• 主题
高级搜索  >
历史搜索 清空历史

您现在的位置：首页>美国卫生研究院文献>Cell Death Discovery

期刊信息

  • 期刊名称：

    -

  • 刊频：
  • NLM标题： Cell Death Discov
  • iso缩写： -
  • ISSN： -

年度选择

更多>>

  • 排序：
  • 显示：
  • 每页：
全选（0）
<9/20>
共524条结果
  • 1.

    【2hr】2-aminopurine suppresses the TGF-β1-induced epithelial–mesenchymal transition and attenuates bleomycin-induced pulmonary fibrosis

    包量

    机译 2-氨基嘌呤抑制TGF-β1诱导的上皮-间质转化并减弱博来霉素诱导的肺纤维化
    摘要：The epithelial–mesenchymal transition (EMT) is a multifunctional cell process involved in the pathogenesis of numerous conditions, including fibrosis and cancer. Idiopathic pulmonary fibrosis (IPF) is a progressive and fatal disease characterized by fibroblast accumulation and collagen deposition in the lungs. The fibroblasts involved in this process partially originate from lung epithelial cells via the EMT. Evidence suggests that the EMT contributes to progression, invasion, and metastasis of various types of cancer. We screened a series of 80 compounds for the ability to interfere with the EMT and potentially be applied as a therapeutic for IPF and/or lung cancer. We identified 2-aminopurine (2-AP), a fluorescent analog of guanosine and adenosine, as a candidate in this screen. Herein, we demonstrate that 2-AP can restore E-cadherin expression and inhibit fibronectin and vimentin expression in TGF-β1–treated A549 lung cancer cells. Moreover, 2-AP can inhibit TGF-β1-induced metastasis of A549 cells. This compound significantly attenuated bleomycin (BLM)-induced pulmonary inflammation, the EMT, and fibrosis. In addition, 2-AP treatment significantly decreased mortality in a mouse model of pulmonary fibrosis. Collectively, we determined that 2-AP could inhibit metastasis in vitro by suppressing the TGF-β1-induced EMT and could attenuate BLM-induced pulmonary fibrosis in vivo. Results of this study suggest that 2-AP may have utility as a treatment for lung cancer and pulmonary fibrosis.
  • 2.

    【2hr】Flubendazole inhibits glioma proliferation by G2/M cell cycle arrest and pro-apoptosis

    包量

    机译 氟苯达唑通过抑制G2 / M细胞周期阻滞和促凋亡来抑制神经胶质瘤增殖
    摘要：Flubendazole, FDA-approved anthelmintic, has been widely used in treating testinal parasites. In the recent years, Flubendazole has been reported to exert anticancer activities. On the other hand, little was known about the effects of Flubendazole on gliomas. Here we demonstrated a novel effect of flubendazole on glioma cells. We found that Flubendazole inhibited cell proliferation and promoted cell apoptosis of glioma cell lines in vitro, and suppressed tumor growth in xenograft models by intraperitoneal injection. However, Flubendazole might have no influence on cell migration. Mechanism study reaveled that Flubendazole caused cell cycle arrest in G2/M phase, which partly account for the suppressed proliferation. Consistently, Flubendazole induced P53 expression and reduced Cyclin B1 and p-cdc2 expression in glioma cells. In addition, Flubendazole promoted cell apoptosis by regulating the classical apoptosis protein BCL-2 expression. These observations suggest that Flubendazole exerts anti-proliferation and pro-apoptosis effects in Glioma through affecting the cell cycle and intrinsic apoptotic signaling, and indicate a novel utilization of Flubendazole in the treatment of Glioma.
  • 3.

    【2hr】Gomesin peptides prevent proliferation and lead to the cell death of devil facial tumour disease cells

    包量

    机译 Gomesin肽阻止恶性面部肿瘤疾病细胞的增殖并导致其死亡
    摘要：The Tasmanian devil faces extinction due to devil facial tumour disease (DFTD), a highly transmittable clonal form of cancer without available treatment. In this study, we report the cell-autonomous antiproliferative and cytotoxic activities exhibited by the spider peptide gomesin (AgGom) and gomesin-like homologue (HiGom) in DFTD cells. Mechanistically, both peptides caused a significant reduction at G0/G1 phase, in correlation with an augmented expression of the cell cycle inhibitory proteins p53, p27, p21, necrosis, exacerbated generation of reactive oxygen species and diminished mitochondrial membrane potential, all hallmarks of cellular stress. The screening of a novel panel of AgGom-analogues revealed that, unlike changes in the hydrophobicity and electrostatic surface, the cytotoxic potential of the gomesin analogues in DFTD cells lies on specific arginine substitutions in the eight and nine positions and alanine replacement in three, five and 12 positions. In conclusion, the evidence supports gomesin as a potential antiproliferative compound against DFTD disease.
  • 4.

    【2hr】Preserving self-renewal of porcine pluripotent stem cells in serum-free 3i culture condition and independent of LIF and b-FGF cytokines

    包量

    机译 在无血清3i培养条件下保持猪多能干细胞的自我更新，并且独立于LIF和b-FGF细胞因子
    摘要：Derivation of bona fide porcine pluripotent stem cells is still a critical issue because porcine embryonic stem cells (ESCs) are not available yet, and most of the culture conditions to maintain porcine induced pluripotent stem cells (piPSCs) are based on conditions for mouse and human iPS cells. In this study, we generated a doxycycline-inducible porcine iPS cell line (DOX-iPSCs) and used it to screen the optimal culture condition to sustain the self-renewal of piPSCs. We found that LIF and b-FGF were required for porcine cell reprogramming, but were not essential cytokines for maintaining the self-renewal and pluripotency of piPSCs. A serum-free 3i medium, which includes three inhibitors CHIR99021, SB431542, and PD0325901, three cytokines BMP4, SCF, and IL-6, and human platelet lysates (PL), was made through serious selections. In 3i condition, the doxycycline-inducible iPSCs could be passaged for a long term without the addition of doxycycline, and the flattened morphology of intermediate state piPSCs could convert to the naïve-like morphology with the increase in endogenous pluripotent gene expressions. Additionally, pPSC cell line isolated from 5.5 days blastocysts could be sustained in 3i medium and the expression of endogenous pluripotent genes OCT4, ESRRB, and STELLA was significantly increased. Our finding directed a new reprogramming strategy by using 3i condition to maintain and convert primed piPSCs into naïve-like pluripotent state. A combination of traditional LIF/b-FGF conditions and 3i condition may help us to find out an appropriate reprogramming approach to generate the naïve state of porcine iPSCs.
  • 5.

    【2hr】Mechanism of inhibition of Shiga-toxigenic Escherichia coli SubAB cytotoxicity by steroids and diacylglycerol analogues

    包量

    机译 类固醇和二酰基甘油类似物抑制志贺毒素大肠杆菌SubAB细胞毒性的机制
    摘要：Shiga toxigenic Escherichia coli (STEC) are responsible for a worldwide foodborne disease, which is characterized by severe bloody diarrhea and hemolytic uremic syndrome (HUS). Subtilase cytotoxin (SubAB) is a novel AB5 toxin, which is produced by Locus for Enterocyte Effacement (LEE)-negative STEC. Cleavage of the BiP protein by SubAB induces endoplasmic reticulum (ER) stress, followed by induction of cytotoxicity in vitro or lethal severe hemorrhagic inflammation in mice. Here we found that steroids and diacylglycerol (DAG) analogues (e.g., bryostatin 1, Ingenol-3-angelate) inhibited SubAB cytotoxicity. In addition, steroid-induced Bcl-xL expression was a key step in the inhibition of SubAB cytotoxicity. Bcl-xL knockdown increased SubAB-induced apoptosis in steroid-treated HeLa cells, whereas SubAB-induced cytotoxicity was suppressed in Bcl-xL overexpressing cells. In contrast, DAG analogues suppressed SubAB activity independent of Bcl-xL expression at early time points. Addition of Shiga toxin 2 (Stx2) with SubAB to cells enhanced cytotoxicity even in the presence of steroids. In contrast, DAG analogues suppressed cytotoxicity seen in the presence of both toxins. Here, we show the mechanism by which steroids and DAG analogues protect cells against SubAB toxin produced by LEE-negative STEC.
  • 6.

    【2hr】Warm blood cardioplegia versus cold crystalloid cardioplegia for myocardial protection during coronary artery bypass grafting surgery

    包量

    机译 冠状动脉搭桥术中热血停搏与冷晶体停搏对心肌的保护
    摘要：We retrospectively analyzed early results of coronary artery bypass grafting (CABG) surgery using two different types of cardioplegia for myocardial protection: antegrade intermittent warm blood or cold crystalloid cardioplegia. From January 2015 to October 2016, 330 consecutive patients underwent isolated on-pump CABG. Cardiac arrest was obtained with use of warm blood cardioplegia (WBC group, n = 297) or cold crystalloid cardioplegia (CCC group, n = 33), according to the choice of the surgeon. Euroscore II and preoperative characteristics were similar in both groups, except for the creatinine clearance, slightly lower in WBC group (77.33 ± 27.86 mL/min versus 88.77 ± 51.02 mL/min) (P < 0.05). Complete revascularization was achieved in both groups. In-hospital mortality was 2.0% (n = 6) in WBC group, absent in CCC group. The required mean number of cardioplegia’s doses per patient was higher in WBC group (2.3 ± 0.8) versus CCC group (2.0 ± 0.7) (P = 0.045), despite a lower number of distal coronary artery anastomoses (2.7 ± 0.8 versus 3.2 ± 0.9) (P = 0.0001). Cardiopulmonary and aortic cross-clamp times were similar in both groups. The incidence of perioperative myocardial infarction (WBC group 3.4% versus CCC group 3.0%) and low cardiac output syndrome (4.4% versus 3.0%) were similar in both groups. As compared with WBC group, in CCC group CK-MB/CK ratio >10% was lower during each time points of evaluation, with a statistical significant difference at time 0 (4% ± 1.6% versus 5% ± 2.5%) (P = 0.021). In presence of complete revascularization, despite the value of CK-MB/CK ratio >10% was less in the CCC group, clinical results were not affected by both types of cardioplegia adopted to myocardial protection. As compared with cold crystalloid, warm blood cardioplegia requires a shorter interval of administration to achieve better myocardial protection.
  • 7.

    【2hr】#2714, a novel active inhibitor with potent G2/M phase arrest and antitumor efficacy in preclinical models

    包量

    机译 ＃2714，在临床前模型中具有有效的G2 / M期阻滞和抗肿瘤功效的新型活性抑制剂
    摘要：Arresting cell cycle has been one of the most common approaches worldwide in cancer therapy. Specifically, arresting cells in the G2/M phase is a promising therapeutic approach in the battle against lung cancer. In the present study, we demonstrated the anticancer activities and possible mechanism of compound #2714, which can prompt G2/M phase arrest followed by cell apoptosis induction in Lewis lung carcinoma LL/2 cells. In vitro, #2714 significantly inhibited LL/2 cell viability in a concentration- and time-dependent manner while exhibiting few toxicities on non-cancer cells. The mechanism study showed that cell proliferation inhibition due to the treatment with #2714 correlated with G2/M phase arrest and was followed by LL/2 cell apoptosis. The characterized changes were associated with the downregulation of phosphorylated cell division cycle 25C (Cdc25C) and upregulation of p53. Apoptosis-associated activation of cleaved caspase-3 was also detected. Moreover, #2714 strongly attenuated LL/2 cell proliferation by disrupting the phosphorylation of p44/42 mitogen-activated protein kinase (MAPK). In vivo, intraperitoneal administration of #2714 (25–100 mg/kg/day) to mice bearing established tumors in xenograft models significantly prevented LL/2 tumor growth (58.1%) without detectable toxicity. Compound #2714 significantly increased apoptosis in LL/2 lung cancer cells in mice models, as observed via terminal deoxynucleotidyl transferase (TdT) dUTP nick-end labeling (TUNEL) assay, and the data from an immunohistochemical analysis showed that #2714 remarkably inhibited the proliferation and angiogenesis of lung cancer in vivo. Taken together, our data suggest that #2714 has a high potential anti-lung cancer efficacy with a pathway-specific mechanism of G2/M phase arrest and subsequent apoptosis induction both in vitro and in vivo; its potential to be an anticancer candidate warrants further investigation.
  • 8.

    【2hr】GRK2 moderates the acute mitochondrial damage to ionizing radiation exposure by promoting mitochondrial fission/fusion

    包量

    机译 GRK2通过促进线粒体的裂变/融合来缓解线粒体对电离辐射暴露的急性损伤
    摘要：The modern understanding of the G protein-coupled receptor kinase 2 has grown towards the definition of a stress protein, for its ability to rapidly compartmentalize within the cell in response to acute stimulation. Also, mitochondria can be regulated by GRK2 localization. We show that Ionizing Radiation (IR) exposure acutely damages mitochondria regarding mass, morphology, and respiration, with recovery in a framework of hours. This phenomenon is actively regulated by GRK2, whose overexpression results to be protective, and reciprocally, deletion accelerates degenerative processes. The regulatory effects of the kinase involve a new interactome that includes binding HSP90 and binding and phosphorylation of the key molecules involved in the process of mitochondrial fusion and recovery: MFN-1 and 2.
  • 9.

    【2hr】Sotetsuflavone suppresses invasion and metastasis in non-small-cell lung cancer A549 cells by reversing EMT via the TNF-α/NF-κB and PI3K/AKT signaling pathway

    包量

    机译 Sotetsuflavone通过经由TNF-α/NF-κB和PI3K / AKT信号通路逆转EMT抑制非小细胞肺癌A549细胞的侵袭和转移
    摘要：Epithelial-mesenchymal transition (EMT) is associated with tumor invasion and metastasis, and offers insight into novel strategies for cancer treatment. Sotetsuflavone was isolated from Cycas revolute, which has excellent anticancer activity in the early stages. The present study aims to evaluate the anti-metastatic potential of sotetsuflavone in vitro. Our data demonstrated that sotetsuflavone inhibits metastasis of A549 cells, and EMT. This inhibition was reflected in the upregulation of E-cadherin, and downregulation of N-cadherin, vimentin, and Snail. Mechanistically, our study demonstrated that HIF-1α played an important role in the anti-metastatic effect of sotetsuflavone in non-small-cell lung cancer A549 cells. Sotetsuflavone not only mediated VEGF expression but also downregulated VEGF and upregulated angiostatin, and simultaneously affected the expression of MMPs and decreased MMP-9 and MMP-13 expression. More importantly, HIF-1α expression may be regulated by the inhibition of PI3K/AKT and TNF-α/NF-κB pathways. These results suggest that sotetsuflavone can reverse EMT, thereby inhibiting the migration and invasion of A549 cells. This process may be associated with both PI3K/AKT and TNF-α/NF-κB pathways, and sotetsuflavone may be efficacious in the treatment of non-small-cell lung cancer.
  • 10.

    【2hr】NR4A2 protects cardiomyocytes against myocardial infarction injury by promoting autophagy

    包量

    机译 NR4A2通过促进自噬保护心肌细胞免受心肌梗塞损伤
    摘要：Myocardial infarction (MI), characterized by ischemia-induced cardiomyocyte apoptosis, is the leading cause of mortality worldwide. NR4A2, a member of the NR4A orphan nucleus receptor family, is upregulated in mouse hearts with MI injury. Furthermore, NR4A2 knockdown aggravates heart injury as evidenced by enlarged hearts and increased apoptosis. To elucidate the underlying mechanisms of NR4A2-regulated apoptosis, we used H9c2 cardiomyocytes deprived of serum and neonatal rat cardiomyocytes (NRCMs) exposed to hypoxia to mimic ischemic conditions in vivo. As NR4A2 knockdown aggravates cardiomyocyte apoptosis, while NR4A2 overexpression ameliorates it, NR4A2 upregulation was considered an adaptive response to ischemia-induced cardiomyocyte apoptosis. By detecting changes in LC3 and using autophagy detection tools including Bafilomycin A1, 3MA and rapamycin, we found that NR4A2 knockdown promoted apoptosis through blocking autophagic flux. This apoptotic response was phenocopied by downregulation of NR4A2 after autophagic flux was impaired by Bafilomycin A1. Further study showed that NR4A2 binds to p53 directly and decreases its levels when it inhibits apoptosis; thus, p53/Bax is the downstream effector of NR4A2-mediated apoptosis, as previously reported. Changes in p53/Bax that were regulated by NR4A2 were also detected in injured hearts with NR4A2 knockdown. In addition, miR-212-3p is the upstream regulator of NR4A2, and it could downregulate the expression of NR4A2, as well as p53/Bax. The mechanism underlying the role of NR4A2 in apoptosis and autophagy was elucidated, and NR4A2 may be a therapeutic drug target for heart failure.
  • 11.

    【2hr】Magnolol restores the activity of meropenem against NDM-1-producing Escherichia coli by inhibiting the activity of metallo-beta-lactamase

    包量

    机译 厚朴酚通过抑制金属β-内酰胺酶的活性来恢复美罗培南对产生NDM-1的大肠杆菌的活性
    摘要：The emergence of plasmid-mediated New Delhi metallo-β-lactamase-1 (NDM-1) in carbapenem-resistant Gram-negative pathogens is an increasing clinical threat. Here we report the discovery of an NDM-1 inhibitor, magnolol, through enzyme inhibition screening. We showed that magnolol significantly inhibited NDM enzyme activity (IC50 = 6.47 µg/mL), and it restored the activity of meropenem against Escherichia coli ZC-YN3, an NDM-1-producing E. coli isolate, in in vitro antibacterial activity assays. Magnolol lacked direct antibacterial activity, but compared with meropenem alone, it reduced the MICs of meropenem against E. coli ZC-YN3 by 4-fold and killed almost all the bacteria within 3 h. Molecular modeling and a mutational analysis demonstrated that magnolol binds directly to the catalytic pocket (residues 110 to 200) of NDM-1, thereby blocking the binding of the substrate to NDM-1 and leading to its inactivation. Our results demonstrate that the combination of magnolol and meropenem may have the potential to treat infections caused by NDM-1-positive, carbapenem-resistant Gram-negative pathogens.
  • 12.

    【2hr】BIX-01294 sensitizes renal cancer Caki cells to TRAIL-induced apoptosis through downregulation of survivin expression and upregulation of DR5 expression

    包量

    机译 BIX-01294通过下调survivin表达和上调DR5表达使肾癌Caki细胞对TRAIL诱导的凋亡敏感
    摘要：BIX-01294 (BIX), a G9a histone methyltransferase inhibitor, has been reported for its anti-proliferative and anticancer activities against various cancer cell lines. In this study, we investigated whether BIX could sensitize TRAIL-mediated apoptosis in various cancer cells. Combined treatment with BIX and TRAIL markedly induced apoptosis in human renal carcinoma (Caki, ACHN, and A498), breast carcinoma (MCF-7), and lung carcinoma (A549) cells. In contrast, BIX and TRAIL co-treatment did not induce apoptosis in normal cells, specifically mouse kidney cell (TCMK-1) and human skin fibroblast (HSF). BIX downregulated protein expression levels of XIAP and survivin at the post-translational level. Overexpression of survivin markedly blocked combined BIX and TRAIL treatment-induced apoptosis, but XIAP had no effect. Furthermore, BIX induced upregulation of DR5 expression at the transcriptional levels, and knockdown of DR5 expression using small interfering RNAs (siRNAs) markedly attenuated BIX and TRAIL-induced apoptosis. Interestingly, siRNA-mediated G9a histone methyltransferase knockdown also enhanced TRAIL-induced apoptosis in Caki cells. However, knockdown of G9a did not change expression levels of XIAP, survivin, and DR5. Therefore, BIX-mediated TRAIL sensitization was independent of histone methyltransferase G9a activity. Taken together, these results suggest that BIX facilitates TRAIL-mediated apoptosis via downregulation of survivin and upregulation of DR5 expression in renal carcinoma Caki cells.▶ BIX facilitates TRAIL-mediated apoptosis in human renal carcinoma Caki cells.▶ Downregulation of survivin contributes to BIX plus TRAIL-induced apoptosis.▶ Upregulation of DR5 is involved in BIX plus TRAIL-mediated apoptosis.▶ BIX-mediated TRAIL sensitization is independent of ROS production.
  • 13.

    【2hr】Mycobacterium fortuitum-induced ER-Mitochondrial calcium dynamics promotes calpain/caspase-12/caspase-9 mediated apoptosis in fish macrophages

    包量

    机译 福特分枝杆菌诱导的ER-线粒体钙动力学促进鱼巨噬细胞中钙蛋白酶/ caspase-12 / caspase-9介导的细胞凋亡
    摘要：Mycobacterium fortuitum is a natural fish pathogen. It induces apoptosis in headkidney macrophages (HKM) of catfish, Clarias sp though the mechanism remains largely unknown. We observed M. fortuitum triggers calcium (Ca2+) insult in the sub-cellular compartments which elicits pro-apototic ER-stress factor CHOP. Alleviating ER-stress inhibited CHOP and attenuated HKM apoptosis implicating ER-stress in the pathogenesis of M. fortuitum. ER-stress promoted calpain activation and silencing the protease inhibited caspase-12 activation. The study documents the primal role of calpain/caspase-12 axis on caspase-9 activation in M. fortuitum-pathogenesis. Mobilization of Ca2+ from ER to mitochondria led to increased mitochondrial Ca2+ (Ca2+)m load,, mitochondrial permeability transition (MPT) pore opening, altered mitochondrial membrane potential (ΔΨm) and cytochrome c release eventually activating the caspase-9/-3 cascade. Ultra-structural studies revealed close apposition of ER and mitochondria and pre-treatment with (Ca2+)m-uniporter (MUP) blocker ruthenium red, reduced Ca2+ overload suggesting (Ca2+)m fluxes are MUP-driven and the ER-mitochondria tethering orchestrates the process. This is the first report implicating role of sub-cellular Ca2+ in the pathogenesis of M. fortuitum. We summarize, the dynamics of Ca2+ in sub-cellular compartments incites ER-stress and mitochondrial dysfunction, leading to activation of pro-apoptotic calpain/caspase-12/caspase-9 axis in M. fortuitum-infected HKM.
  • 14.

    【2hr】Thrombospondin-1 protects against Aβ-induced mitochondrial fragmentation and dysfunction in hippocampal cells

    包量

    机译 血小板反应蛋白-1可预防Aβ诱导的海马细胞线粒体片段化和功能障碍
    摘要：Alzheimer’s disease (AD) is often characterized by the impairment of mitochondrial function caused by excessive mitochondrial fragmentation. Thrombospondin-1 (TSP-1), which is primarily secreted from astrocytes in the central nervous system (CNS), has been suggested to play a role in synaptogenesis, spine morphology, and synaptic density of neurons. In this study, we investigate the protective role of TSP-1 in the recovery of mitochondrial morphology and function in amyloid β (Aβ)-treated mouse hippocampal neuroblastoma cells (HT22). We observe that TSP-1 inhibits Aβ-induced mitochondrial fission by maintaining phosphorylated-Drp1 (p-Drp1) levels, which results in reduced Drp1 translocation to the mitochondria. By using gabapentin, a drug that antagonizes the interaction between TSP-1 and its neuronal receptor α2δ1, we observe that α2δ1 acts as one of the target receptors for TSP-1, and blocks the reduction of the p-Drp1 to Drp1 ratio, in the presence of Aβ. Taken together, TSP-1 appears to contribute to maintaining the balance in mitochondrial dynamics and mitochondrial functions, which is crucial for neuronal cell viability. These data suggest that TSP-1 may be a potential therapeutic target for AD.
  • 15.

    【2hr】The genomic tool-kit of the truffle Tuber melanosporum programmed cell death

    包量

    机译 松露块茎黑色素细胞编程性细胞死亡的基因组工具包
    摘要：A survey of the truffle Tuber melanosporum genome has shown the presence of 67 programmed cell death (PCD)-related genes. The 67 genes are all expressed during fruit body (FB) development of T. melanosporum development; their expression has been detected by DNA microarrays and qPCR. A set of 14 PCD-related genes have been chosen, those with the highest identities to the homologs of other species, for a deeper investigation. That PCD occurs during T. melanosporum development has been demonstrated by the TUNEL reaction and transmission electron microscopy. The findings of this work, in addition to the discovery of PCD-related genes in the T. melanosporum genome and their expression during the differentiation and development of the FB, would suggest that one of the PCD subroutines, maybe autophagy, is involved in the FB ripening, i.e., sporogenesis.
  • 16.

    【2hr】Multiscale analysis of a regenerative therapy for treatment of volumetric muscle loss injury

    包量

    机译 再生疗法治疗容积性肌肉丢失损伤的多尺度分析
    摘要：Skeletal muscle possesses a remarkable capacity to regenerate when injured, but when confronted with major traumatic injury resulting in volumetric muscle loss (VML), the regenerative process consistently fails. The loss of muscle tissue and function from VML injury has prompted development of a suite of therapeutic approaches but these strategies have proceeded without a comprehensive understanding of the molecular landscape that drives the injury response. Herein, we administered a VML injury in an established rodent model and monitored the evolution of the healing phenomenology over multiple time points using muscle function testing, histology, and expression profiling by RNA sequencing. The injury response was then compared to a regenerative medicine treatment using orthotopic transplantation of autologous minced muscle grafts (~1 mm3 tissue fragments). A chronic inflammatory and fibrotic response was observed at all time points following VML. These results suggest that the pathological response to VML injury during the acute stage of the healing response overwhelms endogenous and therapeutic regenerative processes. Overall, the data presented delineate key molecular characteristics of the pathobiological response to VML injury that are critical effectors of effective regenerative treatment paradigms.
  • 17.

    【2hr】Common medium versus advanced IVF medium for cryopreserved oocytes in heterologous cycles

    包量

    机译 异源循环中冻存卵母细胞的普通培养基与高级IVF培养基
    摘要：Granulocyte-macrophage colony-stimulation factor plays different crucial roles during embryo implantation and subsequent development. Here we aimed to evaluate the effects of embryo cell culture medium, with the inclusion of granulocyte-macrophage colony-stimulation factor (GM-CSF), on embryo development and pregnancy rate. To this end, we took advantage of our retrospective observational study to correlate the outcomes from two different culture media. We included in this study 25 unselected patient from our IVF Center that underwent heterologous IVF cycle with crypreserved oocytes. We analyze the fertilization rate, pregnancy rate, and embryo quality at different day of transfer obtained from two different media composition. Our results show that the rate of fertilization and the pregnancy rate were increased using medium added with this particular type of cytokines (GM-CSF).
  • 18.

    【2hr】Characterization of dysregulated lncRNA-mRNA network based on ceRNA hypothesis to reveal the occurrence and recurrence of myocardial infarction

    包量

    机译 基于ceRNA假说表征失调的lncRNA-mRNA网络，以揭示心肌梗塞的发生和复发
    摘要：Accumulating evidence has demonstrated that long non-coding RNAs (lncRNAs) acting as competing endogenous RNAs (ceRNAs) play important roles in initiation and development of human diseases. However, the mechanism of ceRNA regulated by lncRNA in myocardial infarction (MI) remained unclear. In this study, we performed a multi-step computational method to construct dysregulated lncRNA-mRNA networks for MI occurrence (DLMN_MI_OC) and recurrence (DLMN_MI_Re) based on “ceRNA hypothesis”. We systematically integrated lncRNA and mRNA expression profiles and miRNA-target regulatory interactions. The constructed DLMN_MI_OC and DLMN_MI_Re both exhibited biological network characteristics, and functional analysis demonstrated that the networks were specific for MI. Additionally, we identified some lncRNA-mRNA ceRNA modules involved in MI occurrence and recurrence. Finally, two new panel biomarkers defined by four lncRNAs (RP1-239B22.5, AC135048.13, RP11-4O1.2, RP11-285F7.2) from DLMN_MI_OC and three lncRNAs (RP11-363E7.4, CTA-29F11.1, RP5-894A10.6) from DLMN_MI_Re with high classification performance were, respectively, identified in distinguishing controls from patients, and patients with recurrent events from those without recurrent events. This study will provide us new insight into ceRNA-mediated regulatory mechanisms involved in MI occurrence and recurrence, and facilitate the discovery of candidate diagnostic and prognosis biomarkers for MI.
  • 19.

    【2hr】Novel biomarker ZCCHC13 revealed by integrating DNA methylation and mRNA expression data in non-obstructive azoospermia

    包量

    机译 通过整合DNA甲基化和mRNA表达数据在非阻塞性无精症中揭示新型生物标志物ZCCHC13
    摘要：The objective of this study was to identify genes regulated by methylation that were involved in spermatogenesis failure in non-obstructive azoospermia (NOA). Testis biopsies of patients with NOA and OA (with normal spermatogenesis) were evaluated by microarray analysis to examine DNA methylation and mRNA expression using our established integrative approach. Of the coordinately hypermethylated and down-regulated gene list, zinc-finger CCHC-type containing 13 (ZCCHC13) was present within the nuclei of germ cells of testicular tissues according immunohistochemistry, and there was decreased protein expression in men with NOA compared with OA controls. Mechanistic analyses indicated that ZCCHC13 increased c-MYC expression through the p-AKT and p-ERK pathways. To confirm the changes in ZCCHC13 expression in response to methylation, 5-aza-2′-deoxycitidine (5-Aza), a hypomethylating agent, was administered to mouse spermatogonia GC-1 cells. We demonstrated that 5-Aza enhanced protein and mRNA expression of ZCCHC13 epigenetically, which was accompanied by activation of p-AKT and p-ERK signaling. Our data, for the first time, demonstrate that ZCCHC13 is an important signaling molecule that positively regulates the AKT/MAPK/c-MYC pathway and that methylation aberrations of ZCCHC13 may cause defects in testis development in human disease, such as NOA.
  • 20.

    【2hr】Bcl-2 regulates store-operated Ca2+ entry to modulate ER stress-induced apoptosis

    包量

    机译 Bcl-2调节存储操作的Ca2 +进入，以调节内质网应激诱导的细胞凋亡
    摘要：Ca2+ plays a significant role in linking the induction of apoptosis. The key anti-apoptotic protein, Bcl-2, has been reported to regulate the movement of Ca2+ across the ER membrane, but the exact effect of Bcl-2 on Ca2+ levels remains controversial. Store-operated Ca2+ entry (SOCE), a major mode of Ca2+ uptake in non-excitable cells, is activated by depletion of Ca2+ in the ER. Depletion of Ca2+ in the ER causes translocation of the SOC channel activator, STIM1, to the plasma membrane. Thereafter, STIM1 binds to Orai1 or/and TRPC1 channels, forcing them to open and thereby allow Ca2+ entry. In addition, several anti-cancer drugs have been reported to induce apoptosis of cancer cells via the SOCE pathway. However, the detailed mechanism underlying the regulation of SOCE by Bcl-2 is not well understood. In this study, a three-amino acid mutation within the Bcl-2 BH1 domain was generated to verify the role of Bcl-2 in Ca2+ handling during ER stress. The subcellular localization of the Bcl-2 mutant (mt) is similar to that in the wild-type Bcl-2 (WT) in the ER and mitochondria. We found that mt enhanced thapsigargin and tunicamycin-induced apoptosis through ER stress-mediated apoptosis but not through the death receptor- and mitochondria-dependent apoptosis, while WT prevented thapsigargin- and tunicamycin-induced apoptosis. In addition, mt depleted Ca2+ in the ER lumen and also increased the expression of SOCE-related molecules. Therefore, a massive Ca2+ influx via SOCE contributed to caspase activation and apoptosis. Furthermore, inhibiting SOCE or chelating either extracellular or intracellular Ca2+ inhibited mt-mediated apoptosis. In brief, our results explored the critical role of Bcl-2 in Ca2+ homeostasis and the modulation of ER stress.
题名 作者 来源 发表时间

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号