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1.
Biomed Pharmacother ; 174: 116572, 2024 May.
Artículo en Inglés | MEDLINE | ID: mdl-38626519

RESUMEN

Epigenetic regulation and mitochondrial dysfunction are essential to the progression of idiopathic pulmonary fibrosis (IPF). Curcumin (CCM) in inhibits the progression of pulmonary fibrosis by regulating the expression of specific miRNAs and pulmonary fibroblast mitochondrial function; however, the underlying mechanism is unclear. C57BL/6 mice were intratracheally injected with bleomycin (5 mg/kg) and treated with CCM (25 mg/kg body weight/3 times per week, intraperitoneal injection) for 28 days. Verhoeff-Van Gieson, Picro sirius red, and Masson's trichrome staining were used to examine the expression and distribution of collagen and elastic fibers in the lung tissue. Pulmonary fibrosis was determined using micro-computed tomography and transmission electron microscopy. Human pulmonary fibroblasts were transfected with miR-29a-3p, and RT-qPCR, immunostaining, and western blotting were performed to determine the expression of DNMT3A and extracellular matrix collagen-1 (COL1A1) and fibronectin-1 (FN1) levels. The expression of mitochondrial electron transport chain complex (MRC) and mitochondrial function were detected using western blotting and Seahorse XFp Technology. CCM in increased the expression of miR-29a-3p in the lung tissue and inhibited the DNMT3A to reduce the COL1A1 and FN1 levels leading to pulmonary extracellular matrix remodeling. In addition, CCM inhibited pulmonary fibroblasts MRC and mitochondrial function via the miR-29a-3p/DNMT3A pathway. CCM attenuates pulmonary fibrosis via the miR-29a-3p/DNMT3A axis to regulate extracellular matrix remodeling and mitochondrial function and may provide a new therapeutic intervention for preventing pulmonary fibrosis.


Asunto(s)
Curcumina , ADN Metiltransferasa 3A , Matriz Extracelular , Fibroblastos , Ratones Endogámicos C57BL , MicroARNs , Mitocondrias , Animales , MicroARNs/genética , MicroARNs/metabolismo , Curcumina/farmacología , Mitocondrias/efectos de los fármacos , Mitocondrias/metabolismo , ADN Metiltransferasa 3A/metabolismo , Matriz Extracelular/metabolismo , Matriz Extracelular/efectos de los fármacos , Humanos , Ratones , Masculino , Fibroblastos/efectos de los fármacos , Fibroblastos/metabolismo , Fibroblastos/patología , Bleomicina , Fibrosis Pulmonar/genética , Fibrosis Pulmonar/patología , Fibrosis Pulmonar/metabolismo , Fibrosis Pulmonar/tratamiento farmacológico , Pulmón/efectos de los fármacos , Pulmón/patología , Pulmón/metabolismo , ADN (Citosina-5-)-Metiltransferasas/metabolismo , ADN (Citosina-5-)-Metiltransferasas/genética , Fibrosis Pulmonar Idiopática/patología , Fibrosis Pulmonar Idiopática/genética , Fibrosis Pulmonar Idiopática/tratamiento farmacológico , Fibrosis Pulmonar Idiopática/metabolismo , Modelos Animales de Enfermedad
3.
Phytomedicine ; 110: 154597, 2023 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-36603340

RESUMEN

BACKGROUND: Retinoblastoma, the most common pediatric intraocular malignancy, can develop during embryogenesis, with most children being diagnosed at 3-4 years of age. Multimodal therapies are typically associated with high levels of cytotoxicity and side effects. Therefore, the development of novel treatments with minimal side effects is crucial. Magnolol has a significant anti-tumor effect on various cancers. However, its antitumor effect on retinoblastoma remains unclear. PURPOSE: The study aimed to determine the effects of magnolol on the regulation of EMT, migration, invasion, and cancer progression in retinoblastoma and the modulation of miR-200c-3p expression and the Wnt/ zinc finger E-box binding homeobox 1 (ZEB1)/E-cadherin axis in vivo and in vitro. METHODS: The 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide) (MTT) assay was used to evaluate magnolol-induced cell toxicity in the Y79 retinoblastoma cell line. Flow cytometry and immunostaining assays were performed to investigate the magnolol-regulated mitochondrial membrane potential and the intracellular and mitochondrial reactive oxygen species levels in Y79 retinoblastoma cells. Orthotopic and subcutaneous xenograft experiments were performed in eight-week-old male null mice to study retinoblastoma progression and metastasis. In situ hybridization and quantitative reverse transcription polymerase chain reaction (RT-qPCR) assays were performed to evaluate the level of the anti-cancer miRNA miR-200c-3p. The mRNA and protein levels of E-cadherin, ß-catenin, α-smooth muscle actin (α-SMA), fibronectin-1, and ZEB1 were analyzed using RT-qPCR, immunoblot, immunocytochemistry, and immunohistochemistry assays in vitro and in vivo. RESULTS: Magnolol increased E-cadherin levels and reduced the activation of the EMT signaling pathway, EMT, tumor growth, metastasis, and cancer progression in the Y79 retinoblastoma cell line as well as in the orthotopic and subcutaneous xenograft animal models. Furthermore, magnolol increased the expression of miR-200c-3p. Our results demonstrate that miRNA-200c-3p inhibits EMT progression through the Wnt16/ß-catenin/ZEB1/E-cadherin axis, and the ZEB1 silencing response shows that miR-200c-3p regulates ZEB1-mediated EMT in retinoblastoma. CONCLUSION: Magnolol has an antitumor effect by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma. The anti-tumor effect of magnolol by increasing E-cadherin and miRNA-200c-3p expression to regulate ZEB1-mediated EMT and cancer progression in retinoblastoma has been elucidated for the first time.


Asunto(s)
MicroARNs , Neoplasias de la Retina , Retinoblastoma , Animales , Ratones , Humanos , Masculino , Transición Epitelial-Mesenquimal/genética , Retinoblastoma/tratamiento farmacológico , Retinoblastoma/genética , Línea Celular Tumoral , MicroARNs/genética , MicroARNs/metabolismo , Cadherinas/metabolismo , Neoplasias de la Retina/genética , Regulación Neoplásica de la Expresión Génica , Movimiento Celular/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/genética , Homeobox 1 de Unión a la E-Box con Dedos de Zinc/metabolismo
4.
Sci Rep ; 12(1): 18670, 2022 11 04.
Artículo en Inglés | MEDLINE | ID: mdl-36333461

RESUMEN

This study aims at identifying characteristics, risk factors and mortality of community-acquired (CAP) and health-care-associated pneumonia (HCAP) by Staphylococcus aureus (S. aureus). We retrieved adults with S. aureus CAP or HCAP diagnosed by blood or pleural effusion culture in 2.6 years, and compared with those of Streptococcus pneumoniae (S. pneumoniae) CAP or HCAP diagnosed by blood or respiratory culture, or urine antigen. We found 18 patients with CAP and 9 HCAP due to S. aureus (female 33%, 66.6 ± 12.4 years-old), and 48 patients with CAP and 15 HCAP due to S pneumoniae (female 41%, 69.5 ± 17.5 years). Diabetes mellitus (52% vs. 24%, p = 0.019), hemodialysis (11% vs. 0%, p = 0.046), skin lesions (44% vs. 0%, p < 0.001), cavitary nodules (37% vs. 1.6%, p < 0.001) and pleural effusions (48% vs. 18%, p = 0.007) were more common in staphylococcal than pneumococcal group. Three patients with staphylococcal pneumonia had acute myocardial infarction. Pneumonia severity index (139 ± 52 vs. 109 ± 43, p = 0.005) and 30-day mortality (41% vs. 9.5%, p = 0.001) were higher in staphylococcal group. Multivariate analysis showed underlying disease (especially cancer and cirrhosis), risk class 4/5, altered mentality, shock and bilateral pneumonia were risk factors for 30-day mortality.


Asunto(s)
Infecciones Comunitarias Adquiridas , Infección Hospitalaria , Neumonía Asociada a la Atención Médica , Neumonía Estafilocócica , Neumonía , Adulto , Humanos , Femenino , Persona de Mediana Edad , Anciano , Staphylococcus aureus , Infecciones Comunitarias Adquiridas/diagnóstico , Neumonía Estafilocócica/epidemiología , Neumonía Estafilocócica/tratamiento farmacológico , Infección Hospitalaria/tratamiento farmacológico , Estudios Retrospectivos , Neumonía/tratamiento farmacológico , Neumonía Asociada a la Atención Médica/tratamiento farmacológico , Streptococcus pneumoniae , Factores de Riesgo , Antibacterianos/uso terapéutico
5.
Int J Mol Sci ; 22(7)2021 Mar 31.
Artículo en Inglés | MEDLINE | ID: mdl-33807275

RESUMEN

High mobility group box 1 (HMGB1) has been demonstrated to promote the migration and invasion of non-small cell lung cancer (NSCLC). However, the mechanism of action of HMGB1 in regulating tumor mobility remains unclear. Therefore, we aimed to investigate whether HMGB1 affects mitochondria distribution and regulates dynamin-related protein 1 (DRP1)-mediated lamellipodia/filopodia formation to promote NSCLC migration. The regulation of mitochondrial membrane tension, dynamics, polarization, fission process, and cytoskeletal rearrangements in lung cancer cells by HMGB1 was analyzed using confocal microscopy. The HMGB1-mediated regulation of DRP1 phosphorylation and colocalization was determined using immunostaining and co-immunoprecipitation assays. The tumorigenic potential of HMGB1 was assessed in vivo and further confirmed using NSCLC patient samples. Our results showed that HMGB1 increased the polarity and mobility of cells (mainly by regulating the cytoskeletal system actin and microtubule dynamics and distribution), promoted the formation of lamellipodia/filopodia, and enhanced the expression and phosphorylation of DRP1 in both the nucleus and cytoplasm. In addition, HMGB1 and DRP1 expressions were positively correlated and exhibited poor prognosis and survival in patients with lung cancer. Collectively, HMGB1 plays a key role in the formation of lamellipodia and filopodia by regulating cytoskeleton dynamics and DRP1 expression to promote lung cancer migration.


Asunto(s)
Dinaminas/metabolismo , Proteína HMGB1/metabolismo , Neoplasias Pulmonares/metabolismo , Células A549 , Animales , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/metabolismo , Línea Celular Tumoral , Movimiento Celular/genética , Dinaminas/fisiología , Femenino , Regulación Neoplásica de la Expresión Génica/genética , Proteínas HMGB/metabolismo , Proteína HMGB1/fisiología , Humanos , Neoplasias Pulmonares/genética , Masculino , Ratones , Ratones SCID , Microscopía Confocal/métodos , Mitocondrias/genética , Dinámicas Mitocondriales , Proteínas Mitocondriales/metabolismo , Fosforilación , Seudópodos/metabolismo
6.
Biochim Biophys Acta Mol Cell Res ; 1867(11): 118798, 2020 11.
Artículo en Inglés | MEDLINE | ID: mdl-32693109

RESUMEN

GSK3 are involved in different physical and pathological conditions and inflammatory regulated by macrophages contribute to significant mechanism. Infection stimuli may modulate GSK3 activity and influence host cell adaption, immune cells infiltration or cytokine expressions. To further address the role of GSK3 modulation in macrophages, the signal transduction of three major organs challenged by endotoxin, virus and genetic inherited factors are briefly introduced (lung injury, myocarditis and autosomal dominant polycystic kidney disease). As a result of pro-inflammatory and anti-inflammatory functions of GSK3 in different microenvironments and stages of macrophages (M1/M2), the rational resolution should be considered by adequately GSK3.


Asunto(s)
Lesión Pulmonar Aguda/genética , Glucógeno Sintasa Quinasa 3 beta/genética , Miocarditis/genética , Enfermedades Renales Poliquísticas/genética , Lesión Pulmonar Aguda/patología , Aneurisma/genética , Aneurisma/patología , Humanos , Lesión Pulmonar/genética , Lesión Pulmonar/patología , Macrófagos/metabolismo , Macrófagos/patología , Miocarditis/patología , Enfermedades Renales Poliquísticas/patología
7.
Microorganisms ; 7(11)2019 Nov 05.
Artículo en Inglés | MEDLINE | ID: mdl-31694308

RESUMEN

OBJECTS: Invasive pulmonary mold infection usually has devastating outcomes. Timely differentiation between invasive pulmonary aspergillosis (IPA) from pulmonary mucormycosis (PM) is critical for treatment decision-making. However, information on IPA and PM differentiation is limited. METHODS: We conducted a retrospective, multicenter, observational study, with proven and probable IPA and PM patients from January 2004 to December 2017. Demographics, clinical manifestations, image reports, histopathological findings, and outcomes were analyzed. RESULTS: A total of 46 IPA (33 proven and 13 probable) and 19 PM (18 proven and one probable) cases were analyzed. The majority of tissues (81% in IPA and 61% in PM) were obtained using bronchoscopy. Prior influenza infection was a predisposing factor for IPA, and abscess formation in CT scan was associated with PM (p = 0.0491, p = 0.0454, respectively). The positive culture rate for PM was lower than that for IPA (37% vs. 67%, p = 0.0294). The galactomannan (GM) level from serum and bronchoalveolar lavage (BAL) fluid was significantly higher in IPA than in PM (3.3 ± 0.5 vs. 0.8 ± 0.6, p = 0.0361; 4.0 ± 0.6 vs. 0.59 ± 0.1, p = 0.0473, respectively). The overall mortality rate was 65%, which was similar among IPA and PM groups. Systemic steroid exposure and high Acute Physiology and Chronic Health Evaluation II (APACHE II) scores on admission were independently correlated to mortality in IPA (p = 0.027, p = 0.026, respectively). However, there was no predictor for mortality found in PM patients. CONCLUSIONS: Influenza infection, abscess formation in CT scan, and GM level may help physicians to differentiate IPA and PM. Bronchoscopy-guided biopsy and lavage specimen provide timely and definite diagnosis. The prognosis of IPA is associated with systemic steroid exposure and higher APACHE II scores on admission.

8.
J Microbiol Immunol Infect ; 52(4): 612-619, 2019 Aug.
Artículo en Inglés | MEDLINE | ID: mdl-28886952

RESUMEN

OBJECTIVE: This retrospective study investigated clinical manifestations of candidemia caused by uncommon Candida species and antifungal susceptibility of the isolates in a regional hospital in Taiwan. METHODS: The uncommon Candida species was initially defined as Candida species other than C. albicans, C. tropicalis, C. glabrata complex, C. parapsilosis complex and C. krusei. All uncommon Candida isolates were identified and confirmed by molecular methods. In vitro susceptibility testing of the uncommon Candida species to nine antifungal agents was conducted using the broth microdilution method with the Sensititre YeastOne (SYO) system (Trek Diagnostic Systems, Ltd., East Grimstead, UK). RESULTS: Twenty-one patients, comprising 11 males and 10 females with a median age of 69 years, were recruited. Cancer (n = 11) was the most common underlying disease, 19 (90.5%) cases had prior antibiotic exposure, and only two patients had prior antifungal use. The overall in-hospital mortality rate was 38.1% (n = 8). C. guilliermondii (n = 11) was the most common pathogen, followed by C. curvata (n = 3). C. guilliermondii isolates exhibited relatively high rates of azole minimum inhibitory concentrations (MICs) above epidemiological cut-off values (ECVs), whereas C. pelliculosa and C. lusitaniae isolates all remained susceptible to azoles. All three C. curvata isolates had high caspofungin (>8 mg/L) and fluconazole MICs (8 mg/L) and could be defined as multidrug-resistant. CONCLUSIONS: Uncommon Candida species frequently exhibit high rates of non-susceptibility to antifungals. Identification of all Candida isolates at the species level from blood samples is of value for treatment.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Candida/aislamiento & purificación , Candidemia/microbiología , Adulto , Anciano , Anciano de 80 o más Años , Azoles/farmacología , Candida/clasificación , Candida/genética , Candida glabrata , Candidemia/epidemiología , Caspofungina/farmacología , Infección Hospitalaria/microbiología , Farmacorresistencia Fúngica Múltiple/efectos de los fármacos , Equinocandinas/farmacología , Femenino , Fluconazol/farmacología , Humanos , Lactante , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Tipificación Molecular , Técnicas de Tipificación Micológica/métodos , Fenotipo , ARN Ribosómico 28S/genética , Estudios Retrospectivos , Taiwán/epidemiología
9.
J Thorac Dis ; 10(7): 4118-4126, 2018 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-30174856

RESUMEN

BACKGROUND: This study aims to investigate lung cancer patients' risk factors for: intensive care unit (ICU) admission, infectious complications and organ dysfunction in the ICU, and prognosis after ICU admission. METHODS: The records of all patients with lung-cancer catastrophic-illness cards admitted to the ICU between 2003 and 2012 were reviewed. The primary endpoint was 1-year mortality. RESULTS: We finally analyzed the records of index-date-, age-, and sex-matched ICU-admitted (ICU+) lung cancer patients (n=17,687) and ICU-non-admitted (ICU-) lung cancer patients (n=35,374). The overall 1-year mortality rate was significantly (P<0.0001) higher for ICU+ patients (49.91%) than for ICU- patients (44.86%). Most ICU+ patients (56.16%) had infectious complications and organ dysfunction (52.33%), and overall, 6,893 (38.97%) had sepsis. Independent mortality risk factors were age (≥75 years) [adjusted hazard ratio (AHR), 1.22; 95% confidence interval (CI), 1.16-1.29], male sex: (AHR, 1.18; 95% CI, 1.13-1.23), recent radiotherapy (AHR, 1.09; 95% CI, 1.04-1.15), infectious complications (AHR: 1.23; 95% CI: 1.17-1.29), organ dysfunction (AHR, 1.57; 95% CI, 1.50-1.65), and hospital level (regional hospital: AHR, 1.11; 95% CI, 1.06-1.16; local hospital: AHR, 1.28; 95% CI, 1.18-1.37). CONCLUSIONS: ICU admission for lung cancer patients is associated with higher mortality. Several risk factors of mortality for ICU+ patients should help physicians provide patients personalized and better-informed lung cancer therapy decisions.

10.
Emerg Microbes Infect ; 6(10): e87, 2017 Oct 11.
Artículo en Inglés | MEDLINE | ID: mdl-29018251

RESUMEN

Candidemia is a growing concern worldwide, and its species distribution has shifted toward non-albicans Candida in recent decades, especially in patients with malignancy. This study aimed to update the epidemiology and antifungal susceptibility of non-albicans candidemia isolates from the cancer patients. Adult cancer patients with non-albicans candidemia were recruited, and clinical data were retrospectively collected from five medical centers in Taiwan from 1 July 2011 to 30 June 2014. In vitro susceptibility was determined by the broth dilution method using a Sensititre YeastOne system and interpreted according to the guidelines of the Clinical and Laboratory Standards Institute. A total of 346 episodes of non-albicans candidemia were identified in cancer patients. Candida tropicalis was the most common species (n=145, 41.9%) and had the highest resistance rate to fluconazole (n=17, 13.9%) among all the preserved isolates, including C. tropicalis, Candida glabrata and Candida parapsilosis. A higher Charlson comorbidity index, non-albicans candidemia due to C. tropicalis, neutropenia and septic shock were independent predictors of 28-day mortality. In conclusion, the species distribution and antifungal susceptibility of non-albicans candidemia isolates in our study differed from those in Western countries, providing useful information about local epidemiology for the selection of empirical antifungal agents for cancer patients.


Asunto(s)
Antifúngicos/farmacología , Candida/efectos de los fármacos , Candidemia/microbiología , Neoplasias/complicaciones , Candida/clasificación , Candida/aislamiento & purificación , Candidemia/complicaciones , Candidemia/epidemiología , Candidemia/mortalidad , Farmacorresistencia Fúngica , Femenino , Humanos , Masculino , Pruebas de Sensibilidad Microbiana , Persona de Mediana Edad , Neoplasias/microbiología , Estudios Retrospectivos , Factores de Riesgo , Taiwán/epidemiología
11.
PLoS One ; 12(7): e0180844, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-28727734

RESUMEN

MicroRNAs (miRs) play critical roles in cancer development, proliferation, epithelial-mesenchymal transition (EMT), invasion, and migration through regulating the expression of oncogenes and tumour suppressor genes. Previous studies have indicated that miR-200c acts as a tumour suppressor in various cancers by downregulating high-mobility group box 1 (HMGB1) and thereby suppressing EMT and metastasis. In addition, miR-200c was reported to be downregulated and correlated with poor outcomes in non-small cell lung cancer (NSCLC). However, its functional role in HMGB1 regulation in NSCLC is still unclear. This study aimed to clarify whether miR-200c acts as a tumour suppressor in NSCLC by downregulating HMGB1, which is associated with EMT, invasion, cytoskeleton rearrangement, and migration in vitro and in vivo. In order to demonstrate HMGB1 downregulation by miR-200c, the NSCLC cell line A549 was transfected with miR-200c mimic or inhibitor. The mimic significantly reduced HMGB1 expression and suppressed EMT, invasion, and migration, while the inhibitor generated the opposite effects. Additionally, using xenograft mouse models, we confirmed that HMGB1 overexpression increased tumour EMT. In summary, our results demonstrated that miR-200c could suppress EMT, invasion, and migration of NSCLC cells by downregulating HMGB1.


Asunto(s)
Adenocarcinoma/genética , Movimiento Celular/genética , Transición Epitelial-Mesenquimal/genética , Proteína HMGB1/genética , Neoplasias Pulmonares/genética , MicroARNs/genética , Invasividad Neoplásica/genética , Adenocarcinoma/metabolismo , Adenocarcinoma/patología , Animales , Línea Celular Tumoral , Regulación Neoplásica de la Expresión Génica , Proteína HMGB1/metabolismo , Xenoinjertos , Humanos , Pulmón/metabolismo , Pulmón/patología , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patología , Ratones , MicroARNs/metabolismo , Invasividad Neoplásica/patología , Trasplante de Neoplasias , ARN Interferente Pequeño
12.
Molecules ; 22(6)2017 Jun 03.
Artículo en Inglés | MEDLINE | ID: mdl-28587210

RESUMEN

Metastasis is common in lung cancer and is associated with poor clinical outcomes and increased mortality. Curcumin is a natural anti-cancer agent that inhibits the metastasis of various cancers by modulating the expression of micro (mi) RNAs such as miR-98, which acts as a tumor suppressor. This study investigated the effect of curcumin on miR-98 expression and in vitro cell line growth and invasiveness in lung cancer. Curcumin treatment enhanced the expression of miR-98 and reduced that of the miR-98 target gene LIN28A as well as matrix metalloproteinase (MMP) 2 and MMP9 in vitro and in vivo. MiR-98 overexpression suppressed lung cancer cell migration and invasion by inhibiting LIN28A-induced MMP2 and MMP9 expression. Meanwhile, LIN28A level was downregulated by overexpression of miR-98 mimic. Induction of miR-98 by curcumin treatment suppressed MMP2 and MMP9 by targeting LIN28A. These findings provide insight into the mechanisms by which curcumin suppresses lung cancer cell line growth in vitro and in vivo and invasiveness in vitro.


Asunto(s)
Antineoplásicos/farmacología , Curcumina/farmacología , Neoplasias Pulmonares/genética , MicroARNs/genética , Proteínas de Unión al ARN/genética , Activación Transcripcional/efectos de los fármacos , Regiones no Traducidas 3' , Animales , Ciclo Celular/efectos de los fármacos , Línea Celular Tumoral , Movimiento Celular/efectos de los fármacos , Modelos Animales de Enfermedad , Regulación Neoplásica de la Expresión Génica/efectos de los fármacos , Humanos , Metaloproteinasa 2 de la Matriz/genética , Metaloproteinasa 2 de la Matriz/metabolismo , Metaloproteinasa 9 de la Matriz/genética , Metaloproteinasa 9 de la Matriz/metabolismo , Interferencia de ARN , Ensayos Antitumor por Modelo de Xenoinjerto
13.
Ann Intensive Care ; 7(1): 9, 2017 Dec.
Artículo en Inglés | MEDLINE | ID: mdl-28083768

RESUMEN

BACKGROUND: Invasive fungal tracheobronchitis (IFT) is a severe form of pulmonary fungal infection that is not limited to immunocompromised patients. Although respiratory failure is a crucial predictor of death, information regarding IFT in critically ill patients is limited. METHODS: In this retrospective, multicenter, observational study, we enrolled adults diagnosed as having IFT who had been admitted to the intensive care unit between January 2007 and December 2015. Their demographics, clinical imaging data, bronchoscopic and histopathological findings, and outcomes were recorded. RESULTS: This study included 31 patients who had been diagnosed as having IFT, comprising 24 men and 7 women with a mean age of 64.7 ± 13.7 years. All patients developed respiratory failure and received mechanical ventilation before diagnosis. Eighteen (58.1%) patients had diabetes mellitus, and 12 (38.7%) had chronic lung disease. Four (12.9%) patients had hematologic disease, and none of the patients had neutropenia. Twenty-five (80.6%) patients were diagnosed as having proven IFT, and the remaining patients had probable IFT. Aspergillus spp. (61.3%) were the most common pathogenic species, followed by Mucorales (25.8%) and Candida spp. (6.5%). The diagnoses in six (19.4%) patients were confirmed only through bronchial biopsy and histopathological examination, whereas their cultures of bronchoalveolar lavage fluid were negative for fungi. The overall in-hospital mortality rate was 93.5%. CONCLUSIONS: IFT in critically ill patients results in a high mortality rate. Diabetes mellitus is the most prevalent underlying disease, followed by chronic lung disease. In addition to Aspergillus spp., Mucorales is another crucial pathogenic species. Bronchial lesion biopsy is the key diagnostic strategy.

14.
J Agric Food Chem ; 63(43): 9480-7, 2015 Nov 04.
Artículo en Inglés | MEDLINE | ID: mdl-26466890

RESUMEN

Reducing oxidative stress is crucial to prevent hypoxia-reoxygenation (H/R)-induced lung injury. Resveratrol has excellent antioxidant and anti-inflammatory effects, and this study investigated its role in H/R-induced type II pneumocyte dysfunction. H/R conditions increased expression of inflammatory cytokines including interleukin (IL)-1ß (142.3 ± 21.2%, P < 0.05) and IL-6 (301.9 ± 35.1%, P < 0.01) in a type II alveolar epithelial cell line (A549), while the anti-inflammatory cytokine IL-10 (64.6 ± 9.8%, P < 0.05) and surfactant proteins (SPs) decreased. However, resveratrol treatment effectively inhibited these effects. H/R significantly activated an inflammatory transcription factor, nuclear factor (NF)-κB, while resveratrol significantly inhibited H/R-induced NF-κB transcription activities. To the best of our knowledge, this is the first study showing resveratrol-mediated reversal of H/R-induced inflammatory responses and dysfunction of type II pneumocyte cells in vitro. The effects of resveratrol were partially mediated by promoting SP expression and inhibiting inflammation with NF-κB pathway involvement. Therefore, our study provides new insights into mechanisms underlying the action of resveratrol in type II pneumocyte dysfunction.


Asunto(s)
Antiinflamatorios/farmacología , Células Epiteliales/efectos de los fármacos , Hipoxia/tratamiento farmacológico , Lesión Pulmonar/tratamiento farmacológico , Alveolos Pulmonares/efectos de los fármacos , Estilbenos/farmacología , Línea Celular , Células Epiteliales/inmunología , Células Epiteliales/metabolismo , Humanos , Hipoxia/inmunología , Hipoxia/metabolismo , Interleucina-1beta/inmunología , Interleucina-6/inmunología , Lesión Pulmonar/inmunología , Lesión Pulmonar/metabolismo , Oxígeno/metabolismo , Alveolos Pulmonares/citología , Alveolos Pulmonares/inmunología , Resveratrol
15.
Geriatr Gerontol Int ; 15(6): 688-93, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25256556

RESUMEN

AIM: The present retrospective study was carried out to investigate the epidemiological characteristics and the prognostic factors of candidemia among elderly patients. METHODS: From 2009 to 2012, elderly patients with candidemia were identified at the Chi Mei medical center, a 900-bed regional hospital in southern Taiwan, and their medical records retrospectively reviewed. RESULTS: During the 4-year period, a total of 175 episodes of candidemia among elderly patients were identified. The patients ranged in age from 65 to 98 years (mean 76.4 years) and the mean (±standard deviation) Charlson Comorbidity Index score was 7.6 (±2.7). Cancer was the most common underlying disease (n = 127, 72.6%), followed by diabetes mellitus (n = 69, 39.4%). Candida albicans (n = 96, 54.9%) was the most common pathogen, followed by C. tropicalis (n = 39, 22.3%), C. parapsilosis (n = 24, 13.7%), C. glabrata (n = 22, 12.6%), C. guilliermondii (n = 2, 1.1%) and Candida species (n = 3, 1.7%). The ratio of C. albicans causing candidemia was significantly higher in young-old than old-old patients (64.1% vs 47.4%, P = 0.027). The overall in-hospital mortality was 50.3%. Multivariate analysis showed that the in-hospital mortality was only significantly associated with jaundice (P = 0.004), no use of antifungal agent (P = 0.021) and intensive care unit admission (P < 0.001). CONCLUSIONS: Candidemia can develop in elderly patients, especially patients with cancer or other risk factors. C. albicans is the most common Candida species causing candidemia among elderly patients, followed by C. tropicalis. The mortality of candidemia among elderly patients remains high.


Asunto(s)
Candidemia/epidemiología , Anciano , Anciano de 80 o más Años , Antifúngicos/uso terapéutico , Candida tropicalis , Candidemia/tratamiento farmacológico , Candidemia/mortalidad , Comorbilidad , Diabetes Mellitus/epidemiología , Femenino , Fluconazol/uso terapéutico , Mortalidad Hospitalaria , Humanos , Masculino , Análisis Multivariante , Neoplasias/epidemiología , Pronóstico , Insuficiencia Respiratoria/epidemiología , Estudios Retrospectivos , Taiwán/epidemiología
16.
Am J Infect Control ; 42(11): 1238-40, 2014 Nov.
Artículo en Inglés | MEDLINE | ID: mdl-25238665

RESUMEN

From 2009-2012, a total of 281 episodes of central line-associated candidemia were identified, and the overall incidence was 2.05 episodes per 1,000 hospital admissions. More than half of the patients were classified as older adults, with an age ≥65 years. Cancer was the most common underlying disease (n = 231, 82.2%). Twenty patients had polycandidal candidemia, and 94 had concomitant bacteremia. The overall in-hospital mortality rate was 50.9%, and a multivariable analysis showed that this rate was only significantly associated with a Charlson comorbidity index score >5, jaundice, no antifungal agent use, and use of mechanical ventilators.


Asunto(s)
Candidemia/mortalidad , Candidemia/patología , Infecciones Relacionadas con Catéteres/mortalidad , Infecciones Relacionadas con Catéteres/patología , Anciano , Anciano de 80 o más Años , Bacteriemia/complicaciones , Candidemia/diagnóstico , Candidemia/epidemiología , Infecciones Relacionadas con Catéteres/diagnóstico , Infecciones Relacionadas con Catéteres/epidemiología , Coinfección/epidemiología , Coinfección/microbiología , Comorbilidad , Femenino , Humanos , Incidencia , Masculino , Pronóstico , Estudios Retrospectivos , Factores de Riesgo , Análisis de Supervivencia
17.
Nutrients ; 6(8): 3101-16, 2014 Aug 05.
Artículo en Inglés | MEDLINE | ID: mdl-25100435

RESUMEN

Inadequate ventilator settings may cause overwhelming inflammatory responses associated with ventilator-induced lung injury (VILI) in patients with acute respiratory distress syndrome (ARDS). Here, we examined potential benefits of glutamine (GLN) on a two-hit model for VILI after acid aspiration-induced lung injury in rats. Rats were intratracheally challenged with hydrochloric acid as a first hit to induce lung inflammation, then randomly received intravenous GLN or lactated Ringer's solution (vehicle control) thirty min before different ventilator strategies. Rats were then randomized to receive mechanical ventilation as a second hit with a high tidal volume (TV) of 15 mL/kg and zero positive end-expiratory pressure (PEEP) or a low TV of 6 mL/kg with PEEP of 5 cm H2O. We evaluated lung oxygenation, inflammation, mechanics, and histology. After ventilator use for 4 h, high TV resulted in greater lung injury physiologic and biologic indices. Compared with vehicle treated rats, GLN administration attenuated lung injury, with improved oxygenation and static compliance, and decreased respiratory elastance, lung edema, extended lung destruction (lung injury scores and lung histology), neutrophil recruitment in the lung, and cytokine production. Thus, GLN administration improved the physiologic and biologic profiles of this experimental model of VILI based on the two-hit theory.


Asunto(s)
Lesión Pulmonar Aguda/prevención & control , Glutamina/administración & dosificación , Neumonía por Aspiración/tratamiento farmacológico , Lesión Pulmonar Aguda/etiología , Administración Intravenosa , Animales , Líquido del Lavado Bronquioalveolar/química , Quimiocina CXCL1/metabolismo , Modelos Animales de Enfermedad , Interleucina-10/metabolismo , Interleucina-1beta/metabolismo , Interleucina-6/metabolismo , Masculino , Neumonía por Aspiración/complicaciones , Respiración con Presión Positiva , Ratas , Ratas Sprague-Dawley , Síndrome de Dificultad Respiratoria/tratamiento farmacológico , Síndrome de Dificultad Respiratoria/etiología , Volumen de Ventilación Pulmonar , Factor de Necrosis Tumoral alfa/metabolismo , Lesión Pulmonar Inducida por Ventilación Mecánica/complicaciones , Lesión Pulmonar Inducida por Ventilación Mecánica/tratamiento farmacológico
18.
PLoS One ; 9(6): e99103, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24901336

RESUMEN

AIM: The study of candidemia in cancer patients has been limited. This retrospective study aims to investigate the epidemiologic characteristics and prognostic factors of candidemia among cancer patients. MATERIALS AND METHODS: From 2009 to 2012, cancer patients with candidemia were identified at a hospital in Taiwan. The medical records of all patients with bloodstream infections due to Candida species were retrospectively reviewed. RESULTS: During the four-year period, a total of 242 episodes of candidemia were identified among cancer patients. Half of these patients were classified as elderly (≥65 years old), and more than 95% of the candidemia episodes were classified as healthcare-associated infections. Among the 242 cancer patients with candidemia, head and neck cancer was the most common, followed by gastrointestinal tract and lung cancer. Additionally, most of the patients had variable underlying conditions, such as the presence of CVC (99%) or prior exposure to broad-spectrum antibiotics (93%) and were receiving an immunosuppressant (86%). Overall, C. albicans (n = 132, 54.5%) was the most common pathogen, followed by C. tropicalis (n = 52, 21.5%), C. parapsilosis (n = 38, 15.7%), and C. glabrata (n = 29, 12.0%). Seventeen patients had polycandidal candidemia, and 77 patients had concomitant bacteremia. Approximately one-third of the patients required admission to the intensive care unit (ICU) or mechanical ventilation, and the overall in-hospital mortality was 50.8%. Multivariable analysis showed that the in-hospital mortality was significantly associated with only the non-use of antifungal agents and acute respiratory failure (P<.001). CONCLUSIONS: Candidemia can develop in patients with both solid cancer and hematological malignancy, especially for patients with underlying conditions. Overall, the associated morbidity and mortality due to Candidemia remain high. It was also determined that the non-use of antifungal agents and acute respiratory failure conditions were associated with in-hospital mortality.


Asunto(s)
Candidiasis/diagnóstico , Neoplasias/complicaciones , Anciano , Anciano de 80 o más Años , Bacteriemia/complicaciones , Bacteriemia/diagnóstico , Candida albicans/aislamiento & purificación , Candida glabrata/aislamiento & purificación , Candida tropicalis/aislamiento & purificación , Candidiasis/complicaciones , Candidiasis/epidemiología , Femenino , Mortalidad Hospitalaria , Hospitales , Humanos , Inmunosupresores/uso terapéutico , Unidades de Cuidados Intensivos , Masculino , Persona de Mediana Edad , Neoplasias/tratamiento farmacológico , Neoplasias/mortalidad , Pronóstico , Respiración Artificial , Estudios Retrospectivos
19.
Diagn Microbiol Infect Dis ; 73(1): 84-5, 2012 May.
Artículo en Inglés | MEDLINE | ID: mdl-22578941

RESUMEN

Vibrio cholerae is known as a common etiology of epidemic diarrheal disease and rarely causes extra-intestinal infections. In this report, we described a cirrhotic patient with hepatocellular carcinoma who developed spontaneous bacterial empyema due to non-O1, non-O139 V. cholerae. The patient was successfully treated with antimicrobial agents and percutaneous drainage.


Asunto(s)
Carcinoma Hepatocelular/complicaciones , Empiema/diagnóstico , Empiema/microbiología , Cirrosis Hepática/complicaciones , Neoplasias Hepáticas/complicaciones , Vibrio cholerae/aislamiento & purificación , Antibacterianos/administración & dosificación , Cólera/diagnóstico , Cólera/microbiología , Cólera/patología , Cólera/terapia , Drenaje , Empiema/patología , Empiema/terapia , Humanos , Masculino , Persona de Mediana Edad , Radiografía Torácica , Vibrio cholerae/clasificación
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