与宁夏人群强直性脊柱炎关联的新基因淋巴毒素-α(LTA)的识别

淋巴毒素-α(Lymphotoxin-alpha,LTA)基因与系统性红斑狼疮、银屑病及类风湿性关节炎的遗传性有关,但目前还未有关于LTA基因与强直性脊柱炎(Ankylosing spondylitis,AS)关联的报道。文章采用病例-对照设计,在宁夏人群中对人类白细胞抗原(Human leukocyte antigen,HLA)的Ⅲ类基因约58 kb区域进行了高密度标志的基因组扫描,在33个SNPs及其单倍型中,仅定位于LTA基因中的SNPs组成的TCC单倍型的分布在病例-对照间比较有统计学意义(P=0.0005)。在宁夏群体(病例组:300,对照组:385)中发现,LTA基因中的rs909253 T/C多态性在AS患者中出现的频率显著高于正常对照(28.5%vs 19.7%,P=2×10-6)。结果表明LTA基因变异和AS易感性之间存在相关性,由此识别LTA基因可能与宁夏人群AS关联。     

FSCB phosphorylation in mouse spermatozoa capacitation

It is generally accepted that spermatozoa capacitation is associated with protein kinase A-mediated tyrosine phosphorylation. In our previous study, we identified the fibrous sheath CABYR binding protein (FSCB), which was phosphorylated by PKA. However, the phosphorylation status of FSCB protein during spermatozoa capacitation should be further investigated. To this aim, in this study, we found that phosphorylation of this 270-kDa protein occurred as early as 1 min after mouse spermatozoa capacitation, which increased over time and remained stable after 60 min. Immunoprecipitation assays demonstrated that the tyrosine and Ser/Thr phosphorylation of FSCB occurred during spermatozoa capacitation. The extent of phosphorylation and was closely associated with the PKA activity and spermatozoa motility characteristics. FSCB phosphorylation could be induced by PKA agonist DB-cAMP, but was blocked by PKA antagonist H-89.Therefore, FSCB contributes to spermatozoa capacitation in a tyrosine-phosphorylated format, which may help in further elucidating the molecular mechanism of spermatozoa capacitation.     

Omega-3 fatty acid deficiency during brain maturation reduces neuronal and behavioral plasticity in adulthood

Omega-3-fatty acid DHA is a structural component of brain plasma membranes, thereby crucial for neuronal signaling; however, the brain is inefficient at synthesizing DHA. We have asked how levels of dietary n-3 fatty acids during brain growth would affect brain function and plasticity during adult life. Pregnant rats and their male offspring were fed an n-3 adequate diet or n-3 deficient diets for 15 weeks. Results showed that the n-3 deficiency increased parameters of anxiety-like behavior using open field and elevated plus maze tests in the male offspring. Behavioral changes were accompanied by a level reduction in the anxiolytic-related neuropeptide Y-1 receptor, and an increase in the anxiogenic-related glucocorticoid receptor in the cognitive related frontal cortex, hypothalamus and hippocampus. The n-3 deficiency reduced brain levels of docosahexaenoic acid (DHA) and increased the ratio n-6/n-3 assessed by gas chromatography. The n-3 deficiency reduced the levels of BDNF and signaling through the BDNF receptor TrkB, in proportion to brain DHA levels, and reduced the activation of the BDNF-related signaling molecule CREB in selected brain regions. The n-3 deficiency also disrupted the insulin signaling pathways as evidenced by changes in insulin receptor (IR) and insulin receptor substrate (IRS). DHA deficiency during brain maturation reduces plasticity and compromises brain function in adulthood. Adequate levels of dietary DHA seem crucial for building long-term neuronal resilience for optimal brain performance and aiding in the battle against neurological disorders.     

Multifunctionality of biocrusts is positively predicted by network topologies consistent with interspecies facilitation

The potential of biodiversity loss to impair the delivery of ecosystem services has motived ecologists to better understand the relationship between biodiversity and ecosystem functioning. Although increasing evidence underlines the collective contribution of different biodiversity components on the simultaneous performance of multiple functions (multifunctionality), we know little about the trade‐offs between individual diversity effects and the extent to which they determine multifunctionality differentially. Here, at a subcontinental scale of 62 dryland sites, we show in phototrophic microbiota of biological soil crusts (biocrusts) that, whereas richness alone is unable to guarantee the maxima of multifunctional performance, interspecies facilitation and compositional identity are particularly stronger but often neglected predictors. The inconsistent effects of different biodiversity components imply that soil multifunctionality can be lost despite certain species remaining present. Moreover, we reveal a significant empirical association between species functional importance and its topological feature in co‐occurrence networks, indicating a functional signal of species interaction. Nevertheless, abundant species tend to isolate and merely interact within small topological structures, but rare species were tightly connected in complicated network modules. Our findings suggest that abundant and rare species of soil phototrophs exhibit distinct functional relevance. These results give a comprehensive view of how soil constructive species drive multifunctionality in biocrusts and ultimately promote a deeper understanding of the consequences of biodiversity loss in real‐world ecosystems.     

HIP/PAP protects against bleomycin‐induced lung injury and inflammation and subsequent fibrosis in mice

Hepatocarcinoma‐intestine‐pancreas/pancreatitis‐associated protein (HIP/PAP), a C‐type lectin, exerts anti‐oxidative, anti‐inflammatory, bactericidal, anti‐apoptotic, and mitogenic functions in several cell types and tissues. In this study, we explored the role of HIP/PAP in pulmonary fibrosis (PF). Expression of HIP/PAP and its murine counterpart, Reg3B, was markedly increased in fibrotic human and mouse lung tissues. Adenovirus‐mediated HIP/PAP expression markedly alleviated bleomycin (BLM)‐induced lung injury, inflammation, and fibrosis in mice. Adenovirus‐mediated HIP/PAP expression alleviated oxidative injury and lessened the decrease in pulmonary superoxide dismutase (SOD) activity in BLM‐treated mice, increased pulmonary SOD expression in normal mice, and HIP/PAP upregulated SOD expression in cultured human alveolar epithelial cells (A549) and human lung fibroblasts (HLF‐1). Moreover, in vitro experiments showed that HIP/PAP suppressed the growth of HLF‐1 and ameliorated the H₂O₂‐induced apoptosis of human alveolar epithelial cells (A549 and HPAEpiC) and human pulmonary microvascular endothelial cells (HPMVEC). In HLF‐1, A549, HPAEpiC, and HPMVEC cells, HIP/PAP did not affect the basal levels, but alleviated the TGF‐β1‐induced down‐regulation of the epithelial/endothelial markers E‐cadherin and vE‐cadherin and the over‐expression of mesenchymal markers, such as α‐SMA and vimentin. In conclusion, HIP/PAP was found to serve as a potent protective factor in lung injury, inflammation, and fibrosis by attenuating oxidative injury, promoting the regeneration of alveolar epithelial cells, and antagonizing the pro‐fibrotic actions of the TGF‐β1/Smad signaling pathway.     

Quantitative Assessment of the Association between rs2046210 at 6q25.1 and Breast Cancer Risk

Genome-wide association studies (GWAS) have identified several genetic susceptibility loci for breast cancer (BC). One of them, conducted among Chinese women, found an association of rs2046210 at 6q25.1 with the risk of BC recently. Since then, numerous association studies have been carried out to investigate the relationship between this polymorphism and BC risk in various populations. However, these have yielded contradictory results. We therefore performed a meta-analysis to clarify this inconsistency. Overall, a total of 235003 subjects based on 13 studies were included in our study. Significantly increased BC risk was detected in the pooled analysis [allele contrast: OR = 1.13, 95%CI = 1.10–1.17, P(Z) <10⁻⁵, P(Q) <10⁻⁴; dominant model: OR = 1.21, 95%CI = 1.14–1.27, P(Z) <10⁻⁵, P(Q) <10⁻⁴; recessive model: OR = 1.18, 95%CI = 1.12–1.24, P(Z) <10⁻⁵, P(Q) = 0.04]. In addition, our data revealed that rs2046210 conferred greater risk in estrogen receptor (ER)-negative tumors [OR = 1.27, 95%CI = 1.15–1.40, P(Z) <10⁻⁵, P(Q) <10⁻⁴] than in ER-positive ones [OR = 1.18, 95%CI = 1.09–1.28, P(Z) <10⁻⁴, P(Q) = 0.0003]. When stratified by ethnicity, significant associations were found in Caucasian and Asian populations, but not detected among Africans. There was evidence of heterogeneity (P<0.05), however, the heterogeneity largely disappeared after stratification by ethnicity. The present meta-analysis demonstrated that the rs2046210 polymorphism may be associated with increased BC susceptibility, but this association varies in different ethnicities.     

Effects of Ambient Particulate Matter on Human Breast Cancer: Is Xenogenesis Responsible?

Background

Recently, evidence from several studies has revealed that air pollution is associated with the increased morbidity and mortality of breast cancer patients. However, to date, the underlying mechanism remains largely unclear. Considering the high prevalence of air pollution and breast cancer in China, it is necessary to understand how air pollution may affect breast cancer.

Methods

We analyzed 1,832 female patients who had resided in the same cities for at least 10 years prior to their diagnosis. Variables including demographic data as well as clinical and tumor characteristics, including the patient’s age at menarche, family history of breast cancer, tumor histopathological type, tumor size, lymph node metastasis, distant metastasis, histological grade, estrogen receptor (ER) status, progesterone receptor (PR) status and human epidermal growth factor receptor 2 (HER-2) status at the time of diagnosis were analyzed.

Results

Compared to patients residing in low-pollution areas, patients living in high-pollution areas demonstrated a younger age at menarche (p<0.001), a greater family history of breast cancer (p = 0.034) and more invasive cancers (p = 0.028) with higher tumor grades (p = 0.028) and estrogen receptor (ER)-positive status (p = 0.022). Differences in tumor grade were only found in ER-positive cases.

Conclusions

Our findings and clinical data indicate that long-term air pollution exposure may contribute to the development of breast cancer by playing the role of a xenoestrogen, and also provides new insight into the association between air pollution and the morbidity and mortality of breast cancer patients. Furthermore, it is urgently necessary to study the association between air pollution and breast cancer to improve the living quality and health of females, and applicable public health strategies may need to be established or modified as soon as possible.     

Post-Mastectomy Radiotherapy for Breast Cancer Patients with T1-T2 and 1-3 Positive Lymph Nodes: a Meta-Analysis

Background

The role of post-mastectomy radiotherapy (PMRT) in patients with T1-2 and 1-3 positive lymph nodes remains controversial. The aim of this study is to investigate the possible benefits of PMRT for this subgroup.

Methods

Three electronic databases were systematically quarried (Cochrane Library, MEDLINE, and EMBASE) for published studies evaluating the effects of PMRT on breast cancer patients with T1-T2 tumors with 1-3 positive lymph nodes. Of the 334 studies identified, information was available for 3432 patients from 10 clinical studies. Pooled relative risk estimates (RR) and overall survival (OS) were calculated using the inverse variance weighted approach, publication bias and chi-square test were also calculated.

Results

From the 10 studies, the pooled RR (RRs) for locoregional recurrence (LRR) with PMRT was 0.348 (95% CI = 0.254 to 0.477), suggesting a significant benefit for PMRT to decrease the risk of LRR in patients with T1-T2 tumors and 1-3 positive nodes (p<0.05). Reporting bias ( Begg’s p = 0.152; Egger’s p = 0.107) or significant heterogeneity (Cochran’s p = 0.380; I² = 6.7%) were not detected. For further subset analysis, the RR for T1, N1-3+ tumors was 0.330 (95% CI = 0.171 to 0.639); for T2, N1-3+ tumors the RR was 0.226 (95% CI = 0.121 to 0.424). The pooled RR for overall survival (OS) was not significantly different between PMRT and no-PMRT group (1.051, 95% CI =1.001 to 1.104).

Conclusions

Our pooled analysis revealed that PMRT significantly reduces the risk of LRR in patients with TI-T2 tumors with 1-3 positive nodes, and the magnitude of the LRR risk reduction is slightly greater for larger tumors. Our results suggest that PMRT should be considered for patients with T1/T2 tumors with 1-3 positive nodes to decrease the relatively high risk of LRR.