an-vitro-model-to-study-effect-5-aminolevulinic-acid-mediated

An <em>In Vitro</em> Model to Study the Effect of 5-Aminolevulinic Acid-mediated Photodynamic Therapy on <em>Staphylococcus aureus</em> Biofilm

Staphylococcus aureus (S. aureus) is a common human pathogen, which causes pyogenic and systemic infections. S. aureus infections are difficult to ...

endoscopic-septoplasty-with-limited-two-line-resection-minimally

Endoscopic Septoplasty with Limited Two-line Resection: Minimally Invasive Surgery for Septal Deviation

Endoscopic septoplasty is a surgical procedure in otolaryngology that is commonly performed to treat nasal airway obstruction caused by nasal septal ...

combined-endoscopic-and-transoral-approach-for-total-maxillectomy

Combined Endoscopic and Transoral Approach for Total Maxillectomy

The technique of maxillectomy has been revised since it was first described in the 1820s. During the past decade, the endoscopic approach has been widely ...

Fudan University

Cigarette smokers and those exposed to second hand smoke are more susceptible to life threatening infection than non-smokers. While much is known about the devastating effect tobacco exposure has on the human body, less is known about the effect of tobacco smoke on the commensal and commonly found pathogenic bacteria of the human respiratory tract, or human respiratory tract microbiome. Chronic rhinosinusitis (CRS) is a common medical complaint, affecting 16% of the US population with an estimated aggregated cost of $6 billion annually. Epidemiologic studies demonstrate a correlation between tobacco smoke exposure and rhinosinusitis. Although a common cause of CRS has not been defined, bacterial presence within the nasal and paranasal sinuses is assumed to be contributory. Here we demonstrate that repetitive tobacco smoke exposure induces biofilm formation in a diverse set of bacteria isolated from the sinonasal cavities of patients with CRS. Additionally, bacteria isolated from patients with tobacco smoke exposure demonstrate robust in vitro biofilm formation when challenged with tobacco smoke compared to those isolated from smoke naïve patients. Lastly, bacteria from smoke exposed patients can revert to a non-biofilm phenotype when grown in the absence of tobacco smoke. These observations support the hypothesis that tobacco exposure induces sinonasal biofilm formation, thereby contributing to the conversion of a transient and medically treatable infection to a persistent and therapeutically recalcitrant condition.

Tobacco smoke mediated induction of sinonasal microbial biofilms.

Sinonasal mucosal biofilms are recognized as contributors to the pathogenesis of chronic rhinosinusitis (CRS). Attachment of bacteria to the sinonasal surface is an initial step in biofilm formation. A critical defense against this occurrence is mucociliary clearance (MCC). To ascertain whether the ciliary component of MCC is uniform throughout the airway we compared ciliary beat frequency (CBF) in the murine nasal septum and trachea at baseline and after challenge with Pseudomonas aeruginosa, a common pathogen of CRS.

Inherent differences in nasal and tracheal ciliary function in response to Pseudomonas aeruginosa challenge.

&#x7EA4;&#x6BDB;&#x6E05;&#x9664;&#x529F;&#x80FD;&#x662F;&#x9488;&#x5BF9;&#x5438;&#x5165;&#x7684;&#x75C5;&#x539F;&#x4F53;&#x548C;&#x6BD2;&#x7D20;&#x4E3B;&#x5148;&#x5929;&#x7269;&#x7406;&#x9632;&#x5FA1;&#x673A;&#x5236;&#x3002;&#x77E2;&#x91CF;&#x79BB;&#x5B50;&#x4F20;&#x8F93;&#xFF0C;&#x4E3B;&#x8981;&#x662F;&#x94A0;&#x5438;&#x6536;&#x548C;&#x9634;&#x79BB;&#x5B50;&#x5206;&#x6CCC;&#xFF0C;&#x7531;&#x547C;&#x5438;&#x9053;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x652F;&#x6301;&#x7EA4;&#x6BDB;&#x6E05;&#x9664;&#x529F;&#x80FD;&#x3002;&#x8FD9;&#x88AB;&#x660E;&#x8BC1;&#x7684;&#x56CA;&#x6027;&#x7EA4;&#x7EF4;&#x5316;&#x548C; pseudohypoaldosteronism &#x7B49;&#x5F02;&#x5E38;&#x79BB;&#x5B50;&#x8FD0;&#x8F93;&#x7EA4;&#x6BDB;&#x6E05;&#x9664;&#x529F;&#x80FD;&#x7684;&#x53D8;&#x5316;&#x4E3A;&#x7279;&#x5F81;&#x7684;&#x75BE;&#x75C5;&#x3002;&#x94A0;&#x5438;&#x6536;&#x548C;&#x652F;&#x6C14;&#x7BA1;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x4E2D;&#x7684;&#x6C2F;&#x79BB;&#x5B50;&#x5206;&#x6CCC;&#x53D6;&#x51B3;&#x4E8E;&#x94BE;&#x901A;&#x9053;&#x6D3B;&#x52A8;&#xFF0C;&#x90FD;&#x7531;&#x6839;&#x5C16;&#x7EC6;&#x80DE;&#x819C;&#x8D85;&#x6781;&#x5316;&#x521B;&#x5EFA;&#x826F;&#x597D;&#x7684;&#x7535;&#x5316;&#x5B66;&#x68AF;&#x5EA6;&#x3002;&#x867D;&#x7136;&#x57FA;&#x5E95;&#x5916;&#x4FA7;&#x819C;&#x94BE;&#x901A;&#x9053;&#x7684;&#x4F5C;&#x7528;&#x662F;&#x7262;&#x56FA;&#x786E;&#x7ACB;&#x548C;&#x5E7F;&#x6CDB;&#x7814;&#x7A76;&#xFF0C;&#x4E5F;&#x88AB;&#x63CF;&#x8FF0;&#x4E3A;&#x6839;&#x5C16;&#x7EC6;&#x80DE;&#x819C;&#x94BE;&#x79BB;&#x5B50;&#x901A;&#x9053;&#x7684;&#x4F5C;&#x7528;&#x3002;&#x5728;&#x8FD9;&#x91CC;&#xFF0C;&#x6211;&#x4EEC;&#x53EF;&#x4EE5;&#x5C55;&#x793A;&#x5E03;&#x6BD4;&#x5361;&#x56E0;&#x548C;&#x594E;&#x5C3C;&#x4E01;&#xFF0C;&#x56DB;&#x4E2A;&#x8DE8;&#x819C;&#x57DF;&#xFF0C;&#x4E24;&#x5B54;&#x94BE; (K2P) &#x901A;&#x9053;&#xFF0C;&#x53D7;&#x4F53;&#x963B;&#x6EDE;&#x5242;&#x6291;&#x5236;&#x963F;&#x7C73;&#x6D1B;&#x5229;&#x654F;&#x611F;&#x94A0;&#x5438;&#x6536;&#x548C;&#x773C;&#x538B;&#x5347;&#x9AD8;-&#x9634;&#x79BB;&#x5B50;&#x5206;&#x6CCC;&#x7684;&#x6781;&#x5316;&#x3001; &#x6B63;&#x5E38;&#x652F;&#x6C14;&#x7BA1;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x5728;&#x4F4E;&#x6D53;&#x5EA6;&#x65F6;&#x5E94;&#x7528;&#x4E8E;&#x6BD4;&#x65F6;&#x5E94;&#x7528;&#x4E8E;&#x6D46;&#x819C;&#x8868;&#x9762;&#x9ECF;&#x819C;&#x8868;&#x9762;&#x3002;&#x4ECE;&#x56DB;&#x4E2A;&#x57FA;&#x56E0;&#xFF0C;KCNK1 &#x7684;&#x6210;&#x7EE9;&#x5355; (TWIK-1&#xFF09;&#xFF0C;KCNK2 &#xFF08;&#x661F;&#x9645;&#x65C5;&#x884C; &#x300B;-1&#xFF09;&#xFF0C;KCNK5 &#xFF08;&#x4EFB;&#x52A1;-2) &#x548C; KCNK6 (TWIK-2&#xFF09; &#x7F16;&#x7801;&#x7684; K2P &#x6E20;&#x9053;&#x53D1;&#x73B0;&#x9006;&#x8F6C;&#x5F55;-&#x805A;&#x5408;&#x9176;&#x94FE;&#x53CD;&#x5E94;&#x3002;&#x5728;&#x9876;&#x7AEF;&#x7684;&#x819C;&#x86CB;&#x767D;&#x8868;&#x8FBE;&#x514D;&#x75AB;&#x8367;&#x5149;&#x6240;&#x8BC1;&#x5B9E;&#x3002;&#x6211;&#x4EEC;&#x7684;&#x6570;&#x636E;&#x63D0;&#x4F9B;&#x8FDB;&#x4E00;&#x6B65;&#x7684;&#x8BC1;&#x636E;&#xFF0C;&#x94BE;&#x901A;&#x9053;&#xFF0C;&#x5728;&#x7279;&#x5B9A;&#x7684; K2P &#x6E20;&#x9053;&#xFF0C;&#x8868;&#x8FBE;&#x548C;&#x529F;&#x80FD;&#x4E2D;&#x7684;&#x9876;&#x819C;&#x7684;&#x6C14;&#x9053;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x53EF;&#x80FD;&#x5730;&#x65B9;&#x6CBB;&#x7597;&#x64CD;&#x4F5C;&#x7684;&#x76EE;&#x6807;&#x3002;

&#x4E24;&#x5B54; K&#x207A; &#x901A;&#x9053;&#x8C03;&#x5236; Na&#x207A; &#x5438;&#x6536;&#x548C; Cl&#x207B; &#x5728;&#x6B63;&#x5E38;&#x4EBA;&#x7684;&#x652F;&#x6C14;&#x7BA1;&#x4E0A;&#x76AE;&#x7EC6;&#x80DE;&#x5206;&#x6CCC;&#x7684;&#x4F5C;&#x7528;&#x3002;

Mucociliary clearance is the primary innate physical defense mechanism against inhaled pathogens and toxins. Vectorial ion transport, primarily sodium absorption and anion secretion, by airway epithelial cells supports mucociliary clearance. This is evidenced by diseases of abnormal ion transport such as cystic fibrosis and pseudohypoaldosteronism that are characterized by changes in mucociliary clearance. Sodium absorption and chloride secretion in human bronchial epithelial cells depend on potassium channel activity, which creates a favorable electrochemical gradient for both by hyperpolarizing the apical plasma membrane. Although the role of basolateral membrane potassium channels is firmly established and extensively studied, a role for apical membrane potassium channels has also been described. Here, we demonstrate that bupivacaine and quinidine, blockers of four-transmembrane domain, two-pore potassium (K2P) channels, inhibit both amiloride-sensitive sodium absorption and forskolin-stimulated anion secretion in polarized, normal human bronchial epithelial cells at lower concentrations when applied to the mucosal surface than when applied to the serosal surface. Transcripts from four genes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2), and KCNK6 (TWIK-2), encoding K2P channels were identified by RT-PCR. Protein expression at the apical membrane was confirmed by immunofluorescence. Our data provide further evidence that potassium channels, in particular K2P channels, are expressed and functional in the apical membrane of airway epithelial cells where they may be targets for therapeutic manipulation.

A role for two-pore Kâº channels in modulating Naâº absorption and Clâ» secretion in normal human bronchial epithelial cells.

Clairance mucociliaire est le principal m&eacute;canisme de d&eacute;fense physique inn&eacute; contre l&#39;inhalation de pathog&egrave;nes et de toxines. Transport des ions vectorielle, principalement l&#39;absorption de sodium et la s&eacute;cr&eacute;tion de l&#39;anion, par les cellules &eacute;pith&eacute;liales des voies respiratoires prend en charge la clairance mucociliaire. Ceci est d&eacute;montr&eacute; par les maladies du transport des ions anormales telles que la fibrose kystique et Pseudohypoaldost&eacute;ronisme qui sont caract&eacute;ris&eacute;es par des changements dans la clairance mucociliaire. Absorption de sodium et de la s&eacute;cr&eacute;tion de chlore dans les cellules &eacute;pith&eacute;liales bronchiques humaines reposent sur l&#39;activit&eacute; des canaux potassium, qui cr&eacute;e un gradient &eacute;lectrochimique favorable pour les deux par hyperpolarisant la membrane plasmique apicale. Bien que le r&ocirc;le des canaux de potassium membrane basolat&eacute;rale est fermement &eacute;tablie et &eacute;tudi&eacute;s, un r&ocirc;le pour les canaux de potassium de la membrane apicale a &eacute;galement &eacute;t&eacute; d&eacute;crite. Ici, nous d&eacute;montrons que la bupivaca&iuml;ne et la quinidine, inhibiteurs calciques du domaine quatre domaines transmembranaire, canaux potassiques deux pores (K2P), inhibent l&#39;absorption de sodium sensibles &agrave; l&#39;amiloride et la s&eacute;cr&eacute;tion stimul&eacute;e par la forskoline anion polaris&eacute;e, normal cellules &eacute;pith&eacute;liales bronchiques humaines &agrave; des concentrations plus faibles lorsqu&#39;il est appliqu&eacute; &agrave; la surface des muqueuses que lorsque appliqu&eacute; &agrave; la surface s&eacute;reuse. Relev&eacute;s de notes des quatre g&egrave;nes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2) et KCNK6 (TWIK-2), encodage K2P canaux ont &eacute;t&eacute; identifi&eacute;s par RT-PCR. Expression de la prot&eacute;ine dans la membrane apicale a &eacute;t&eacute; confirm&eacute;e par immunofluorescence. Nos r&eacute;sultats fournissent une preuve suppl&eacute;mentaire que les canaux potassiques, dans certains canaux K2P, sont exprim&eacute;es et fonctionnelles dans la membrane apicale des voies a&eacute;riennes de cellules &eacute;pith&eacute;liales o&ugrave; ils pourraient &ecirc;tre des cibles pour des manipulations th&eacute;rapeutiques.

Un r&ocirc;le pour les canaux K&#x207A; deux pores dans la modulation Na&#x207A; d&#39;absorption et de s&eacute;cr&eacute;tion Cl&#x207B; dans les cellules &eacute;pith&eacute;liales bronchiques humaines normales.

Mukozili&auml;re Clearance ist die prim&auml;re angeborene k&ouml;rperliche Verteidigungsmechanismus gegen eingeatmete Krankheitserreger und Giftstoffe. Vektorielles Ionentransport, vor allem Natrium-Resorption und Anion Sekretion von Epithelzellen der Atemwege unterst&uuml;tzt mukozili&auml;re Clearance. Dies wird durch Erkrankungen des anormalen Ionentransport wie Mukoviszidose und Pseudohypoaldosteronismus belegt, die durch Ver&auml;nderungen in der mukozili&auml;ren Clearance gekennzeichnet sind. Resorption von Natrium und Chlorid-Sekretion in menschlichen bronchialen Epithelzellen h&auml;ngen von Kalium-Kanal-Aktivit&auml;t, die einen g&uuml;nstigen elektrochemische Gradienten f&uuml;r beide durch die apikale Plasmamembran hyperpolarizing erstellt. Obwohl die Rolle der Basolateraler Membran Kaliumkan&auml;le fest verankerte und ausgiebig studiert, wurde eine Rolle f&uuml;r die apikale Membran Kaliumkan&auml;len auch beschrieben. Hier zeigen wir, dass Bupivacain und Chinidin, Blocker vier Transmembran-Dom&auml;ne, zwei-Pore Kaliumkan&auml;le (K2P), Amilorids-Sensitive Natrium-Resorption und Anion Forskolin stimuliert Sekretion polarisierte, normalen menschlichen bronchialen Epithelzellen in niedrigeren Konzentrationen angewendet auf die Schleimhaut-Oberfl&auml;che als wenn angewendet zur serosal Oberfl&auml;che hemmen. Abschriften aus vier Gene, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2), und KCNK6 (TWIK-2), Codierung K2P Kan&auml;le durch RT-PCR erkannt wurden. Immunofluoreszenz Proteinausdruck an die apikale Membran best&auml;tigte. Unsere Daten liefern weiteren Beweise daf&uuml;r, dass Kaliumkan&auml;le, in bestimmten K2P-Kan&auml;len, ausgedr&uuml;ckt werden und funktional in der apikalen Membran von Airway epitheliale Zellen wo sie Ziele f&uuml;r therapeutische Manipulation sein k&ouml;nnen.

Eine Rolle f&uuml;r zwei-Pore K&#x207A; Kan&auml;le in modulierenden Na&#x207A; Absorptions- und Cl&#x207B; Sekretion in normalen menschlichen bronchialen Epithelzellen.

Clearance mucociliare &egrave; meccanismo di difesa del fisico innato primario contro inalati patogeni e tossine. Trasporto ionico vettoriale, principalmente assorbimento di sodio e la secrezione di anioni, dalle cellule epiteliali delle vie aeree supporta la clearance mucociliare. Ci&ograve; &egrave; evidenziato dalle malattie del trasporto di ioni anomali come la fibrosi cistica e Pseudoipoaldosteronismo che sono caratterizzate da cambiamenti nella clearance mucociliare. Assorbimento di sodio e la secrezione di cloruro in cellule epiteliali bronchiali umane dipendono dalla attivit&agrave; del canale del potassio, che crea un gradiente elettrochimico favorevole per entrambi da hyperpolarizing la membrana plasmatica apicale. Anche se il ruolo dei canali di potassio membrana basolaterale &egrave; fermamente stabilito e ampiamente studiato, un ruolo per i canali del potassio membrana apicale &egrave; stata anche descritta. Qui, ci dimostrano che la bupivacaina e chinidina, bloccanti del dominio transmembrana quattro canali potassio poro due (K2P), inibiscono sia sodio amiloride-sensibile assorbimento e secrezione stimolata la forskolina anione in polarizzata, normale bronchiale cellule epiteliali umane a concentrazioni inferiori quando applicato alla superficie della mucosa rispetto a quando applicata sulla superficie sierosa. Trascrizioni da quattro geni, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2) e KCNK6 (TWIK-2), codifica K2P canali sono stati identificati mediante RT-PCR. Espressione della proteina alla membrana apicale &egrave; stato confermato dall&#39;immunofluorescenza. I nostri dati forniscono un&#39;ulteriore prova che sono espressi in particolare K2P canali, canali di potassio e cellule epiteliali funzionale nella membrana apicale delle vie aeree dove possono essere gli obiettivi per la manipolazione terapeutica.

Un ruolo per i canali K&#x207A; due-poro nel modulare Na&#x207A; assorbimento e secrezione Cl&#x207B; in cellule epiteliali bronchiali umane normali.

&#x7C98;&#x6DB2;&#x7DDA;&#x6BDB;&#x30AF;&#x30EA;&#x30A2;&#x30E9;&#x30F3;&#x30B9;&#x5438;&#x5165;&#x75C5;&#x539F;&#x4F53;&#x3084;&#x6BD2;&#x7D20;&#x306B;&#x5BFE;&#x3059;&#x308B;&#x4E00;&#x6B21;&#x751F;&#x6765;&#x7269;&#x7406;&#x9632;&#x5FA1;&#x6A5F;&#x69CB;&#x3067;&#x3059;&#x3002;&#x30D9;&#x30AF;&#x30C8;&#x30EB;&#x306E;&#x30A4;&#x30AA;&#x30F3;&#x8F38;&#x9001;&#x3001;&#x4E3B;&#x306B;&#x30CA;&#x30C8;&#x30EA;&#x30A6;&#x30E0;&#x306E;&#x5438;&#x53CE;&#x3068;&#x306B;&#x3088;&#x308B;&#x6C17;&#x9053;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306E;&#x9670;&#x30A4;&#x30AA;&#x30F3;&#x5206;&#x6CCC;&#x7C98;&#x6DB2;&#x7DDA;&#x6BDB;&#x30AF;&#x30EA;&#x30A2;&#x30E9;&#x30F3;&#x30B9;&#x3092;&#x30B5;&#x30DD;&#x30FC;&#x30C8;&#x3057;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x308C;&#x306F;&#x3001;&#x7C98;&#x6DB2;&#x7DDA;&#x6BDB;&#x30AF;&#x30EA;&#x30A2;&#x30E9;&#x30F3;&#x30B9;&#x306E;&#x5909;&#x5316;&#x306B;&#x3088;&#x3063;&#x3066;&#x7279;&#x5FB4;&#x4ED8;&#x3051;&#x3089;&#x308C;&#x308B;&#x75BE;&#x60A3;&#x306E;&#x56A2;&#x80DE;&#x6027;&#x7DDA;&#x7DAD;&#x75C7;&#x3084; pseudohypoaldosteronism &#x306A;&#x3069;&#x306E;&#x7570;&#x5E38;&#x306A;&#x30A4;&#x30AA;&#x30F3;&#x8F38;&#x9001;&#x306B;&#x3088;&#x3063;&#x3066;&#x8A3C;&#x660E;&#x3055;&#x308C;&#x307E;&#x3059;&#x3002;&#x30CA;&#x30C8;&#x30EA;&#x30A6;&#x30E0;&#x306E;&#x5438;&#x53CE;&#x304A;&#x3088;&#x3073;&#x3072;&#x3068;&#x6C17;&#x7BA1;&#x652F;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B;&#x5869;&#x5316;&#x5206;&#x6CCC;&#x597D;&#x307E;&#x3057;&#x3044;&#x96FB;&#x6C17;&#x5316;&#x5B66;&#x52FE;&#x914D;&#x30A2;&#x30D4;&#x30AB;&#x30EB;&#x819C;&#x6775;&#x306E;&#x4E21;&#x65B9;&#x304C;&#x4F5C;&#x6210;&#x3055;&#x308C;&#x307E;&#x3059;&#x30AB;&#x30EA;&#x30A6;&#x30E0; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x6D3B;&#x6027;&#x306B;&#x4F9D;&#x5B58;&#x3057;&#x307E;&#x3059;&#x3002;&#x30A2;&#x30D4;&#x30AB;&#x30EB;&#x819C;&#x30AB;&#x30EA;&#x30A6;&#x30E0; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x5F79;&#x5272;&#x306F;&#x3001;&#x57FA;&#x5E95;&#x819C;&#x30AB;&#x30EA;&#x30A6;&#x30E0; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x5F79;&#x5272;&#x3092;&#x3057;&#x3063;&#x304B;&#x308A;&#x3068;&#x78BA;&#x7ACB;&#x3055;&#x308C;&#x3001;&#x5E83;&#x304F;&#x8ABF;&#x67FB;&#x3067;&#x3059;&#x306B;&#x3082;&#x8A18;&#x8F09;&#x3055;&#x308C;&#x3066;&#x3044;&#x307E;&#x3059;&#x3002;&#x3053;&#x3053;&#x3067;&#x306F;&#x3001;&#x30D6;&#x30D4;&#x30D0;&#x30AB;&#x30A4;&#x30F3;&#x3001;&#x30AD;&#x30CB;&#x30B8;&#x30F3;&#x3001;&#x30D6;&#x30ED;&#x30C3;&#x30AB;&#x30FC; 4 &#x819C;&#x8CAB;&#x901A;&#x30C9;&#x30E1;&#x30A4;&#x30F3;&#x3001;2 &#x7D30;&#x5B54;&#x30AB;&#x30EA;&#x30A6;&#x30E0; (K2P) &#x30C1;&#x30E3;&#x30F3;&#x30CD;&#x30EB;&#x306E;&#x30A2;&#x30DF;&#x30ED;&#x30E9;&#x30A4;&#x30C9;&#x611F;&#x53D7;&#x6027;&#x30CA;&#x30C8;&#x30EA;&#x30A6;&#x30E0;&#x5438;&#x53CE;&#x3068;&#x504F;&#x5149;&#x3001;&#x6B63;&#x5E38;&#x3072;&#x3068;&#x6C17;&#x7BA1;&#x652F;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B;&#x6F3F;&#x819C;&#x9762;&#x306B;&#x9069;&#x7528;&#x3059;&#x308B;&#x3068;&#x304D;&#x3088;&#x308A;&#x3082;&#x7C98;&#x819C;&#x306E;&#x8868;&#x9762;&#x306B;&#x9069;&#x7528;&#x3059;&#x308B;&#x5834;&#x5408;&#x306E;&#x4F4E;&#x6FC3;&#x5EA6;&#x30A2;&#x30CB;&#x30AA;&#x30F3; &#x30D5;&#x30A9;&#x30EB;&#x30B9;&#x30B3;&#x30EA;&#x30F3;&#x523A;&#x6FC0;&#x5206;&#x6CCC;&#x3092;&#x963B;&#x5BB3;&#x3092;&#x793A;&#x3057;&#x307E;&#x3059;&#x3002;4 &#x3064;&#x306E;&#x907A;&#x4F1D;&#x5B50;&#x3001;KCNK1 &#x304B;&#x3089;&#x306E;&#x6210;&#x7E3E;&#x8A3C;&#x660E;&#x66F8; (TWIK 1)&#x3001;KCNK2 &#xFF08;&#x30C8;&#x30EC;&#x30C3;&#x30AF;-1)&#x3001;KCNK5 (&#x30BF;&#x30B9;&#x30AF; 2)&#x3001;&#x304A;&#x3088;&#x3073; KCNK6 &#xFF08;TWIK-2&#xFF09;&#x3001;&#x30C1;&#x30E3;&#x30F3;&#x30CD;&#x30EB;&#x304C; RT-PCR &#x306B;&#x3088;&#x3063;&#x3066;&#x8B58;&#x5225;&#x3055;&#x308C;&#x305F; K2P &#x30A8;&#x30F3;&#x30B3;&#x30FC;&#x30C7;&#x30A3;&#x30F3;&#x30B0;&#x3057;&#x307E;&#x3059;&#x3002;&#x30A2;&#x30D4;&#x30AB;&#x30EB;&#x819C;&#x86CB;&#x767D;&#x8CEA;&#x306E;&#x8868;&#x73FE;&#x306F;&#x87A2;&#x5149;&#x6297;&#x4F53;&#x6CD5;&#x3092;&#x78BA;&#x8A8D;&#x3057;&#x307E;&#x3057;&#x305F;&#x3002;&#x79C1;&#x305F;&#x3061;&#x306E;&#x30C7;&#x30FC;&#x30BF; &#x30AB;&#x30EA;&#x30A6;&#x30E0; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x7279;&#x5B9A; K2P &#x30C1;&#x30E3;&#x30F3;&#x30CD;&#x30EB;&#x3067;&#x8868;&#x73FE;&#x3057;&#x3001;&#x5F7C;&#x3089;&#x306F;&#x6CBB;&#x7642;&#x4E0A;&#x306E;&#x64CD;&#x4F5C;&#x306E;&#x305F;&#x3081;&#x306E;&#x30BF;&#x30FC;&#x30B2;&#x30C3;&#x30C8;&#x3092;&#x304B;&#x3082;&#x3057;&#x308C;&#x306A;&#x3044;&#x6A5F;&#x80FD;&#x7684;&#x306A;&#x6C17;&#x9053;&#x306E;&#x9802;&#x5074;&#x819C;&#x306B;&#x304A;&#x3051;&#x308B;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306E;&#x3055;&#x3089;&#x306A;&#x308B;&#x8A3C;&#x62E0;&#x3092;&#x63D0;&#x4F9B;&#x3057;&#x307E;&#x3059;&#x3002;

Na&#x207A; &#x5438;&#x53CE;&#x3068;&#x6B63;&#x5E38;&#x3072;&#x3068;&#x6C17;&#x7BA1;&#x652F;&#x4E0A;&#x76AE;&#x7D30;&#x80DE;&#x306B;&#x304A;&#x3051;&#x308B; Cl&#x207B; &#x5206;&#x6CCC;&#x5909;&#x8ABF;&#x3067; 2 &#x7D30;&#x5B54; K&#x207A; &#x30C1;&#x30E3;&#x30CD;&#x30EB;&#x306E;&#x30ED;&#x30FC;&#x30EB;&#x3002;

Mucociliary &#xD074;&#xB9AC;&#xC5B4;&#xB7F0;&#xC2A4; &#xD761;&#xC785;&#xB41C; &#xBCD1;&#xC6D0; &#xCCB4;&#xC640; &#xB3C5; &#xC18C;&#xC5D0; &#xB300; &#xD55C; &#xAE30;&#xBCF8; &#xD0C0;&#xACE0; &#xB09C; &#xC2E0;&#xCCB4;&#xC801; &#xBC29;&#xC5B4; &#xBA54;&#xCEE4;&#xB2C8;&#xC998;&#xC785;&#xB2C8;&#xB2E4;. Vectorial &#xC774;&#xC628; &#xC804;&#xC1A1;, &#xC8FC;&#xB85C; &#xB098;&#xD2B8;&#xB968; &#xD761;&#xC218; &#xD558; &#xACE0; &#xC74C;&#xC774;&#xC628; &#xBD84; &#xBE44; &#xAE30;&#xB3C4; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC5D0; &#xC758;&#xD574; mucociliary &#xD074;&#xB9AC;&#xC5B4;&#xB7F0;&#xC2A4;&#xB97C; &#xC9C0;&#xC6D0;&#xD569;&#xB2C8;&#xB2E4;. &#xC774;&#xAC83;&#xC740; mucociliary &#xD074;&#xB9AC;&#xC5B4;&#xB7F0;&#xC2A4;&#xC758; &#xBCC0;&#xD654;&#xC5D0; &#xC758;&#xD574; &#xD2B9;&#xC9D5;&#xC740; &#xB0AD; &#xC131; &#xC12C;&#xC720; &#xC99D; &#xBC0F; pseudohypoaldosteronism &#xAC19;&#xC740; &#xBE44;&#xC815;&#xC0C1;&#xC801;&#xC778; &#xC774;&#xC628; &#xC218;&#xC1A1;&#xC758; &#xC9C8;&#xBCD1;&#xC5D0; &#xC758;&#xD574; &#xC785;&#xC99D; &#xB429;&#xB2C8;&#xB2E4;. &#xB098;&#xD2B8;&#xB968; &#xD761;&#xC218;&#xC640; &#xC778;&#xAC04;&#xC758; &#xAE30;&#xAD00;&#xC9C0; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; &#xBD84; &#xBE44; &#xC5FC;&#xD654; &#xAF2D;&#xB300;&#xAE30; &#xD50C;&#xB77C;&#xC988;&#xB9C8; &#xBA64;&#xBE0C;&#xB808;&#xC778; hyperpolarizing&#xC5D0; &#xC758;&#xD574; &#xB458; &#xBAA8;&#xB450;&#xB97C; &#xC704;&#xD574; &#xC720;&#xB9AC;&#xD55C; &#xC804;&#xAE30; &#xD654;&#xD559; &#xADF8;&#xB77C;&#xB370;&#xC774;&#xC158;&#xC744; &#xB9CC;&#xB4E4;&#xACE0; &#xCE7C;&#xB968; &#xCC44;&#xB110; &#xD65C;&#xB3D9;&#xC5D0; &#xB530;&#xB77C; &#xB2EC;&#xB77C; &#xC9D1;&#xB2C8;&#xB2E4;. Basolateral &#xB9C9; &#xCE7C;&#xB968; &#xCC44;&#xB110;&#xC758; &#xC5ED;&#xD560;&#xC740; &#xD655;&#xACE0; &#xD558; &#xAC8C; &#xC124;&#xB9BD; &#xD558; &#xACE0; &#xAD11;&#xBC94;&#xC704; &#xD558; &#xAC8C; &#xACF5;&#xBD80;, &#xD600;&#xB05D; &#xB9C9; &#xCE7C;&#xB968; &#xCC44;&#xB110;&#xC5D0; &#xB300; &#xD55C; &#xC5ED;&#xD560; &#xC124;&#xBA85;&#xB3C4; &#xD558;&#xACE0;&#xC788;&#xB2E4;. &#xC5EC;&#xAE30;, &#xC6B0;&#xB9AC;&#xAC00; bupivacaine &#xBC0F; quinidine, 4 &#xB9C9; &#xD6A1;&#xB2E8; &#xB3C4;&#xBA54;&#xC778;, 2 &#xAE30; &#xACF5; &#xCE7C;&#xB968; (K2P) &#xCC44;&#xB110; &#xCC28;&#xB2E8;&#xC81C; amiloride &#xBBFC;&#xAC10;&#xD55C; &#xB098;&#xD2B8;&#xB968; &#xD761;&#xC218; &#xBC0F; &#xD3B8;&#xAD11;, &#xC815;&#xC0C1;&#xC801;&#xC778; &#xC778;&#xAC04;&#xC758; &#xAE30;&#xAD00;&#xC9C0; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; serosal &#xD45C;&#xBA74;&#xC5D0; &#xC801;&#xC6A9; &#xBCF4;&#xB2E4; &#xC810; &#xB9C9; &#xD45C;&#xBA74;&#xC5D0; &#xC801;&#xC6A9; &#xB420; &#xB54C; &#xB0AE;&#xC740; &#xB18D;&#xB3C4;&#xC5D0;&#xC11C; &#xC74C;&#xC774;&#xC628; forskolin &#xC790;&#xADF9; &#xBD84; &#xBE44; &#xC5B5;&#xC81C; &#xD558;&#xB294; &#xBC29;&#xBC95;&#xC744; &#xBCF4;&#xC5EC; &#xC90D;&#xB2C8;&#xB2E4;. 4 &#xAC1C;&#xC758; &#xC720;&#xC804;&#xC790;, kcnk1&#xC5D0;&#xC11C;&#xC5D0;&#xC11C; &#xC131;&#xC801; &#xC99D;&#xBA85;&#xC11C; (TWIK-1) KCNK2 (&#xD2B8; &#xB809;-1) KCNK5 (&#xC791;&#xC5C5;-2) &#xBC0F; KCNK6 (TWIK-2), &#xC778;&#xCF54;&#xB529; K2P &#xCC44;&#xB110; &#xC2E4;&#xC2DC;&#xAC04; PCR&#xC5D0; &#xC758;&#xD574; &#xD655;&#xC778; &#xB418;&#xC5C8;&#xB2E4;. &#xD600;&#xB05D; &#xBA64;&#xBE0C;&#xB808;&#xC778;&#xC5D0; &#xB2E8;&#xBC31;&#xC9C8; &#xC2DD; &#xBA74;&#xC5ED; &#xD615;&#xAD11; &#xAC80;&#xC0AC;&#xC5D0; &#xC758;&#xD574; &#xD655;&#xC778; &#xB418;&#xC5C8;&#xB2E4;. &#xC6B0;&#xB9AC;&#xC758; &#xB370;&#xC774;&#xD130; &#xCE7C;&#xB968; &#xCC44;&#xB110; &#xD2B9;&#xC815; K2P &#xCC44;&#xB110;&#xC5D0; &#xD45C;&#xD604; &#xB429;&#xB2C8;&#xB2E4; &#xADF8;&#xB9AC;&#xACE0; &#xADF8;&#xB4E4;&#xC740; &#xCE58;&#xB8CC; &#xC801; &#xC870;&#xC791;&#xC5D0; &#xB300; &#xD55C; &#xBAA9;&#xD45C; &#xC218; &#xAE30;&#xB3C4;&#xC758; &#xAF2D;&#xB300;&#xAE30; &#xBA64;&#xBE0C;&#xB808;&#xC778;&#xC5D0; &#xAE30;&#xB2A5;&#xC131; &#xC0C1;&#xD53C; &#xC138;&#xD3EC; &#xCD94;&#xAC00; &#xC99D;&#xAC70;&#xB97C; &#xC81C;&#xACF5; &#xD569;&#xB2C8;&#xB2E4;.

2 &#xAE30; &#xACF5; K&#x207A; &#xCC44;&#xB110; Na&#x207A; &#xD761;&#xC218;&#xC640; &#xC815;&#xC0C1;&#xC801;&#xC778; &#xC778;&#xAC04;&#xC758; &#xAE30;&#xAD00;&#xC9C0; &#xC0C1;&#xD53C; &#xC138;&#xD3EC;&#xC5D0;&#xC11C; Cl&#x207B; &#xBD84; &#xBE44; &#xBCC0;&#xC870;&#xC5D0; &#xC5ED;&#xD560;.

Mucociliar es el principal mecanismo de defensa f&iacute;sico innato contra pat&oacute;genos inhalados y toxinas. Transporte de iones vectorial, principalmente la absorci&oacute;n de sodio y la secreci&oacute;n de ani&oacute;n, por c&eacute;lulas epiteliales de las v&iacute;as respiratorias apoya mucociliar. Esto se evidencia por enfermedades de transporte i&oacute;nico anormal como la fibrosis qu&iacute;stica y pseudohypoaldosteronism que se caracterizaron por cambios en la depuraci&oacute;n mucociliar. Absorci&oacute;n de sodio y la secreci&oacute;n de cloruro en las c&eacute;lulas epiteliales bronquiales humanas dependen de la actividad del canal de potasio, que crea un gradiente electroqu&iacute;mico favorable para ambos por hyperpolarizing la membrana apical. Aunque el papel de canales de potasio de membrana basolateral es firmemente establecida y ampliamente estudiados, tambi&eacute;n se ha descrito un papel para los canales de potasio de membrana apical. Aqu&iacute;, demostramos que la bupivaca&iacute;na y quinidina, bloqueadores de dominio transmembrana de cuatro canales de potasio de dos poro (K2P) inhiben tanto absorci&oacute;n de sodio sensible a la amilorida y la secreci&oacute;n de aniones forskoline-estimulado en polarizado, normales bronquiales epiteliales c&eacute;lulas humanas en concentraciones m&aacute;s bajas cuando se aplica a la superficie de la mucosa que cuando se aplica a la superficie serosal. Transcripciones de cuatro genes, KCNK1 (TWIK-1), KCNK2 (TREK-1), KCNK5 (TASK-2) y KCNK6 (TWIK-2), codificaci&oacute;n K2P canales fueron identificados por RT-PCR. Expresi&oacute;n de la prote&iacute;na en la membrana apical fue confirmada por inmunofluorescencia. Nuestros datos proporcionan evidencia adicional que se expresan en particulares K2P canales, canales de potasio y c&eacute;lulas epiteliales funcionales en la membrana apical de las v&iacute;as respiratorias donde pueden ser objetivos para la manipulaci&oacute;n terap&eacute;utica.

Un papel de poro dos canales K&#x207A; en la modulaci&oacute;n Na&#x207A; absorci&oacute;n y secreci&oacute;n de Cl&#x207B; en c&eacute;lulas epiteliales bronquiales humanas normales.

Cilia are complex and powerful cellular structures of the respiratory mucosa that play a critical role in airway defense. Respiratory epithelium is lined with cilia that perform an integrated and coordinated mechanism called mucociliary clearance. Mucociliary  clearance is the process by which cilia transport the mucus blanket overlying respiratory mucosa to the gastrointestinal tract for ingestion. It is the primary means by which the airway clears pathogens, allergens, debris, and toxins. The complex structure and regulatory mechanisms that dictate  the form and function of normal cilia are not entirely understood, but it is clear that ciliary dysfunction results in impaired respiratory defense.

Acquired cilia dysfunction in chronic rhinosinusitis.

Staphylococcus aureus (S. aureus) is hard to be eradicated, not only due to the emergence of antibiotic resistant strains but also because of its ability to form biofilm. Antibiotics are the major approach to treating biofilm infections, but their effects are unsatisfactory. One of the potential alternative treatments for controlling biofilm infections is photodynamic therapy (PDT), which requires the administration of photosensitizer, followed by light activation. 5-aminolevulinic acid (ALA), a natural photosensitizer prodrug, presents favorable characteristics, such as easy penetration and rapid clearance. These advantages enable ALA-based PDT (ALA-PDT) to be well-tolerated by patients and it can be repeatedly applied without cumulative toxicity or serious side effects. ALA-PDT has been proven to be an effective treatment for multidrug resistant pathogens; however, the study of its effect on S. aureus biofilm is limited. Here, we established our PDT system based on the utilization of ALA and a light-emitting diode, and we tested the effect of ALA-PDT on S. aureus biofilm as well as the combined effect of ALA-PDT and antibiotics on S. aureus biofilm. Our results showed that ALA-PDT has a strong antibacterial effect on S. aureus biofilm, which was confirmed by the confocal laser scanning microscope. We also found that lethal photosensitization occurred predominantly in the upper layer of the biofilm, while the residual live bacteria were located in the lower layer of the biofilm. In addition, the improved bactericidal effect was observed in the combined treatment group but in a strain-dependent manner. Our results suggest that ALA-PDT is a potential alternative approach for future clinical use to treat S. aureus biofilm-associated infections, and some patients may benefit from the combined treatment of ALA-PDT and antibiotics, but drug sensitivity testing should be performed in advance.

5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm.

Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS.

Effects of mometasone furoate-impregnated biodegradable nasal dressing on endoscopic appearance in healing process following endoscopic sinus surgery: a randomized, double-blind, placebo-controlled study.

 is a common bacterial colonizer of human skin and mucous membranes, yet it has emerged as an important nosocomial pathogen largely due to its ability to form biofilms. Tobacco smoke has been demonstrated as a contributor to various infection diseases by improving the biofilm formation of multiple bacterial species; however, the association between tobacco smoke and  biofilm is still unclear. In this study, we tested the effect of nicotine, one of the most active components of tobacco, on  biofilm formation, and we studied the underlying mechanisms. Our results showed that nicotine promoted the biofilm formation of  1457 strain (SE1457) and enhanced its initial attachment to a polyethylene surface as well as polysaccharide intercellular adhesin (PIA) production. In addition, an increased extracellular DNA release and a higher autolysis rate of SE1457 was detected after nicotine treatment, which was consistent with the increased ratio of dead cells in nicotine-treated SE1457 biofilm observed with confocal laser-scanning microscopy. Furthermore, the effect of nicotine on several autolysis-related and biofilm-related gene knockout mutants of SE1457 was tested. It showed that in , and , nicotine induced increase in biofilm formation was similar to that in SE1457; but in , and , the effect was obviously impaired. Consistently, the increase of the bacterial autolysis rate in  and  induced by nicotine was not as significant as that in SE1457. Meanwhile, the growth inhibition of nicotine on SE1457 was observed, and it was much less on  and restored by the  complementation. The  transcription in SE1457 was inhibited by nicotine during cultivation as indicated by a promoter reporter assay using green fluoresent protein. Taken together, our study indicates that nicotine improves  biofilm formation by promoting its initial attachment and intercellular accumulation; the , and  genes mediating bacterial autolysis and PIA production play an important role in this process.

Nicotine Enhances  Biofilm Formation by Altering the Bacterial Autolysis, Extracellular DNA Releasing, and Polysaccharide Intercellular Adhesin Production.

Staphylococcus aureus is a common pathogen in chronic rhinosinusitis (CRS) patients, the pathogenesis of which involves the ability to form biofilms and produce various virulence factors. Tobacco smoke, another risk factor of CRS, facilitates S. aureus biofilm formation; however, the mechanisms involved are unclear. Here, we studied the effect of nicotine on S. aureus biofilm formation and the expression of virulence-related genes. S. aureus strains isolated from CRS patients and a USA300 strain were treated with nicotine or were untreated (control). Nicotine-treated S. aureus strains showed dose-dependent increases in biofilm formation, lower virulence, enhanced initial attachment, increased extracellular DNA release, and a higher autolysis rate, involving dysregulation of the accessory gene regulator (Agr) quorum-sensing system. Consequently, the expression of autolysis-related genes lytN and atlA, and the percentage of dead cells in biofilms was increased. However, the expression of virulence-related genes, including hla, hlb, pvl, nuc, ssp, spa, sigB, coa, and crtN was downregulated and there was reduced bacterial invasion of A549 human alveolar epithelial cells. The results of this study indicate that nicotine treatment enhances S. aureus biofilm formation by promoting initial attachment and extracellular DNA release but inhibits the virulence of this bacterium.

ArticleTotal : 3	Year
Publication title Cited by 7	2018
Publication title Cited by 4	2018
Publication title Cited by 2	2021

Article	Year
Tobacco smoke mediated induction of sinonasal microbial biofilms. PloS one\| PubMed ID: 21253587	2011
Inherent differences in nasal and tracheal ciliary function in response to Pseudomonas aeruginosa challenge. American journal of rhinology & allergy\| PubMed ID: 21819755	2011
A role for two-pore Kâº channels in modulating Naâº absorption and Clâ» secretion in normal human bronchial epithelial cells. American journal of physiology. Lung cellular and molecular physiology\| PubMed ID: 21964404	2012
Acquired cilia dysfunction in chronic rhinosinusitis. American journal of rhinology & allergy\| PubMed ID: 22391065	2012
5-aminolevulinic acid-mediated photodynamic therapy and its strain-dependent combined effect with antibiotics on Staphylococcus aureus biofilm. PloS one\| PubMed ID: 28358851	2017
Effects of mometasone furoate-impregnated biodegradable nasal dressing on endoscopic appearance in healing process following endoscopic sinus surgery: a randomized, double-blind, placebo-con... International forum of allergy & rhinology\| PubMed ID: 30281941	2018
Nicotine Enhances Biofilm Formation by Altering the Bacterial Autolysis, Extracellular DNA Releasing, and Polysaccharide Intercellular Adhesin Production. Frontiers in microbiology\| PubMed ID: 30420846	2018
Effect of nicotine on Staphylococcus aureus biofilm formation and virulence factors. Scientific reports\| PubMed ID: 31882881	2019

Ke-Qing Zhao

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