通讯机构：
[Lili Chen] D;Department of public health laboratory sciences, College of Public Health, University of South China, Hengyang, China<&wdkj&>Key Laboratory of Hengyang for Health Hazard Factors Inspection and Quarantine, Hengyang, China
摘要：
Background: Chlamydia psittaci is a pathogen of birds that can cause zoonotic disease in mammals including pneumonia in humans. MicroRNAs (miRNAs) are a class of small non-coding RNA fragments with a length of about 22 nt, which play an important role in regulating gene expression after transcription. Chlamydia infection can cause changes in host cell miRNA expression, but the potential biological function of miRNAs in C. psittaci infection and pathogenesis is not well understood. Methods: Small RNA sequencing (sRNA-Seq) technology was used to characterise miRNA expression in human bronchial epithelial (HBE) cells after C. psittaci infection, and differentially expressed miRNAs were identified. Candidate target genes for these miRNAs were then functionally annotated by Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway analysis. The sRNA-Seq results were partially validated by quantitative real time polymerase chain reaction (qRT-PCR) and miRNA-target networks were constructed using visualization software. Results: We identified 151 differentially expressed miRNAs (46 known miRNAs and 105 novel miRNAs) in C. psittaci-infected HBE cells, of which 140 were upregulated and 11 were downregulated. Of these, 17 known miRNAs were significantly upregulated and two were downregulated using P < 0.05 and |log2FoldChange|>1.5 as threshold criteria. GO enrichment results showed that the predicted targets of these differentially expressed miRNAs were mainly involved in transcriptional regulation and ATP binding. KEGG pathway analysis suggested that the candidate target genes were involved in several important signaling pathways such as MAPK, ErbB, cGMP-PKG, cAMP, mTOR, GNRH, oxytocin, PI3K-Akt and AMPK, which are primarily related to biological processes such as transcription and signal transduction. The qRT-PCR results for miR-2116 & ndash;3p, miR-3195, miR663a, miR-10401 & ndash;5p, miR-124 & ndash;3p, miR-184, miR-744 & ndash;5p and hsa-miR-514b-5p were consistent with the sRNASeq data. Conclusions: A large amount of miRNA expression profile data relating to C. psittaci infection was obtained, which provides a useful experimental and theoretical basis for further understanding the pathogenic mechanisms of C. psittaci infection.
摘要：
Polycystic ovary syndrome (PCOS) is the most typical and common metabolic abnormalities in women of reproductive age. This study examined the protective effects of Dendrobium nobile Lindl. polysaccharides (DNLP) on ovarian follicular development in letrozole-induced PCOS rats and explored the underlying molecular mechanisms. The PCOS rats showed the increased body weight, serum testosterone and luteinizing hormone levels and insulin resistance. DNLP treatment reduced the body weight, serum testosterone level and insulin resistance, but failed to affect luteinizing hormone level in the PCOS rats. DNLP treatment recovered disrupted estrous cycle in the PCOS rats. DNLP treatment decreased antral follicles and increased the thickness of the granular cell layer. DNLP treatment increased the PCNA mRNA and protein expression levels in the PCOS ovarian tissues, and inhibited cell apoptosis in the PCOS ovarian tissues via regulating apoptosis-related proteins including Bax, Bcl-2 and caspase-3. In summary, this study demonstrated the protective effects of DNLP on the ovaries in the letrozole-induced PCOS rat model. DNLP exerted its protective effects via improving follicular development and inhibiting apoptosis of ovarian granular cells in PCOS rats. This study will provide experimental basis for the future clinical application of DNLP in the treatment of PCOS. (C) 2020 Published by Elsevier B.V.
期刊：
International Journal of Cancer,2019年144(3):651-664 ISSN：0020-7136
通讯作者：
Zu, Xuyu;Jiang, Yuyang
作者机构：
[Zhong, Jing; Zu, Xuyu; Cao, Renxian; Peng, Xiuda; Liu, Jianghua; Ding, Wenjun; Shen, Yingying] Univ South China, Inst Clin Med, Affiliated Hosp 1, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;[Zhang, Wei] Tsinghua Univ, Sch Med, Dept Biol, Beijing, Peoples R China.;[Cao, Renxian; Liu, Jianghua] Univ South China, Affiliated Hosp 1, Dept Metab & Endocrinol, Hengyang, Hunan, Peoples R China.;[He, Jun] Univ South China, Affiliated Hosp 1, Dept Spine Surg, Hengyang, Hunan, Peoples R China.;[Chen, Xiguang] Univ South China, Affiliated Hosp 1, Dept Med Oncol, Hengyang, Hunan, Peoples R China.
通讯机构：
[Zu, Xuyu] U;[Jiang, Yuyang] T;Univ South China, Inst Clin Med, Affiliated Hosp 1, 69 Chuanshan Rd, Hengyang 421001, Hunan, Peoples R China.;Tsinghua Univ, Grad Sch Shenzhen, Guangdong Prov Key Lab Chem Biol, Lishui Rd, Shenzhen 518055, Peoples R China.
关键词：
*AXL;*DCC-2036;*MET;*PDX;*TNBC
摘要：
Triple-negative breast cancer (TNBC) is insensitive to endocrine therapies and targeted therapies to human epidermal growth factor receptor-2 (HER2), estrogen receptor (ER) and progesterone receptor (PR). New targets and new targeted therapeutic drugs for TNBC are desperately needed. Our study confirmed that DCC-2036 inhibited the proliferation, invasion, migration and epithelial-mesenchymal transition (EMT) of TNBC cells as well as induced apoptosis. Moreover, the antiproliferative activity of DCC-2036 was more efficient than that of most clinical drugs. In addition, the combination of DCC-2036 and cisplatin or lapatinib had synergistic effects on TNBC cells. Mechanistically, DCC-2036 targeted AXL/MET, especially AXL, and regulated the downstream PI3K/Akt-NFkappaB signaling to exert its antitumor effect in TNBC. DCC-2036 also inhibited the growth and metastasis of xenografted MDA-MB-231 cells (AXL/MET-high TNBC cells) but not MDA-MB-468 cells (AXL-low TNBC cells) in NSG mice in vivo. Furthermore, DCC-2036 significantly inhibited tumor growth and invasion of AXL/MET-high TNBC PDX tumors but not AXL/MET-low TNBC PDX tumors. These results highlighted the roles of AXL/MET in cancer growth and metastasis and further verified that the critical targets of DCC-2036 are AXL and MET, especially AXL. In addition, there was no significant toxicity of DCC-2036 even at a high dosage. Therefore, DCC-2036 may be a potential compound to treat TNBC, especially for tumors with AXL/MET overexpression.
作者机构：
[乃爱桃; 艾小红] Department of Radiation Oncology, The First Affiliated Hospital of University of South China, Hengyang, 421001, China;[王五洲; 陈熙; Wan W.; 曹文宇; 王逸轩] Clinical Anatomy & Reproductive Medicine Application Institute, Medical College, University of South China, Hengyang, 421001, China;[罗丹; 何洁] Department of Pathology, Medical College, University of South China, Hengyang, 421001, China;[万炜; 何淑雅] Department of Radiation Medicine, School of Public Health, University of South China, Hengyang, 421001, China;[徐杨] Department of Physiology, Medical College, University of South China, Hengyang, 421001, China
通讯机构：
[Xu, Y.; Ai, X.] D;Department of Physiology, China;Department of Radiation Oncology, China
关键词：
电离辐射;前额叶皮质区;NLRP3炎性小体;认知功能障碍
摘要：
探讨电离辐射诱导小鼠认知功能障碍的可能机制.20只雌性昆明小鼠随机分为对照组和辐照组,辐照组小鼠接受137Cs γ射线单次全身辐照至吸收剂量4 Gy.35 d后采用新旧事物识别实验检测小鼠认知功能;免疫组织化学法检测小鼠前额叶皮质区小胶质细胞标记物离子钙接头蛋白-1(IBA-1)的表达;蛋白质印迹法检测前额叶皮质区核苷酸结合寡聚化结构域样受体蛋白3(NLRP3)、凋亡相关斑点样蛋白(ASC)、半胱氨酸天门冬氨酸蛋白酶-1(Caspase-1)、白细胞介素-1β(IL-1 β)和白细胞介素-18(IL-18)蛋白的表达变化;荧光定量PCR(RT-PCR)检测前额叶皮质IBA-1、NLRP3、ASC和Caspase-1 mRNA的表达情况.结果显示:与对照组相比,辐照组小鼠在新旧事物识别实验中对新事物的分辨率明显降低(38.39 ± 3.69 vs. 28.82 ± 2.08, p<0.05);前额叶皮质区IBA-1阳性细胞数(138.2 ± 3.7 vs. 159.6 ± 6.9, p<0.05)和mRNA表达(1.000 ± 0.031 vs. 1.173 ± 0.055, p<0.05)均显著上调;前额叶皮质区NLRP3、ASC、Caspase-1蛋白(1.000 ± 0.066 vs. 1.341 ± 0.119, p<0.05;1.000 ± 0.073 vs. 1.298 ± 0.083, p<0.05;1.000 ± 0.039 vs. 1.603 ± 0.159, p<0.01)及NLRP3、 ASC mRNA表达(1.000 ± 0.046 vs. 1.372 ± 0.071, p<0.01; 1.000 ± 0.068 vs. 1.225 ± 0.069, p<0.05)均明显上调;前额叶皮质区炎性细胞因子IL-1β和IL-18的表达(1.000 ± 0.033 vs. 1.167 ± 0.059, p<0.05;1.000 ± 0.196 vs. 1.614 ± 0.163, p<0.05)均明显上调.结果提示,电离辐射可能是通过激活前额叶皮质区小胶质细胞,活化NLRP3炎性小体,诱导炎症因子释放引起认知功能障碍的.
摘要：
The chemical compound LY2874455 has the potential to overcome drug resistance driven by FGFR gatekeeper mutations. X-ray crystallographic studies provide the structural explanation for why this compound is effective against the FGFR gatekeeper mutations.
摘要：
Bin Wang,1 Yuanwei Guo,2 Xiaofeng Chen,3 Chao Zeng,1 Qikang Hu,1 Wei Yin,1 Wei Li,1 Hui Xie,1 Bingyu Zhang,1 Xingchun Huang,1 Fenglei Yu1 1Department of Thoracic Surgery, The Second Xiangya Hospital of Central South University, Changsha 410011, People’s Republic of China; 2Center for Clinical Pathology, Affiliated to The First People’s Hospital of Chenzhou, University of South China, Chenzhou 432000, People’s Republic of China; 3Department of Anesthesiology, The Second Xiangya Hospital of Central South University, Changsha 410011, People’s Republic of China Background: Stromal cell-derived factor 1 (SDF-1) is an important chemokine for stem cell mobilization, and plays a critical role in mobilization of mesenchymal stem cells (MSCs). Bone morphogenetic protein 2 (BMP-2) plays a critical role in osteogenesis of MSCs. However, the use of SDF-1 and BMP-2 in bone tissue engineering is limited by their short half-lives and rapid degradation in vitro and in vivo. Methods: The chitosan oligosaccharide/ heparin nanoparticles (CSO/H NPs) were first prepared via self-assembly. Chitosan-agarose-gelatin (CAG) Scaffolds were then synthesized via gelation technology using cross-linked chitosan, agarose, and gelatin, and were modified by CSO/H NPs. The encapsulation efficiency and release kinetics of SDF-1 and BMP-2 were quantified using an enzyme-linked immunosorbent assay. A CCK-8 assays were used to evaluate biocompatibility of NP-modified scaffolds. The biological activity of the loaded SDF-1 and BMP-2 was evaluated using the transwell migration assay and osteogenic induction assay. An animal MSC recruitment model was used to study the ability of SDF-1 released from NP-modified scaffolds to induce migration of MSCs. Results: In this study, we developed a novel nanoparticle-modified CAG scaffold for the delivery of SDF-1 and BMP-2. CCK-8 assays demonstrated excellent biocompatibility of NP-modified scaffolds. In addition, we investigated the release of SDF-1 and BMP-2 from NP-modified scaffolds, and evaluated the effect of released SDF-1 on MSC migration. The effect of released BMP-2 on MSC osteogenesis was also examined. In vitro cell migration assays showed that SDF-1 released from NP-modified scaffolds retained its migration activity; osteogenesis studies demonstrated that released BMP-2 exhibited a strong ability to induce differentiation towards osteoblasts. Our in vivo recruitment assays showed continuous chemotactic response of MSCs to SDF-1 released from the NP-modified scaffold.Conclusion: The simplicity of synthesizing CSO/H NP-modified CAG scaffolds, combined with its high cytokine loading capacity and sustained release effect, renders NP-modified CAG scaffold an attractive candidate for sustained release of SDF-1 and BMP-2 to promote bone repair and regeneration. Keywords: cytokine delivery system, nanoparticles, chitosan-agarose-gelatin scaffold, stromal cell-derived factor-1, bone morphogenetic protein-2
