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  • 1.

    【2hr】Creatine kinase/α-crystallin interaction functions in cataract development

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    机译 肌酸激酶/α-晶体蛋白相互作用在白内障发展中的作用
    摘要：Creatine kinase (CK) is an energy storage enzyme that plays an important role in energy metabolism. CK/phosphocreatine functions as an energy buffer and links ATP production sites with ATP utilization sites. Several key mutations in the αA-crystallin ( ) and αB-crystallin ( ) genes have been linked with autosomal-dominant, hereditary human cataracts. The cryaa-R49C mutation was identified in a four-generation Caucasian family. We previously identified an increase in the quantity of CK complexed with α-crystallin in the lenses of knock-in mice expressing the cryaa-R49C mutation using proteomic analyses. Increased levels of CK in postnatal cataractous lenses may indicate increased ATP requirements during early cataract development. To gain a further understanding of the relationship between CK and α-crystallin, we investigated whether α-crystallin interacts with and forms complexes with CK, . Isothermal titration calorimetry (ITC) showed that each CK dimer bound to 28 α-crystallin subunits, with a K of 3.3 × 10  M, and that the interaction between α-crystallin and CK was endothermic, thermodynamically favorable, and entropy-driven. High-salt concentrations did not affect the interaction between CK and α-crystallin, suggesting that the interaction between CK and α-crystallin is primarily hydrophobic. Gel permeation chromatography (GPC) detected water-soluble α-crystallin and CK complexes, as determined by increased light scattering after complex formation. In addition, CK and α-crystallin formed partially-water-insoluble, high-molecular-mass complexes. Enzyme-linked immunosorbent assay (ELISA)-based enzymatic activity analyses of lens homogenates showed a 17-fold increase in CK activity in the postnatal lenses of cryaa-R49C knock-in mice. These studies indicate that the interaction between α-crystallin and CK is functionally important and that increased CK levels may be necessary to meet the increased ATP demands of ATP-dependent functions in cataractous lenses.
  • 2.

    【2hr】The information isn't lost in gene expression

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    机译 信息不会在基因表达中丢失
    摘要：The present question is the possibility of information loss in gene expression? Information loss in the gene expression disrupts the cellular dynamics and can lead to serious defects, including cancer. Using Gottesman and Preskill method for calculating information loss in black holes,a mechanism for calculating the amount of information transformation in gene expression is proposed. In this proposal, there are three different Hilbert spaces that belong to degrees of freedom of DNA, RNA, and protein. The genetic sequence of the DNA is transcribed into protein at two stages. At first stage it is shown that the internal stationary state of the cell can be represented by a maximally entangled two-mode squeezed state of DNA and mRNA.At second stage, the state of the cell is described by a maximally entangled two-mode squeezed state of mRNA and protein. The amount of information transformation can be obtain by projecting the state at first stage on the state at second stage. Evidently for all finite values of the transcription factor concentration y, binding energy E and free energy F of the transcription factor, the information isn't lost in gene expression.
  • 3.

    【2hr】Comparison of autophagy inducibility in various tyrosine kinase inhibitors and their enhanced cytotoxicity via inhibition of autophagy in cancer cells in combined treatment with azithromycin

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    机译 多种酪氨酸激酶抑制剂的自噬诱导作用比较及其通过抑制癌细胞自噬与阿奇霉素联合治疗而增强的细胞毒性
    摘要：Tyrosine kinase inhibitors (TKIs) induce autophagy in many types of cancer cells. We previously reported that gefitinib (GEF) and imatinib (IMA) induce autophagy in epidermal growth factor receptor (EGFR) knock-out A549 and non-BCR-ABL-expressing leukemia cell lines, respectively. This evidence suggests that TKI-induced autophagy is independent of the original target molecules. The present study compared the autophagy-inducing abilities of various TKIs, regardless of their targets, by quantitative autophagy flux assay. We established stable clones expressing the GFP-LC3-mCherry-LC3ΔG plasmid in A549, PC-9, and CAL 27 cell lines and assessed autophagy inducibility by monitoring the fluorescent ratios of GFP-LC3 to mCherry-LC3ΔG using an IncuCyte live cell imaging system during exposure to TKIs viz; GEF, osimertinib (OSI), lapatinib (LAP), lenvatinib (LEN), sorafenib (SOR), IMA, dasatinib (DAS), and tivantinib (TIV). Among these TKIs, DAS, GEF, and SOR exhibited prominent autophagy induction in A549 and PC-9 cells. In CAL 27 cells, IMA, SOR, and LEN, but not GEF, TIV, or OSI, exhibited autophagy induction. In the presence of azithromycin (AZM), which showed an inhibitory effect on autophagy flux, TKIs with prominent autophagy inducibility exhibited enhanced cytotoxicity non-apoptotic cell death relative to effects of TKI alone. Therefore, autophagy inducibility of TKIs differed in the context of cancer cells. However, once induced, they appeared to have cytoprotective functions. Thus, blocking TKI-induced autophagy with AZM may improve the therapeutic effect of TKIs in cancer cells.
  • 4.

    【2hr】A Dictyostelium discoideum mitochondrial fluorescent tagging vector that does not affect respiratory function

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    机译 不影响呼吸功能的盘基网柄线粒体荧光标记载体
    摘要：Visualizing mitochondria in living cells using fluorescent dyes is often problematic due to variability in staining, metabolism of the dyes, and unknown potential effects of the dyes on mitochondrial function. We show that fluorescent labelling of mitochondria, using an N-terminal mitochondrial localization sequence derived from the protein GcvH1 (glycine cleavage system H1) attached to a red fluorescent protein enables clear mitochondrial imaging. We also show that this labelling has no effect upon mitochondria load or respiratory function.
  • 5.

    【2hr】Differentially expressed mRNAs and lncRNAs shared between activated human hepatic stellate cells and nash fibrosis

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    机译 活化的人类星状细胞与纳什纤维化之间共有差异表达的mRNA和lncRNA
    摘要：We previously reported dysregulated expression of liver-derived messenger RNA (mRNA) and long noncoding RNA (lncRNA) in patients with advanced fibrosis resulting from nonalcoholic fatty liver disease (NAFLD). Here we sought to identify changes in mRNA and lncRNA levels associated with activation of hepatic stellate cells (HSCs), the predominant source of extracellular matrix production in the liver and key to NAFLD-related fibrogenesis. We performed expression profiling of mRNA and lncRNA from LX-2 cells, an immortalized human HSC cell line, treated to induce phenotypes resembling quiescent and myofibroblastic states. We identified 1964 mRNAs (1377 upregulated and 587 downregulated) and 1460 lncRNAs (665 upregulated and 795 downregulated) showing statistically significant evidence (FDR ≤0.05) for differential expression (fold change ≥|2|) between quiescent and activated states. Pathway analysis of differentially expressed genes showed enrichment for hepatic fibrosis (FDR = 1.35E-16), osteoarthritis (FDR = 1.47E-14), and axonal guidance signaling (FDR = 1.09E-09). We observed 127 lncRNAs/nearby mRNA pairs showing differential expression, the majority of which were dysregulated in the same direction. A comparison of differentially expressed transcripts in LX-2 cells with RNA-sequencing results from NAFLD patients with or without liver fibrosis revealed 1047 mRNAs and 91 lncRNAs shared between the two datasets, suggesting that some of the expression changes occurring during HSC activation can be observed in biopsied human tissue. These results identify lncRNA and mRNA expression patterns associated with activated human HSCs that appear to recapitulate human NAFLD fibrosis.
  • 6.

    【2hr】Spermine synthesis inhibitor blocks 25-hydroxycholesterol-induced- apoptosis via SREBP2 upregulation in DLD-1 cell spheroids

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    机译 精胺合成抑制剂通过SREBP2上调DLD-1细胞球中的25-羟基胆固醇诱导的细胞凋亡
    摘要：The oxysterol 25-hydroxycholesterol (25-HC) has diverse physiological activities, including the ability to inhibit anchorage-independent growth of colorectal cancer cells. Here, we found that a polyamine synthesis inhibitor, DFMO, prevented 25-HC-induced apoptosis in non-anchored colorectal cancer DLD-1 cells. Additionally, we found that the spermine synthesis inhibitor APCHA also inhibited 25-HC-induced apoptosis in DLD-1 spheroids. Inhibiting the maturation of SREBP2, a critical regulator of cholesterol synthesis, reversed the effects of APCHA. SREBP2 knockdown also abolished the ability of APCHA to counteract 25-HC activity. Furthermore, APCHA induced SREBP2 maturation and upregulated its transcriptional activity, indicating that altered polyamine metabolism can increase SREBP2 activity and block 25-HC-induced apoptosis in spheroids. These results suggest that crosstalk between polyamine metabolism and cholesterol synthetic pathways via SREBP2 governs the proliferative and malignant properties of colorectal cancer cells.
  • 7.

    【2hr】Dhanwantaram kashayam, an Ayurvedic polyherbal formulation, reduces oxidative radicals and reverts lipids profile towards normal in diabetic rats

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    机译 阿育吠陀多草药制剂Dhanwantaram kashayam可减少糖尿病大鼠的氧化自由基并使脂质分布恢复正常
    摘要：Hyperglycemia and hyper oxidative stress are indicators of diabetes mellitus which is also accompanied with decreased levels of antioxidant enzymes. While oxidative stress is important in increasing insulin secretion and controlling blood sugar level at the same time excess oxidative stress leads to the destruction of beta cells of pancreas resulting in to low insulin production and hyperglycemia. A balance between the levels of oxidative radicals and insulin production is needed, but is not defined yet. Hyperglycemia also leads to hyperlipidemia which can contribute to various health conditions like cardiovascular diseases.
  • 8.

    【2hr】Co-inhibition of BCL-XL and MCL-1 with selective BCL-2 family inhibitors enhances cytotoxicity of cervical cancer cell lines

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    机译 BCL-XL和MCL-1与选择性BCL-2家族抑制剂的共抑制作用可增强宫颈癌细胞株的细胞毒性
    摘要：Development of resistance to chemo- and radiotherapy in patients suffering from advanced cervical cancer narrows the therapeutic window for conventional therapies. Previously we reported that a combination of the selective BCL-2 family inhibitors ABT-263 and A-1210477 decreased cell proliferation in C33A, SiHa and CaSki human cervical cancer cell lines. As ABT-263 binds to both BCL-2 and BCL-XL with high affinity, it was unclear whether the synergism of the drug combination was driven either by singly inhibiting BCL-2 or BCL-XL, or inhibition of both. In this present study, we used the BCL-2 selective inhibitor ABT-199 and the BCL-XL selective inhibitor A1331852 to resolve the individual antitumor activities of ABT-263 into BCL-2 and BCL-XL dependent mechanisms. A-1210477 was substituted for the orally bioavailable . Four cervical cancer cell lines were treated with the selective BCL-2 family inhibitors ABT-199, A1331852 and alone and in combination using 2-dimensional (2D) and 3-dimensional (3D) cell culture models. The SiHa, C33A and CaSki cell lines were resistant to single agent treatment of all three drugs, suggesting that none of the BCL-2 family of proteins mediate survival of the cells in isolation. HeLa cells were resistant to single agent treatment of ABT-199 and A1331852 but were sensitive to indicating that they depend on MCL-1 for survival. Co-inhibition of BCL-2 and MCL-1 with ABT-199 and , inhibited cell proliferation of all cancer cell lines, except SiHa. However, the effect of the combination was not as pronounced as combination of A1331852 and . Co-inhibition of BCL-XL and MCL-1 with A1331852 and significantly inhibited cell proliferation of all four cell lines. Similar data were obtained with 3-dimensional spheroid cell culture models generated from two cervical cancer cell lines . Treatment with a combination of A1331852 and resulted in inhibition of growth and invasion of the 3D spheroids. Collectively, our data demonstrate that the combination of MCL-1-selective inhibitors with either selective inhibitors of either BCL-XL or BCL-2 may be potentially useful as treatment strategies for the management of cervical cancer.
  • 9.

    【2hr】Anti-inflammatory effects of miRNA-146a induced in adipose and periodontal tissues

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    机译 脂肪和牙周组织中miRNA-146a的抗炎作用
    摘要：MicroRNA (miRNA) plays an important role in diverse cellular biological processes such as inflammatory response, differentiation and proliferation, and carcinogenesis. miR-146a has been suggested as a negative regulator of the inflammatory reaction. Although, it has been reported as expressed in inflamed adipose and periodontal tissues, however, miR-146a's inhibitory effects against inflammatory response in both the tissues, are not well understood. Therefore, in this study, the inhibitory effects of miR-146a on both adipose and periodontal inflammation, was investigated. study has revealed that miR-146a transfection into either adipocytes or gingival fibroblasts, has resulted in a reduced cytokine gene expression, observed on co-culturing the cells with macrophages in the presence of lipopolysaccharides (LPS), in comparison to the control miRNA transfected. Similarly, miR-146a transfection into macrophages resulted in a reduced expression of TNF-α gene and protein in response to LPS stimulation. study revealed that a continuous intravenous miR-146a administration into mice via tail vein, protected the mice from developing high-fat diet-induced obesity and the inflammatory cytokine gene expression was down-regulated in both adipose and periodontal tissues. miR-146a appeared to be induced by macrophage-derived inflammatory signals such as TNF-α by negative feed-back mechanism, and it suppressed inflammatory reaction in both adipose and periodontal tissues. Therefore, miR-146a could be suggested as a potential therapeutic molecule and as a common inflammatory regulator for both obesity-induced diabetes and related periodontal diseases.
  • 10.

    【2hr】Antimalarial drugs impact chemical messenger secretion by blood platelets

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    机译 抗疟药影响血小板对化学信使的分泌
    摘要：Advances in antimalarial drug development are important for combating malaria. Among the currently identified antimalarial drugs, it is suggested that some interact directly with the malarial parasites while others interact indirectly with the parasites. While this approach leads to parasite elimination, little is known about how these antimalarial drugs impact immune cells that are also critical in malarial response.
  • 11.

    【2hr】Tea extract increases cell fusion via regulation of cell surface DC-STAMP

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    机译 茶提取物通过调节细胞表面DC-STAMP增强细胞融合
    摘要：Mononuclear osteoclast precursor cells fuse with each other to become mature multinucleated osteoclasts, which is regulated by dendritic cell-specific transmembrane protein (DC-STAMP). We evaluated the effects of tea extract and catechins on cell-cell fusion and DC-STAMP expression to elucidate their relationship with osteoclast development. When tea extract or epigallocatechin gallate (EGCg) was applied to RAW264.7 cells, multinucleated cells were increased significantly, while tartrate-resistant acid phosphatase (TRAP) activity was hardly upregulated. Flow cytometric analysis revealed that EGCg suppressed DC-STAMP expression on the cell surface, which is similar to osteoclast development. These observations suggest that TRAP activity is not activated even when suppression of both surface DC-STAMP expression and multinucleation occurs, which might be mediated by another pathway.
  • 12.

    【2hr】The angiogenic effects of exosomes secreted from retinal pigment epithelial cells on endothelial cells

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    机译 视网膜色素上皮细胞分泌的外泌体对血管内皮细胞的血管生成作用
    摘要：Exosomes are informative microvesicles associated with intercellular communication via the transfer of many molecular constituents such as proteins, lipids, and nucleic acids; environmental changes and the cellular status around cells greatly affect exosome components. Cells of the retinal pigment epithelium (RPE) are key players in retinal homeostasis. Transforming growth factor (TGF)-β and tumour necrosis factor (TNF)-α are increased in the vitreous and retina in several retinal diseases and activate and undergo epithelial-mesenchymal transition (EMT) in RPE cells. EMT is closely associated with mechanisms of wound healing, including fibrosis and related angiogenesis; however, whether exosome components depend on the cell status, epithelium or mesenchyme and whether these exosomes have pro- or anti-angiogenic roles in the retina are unknown. We performed this study to investigate whether these EMT inducers affect the kinds of components in exosomes secreted from RPE cells and to assess their angiogenic effects. Exosomes were collected from culture media supernatants of a human RPE cell line (ARPE-19) stimulated with or without 10 ng/ml TNF-α and/or 5 ng/ml TGF-β2. NanoSight tracking analysis and immunoblot analysis using exosome markers were used to qualify harvested vesicles. Angiogenic factor microarray analysis revealed that exosomes derived from ARPE-19 cells cultured with TNF-α alone (Exo-TNF) and co-stimulated with TNF-α and TGF-β2 (Exo-CO) contained more angiogenic factors than exosomes derived from control cells (Exo-CTL) or ARPE-19 cells cultured with TGF-β2 alone (Exo-TGF). To assess the effect on angiogenesis, we performed chemotaxis, tube formation, and proliferation assays of human umbilical vein endothelial cells (HUVECs) stimulated with or without exosomes. HUVECs migrated to RPE-derived exosomes, and exosomes derived from ARPE-19 cells accelerated HUVEC tube formation. In contrast, Exo-TNF and Exo-CO reduced HUVEC proliferation. Our findings provide insight into the mechanisms underlying the relation between angiogenesis and exosomes derived from RPE cells.
  • 13.

    【2hr】Different regulation of lipogenesis in sebocytes and subcutaneous preadipocytes in hamsters in vitro

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    机译 仓鼠皮脂细胞和皮下前脂肪细胞脂肪形成的不同调控
    摘要：Sebaceous gland cells (sebocytes) differentiate to intracellularly accumulate lipid droplets – a phenomenon similar to that found in adipocytes. In the present study, we examined whether the regulation of lipogenesis in sebocytes is the same as that in preadipocytes. When sebocytes and preadipocytes, prepared from auricle and subcutaneous adipose tissues from the inguinal region of hamsters, respectively, were treated with a common differentiation inducer, insulin, intracellular lipid-droplet formation and triacyglycerol (TG) production were dose- and time-dependently augmented in both. Insulin increased the production of perilipin, a differentiation marker in both sebocytes and adipocytes. Insulin-like growth factor 1 (IGF-1) augmented the intracellular level of TG in sebocytes and preadipocytes. In addition, the action of 1α,25-dihydroxyvitamin D [1,25(OH )D ] on TG production was the opposite between sebocytes and preadipocytes. Furthermore, 5α-dihydrotestosterone (5α-DHT) augmented the TG level in sebocytes, whereas it did not alter TG production in preadipocytes. Moreover, insulin-augmented TG production in sebocytes was enhanced by IGF-1 and 5α-DHT, while diminished by 1,25(OH )D . In preadipocytes, the insulin-augmented production of TG was decreased by IGF-1, 1,25(OH )D , and 5α-DHT. These results suggest that sebocytic lipogenesis is partially similar to but substantially different from adipocyte lipogenesis due to the forementioned hormones and growth factors in the skin under physiological conditions.
  • 14.

    【2hr】Detection of superoxide dismutase (Cu–Zn) isoenzymes in leaves and pseudobulbs of Bulbophyllum morphologlorum Kraenzl orchid by comparative proteomic analysis

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    机译 蛋白质组学分析法检测棉铃兰叶片和假鳞茎中超氧化物歧化酶（Cu-Zn）同工酶
    摘要：Typically, biological systems are protected from the toxic effect of free radicals by antioxidant defense. Extracts from orchids have been reported to show high levels of exogenous antioxidant activity including orchids but so far, there have been no reports on antioxidant enzymes. Therefore, differences in protein expression from leaves and pseudobulbs of Kraenzl and Earsakul were studied using two-dimensional gel electrophoresis and mass spectrometry (LC/MS/MS). Interestingly, the largest group of these stress response proteins were associated with antioxidant defense and temperature stress, including superoxide dismutase (Cu–Zn) and heat shock protein 70. The high expression of this antioxidant enzyme from Kraenzl was confirmed by activity staining on native-PAGE, and the two Cu/Zn-SODs isoenzymes were identified as Cu/Zn-SOD 1 and Cu/Zn-SOD 2 by LC/MS/MS. The results suggested that orchid can be a potential plant source for medicines and natural antioxidant supplements.
  • 15.

    【2hr】EGF receptor inhibitors comprehensively suppress hepatitis B virus by downregulation of STAT3 phosphorylation

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    机译 EGF受体抑制剂通过下调STAT3磷酸化来全面抑制乙型肝炎病毒
    摘要：Current antiviral therapy can not cure chronic hepatitis B virus (HBV) infection or eliminate the risk of hepatocellular carcinoma. The licensed epidermal growth factor receptor (EGFR) inhibitors have found to inhibit hepatitis C virus replication via downregulation of signal transducers and activators of transcription 3 (STAT3) phosphorylation. Since STAT3 is also involved in HBV replication, we further studied the anti-HBV efficacy of the EGFR inhibitors in this study. HBV-transfected HepG2.2.15 cells and HBV-infected HepG2-NTCP cells were used as cell models, and HBV replication, the syntheses of viral antigens and the magnitude of the covalently closed circular DNA (cccDNA) reservoir were used as indictors to test the anti-HBV effects of EGFR inhibitors erlotinib and gefitinib. Erlotinib inhibited HBV replication with a half-maximal inhibitory concentration of 1.05 μM. It also reduced the syntheses of viral antigens at concentrations of 2.5 μM or higher. The underlying mechanism was possibly correlated with its inhibition on STAT3 phosphorylation via up-regulation of suppressor of cytokine signaling 3. Gefitinib also inhibited HBV replication and antigen syntheses. Compared with the commonest antiviral drug entecavir, these EGFR inhibitors additionally reduced hepatitis B e antigen and erlotinib also marginally affected the cccDNA reservoir in HBV-infected HepG2-NTCP cells. Interestingly, these promising anti-HBV effects were significantly enhanced by extension of treatment duration. In conclusion, EGFR inhibitors demonstrated a comprehensive anti-HBV potential, highlighting a new strategy to cure HBV infection and suggesting animal model-related studies or clinical try in the future.
  • 16.

    【2hr】Preparation of DPPC liposomes using probe-tip sonication: Investigating intrinsic factors affecting temperature phase transitions

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    机译 使用探针超声处理制备DPPC脂质体：研究影响温度相变的内在因素
    摘要：Liposomes are an important tool and have gained much attention for their promise as an effective means of delivering small therapeutic compounds to targeted sites. In an effort to establish an effective method to produce liposomes from the lipid, dipalmitoyl-phosphatidylcholine or DPPC, we have found important aspects that must be taken into consideration. Here, we used probe-tip sonication to prepare liposomes on a batch scale. During this process we uncovered interesting steps in their preparation that altered the thermodynamic properties and phase transitions of the resulting liposome mixtures. Using differential scanning calorimetry to assess this we found that increasing the sonication time had the most dramatic effect on our sample, producing almost an entirely separate phase transition relative to the main phase transition. This result is consistent with reports from the current literature. We also highlight a smaller transition, which we attribute to traces of unincorporated lipid that seems to gradually disappear as the total lipid concentration decreases. Overall, sonication is an effective means of producing liposomes, but we cannot assert this method is optimal in producing them with precise physical properties. Here we highlight the physical effects at play during this process.
  • 17.

    【2hr】Different effects of carbohydrate binding modules on the viscoelasticity of nanocellulose gels

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    机译 碳水化合物结合模块对纳米纤维素凝胶粘弹性的不同影响
    摘要：Many cellulose degrading and modifying enzymes have distinct parts called carbohydrate binding modules (CBMs). The CBMs have been shown to increase the concentration of enzymes on the insoluble substrate and thereby enhance catalytic activity. It has been suggested that CBMs also have a role in disrupting or dispersing the insoluble cellulose substrate, but dispute remains and explicit evidence of such a mechanism is lacking. We produced the isolated CBMs from two major cellulases (Cel6A and Cel7A) from as recombinant proteins in . We then studied the viscoelastic properties of native unmodified cellulose nanofibrils (CNF) in combination with the highly purified CBMs to detect possible functional effects of the CBMs on the CNF. The two CBMs showed clearly different effects on the viscoelastic properties of CNF. The difference in effects is noteworthy, yet it was not possible to conclude for example disruptive effects. We discuss here the alternative explanations for viscoelastic effects on CNF caused by CBMs, including the effect of ionic cosolutes.
  • 18.

    【2hr】Activation of sarcolipin expression and altered calcium cycling in LMNA cardiomyopathy

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    机译 LMNA心肌病中肌脂蛋白表达的激活和钙循环的改变
    摘要：Cardiomyopathy caused by A-type lamins gene ( ) mutations ( cardiomyopathy) is associated with dysfunction of the heart, often leading to heart failure. cardiomyopathy is highly penetrant with bad prognosis with no specific therapy available. Searching for alternative ways to halt the progression of cardiomyopathy, we studied the role of calcium homeostasis in the evolution of this disease. We showed that sarcolipin, an inhibitor of the sarco/endoplasmic reticulum (SR) Ca ATPase (SERCA) was abnormally elevated in the ventricular cardiomyocytes of mutated mice compared with wild type mice, leading to an alteration of calcium handling. This occurs early in the progression of the disease, when the left ventricular function was not altered. We further demonstrated that down regulation of sarcolipin using adeno-associated virus (AAV) 9-mediated RNA interference delays cardiac dysfunction in mouse model of cardiomyopathy. These results showed a novel role for sarcolipin on calcium homeostasis in heart and open perspectives for future therapeutic interventions to cardiomyopathy.
  • 19.

    【2hr】Neuroplastinβ-mediated upregulation of solute carrier family 22 member 18 antisense (SLC22A18AS) plays a crucial role in the epithelial-mesenchymal transition, leading to lung cancer cells' enhanced motility

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    机译 Neuroplastinβ介导的溶质载体家族22成员18反义（SLC22A18AS）的上调在上皮-间质转化中起关键作用，导致肺癌细胞运动性增强
    摘要：Our recent study revealed an important role of the neuroplastin (NPTN)β downstream signal in lung cancer dissemination in the lung. The molecular mechanism of the signal pathway downstream of NPTNβ is a serial activation of the key molecules we identified: tumor necrosis factor (TNF) receptor-associated factor 2 (TRAF2) adaptor, nuclear factor (NF)IA/NFIB heterodimer transcription factor, and SAM pointed-domain containing ETS transcription factor (SPDEF). The question of how dissemination is controlled by SPDEF under the activated NPTNβ has not been answered. Here, we show that the NPTNβ-SPDEF-mediated induction of solute carrier family 22 member 18 antisense (SLC22A18AS) is definitely required for the epithelial-mesenchymal transition (EMT) through the NPTNβ pathway in lung cancer cells. , the induced EMT is linked to the acquisition of active cellular motility but not growth, and this is correlated with highly disseminative tumor progression . The publicly available data also show the poor survival of SLC22A18AS-overexpressing lung cancer patients. Taken together, these data highlight a crucial role of SLC22A18AS in lung cancer dissemination, which provides novel input of this molecule to the signal cascade of NPTNβ. Our findings contribute to a better understanding of NPTNβ-mediated lung cancer metastasis.
  • 20.

    【2hr】Cellular phosphatidic acid sensor, α-synuclein N-terminal domain, detects endogenous phosphatidic acid in macrophagic phagosomes and neuronal growth cones

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    机译 细胞磷脂酸传感器α-突触核蛋白N端结构域，可检测巨噬细胞吞噬体和神经元生长锥中的内源性磷脂酸
    摘要：Phosphatidic acid (PA) is the simplest phospholipid and is involved in the regulation of various cellular events. Recently, we developed a new PA sensor, the N-terminal region of α-synuclein (α-Syn-N). However, whether α-Syn-N can sense physiologically produced, endogenous PA remains unclear. We first established an inactive PA sensor (α-Syn-N-KQ) as a negative control by replacing all eleven lysine residues with glutamine residues. Using confocal microscopy, we next verified that α-Syn-N, but not α-Syn-N-KQ, detected PA in macrophagic phagosomes in which PA is known to be enriched, further indicating that α-Syn-N can be used as a reliable PA sensor in cells. Finally, because PA generated during neuronal differentiation is critical for neurite outgrowth, we investigated the subcellular distribution of PA using α-Syn-N. We found that α-Syn-N, but not α-Syn-N-KQ, accumulated at the peripheral regions (close to the plasma membrane) of neuronal growth cones. Experiments using a phospholipase D (PLD) inhibitor strongly suggested that PA in the peripheral regions of the growth cone was primarily produced by PLD. Our findings provide a reliable sensor of endogenous PA and novel insights into the distribution of PA during neuronal differentiation.
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