固氮特性研究

我国盐碱土面积约9913万hm²,其中pH值高于9、盐含量大于0.6%的重度盐碱地每年以1.4%的速率增长。利用固氮微生物改善植物根际环境,提高作物产量,是盐碱地改良的重要方法。[目的] 从来自海南省三沙市热带珊瑚岛礁的土壤中,分离鉴定自生固氮菌,为极端盐碱地改良提供候选菌株。[方法] 通过形态学观察、生理生化特征分析和16S rRNA序列测定等方法进行菌种鉴定,分析其固氮、耐盐碱和促生长特性,盆栽试验验证其对玉米主要农艺性状的影响。[结果] 获得1株极端耐盐碱的固氮细菌DJ-1,其菌落呈圆形,菌体杆状,大小（0.5-1.3）μm×（0.3-0.5）μm,革兰氏染色阴性,与根癌土壤杆菌（Agrobacterium tumefaciens）的16S rRNA序列高度同源,确定其为根癌土壤杆菌。DJ-1在pH 9、NaCl含量为1%-4%的培养基上可正常生长,能耐受pH 12、NaCl含量8%的环境。从中克隆到固氮酶基因nifH。盆栽试验结果表明,DJ-1可显著促进玉米生长。[结论] 菌株DJ-1能耐受极端盐碱条件,且具有较强的固氮和促生长能力,有可能作为贫瘠盐碱耕地改良功能菌剂的候选菌株。     

The role of Ca2+/Calcineurin/NFAT signalling pathway in osteoblastogenesis

The bone remodelling process is closely related to bone health. Osteoblasts and osteoclasts participate in the bone remodelling process under the regulation of various factors inside and outside. Excessive activation of osteoclasts or lack of function of osteoblasts will cause occurrence and development of multiple bone‐related diseases. Ca²⁺/Calcineurin/NFAT signalling pathway regulates the growth and development of many types of cells, such as cardiomyocyte differentiation, angiogenesis, chondrogenesis, myogenesis, bone development and regeneration, etc. Some evidences indicate that this signalling pathway plays an extremely important role in bone formation and bone pathophysiologic changes. This review discusses the role of Ca²⁺/Calcineurin/NFAT signalling pathway in the process of osteogenic differentiation, as well as the influence of regulating each component in this signalling pathway on the differentiation and function of osteoblasts, whereby the relationship between Ca²⁺/Calcineurin/NFAT signalling pathway and osteoblastogenesis could be deeper understood.     

Autophagic Impairment Contributes to Systemic Inflammation-Induced Dopaminergic Neuron Loss in the Midbrain

Background

Neuroinflammation plays an important role in the pathogenesis of Parkinson’s disease (PD), inducing and accelerating dopaminergic (DA) neuron loss. Autophagy, a critical mechanism for clearing misfolded or aggregated proteins such as α-synuclein (α-SYN), may affect DA neuron survival in the midbrain. However, whether autophagy contributes to neuroinflammation-induced toxicity in DA neurons remains unknown.

Results

Intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg) into young (3-month-old) and aged (16-month-old) male C57BL/6J mice was observed to cause persistent neuroinflammation that was associated with a delayed and progressive loss of DA neurons and accumulation of α-SYN in the midbrain. The autophagic substrate-p62 (SQSTM1) persistently increased, whereas LC3-II and HDAC6 exhibited early increases followed by a decline. In vitro studies further demonstrated that TNF-α induced cell death in PC12 cells. Moreover, a sublethal dose of TNF-α (50 ng/ml) increased the expression of LC3-II, p62, and α-SYN, implying that TNF-α triggered autophagic impairment in cells.

Conclusion

Neuroinflammation may cause autophagic impairment, which could in turn result in DA neuron degeneration in midbrain.     

A TagSNP in SIRT1 Gene Confers Susceptibility to Myocardial Infarction in a Chinese Han Population

SIRT1 exerts protective effects against endothelial cells dysfunction, inflammation and atherosclerosis, indicating an important role on myocardial infarction (MI) pathogenesis. Nonetheless, the effects of SIRT1 variants on MI risk remain poorly understood. Here we aimed to investigate the influence of SIRT1 polymorphisms on individual susceptibility to MI. Genotyping of three tagSNPs (rs7069102, rs3818292 and rs4746720) in SIRT1 gene was performed in a Chinese Han population, consisting of 287 MI cases and 654 control subjects. In a logistic regression analysis, we found that G allele of rs7069102 had increased MI risk with odds ratio (OR) of 1.57 [95% confidence interval (CI) = 1.15–2.16, Bonferroni corrected P (P_c) = 0.015] after adjustment for conventional risk factors compared to C allele. Similarly, the combined CG/GG genotypes was associated with the increased MI risk (OR = 1.64, 95% CI = 1.14–2.35, P_c = 0.021) compared to the CC genotype. Further stratified analysis revealed a more significant association with MI risk among younger subjects (≤ 55 years old). Consistent with these results, the haplotype rs7069102G-rs3818292A-rs4746720T containing the rs7069102 G allele was also associated with the increased MI risk (OR = 1.41, 95% CI = 1.09–1.84, P_c = 0.040). However, we did not detect any association of rs3818292 and rs4746720 with MI risk. Our study provides the first evidence that the tagSNP rs7069102 and haplotype rs7069102G-rs3818292A-rs4746720T in SIRT1 gene confer susceptibility to MI in the Chinese Han population.     

Divergent responses of different endothelial cell types to infection with Candida albicans and Staphylococcus aureus

Endothelial cells are important in the pathogenesis of bloodstream infections caused by Candida albicans and Staphylococcus aureus. Numerous investigations have used human umbilical vein endothelial cells (HUVECs) to study microbial-endothelial cell interactions in vitro. However, the use of HUVECs requires a constant supply of umbilical cords, and there are significant donor-to-donor variations in these endothelial cells. The use of an immortalized endothelial cell line would obviate such difficulties. One candidate in this regard is HMEC-1, an immortalized human dermal microvascular endothelial cell line. To determine if HMEC-1 cells are suitable for studying the interactions of C. albicans and S. aureus with endothelial cells in vitro, we compared the interactions of these organisms with HMEC-1 cells and HUVECs. We found that wild-type C. albicans had significantly reduced adherence to and invasion of HMEC-1 cells as compared to HUVECs. Although wild-type S. aureus adhered to and invaded HMEC-1 cells similarly to HUVECs, an agr mutant strain had significantly reduced invasion of HMEC-1 cells, but not HUVECs. Furthermore, HMEC-1 cells were less susceptible to damage induced by C. albicans, but more susceptible to damage caused by S. aureus. In addition, HMEC-1 cells secreted very little IL-8 in response to infection with either organism, whereas infection of HUVECs induced substantial IL-8 secretion. This weak IL-8 response was likely due to the anatomic site from which HMEC-1 cells were obtained because infection of primary human dermal microvascular endothelial cells with C. albicans and S. aureus also induced little increase in IL-8 production above basal levels. Thus, C. albicans and S. aureus interact with HMEC-1 cells in a substantially different manner than with HUVECs, and data obtained with one type of endothelial cell cannot necessarily be extrapolated to other types.