Advancement and properties of circular RNAs in prostate cancer: An emerging and compelling frontier for discovering

Prostate cancer (PC) is the most common carcinoma among men worldwide which results in 26% of leading causes of cancer-related death. However, the ideal and effective molecular marker remains elusive. CircRNA, initially observed in plant-infected viruses and Sendai virus in 1979, is generated from pre-mRNA back-splicing and comes in to play by adequate expression. The differential expression in prostate tissues compared with the control reveals the promising capacity in modulating processes including carcinogenesis and metastasis. However, the biological mechanisms of regulatory network in PC needs to systemically concluded. In this review, we enlightened the comprehensive studies on the definite mechanisms of circRNAs affecting tumor progression and metastasis. What''s more, we validated the potential clinical application of circRNAs serving as diagnostic and prognostic biomarker. The discussion and analysis in circRNAs will broaden our knowledge of the pathogenesis of PC and further optimize the current therapies against different condition.     

基于CRISPR/Cas9基因编辑技术的本科教学实验体系的创建与实践

CRISPR/Cas9是新兴的基因编辑技术,在生命科学研究中发挥着重要的作用。将它引入本科生的实验教学,使本科生了解这项前沿科研技术很有意义。我们创建了一个基于CRISPR/ Cas9技术的本科教学实验体系。该实验体系侧重CRISPR/Cas9技术在哺乳动物细胞中的应用,选用一株基因组上被插入mCherry基因的小鼠胚胎成纤维细胞为实验材料,命名为STO-82。首先设计靶向mCherry的sgRNA,构建CRISPR-Cas9/sgRNA共表达质粒。经测序验证无误后,转染到STO-82细胞。采用流式细胞仪分析检测mCherry阴性和阳性两群细胞,分选出阴性单细胞并扩大培养。最后用测序检验单克隆细胞中靶标DNA序列的编辑情况。结果显示,靶位点有插入或缺失突变,说明体系创建成功。该实验体系将sgRNA设计、CRISPR-Cas9/sgRNA共表达质粒的构建、细胞转染、单细胞分选、单克隆细胞培养、测序序列分析等内容融合为一个综合实验,用于高年级本科生的实验教学。根据实际情况,将教学实践内容分解分块教学,也可以做完整性项目教学。本教学实践采用10人左右的小班分块教学,2人一组,经过3个班（共13组）的实践,绝大部分学生都能完成实验,得到预期结果。通过这个实验,学生加深了对CRISPR/Cas9技术的原理和实验流程的理解,锻炼了实验操作能力和严谨的科研思维,也使学生对该技术的医疗应用风险有了一些认识。     

Epithelial cell adhesion molecule promotes breast cancer resistance protein-mediated multidrug resistance in breast cancer by inducing partial epithelial–mesenchymal transition

Overexpression of breast cancer resistance protein (BCRP) plays a crucial role in the acquired multidrug resistance (MDR) in breast cancer. The elucidation of molecular events that confer BCRP-mediated MDR is of major therapeutic importance in breast cancer. Epithelial cell adhesion molecule (EpCAM) has been implicated in tumor progression and drug resistance in various types of cancers, including breast cancer. However, the role of EpCAM in BCRP-mediated MDR in breast cancer remains unknown. In the present study, we revealed that EpCAM expression was upregulated in BCRP-overexpressing breast cancer MCF-7/MX cells, and EpCAM knockdown using siRNA reduced BCRP expression and increased the sensitivity of MCF-7/MX cells to mitoxantrone (MX). The epithelial–mesenchymal transition (EMT) promoted BCRP-mediated MDR in breast cancer cells, and EpCAM knockdown partially suppressed EMT progression in MCF-7/MX cells. In addition, Wnt/β-catenin signaling was activated in MCF-7/MX cells, and the inhibition of this signaling attenuated EpCAM and BCRP expression and partially reversed EMT. Together, this study illustrates that EpCAM upregulation by Wnt/β-catenin signaling induces partial EMT to promote BCRP-mediated MDR resistance in breast cancer cells. EpCAM may be a potential therapeutic target for overcoming BCRP-mediated resistance in human breast cancer.     

A review of the genus Rusa in the indo-malayan archipelago and conservation efforts

Genus Rusa, belonging to the deer family Cervidae is native to the Indo-Malaya Archipelago (IMA). However, detailed information on the Rusa genus in the IMA is limited. This review provides comprehensive information on the Rusa genus in the IMA including, threats and conservation efforts. There are four species of deer in Rusa genus, which is Sambar deer (Rusa unicolor), Javan deer (Rusa timorensis), Visayan spotted deer (Rusa alfredi) and Philippine deer (Rusa marianna). Despite their wide distribution in the South Asian and Southeast Asian regions, they are under serious threats. Some conservation efforts that are being done to protect and conserve them among others are; (1) facilities protection, (2) habitat enrichment programme, (3) Ex-situ conservation, (4) legislations, and (5) captive breeding. Conservation through genetics is also an important step in conserving these species. Recommendations for conservation of the genus are also discussed; 1. maintenance of ecosystem. 2. more effective monitoring system on the existing protected area. 3. ex-situ conservation, and 4. habitat monitoring.     

功能核酸概念的内涵与外延

对功能核酸概念的分析需要建立在对功能核酸研究的基础上,从内涵和外延两个方面来进行探析。从内涵来看,它是对具有特殊结构、执行特定生物功能的核酸分子的统称;从外延来看,它包括适体、核酸核酶、核糖开关、发光核酸、修饰核酸、功能核酸裁剪、核酸自组装、功能核酸纳米材料、核酸纳米酶、核酸药物、核酸补充剂以及DNA存储技术等。目前功能核酸已成功地应用于生物传感、生物成像、生物医学等诸多领域。对功能核酸这一概念进行了探讨,并尝试对其范畴、特点进行归纳总结,以期梳理和完善功能核酸的基本概念,促进该领域的进一步发展。     

双斑蟋营养成分分析及评价

由于具有较好的营养价值以及较高的食物转化效率,食用昆虫特别是蟋蟀受到普遍关注。在双斑蟋（Gryllus bimaculatus,GB）营养成分测定的基础上,对比家蟋（Acheta domesticus,AD）和黑蟋（Gryllus testaceus,GT）的营养及含量,分析评价了双斑蟋的使用价值。结果显示：双斑蟋水分含量71.0%、粗蛋白含量58.60%（干重）、粗脂肪含量28.90%（干重）、粗纤维含量7.23%（干重）、灰分4.93%（干重）;蛋白含量与黑蟋相当而高于家蟋,粗脂肪和灰分含量要高于家蟋和黑蟋;双斑蟋含有17种氨基酸,总氨基酸含量51.03%（干重）,必需氨基酸含量24.76%（干重）、占总氨基酸的48.3%,氨基酸含量低于其他两种蟋蟀;双斑蟋中常量元素含量最高的为钾（6 416 mg/kg,干重）、含量最低的是钙（92 mg/kg,干重）,微量元素中锌含量较高（241 mg/kg,干重）;双斑蟋油脂中不饱和脂肪酸的相对含量为65.33%,以亚油酸（37.05%）和油酸（25.86%）为主、饱和脂肪酸以棕榈酸（25.44%）和硬脂酸（8.74%）为主。双斑蟋的脂肪酸组成、含量与家蟋相近,而与黑蟋的脂肪酸组成差别较大,三种蟋蟀中含量最高的饱和脂肪酸为棕榈酸,而含量最高的不饱和酸为亚油酸。结果表明,双斑蟋的必需氨基酸组成符合FAO/WHO推荐的氨基酸构成比例的蛋白条件,具有较高的营养价值和食用价值。     

Phylogeography of Fischer’s blue,Tongeia fischeri,in Japan: Evidence for introgressive hybridization

The widespread lycaenid butterfly Tongeia fischeri is distributed from eastern Europe to northeastern Asia and represented by three geographically isolated populations in Japan. In order to clarify the phylogeographic history of the species, we used sequences of three mitochondrial (COI, Cyt b and ND5) and two nuclear (Rpl5 and Ldh) genes of 207 individuals collected from 55 sites throughout Japan and five sites on the Asian continent. Phylogenetic trees and the median-joining network revealed six evolutionary mitochondrial haplotype clades, which corresponded to the geographic distribution of the species. Common ancestors of Japanese T. fischeri might have come to Japan during the mid-Pleistocene by multiple dispersals of continental populations, probably via a land bridge or narrow channel between western Japan and the Korean Peninsula. The geographical patterns of variation of mitochondrial and nuclear markers are discordant in northeastern Kyushu, possibly as a result of introgressive hybridization during the ancient contact between the Kyushu and Shikoku populations in the last glacial maximum. The phylogeographic pattern of T. fischeri in Japan are probably related to the geological history, Pleistocene climatic oscillations and distribution of the host plant.     

Bone morphogenetic protein 9 overexpression reduces osteosarcoma cell migration and invasion

Transforming growth factor-β (TGF-β) is known to promote tumor migration and invasion. Bone morphogenetic proteins (BMPs) are members of the TGF-β family expressed in a variety of human carcinoma cell lines. The role of bone morphogenetic protein 9 (BMP9), the most powerful osteogenic factor, in osteosarcoma (OS) progression has not been fully clarified. The expression of BMP9 and its receptors in OS cell lines was analyzed by RT-PCR. We found that BMP9 and its receptors were expressed in OS cell lines. We further investigated the influence of BMP9 on the biological behaviors of OS cells. BMP9 overexpression in the OS cell lines 143B and MG63 inhibited in vitro cell migration and invasion. We further investigated the expression of a panel of cancer-related genes and found that BMP9 overexpression increased the phosphorylation of Smad1/5/8 proteins, increased the expression of ID1, and reduced the expression and activity of matrix metalloproteinase 9 (MMP9) in OS cells. BMP9 silencing induced the opposite effects. We also found that BMP9 may not affect the chemokine (C-X-C motif) ligand 12 (CXCL12)/C-X-C chemokine receptor type 4 (CXCR4) axis to regulate the invasiveness and metastatic capacity of OS cells. Interestingly, CXCR4 was expressed in both 143B and MG63 cells, while CXCL12 was only detected in MG63 cells. Taken together, we hypothesize that BMP9 inhibits the migration and invasiveness of OS cells through a Smad-dependent pathway by downregulating the expression and activity of MMP9.     

Maintenance of CMV-specific CD8+ T cell responses and the relationship of IL-27 to IFN-γ levels with aging

We investigated whether healthy young (age ? 40) and elderly (age ? 65) people infected with cytomegalovirus (CMV) had similar levels of CD8⁺ T cell cytokine production and proliferation in response to an immunodominant CMV pp65 peptide pool given the role of CD8⁺ T cells in controlling viral infection and the association of CMV with immunosenescence. Plus, we determined the effects of aging and CMV-infectious status on plasma levels of IL-27, an innate immune cytokine with pro- and anti-inflammatory properties, as well as on its relationship to IFN-γ in that IL-27 can promote the production of IFN-γ. The results of our study show that young and elderly people had similar levels of CD8⁺ T cell proliferation, and IFN-γ and TNF-α production in response to CMV pp65 peptides. Plasma levels of IL-27 were similar between the two groups although CMV-infected young and elderly people had a trend toward increased levels of IL-27. Regardless of aging and CMV-infectious status, plasma levels of IL-27 correlated highly with plasma levels of IFN-γ. These findings suggest the maintenance of CMV pp65-specific CD8⁺ T cell proliferation and cytokine production with aging as well as the sustaining of circulatory IL-27 levels and its biological link to IFN-γ in young and elderly people irrespective of CMV infection.     

Bee venom ameliorates ovalbumin induced allergic asthma via modulating CD4+CD25+ regulatory T cells in mice

Asthma is a potentially life-threatening inflammatory disease of the lung characterized by the presence of large numbers of CD4⁺ T cells. These cells produce the Th2 and Th17 cytokines that are thought to orchestrate the inflammation associated with asthma. Bee venom (BV) has traditionally been used to relieve pain and to treat chronic inflammatory diseases. Recent reports have suggested that BV might be an effective treatment for allergic diseases. However, there are still unanswered questions related to the efficacy of BV therapy in treating asthma and its therapeutic mechanism. In this study, we evaluated whether BV could inhibit asthma and whether BV inhibition of asthma could be correlated with regulatory T cells (Treg) activity. We found that BV treatment increased Treg populations and suppressed the production of Th1, Th2 and Th17-related cytokines in an in vitro culture system, including IL2, IL4, and IL17. Interestingly, production of IL10, an anti-inflammatory cytokine secreted by Tregs, was significantly augmented by BV treatment. We next evaluated the effects of BV treatment on allergic asthma in an ovalbumin (OVA)-induced mouse model of allergic asthma. Cellular profiling of the bronchoalveolar lavage (BAL) and histopathologic analysis demonstrated that peribronchial and perivascular inflammatory cell infiltrates were significantly lowered following BV treatment. BV also ameliorated airway hyperresponsiveness, a hallmark symptom of asthma. In addition, IL4 and IL13 levels in the BAL fluid were decreased in the BV treated group. Surprisingly, the beneficial effects of BV treatment on asthma were eradicated following Treg depletion by anti-CD25 antibody injection, suggesting that the major therapeutic targets of BV were Tregs. These results indicate that BV efficiently diminishes bronchial inflammation in an OVA-induced allergic asthma murine model, and that this effect might correlate with Tregs, which play an important role in maintaining immune homeostasis and suppressing the function of other T cells to limit the immune response. These results also suggest that BV has potential therapeutic value for controlling allergic asthma responses.