visualizing-interrenal-steroidogenic-tissue-its-vascular

Visualizing the Interrenal Steroidogenic Tissue and Its Vascular Microenvironment in Zebrafish

This protocol introduces how to detect differentiated interrenal steroidogenic cells through a simple whole-mount enzymatic activity assay. Identifying ...

Tunghai University

Members of Shc family conventionally serve as critical adaptors in tyrosine phosphorylation signal transduction pathways. p66(Shc) protein, a member of Shc family, is predominantly expressed in epithelial cells, whereas the regulation of its expression remains an enigma. We describe the effect of steroid hormones on the protein level of p66(Shc) and growth stimulation in hormone-sensitive human prostate, testicular and breast cancer cells. In DHT-treated androgen-sensitive prostate cancer LNCaP C-33 cells, the protein level of p66(Shc) was elevated by approximately 3-fold, correlating with increased cell growth. This DHT effect on p66(Shc) protein level and growth regulation was also observed in another androgen-sensitive prostate cancer cell line MDA PCa2b as well as 2 testicular cancer cell lines, Tera-1 and Tera-2 cells. Similarly, the female sex hormone estrogen had a stimulating effect on p66(Shc) protein level and proliferation in estrogen-sensitive MCF-7 breast cancer cells. The upregulation of p66(Shc) protein level by DHT was competitively abolished by Casodex, an androgen antagonist used to treat prostate cancer. Moreover, immunohistochemical analyses showed that the p66(Shc) protein level was significantly higher in primary prostate tumors than in adjacent non-cancerous cells (p < 0.05). The data collectively indicate that p66(Shc) protein levels correlate with steroid hormone-stimulated cell growth and prostate carcinogenesis.

p66Shc protein is upregulated by steroid hormones in hormone-sensitive cancer cells and in primary prostate carcinomas.

The hair follicle bulge possesses putative epithelial stem cells. Characterization of these cells has been hampered by the inability to target bulge cells genetically. Here, we use a Keratin1-15 (Krt1-15, also known as K15) promoter to target mouse bulge cells with an inducible Cre recombinase construct or with the gene encoding enhanced green fluorescent protein (EGFP), which allow for lineage analysis and for isolation of the cells. We show that bulge cells in adult mice generate all epithelial cell types within the intact follicle and hair during normal hair follicle cycling. After isolation, adult Krt1-15-EGFP-positive cells reconstituted all components of the cutaneous epithelium and had a higher proliferative potential than Krt1-15-EGFP-negative cells. Genetic profiling of hair follicle stem cells revealed several known and unknown receptors and signaling pathways important for maintaining the stem cell phenotype. Ultimately, these findings provide potential targets for the treatment of hair loss and other disorders of skin and hair.

Capturing and profiling adult hair follicle stem cells.

p66(Shc), an isoform of Shc adaptor proteins, is shown to mediate various signals, including cellular stress. However, little is known about its involvement in carcinogenesis. We previously showed that p66(Shc) protein level is upregulated by steroid hormones in human carcinoma cells and is higher in prostate cancer (PCa) specimens than adjacent noncancerous cells. In this study, we investigated the role of p66(Shc) protein in PCa cell proliferation. Among different PCa cell lines tested, p66(Shc) protein level showed positive correlation with cell proliferation, that is, rapid-growing cells expressed higher p66(Shc) protein than slow-growing cells. Exposure of slow-growing LNCaP C-33 cells to epidermal growth factor (EGF) and 5alpha-dihydrotestosterone (DHT) led to upregulation of proliferation and p66(Shc) protein level. Conversely, growth suppression of fast-growing cells by cellular form of prostatic acid phosphatase (cPAcP) expression, a negative growth regulator, down-regulated their p66(Shc) protein level. Additionally, increased expression of p66(Shc) protein by cDNA transfection in LNCaP C-33 cells resulted in increased cell proliferation. Cell cycle analyses showed higher percentage of p66(Shc)-overexpressing cells at S phase (24%) than control cells (17%), correlating with their growth rates. On the other hand, transient knock-down of p66(Shc) expression by RNAi in rapidly growing cells decreased their proliferation as evidenced by the reduced cell growth as well as S phase in p66(Shc)-knocked down cells. The p66(Shc) signaling in cell growth regulation is apparently mediated by extracellular signal-regulated kinase/mitogen-activated protein kinase (ERK/MAPK). Thus, our results indicate a novel role for p66(Shc) in prostate carcinogenesis, in part, promoting cell proliferation.

Expression of p66(Shc) protein correlates with proliferation of human prostate cancer cells.

&#x5C3D;&#x7BA1;&#x5171;&#x805A;&#x7269;-1 &#xFF08;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1&#xFF09; &#x4E3A;&#x8FD1; 40 &#x5E74;&#x7684;&#x79EF;&#x6781;&#x8C03;&#x67E5;&#x57FA;&#x7840;&#x53CA;&#x5176;&#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x5C5E;&#x6027;&#x7684;&#x673A;&#x5236;&#x4ECD;&#x7136;&#x6709;&#x4E89;&#x8BAE;&#x3002;&#x7136;&#x800C;&#xFF0C;&#x5F53;&#x524D;&#x7684;&#x6559;&#x6761;&#xFF0C;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1 &#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x6D3B;&#x52A8;&#x5728;&#x81EA;&#x8EAB;&#x514D;&#x75AB;&#x6027;&#x795E;&#x7ECF;&#x9000;&#x884C;&#x6027;&#x75BE;&#x75C5;&#x5305;&#x62EC;&#x65C1;&#x89C2;&#x8005;&#x5236;&#x6B62;&#x7684;&#x81EA;&#x8EAB;&#x514D;&#x75AB; T &#x7EC6;&#x80DE;&#x548C;&#x5C0F;&#x80F6;&#x8D28;&#x7EC6;&#x80DE;&#x53CD;&#x5E94;&#x7684;&#x8870;&#x51CF;&#x3002;&#x5728;&#x672C;&#x62A5;&#x544A;&#x4E2D;&#xFF0C;&#x6211;&#x4EEC;&#x8BC1;&#x660E;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1 &#x76F4;&#x63A5;&#x4E0E;&#x4E3B;&#x8981;&#x7684;&#x4EBA;&#x7C7B;&#x795E;&#x7ECF;&#x5143;&#x8FDB;&#x884C;&#x4EA4;&#x4E92;&#xFF0C;&#x5E76;&#x51CF;&#x5C11; staurosporine &#x6216;&#x6C27;&#x5316;&#x5E94;&#x6FC0;&#x6240;&#x81F4;&#x7684;&#x795E;&#x7ECF;&#x7EC6;&#x80DE;&#x6B7B;&#x4EA1;&#x3002;&#x6B64;&#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x662F;&#x901A;&#x8FC7;&#x86CB;&#x767D;&#x6FC0;&#x9176; Calpha &#x548C;&#x8111;&#x6E90;&#x6027;&#x795E;&#x7ECF;&#x8425;&#x517B;&#x56E0;&#x5B50;&#x4ECB;&#x5BFC;&#x7684;&#x3002;&#x6811;&#x7A81;&#x72B6;&#x7EC6;&#x80DE; (DC) &#x5438;&#x6536;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE;-1&#xFF0C;&#x5C06;&#x5176;&#x4F20;&#x9012;&#x7ED9;&#x53D7;&#x4F24;&#x90E8;&#x4F4D;&#xFF0C;&#x7136;&#x540E;&#x91CA;&#x653E;&#x6D3B;&#x52A8;&#x7A97;&#x4F53;&#x4E2D;&#x3002;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1 &#x4E0E; DC &#x4E4B;&#x95F4;&#x7684;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x589E;&#x5F3A;&#x76F4;&#x6D41;&#x8840;&#x8111;&#x5C4F;&#x969C;&#x8FC1;&#x79FB;&#x3002;&#x5927;&#x9F20;&#x6A21;&#x578B;&#x4E0E;&#x89C6;&#x795E;&#x7ECF;&#x538B;&#x69A8;&#x635F;&#x4F24;&#xFF0C;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1 &#x5F85;&#x53D1;&#x76F4;&#x6D41;&#x8BF1;&#x4F7F; T &#x7EC6;&#x80DE;&#x72EC;&#x7ACB;&#x7684;&#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x3002;&#x8FD9;&#x4E9B;&#x7ED3;&#x679C;&#x53EF;&#x80FD;&#x6709;&#x52A9;&#x4E8E;&#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x65B9;&#x6CD5;&#x4F7F;&#x7528;&#x7684;&#x76F4;&#x6D41;&#x4ECB;&#x5BFC;&#x7684;&#x7F14;&#x7EA6;&#x65B9;&#x4F1A;&#x8BAE; 1 &#x4F20;&#x9012;&#x5230;&#x75C5;&#x53D8;&#x795E;&#x7ECF;&#x7EC4;&#x7EC7;&#x7684;&#x53D1;&#x5C55;&#x3002;

T &#x7EC6;&#x80DE;&#x72EC;&#x7ACB;&#x5171;&#x805A;&#x7269;-1 &#x8BF1;&#x5BFC;&#x7684;&#x795E;&#x7ECF;&#x4FDD;&#x62A4;&#x4F5C;&#x7528;&#x7684;&#x673A;&#x5236;&#x3002;

Despite active investigation of copolymer-1 (Cop-1) for nearly 40 years the mechanisms underlying its neuroprotective properties remain contentious. Nonetheless, current dogma for Cop-1 neuroprotective activities in autoimmune and neurodegenerative diseases include bystander suppression of autoimmune T cells and attenuation of microglial responses. In this report, we demonstrate that Cop-1 interacts directly with primary human neurons and decreases neuronal cell death induced by staurosporine or oxidative stress. This neuroprotection is mediated through protein kinase Calpha and brain-derived neurotrophic factor. Dendritic cells (DC) uptake Cop-1, deliver it to the injury site, and release it in an active form. Interactions between Cop-1 and DC enhance DC blood brain barrier migration. In a rat model with optic nerve crush injury, Cop-1-primed DC induce T cell independent neuroprotection. These findings may facilitate the development of neuroprotective approaches using DC-mediated Cop-1 delivery to diseased nervous tissue.

T cell independent mechanism for copolymer-1-induced neuroprotection.

Malgr&#xE9; une enqu&#xEA;te active de copolym&#xE8;re-1 (Cop-1) pour pr&#xE8;s de 40 ans, les m&#xE9;canismes sous-jacents de ses propri&#xE9;t&#xE9;s neuroprotectrices restent sujettes &#xE0; controverse. N&#xE9;anmoins, le dogme actuel de la CdP-1 dans les activit&#xE9;s neuroprotectrices maladies auto-immunes et neurod&#xE9;g&#xE9;n&#xE9;ratives incluent la suppression des cellules T bystander auto-immunes et de l&#x26;#39;att&#xE9;nuation des r&#xE9;ponses microgliales. Dans ce rapport, nous d&#xE9;montrons que la CdP-1 interagit directement avec les neurones humains primaires et diminue la mort des cellules neuronales induite par le stress oxydatif ou la staurosporine. Cette neuroprotection est m&#xE9;di&#xE9;e par la prot&#xE9;ine kinase Calpha et le facteur neurotrophique d&#xE9;riv&#xE9; du cerveau. Les cellules dendritiques (DC) Cop absorption-1, le remettre au site de la l&#xE9;sion, et le rel&#xE2;cher sous une forme active. Interactions entre la CdP-1 et DC am&#xE9;liorer le sang du cerveau DC migrations barri&#xE8;re. Dans un mod&#xE8;le de rat avec une l&#xE9;sion du nerf optique &#xE0; l&#x26;#39;&#xE9;crasement, Cop-1-appr&#xEA;t&#xE9; DC induire une neuroprotection des cellules T ind&#xE9;pendante. Ces r&#xE9;sultats peuvent faciliter le d&#xE9;veloppement d&#x26;#39;approches neuroprotectrices utilisant DC-m&#xE9;diation Cop-1 la livraison du tissu nerveux malade.

M&#xE9;canisme cellulaire T ind&#xE9;pendante pour le copolym&#xE8;re-1 induite par la neuroprotection

Trotz aktiven Untersuchung der Copolymer-1 (Cop-1) seit fast 40 Jahren sind die Mechanismen der neuroprotektiven Eigenschaften umstritten. Dennoch aktuelle Dogma f&uuml;r Cop-1 neuroprotektive Aktivit&auml;ten in Autoimmunerkrankungen und neurodegenerativen Erkrankungen geh&ouml;ren Zuschauer Unterdr&uuml;ckung der autoimmune T-Zellen und D&auml;mpfung von Microglial Antworten. In diesem Bericht zeigen wir, dass Cop-1 direkt mit prim&auml;ren menschlichen Neuronen interagiert und neuronalen Zelltod induziert durch Staurosporine oder oxidativen Stress verringert. Diese Neuroprotektion ist durch Proteinkinase Calpha und Brain-derived Neurotrophic Factor vermittelt. Dendritische Zellen (DC) Aufnahme Cop-1, an der Verletzung-Website &uuml;bermitteln, und lassen Sie es in eine aktive Form. Interaktionen zwischen Cop-1 und DC zu DC Blut-Hirn-Schranke-Migration erh&ouml;hen. In einem Rattenmodell mit Sehnerv crush Verletzungen, Cop-1-grundiert DC induzieren T-Zell-unabh&auml;ngigen Nervenschutz. Diese Erkenntnisse k&ouml;nnen den neuroprotektive Ans&auml;tze mit DC-vermittelte Cop-1 Lieferung an Kranke Gewebe des Zentralnervensystems erleichtern.

T-Zelle unabh&auml;ngigen Mechanismus f&uuml;r Neuroprotektion Copolymer-1 induziert.

Nonostante indagine attivo di copolimero-1 (Cop-1) per quasi 40 anni i meccanismi alla base di sua propriet&agrave; neuroprotettive rimangono controversi. Ci&ograve; nonostante, dogma corrente per attivit&agrave; neuroprotettiva Cop-1 in autoimmuni e malattie neurodegenerative includono astante soppressione delle cellule T autoimmuni e attenuazione delle risposte microgliali. In questa relazione, dimostreremo che Cop-1 interagisce direttamente con i neuroni umani primari e diminuisce la morte delle cellule neuronali indotta da staurosporine o stress ossidativo. Questo neuroprotezione mediata attraverso la chinasi di proteina Calpha e fattore neurotrophic cervello-derivato. Le cellule dendritiche (DC) assorbimento Cop-1, consegnarlo al sito di lesione e rilasciarlo in una forma attiva. Interazioni tra DC e Cop-1 migliorano la migrazione di barriera DC sangue cerebrale. In un modello di ratto con nervo ottico schiacciare lesioni, Cop-1-innescato DC indurre cellule T indipendente neuroprotezione. Questi risultati possono facilitare lo sviluppo di approcci neuroprotective usando DC-mediata Cop-1 consegna al tessuto nervoso malato.

Cellule t meccanismo indipendente per la neuroprotezione copolimero-1-indotta.

&#x307B;&#x307C;40&#x5E74;&#x9593;&#x5171;&#x91CD;&#x5408;&#x4F53;A-1&#xFF08;COP-1&#xFF09;&#x306E;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D6;&#x306A;&#x8ABF;&#x67FB;&#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x3001;&#x795E;&#x7D4C;&#x4FDD;&#x8B77;&#x7279;&#x6027;&#x3092;&#x57FA;&#x790E;&#x3068;&#x306A;&#x308B;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;&#x306F;&#x3001;&#x8AD6;&#x4E89;&#x306E;&#x307E;&#x307E;&#x3067;&#x3059;&#x3002;&#x305D;&#x308C;&#x306B;&#x3082;&#x304B;&#x304B;&#x308F;&#x3089;&#x305A;&#x3001;&#x81EA;&#x5DF1;&#x514D;&#x75AB;&#x75BE;&#x60A3;&#x304A;&#x3088;&#x3073;&#x795E;&#x7D4C;&#x5909;&#x6027;&#x75BE;&#x60A3;&#x3067;&#x306E;COP-1&#x306E;&#x795E;&#x7D4C;&#x6D3B;&#x52D5;&#x306E;&#x305F;&#x3081;&#x306E;&#x73FE;&#x5728;&#x306E;&#x6559;&#x7FA9;&#x306F;&#x3001;&#x30D0;&#x30A4;&#x30B9;&#x30BF;&#x30F3;&#x30C0;&#x30FC;&#x81EA;&#x5DF1;&#x514D;&#x75AB;T&#x7D30;&#x80DE;&#x306E;&#x6291;&#x5236;&#x3068;&#x30DF;&#x30AF;&#x30ED;&#x30B0;&#x30EA;&#x30A2;&#x5FDC;&#x7B54;&#x306E;&#x6E1B;&#x8870;&#x91CF;&#x304C;&#x542B;&#x307E;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x672C;&#x7A3F;&#x3067;&#x306F;&#x3001;COP-1&#x306F;&#x521D;&#x4EE3;&#x30D2;&#x30C8;&#x795E;&#x7D4C;&#x7D30;&#x80DE;&#x306B;&#x76F4;&#x63A5;&#x4F5C;&#x7528;&#x3057;&#x3001;&#x30B9;&#x30BF;&#x30A6;&#x30ED;&#x30B9;&#x30DD;&#x30EA;&#x30F3;&#x3084;&#x9178;&#x5316;&#x30B9;&#x30C8;&#x30EC;&#x30B9;&#x306B;&#x3088;&#x3063;&#x3066;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x308B;&#x795E;&#x7D4C;&#x7D30;&#x80DE;&#x6B7B;&#x3092;&#x6E1B;&#x5C11;&#x3055;&#x305B;&#x308B;&#x3053;&#x3068;&#x3092;&#x793A;&#x3057;&#x3066;&#x3044;&#x308B;&#x3002;&#x3053;&#x306E;&#x795E;&#x7D4C;&#x306F;&#x3001;&#x30BF;&#x30F3;&#x30D1;&#x30AF;&#x8CEA;&#x30AD;&#x30CA;&#x30FC;&#x30BC;Calpha&#x3068;&#x8133;&#x7531;&#x6765;&#x795E;&#x7D4C;&#x6804;&#x990A;&#x56E0;&#x5B50;&#x306B;&#x3088;&#x3063;&#x3066;&#x5A92;&#x4ECB;&#x3055;&#x308C;&#x308B;&#x3002;&#x6A39;&#x72B6;&#x7D30;&#x80DE;&#xFF08;DC&#xFF09;&#x306E;&#x53D6;&#x308A;&#x8FBC;&#x307F;COP-1&#x306F;&#x3001;&#x640D;&#x50B7;&#x90E8;&#x4F4D;&#x306B;&#x305D;&#x308C;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x3001;&#x30A2;&#x30AF;&#x30C6;&#x30A3;&#x30D6;&#x306A;&#x30D5;&#x30A9;&#x30FC;&#x30E0;&#x3067;&#x305D;&#x308C;&#x3092;&#x89E3;&#x653E;&#x3057;&#x307E;&#x3059;&#x3002; COP-1&#x3068;DC&#x306E;&#x9593;&#x306E;&#x76F8;&#x4E92;&#x4F5C;&#x7528;&#x306F;&#x3001;DC&#x8840;&#x6DB2;&#x8133;&#x95A2;&#x9580;&#x306E;&#x79FB;&#x884C;&#x3092;&#x5F37;&#x5316;&#x3057;&#x307E;&#x3059;&#x3002;&#x8996;&#x795E;&#x7D4C;&#x632B;&#x6EC5;&#x640D;&#x50B7;&#x30E9;&#x30C3;&#x30C8;&#x30E2;&#x30C7;&#x30EB;&#x3067;&#x306F;&#x3001;COP-1-&#x30D7;&#x30E9;&#x30A4;&#x30DF;&#x30F3;&#x30B0;DC&#x306F;T&#x7D30;&#x80DE;&#x306E;&#x72EC;&#x7ACB;&#x3057;&#x305F;&#x795E;&#x7D4C;&#x4FDD;&#x8B77;&#x3092;&#x8A98;&#x5C0E;&#x3059;&#x308B;&#x3002;&#x3053;&#x308C;&#x3089;&#x306E;&#x77E5;&#x898B;&#x306F;&#x3001;&#x75C5;&#x6C17;&#x306E;&#x795E;&#x7D4C;&#x7D44;&#x7E54;&#x3078;&#x306E;DC-&#x5A92;&#x4ECB;COP-1&#x914D;&#x4FE1;&#x3092;&#x4F7F;&#x7528;&#x3059;&#x308B;&#x795E;&#x7D4C;&#x4FDD;&#x8B77;&#x30A2;&#x30D7;&#x30ED;&#x30FC;&#x30C1;&#x306E;&#x958B;&#x767A;&#x3092;&#x5BB9;&#x6613;&#x306B;&#x3059;&#x308B;&#x3053;&#x3068;&#x304C;&#x3067;&#x304D;&#x308B;&#x3002;

&#x5171;&#x91CD;&#x5408;&#x4F53;A-1&#x306B;&#x3088;&#x3063;&#x3066;&#x8A98;&#x5C0E;&#x3055;&#x308C;&#x308B;&#x795E;&#x7D4C;&#x4FDD;&#x8B77;&#x306E;&#x305F;&#x3081;&#x306B;T&#x7D30;&#x80DE;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x306A;&#x3044;&#x30E1;&#x30AB;&#x30CB;&#x30BA;&#x30E0;

&#xAC70;&#xC758; 40 &#xB144; &#xB3D9;&#xC548; &#xCF54; &#xD3F4;&#xB9AC;&#xBA38;-1 (&#xC2E0; &#xAC00;&#xC694;-1)&#xC758; &#xC801;&#xADF9;&#xC801;&#xC778; &#xC218;&#xC0AC;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0; &#xC2E0;&#xACBD; &#xBCF4;&#xD638; &#xC18D;&#xC131;&#xC744; &#xAE30;&#xBCF8; &#xBA54;&#xCEE4;&#xB2C8;&#xC998; &#xB17C;&#xC7C1;&#xC774; &#xB0A8;&#xC544; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;. &#xADF8;&#xB7FC;&#xC5D0;&#xB3C4; &#xBD88;&#xAD6C; &#xD558; &#xACE0;, &#xD604;&#xC7AC; &#xC815;&#xC124;&#xC5D0; &#xBA74;&#xC5ED; &#xACBD;&#xCC30; 1 &#xC2E0;&#xACBD; &#xBCF4;&#xD638; &#xD65C;&#xB3D9;&#xC5D0; &#xB300; &#xD55C; &#xC2E0;&#xACBD; &#xD1F4;&#xD589; &#xC131; &#xC9C8;&#xD658; &#xBA74;&#xC5ED; T &#xC138;&#xD3EC;&#xC758; &#xBC29;&#xAD00;&#xC790; &#xC5B5;&#xC81C; &#xB4F1;&#xC774; microglial &#xC751;&#xB2F5; &#xAC10;&#xC1E0; &#xBC0F;. &#xC774; &#xBCF4;&#xACE0;&#xC11C;&#xC5D0;&#xC11C; &#xACBD;&#xCC30; 1 &#xC8FC; &#xC778;&#xAC04;&#xC758; &#xC2E0;&#xACBD; &#xC138;&#xD3EC;&#xC640; &#xC9C1;&#xC811; &#xC0C1;&#xD638; &#xC791;&#xC6A9; &#xD558; &#xACE0; staurosporine &#xB610;&#xB294; &#xC0B0;&#xD654; &#xC2A4;&#xD2B8;&#xB808;&#xC2A4;&#xC5D0; &#xC758;&#xD574; &#xC720;&#xBC1C; &#xB41C; &#xC2E0;&#xACBD; &#xC138;&#xD3EC; &#xC8FD;&#xC74C; &#xAC10;&#xC18C; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. &#xC774; neuroprotection &#xB2E8;&#xBC31;&#xC9C8; &#xD0A4; &#xB2C8; &#xC544; &#xC81C; Calpha &#xBC0F; &#xB450;&#xB1CC; &#xD30C;&#xC0DD; &#xD55C; neurotrophic &#xC694;&#xC778;&#xC744; &#xD1B5;&#xD574; &#xC911;&#xC7AC; &#xB429;&#xB2C8;&#xB2E4;. &#xC218;&#xC9C0;&#xC0C1; &#xC138;&#xD3EC; (DC) &#xAE00;&#xADC0; &#xACBD;&#xCC30; 1 &#xBD80;&#xC0C1; &#xC0AC;&#xC774;&#xD2B8;&#xC5D0; &#xC81C;&#xACF5; &#xD558; &#xACE0; &#xD65C;&#xC131; &#xD3FC;&#xC5D0; &#xB193;&#xC2B5;&#xB2C8;&#xB2E4;. &#xACBD;&#xCC30; 1&#xC640; DC &#xAC04;&#xC758; &#xC0C1;&#xD638; &#xC791;&#xC6A9;&#xC774; &#xD5A5;&#xC0C1; DC &#xD608;&#xC561; &#xB1CC; &#xC7A5;&#xBCBD; &#xB9C8;&#xC774;&#xADF8;&#xB808;&#xC774;&#xC158;. &#xC2DC; &#xC2E0;&#xACBD;&#xC73C;&#xB85C; &#xC950; &#xBAA8;&#xB378;&#xC5D0; &#xD638;&#xAC10;&#xC744; &#xBD80;&#xC0C1;, &#xACBD;&#xCC30; 1 &#xC561; DC T&#xB294; &#xC138;&#xD3EC; &#xB3C5;&#xB9BD; neuroprotection &#xC720;&#xB3C4;. &#xC774;&#xB7EC;&#xD55C; &#xC5F0;&#xAD6C; &#xACB0;&#xACFC; &#xBCD1;&#xC5D0; &#xAC78;&#xB9B0; &#xC2E0;&#xACBD; &#xC870;&#xC9C1;&#xC5D0; &#xACBD;&#xCC30; 1 DC &#xC911;&#xC7AC; &#xBC30;&#xB2EC;&#xC744; &#xC0AC;&#xC6A9; &#xD558; &#xC5EC; &#xC2E0;&#xACBD; &#xBCF4;&#xD638; &#xBC29;&#xC2DD;&#xC758; &#xAC1C;&#xBC1C;&#xC744; &#xCD09;&#xC9C4; &#xC218; &#xC788;&#xC2B5;&#xB2C8;&#xB2E4;.

&#xCF54; &#xD3F4;&#xB9AC;&#xBA38; 1 &#xC720;&#xB3C4; neuroprotection t&#xB294; &#xC138;&#xD3EC; &#xB3C5;&#xB9BD; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC785;&#xB2C8;&#xB2E4;.

A pesar de la investigaci&#xF3;n activa de copol&#xED;mero-1 (COP-1) durante casi 40 a&#xF1;os los mecanismos que subyacen a sus propiedades neuroprotectoras siguen siendo pol&#xE9;micas. Sin embargo, el dogma actual de Cop-1 actividades neuroprotectores en las enfermedades autoinmunes y neurodegenerativas incluyen la supresi&#xF3;n de observador de las c&#xE9;lulas T autoinmunes y la atenuaci&#xF3;n de las respuestas de la microglia. En este informe, demuestran que la CdP-1 interact&#xFA;a directamente con las neuronas humanas primarias y disminuye la muerte neuronal inducida por el estr&#xE9;s oxidativo o estaurosporina. Esta neuroprotecci&#xF3;n es mediado a trav&#xE9;s de la prote&#xED;na quinasa Calpha y el cerebro del factor neurotr&#xF3;fico derivado. Las c&#xE9;lulas dendr&#xED;ticas (DC) la absorci&#xF3;n de 1 CP, que entregar&#xE1; al sitio de la lesi&#xF3;n, y lo liberan en forma activa. Las interacciones entre la CdP-1 y DC DC mejorar la sangre del cerebro la migraci&#xF3;n barrera. En un modelo de rata con lesi&#xF3;n de aplastamiento del nervio &#xF3;ptico, el poli-1-DC preparado inducen neuroprotecci&#xF3;n de las c&#xE9;lulas T independientes. Estos hallazgos podr&#xED;an facilitar el desarrollo de enfoques neuroprotectores con DC-CP-1 mediada por la entrega al tejido nervioso enfermo.

T Mecanismo Independiente de la c&#xE9;lula para el copol&#xED;mero-1-neuroprotecci&#xF3;n inducida

Sickle cell disease can present with neurological manifestations. One such presentation is with posterior reversible leukoencephalopathy also known as reversible posterior leukoencephalopathy. The condition is classically described as reversible over time; it commonly presents with oedematous changes involving the white matter of the occipital and parietal regions. Only a few patients with the association between sickle cell disease and posterior reversible leukoencephalopathy have been described in the adult literature. We present two patients from our institutions to emphasise the association between the two conditions and summarise the published cases in the literature.

Sickle cell disease and posterior reversible leukoencephalopathy.

An 18-year-old woman with hepatic cysts.

In diabetic nephropathy (DN), podocyte cytoskeletal rearrangement occurs followed by podocyte effacement and the development of proteinuria. PTEN (phosphatase and tensin homologue) is a ubiquitously expressed phosphatase that plays a critical role in cell proliferation, cytoskeletal rearrangement, and motility. In mouse models of diabetes mellitus, PTEN expression is reportedly decreased in mesangial cells, contributing to expansion of the mesangial matrix, but how PTEN in the podocyte influences the development of DN is unknown. We observed that PTEN expression is down-regulated in the podocytes of diabetic db/db mice and patients with DN. In cultured podocytes, PTEN inhibition caused actin cytoskeletal rearrangement and this response was associated with unbalanced activation of the small GTPases Rac1/Cdc42 and RhoA. In mice treated with PTEN inhibitor, actin cytoskeletal rearrangement occurred in podocytes and was accompanied by increased albumin excretion. We also created mice with an inducible deletion of PTEN selectively in podocytes. These mice exhibited increased albumin excretion and moderate foot process effacement. When the mice were challenged with a high fat diet, podocyte-specific knockout of PTEN resulted in substantially increased proteinuria and glomeruloclerosis compared to control mice fed a high fat diet or mice with PTEN deletion fed a normal diet. These results indicate that PTEN is involved in the regulation of cytoskeletal rearrangement in podocytes and that loss of PTEN predisposes to the development of proteinuria and DN.

Loss of PTEN promotes podocyte cytoskeletal rearrangement, aggravating diabetic nephropathy.

Can we predict future depression in residents before the start of clinical training?

Addressing Depression and Suicide Among Physician Trainees.

Diabetes is increasing in prevalence and is the leading cause of end-stage renal disease in the United States. Diabetic kidney disease is considered a proteinuric glomerular disease. Although the glomerulus is composed of various cell types, research suggests that podocytes are critical to overall glomerular health. Podocyte injury has been identified as a pivotal event resulting in proteinuric kidney disease, glomerulosclerosis, and loss of renal function. Thus, understanding the signaling mechanisms that trigger podocyte injury in diabetic kidney disease might allow for the development of targeted therapeutics to prevent or ameliorate progression to end-stage renal failure. This review focuses on the role of podocytes in diabetic kidney disease.

Podocytes: the Weakest Link in Diabetic Kidney Disease?

Integration of blood vessels and organ primordia determines organ shape and function. The head kidney in the zebrafish interacts with the dorsal aorta (DA) and the posterior cardinal vein (PCV) to achieve glomerular filtration and definitive hematopoiesis, respectively. How the head kidney co-develops with both the axial artery and vein remains unclear. We found that in endodermless sox32-deficient embryos, the head kidney associated with the PCV but not the DA. Disrupted convergent migration of the PCV and the head kidney in sox32-deficient embryos was rescued in a highly coordinated fashion through the restoration of endodermal cells. Moreover, grafted endodermal cells abutted the host PCV endothelium in the transplantation assay. Interestingly, the severely-disrupted head kidney convergence in the sox32-deficient embryo was suppressed by both the cloche mutation and the knockdown of endothelial genes, indicating that an interaction between the endoderm and the PCV restricts the migration of the head kidney. Furthermore, knockdown of either vegfC or its receptor vegfr3 suppressed the head kidney convergence defect in endodermless embryos and perturbed the head kidney-PCV association in wild-type embryos. Our findings thus underscore a role for PCV and VegfC in patterning the head kidney prior to organ assembly and function.

Jamie Lin

Department of Life Science

Tunghai University

Visualizing the Interrenal Steroidogenic Tissue and Its Vascular Microenvironment in Zebrafish