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Rapid economic development has led to oil pollution and energy shortage. Membrane separation has attracted much attention due to its simplicity and efficiency in oil-water-separation. The development of membrane materials with enhanced separation properties is essential to improve the separation-efficiency. Proton exchange membrane fuel cells (PEMFCs) are expected to replace conventional engines due to their high-power-conversion rates and other favorable properties. Anhydrous-proton-conducting materials are vital components of PEMFCs. However, developing stable proton-conducting materials that exhibit high conductivity at varying temperatures remains challenging. Herein, two covalent organic frameworks (COFs) with long-side-chains are synthesized, and their corresponding COF@SSN membranes. Both membranes can effectively separate oil-water mixtures and water-in-oil emulsions. The TFPT-AF membrane achieves a maximum oil-flux of 6.05 × 105 g h-1 m-2 with an oil-water separation efficiency of above 99%, which is almost unchanged after 20 consecutive uses. COF@H3PO4 doped with different ratios of H3PO4 is prepared, the results show that the perfluorocarbon-chain system has excellent anhydrous proton conductivity , achieving an ultra-high proton-conductivity of 3.98 × 10-1 S cm-1 at 125 °C. This study lays the foundation for tailor-made-functionalization of COF through pre-engineering and surface-modification, highlighting the great potential of COFs for oil-water separation and anhydrous-proton-conductivity.
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Burdock root is the root of Arctium lappa L., a plant of the Compositae family, which has the effects of dispersing wind and heat, detoxifying and reducing swelling. In order to better control the quality of burdock root, a screening study of quality control indicators was carried out. The current research combines biological activity evaluation with chemical analysis to screen and identify the biologically active compounds of burdock root as chemical components for the quality control of herbal medicine. The efficacy of 10 batches of ethanol extracts of burdock roots was evaluated by a tumor inhibition experiment in S180 tumor-bearing mice. The five main chemical components of these extracts were simultaneously quantitatively measured by ultra-high performance liquid chromatography combined with triple quadrupole mass spectrometry. Pearson correlation analysis was used to establish the relationship between these extracts' biological activity and chemical properties. The results showed that chlorogenic acid, caffeic acid and cynarin were positively correlated with the effect of inhibiting tumor growth, and further bioassays confirmed this conclusion. In conclusion, chlorogenic acid, caffeic acid and cynarin can be used as quality control markers for burdock root's antitumor effect.
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Antineoplásicos Fitogénicos , Arctium/química , Cromatografía Líquida de Alta Presión/métodos , Extractos Vegetales , Espectrometría de Masas en Tándem/métodos , Animales , Antineoplásicos Fitogénicos/química , Antineoplásicos Fitogénicos/farmacología , Línea Celular Tumoral , Proliferación Celular/efectos de los fármacos , Límite de Detección , Modelos Lineales , Ratones , Neoplasias Experimentales/patología , Extractos Vegetales/química , Extractos Vegetales/farmacología , Extractos Vegetales/normas , Raíces de Plantas/química , Reproducibilidad de los ResultadosRESUMEN
Surface-enhanced Raman scattering (SERS) by use of noble metal nanoparticles has become a powerful tool to determine a low-concentration target by unique spectral fingerprints, but it is still limited to the Raman-inactive and nonresonant biomolecules such as amine acids, proteins, and hormones. Here, we report an Ehrlich reaction based derivative strategy in combination with gold nanoparticles (Au NPs) hotspots for the selective detection of indole-like plant hormones by SERS spectroscopy. Ehrlich reaction of p-(dimethylamino)benzaldehyde (PDAB) with the indole ring chemically transformed plant hormone indole-3-butyric acid (IBA) into a Raman-active and resonant derivative with an extended π-conjugated system in the form of a cation, which produced a new absorption band at 626 nm. On the other hand, cationic IBA-PDAB highly evoked the aggregation of Au NPs with negative citrate ligands to form the effective Raman hotspots and gave rise to the new absorption ranging from 600 to 800 nm. Significantly, the spectral overlap among IBA-PDAB, aggregated Au NPs, and the exciting laser initiated the multiple optical resonances to generate the ultrahigh Raman scattering with a sensitive limit of 2.0 nM IBA. The IBA in the whole sprouts and various parts of pea, mungbean, soybean, and black bean has been identified and quantified. The reported method opens a novel avenue for the SERS detection of Raman-inactive analyte by a proper derivation.
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Oro/química , Nanopartículas del Metal/química , Reguladores del Crecimiento de las Plantas/análisis , Espectrometría Raman , Benzaldehídos/química , Indoles/análisis , Indoles/química , Límite de Detección , Reguladores del Crecimiento de las Plantas/química , Vigna/metabolismoRESUMEN
An investigation of the potential neuroprotective natural product constituents of the rhizomes of Typhonium giganteum led to the isolation of two new cerebrosides, typhonosides E (1) and F (2), along with 11 known analogues (3-13). The structures of compounds 1 and 2 were elucidated by spectroscopic data interpretation. The activity of these compounds against glutamate-induced cell apoptosis was investigated in PC12 cells. All compounds exhibited such activity, which was related to the length of the fatty acyl chain. Among them, longan cerebroside II (11), with the longest fatty acyl chain, showed the most potent protective effect in PC12 cells from glutamate injury, with an EC50 value of 2.5 µM. Moreover, at the molecular level, longan cerebroside II (11) downregulated the expression of caspase-9, caspase-3, and Bax, upregulated the expression of Bcl-2, and decreased the level of cytosolic cytochrome c in a concentration-dependent manner.
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Cerebrósidos/aislamiento & purificación , Cerebrósidos/farmacología , Fármacos Neuroprotectores/aislamiento & purificación , Fármacos Neuroprotectores/farmacología , Animales , Apoptosis/efectos de los fármacos , Caspasa 3/metabolismo , Caspasa 9/metabolismo , Cerebrósidos/química , Citocromos c/metabolismo , Ácido Glutámico/farmacología , Estructura Molecular , Fármacos Neuroprotectores/química , Células PC12 , Proteínas Proto-Oncogénicas c-bcl-2/metabolismo , Ratas , Rizoma/química , Sapindaceae , Transducción de Señal/efectos de los fármacosRESUMEN
Fluorescent colorimetry test papers are promising for the assays of environments, medicines, and foods by the observation of the naked eye on the variations of fluorescence brightness and color. Unlike dye-absorption-based pH test paper, however, the fluorescent test papers with wide color-emissive variations with target dosages for accurate quantification remain unsuccessful even if the multicolorful fluorescent probes are used. Here, we report the dosage-sensitive fluorescent colorimetry test paper with a very wide/consecutive "from red to cyan" response to the presence and amount of arsenic ions, As(III). Red quantum dots (QDs) were modified with glutathione and dithiothreitol to obtain the supersensitivity to As(III) by the quenching of red fluorescence through the formation of dispersive QDs aggregates. A small amount of cyan carbon dots (CDs) with spectral blue-green components as the photostable internal standard were mixed into the QDs solution to produce a composited red fluorescence. Upon the addition of As(III) into the sensory solution, the fluorescence color could gradually be reversed from red to cyan with a detection limit of 1.7 ppb As(III). When the sensory solution was printed onto a piece of filter paper, surprisingly a serial of color evolution from peach to pink to orange to khaki to yellowish to yellow-green to final cyan with the addition of As(III) was displayed and clearly discerned the dosage scale as low as 5 ppb. The methodology reported here opens a novel pathway toward the real applications of fluorescent test papers.
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p53-induced death domain protein (PIDD) facilitates p53-dependent apoptosis through the interaction with components of the death receptor signaling pathways. However, the role of PIDD in hepatocellular carcinoma (HCC) development remains unknown. In this study, we investigated the expression pattern of PIDD in clinical HCC samples and adjacent non-cancerous tissues using immunohistochemistrical and Western blot analyses. The results showed that PIDD was lowly expressed in HCC tissues and HCC cell lines, compared with the adjacent non-tumorous tissues and LO2 normal hepatocytes. In addition, clinicopathological analysis showed that the expression of PIDD was closely related with multiple clinicopathological variables, such as American Joint Committee on Cancer (AJCC) stage, AFP, and poor prognosis of HCC. Univariate and multivariate survival analyses demonstrated that PIDD could serve as an independent prognostic factor to predict the survival of HCC patients. We used serum starvation-refeeding experiment to explore the involvement of PIDD in HCC cell cycle regulation. We found that PIDD was accumulated in growth-arrested HCC cells and was progressively decreased when cells entered into S phase. Moreover, flow cytometry and cell counting kit-8 (CCK-8) assays indicated that depleting the expression of PIDD could facilitate cell cycle progression and accelerate cell proliferation in HepG2 cells, while overexpression of PIDD could result in cell cycle arrest at G1 phase and hinder the cell proliferation in Hep3B cells. Finally, flow cytometry revealed that overexpression of PIDD slightly increased the apoptosis of HCC cells. Taken together, we concluded that PIDD may be a valuable prognostic marker and promising therapeutic target of HCC.
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Carcinoma Hepatocelular/patología , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/fisiología , Neoplasias Hepáticas/patología , Proteínas de Neoplasias/fisiología , Adulto , Anciano , Apoptosis , Carcinoma Hepatocelular/metabolismo , Ciclo Celular , División Celular , Línea Celular Tumoral , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/análisis , Proteínas Adaptadoras de Señalización del Receptor del Dominio de Muerte/antagonistas & inhibidores , Femenino , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Masculino , Persona de Mediana Edad , Proteínas de Neoplasias/análisis , Proteínas de Neoplasias/antagonistas & inhibidores , Pronóstico , Interferencia de ARN , ARN Interferente Pequeño/genética , Proteínas Recombinantes de Fusión/metabolismo , Transducción de Señal , Adulto JovenRESUMEN
KPNß1, also known as importin ß, P97, is reported as one of soluble transport factors that mediates transportion of proteins and RNAs between the nucleus and cytoplasm in cellular process. Recent studies show that KPNß1 is a tumor gene which is highly expressed in several malignant tumors such as ovarian cancer, cervical tumor, neck cancer, and lung cancer via promoting cell proliferation or inhibiting cell apoptotic pathways. However, the the role of KPNß1 in gastric cancer remains unclear. In this study, Western blot and immunohistochemistrical analyses showed that KPNß1 was significantly upregulated in clinical gastric cancer specimens compared with adjacent noncancerous tissues. KPNß1 was positively correlated with tumor grade, Ki-67, and predicted poor prognosis of gastric cancer. More importantly, through starvation-refeeding model, CCK8 assay, flow cytometry, colony formation assays, the vitro studies demonstrated that KPNß1 promoted proliferation of gastric cancer cells, while KPNß1 knockdown led to decreased cell proliferation and arrested cell cycle at G1 phase. Furthermore, our results also indicated that KPNß1 expression could result in docetaxel resistance. And, KPNß1 could interact with Stat1, contributed to its nucleus import in gastric cancer cells. These findings provided a novel promising therapeutic targets for clinical treatment against human gastric cancer.
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Regulación Neoplásica de la Expresión Génica , Neoplasias Gástricas/genética , Neoplasias Gástricas/mortalidad , beta Carioferinas/genética , Antineoplásicos/farmacología , Biomarcadores , Línea Celular Tumoral , Núcleo Celular/metabolismo , Proliferación Celular , Docetaxel , Resistencia a Antineoplásicos/genética , Femenino , Técnicas de Silenciamiento del Gen , Humanos , Inmunohistoquímica , Masculino , Clasificación del Tumor , Metástasis de la Neoplasia , Estadificación de Neoplasias , Pronóstico , Modelos de Riesgos Proporcionales , Unión Proteica , Factor de Transcripción STAT1/metabolismo , Transducción de Señal/efectos de los fármacos , Neoplasias Gástricas/patología , Taxoides/farmacología , Regulación hacia Arriba , beta Carioferinas/metabolismoRESUMEN
Far-upstream element (FUSE)-binding protein 2 (FBP2) was a member of single-stranded DNA-binding protein family; it played an important role in regulating transcription and post-transcription and is involved in the regulation of C-MYC gene expression in liver tumors. However, the role of FBP2 in breast cancer and its mechanism has not been studied yet. Here, we discovered that FBP2 was up-regulated in breast cancer tissues and breast cancer cell lines. Moreover, immunohistochemistry analysis demonstrated that up-regulated FBP2 was highly associated with tumor grade, Ki-67, and poor prognosis, which was an independent prognostic factor for survival of breast cancer patients. At the cellular level, we found that FBP2 was correlated with cell cycle progression by accelerating G1/S transition, and knockdown of FBP2 could weaken cell proliferation, anchorage-independent cell growth, while enhancing the sensitivity of breast cancer cells to doxorubicin. More importantly, we found that activation of PI3K/AKT pathway could phosphorylate FBP2, and then make FBP2 shuttle from cytoplasm into the nucleus, which was the main mechanism of breast cancer cell proliferation and drug resistance. Taken together, our findings supported the notion that FBP2 might via PI3K/AKT pathway influence breast cancer progression and drug resistance, which might provide a new target for the design of anti-cancer drugs for breast cancer patients.
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Biomarcadores de Tumor/metabolismo , Neoplasias de la Mama/patología , Carcinoma Ductal de Mama/patología , Proliferación Celular/efectos de los fármacos , Doxorrubicina/farmacología , Resistencia a Antineoplásicos , Proteínas de Unión al ARN/metabolismo , Transactivadores/metabolismo , Antibióticos Antineoplásicos/farmacología , Apoptosis/efectos de los fármacos , Western Blotting , Mama/metabolismo , Mama/patología , Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/metabolismo , Carcinoma Ductal de Mama/tratamiento farmacológico , Carcinoma Ductal de Mama/metabolismo , Estudios de Casos y Controles , Femenino , Estudios de Seguimiento , Humanos , Técnicas para Inmunoenzimas , Persona de Mediana Edad , Clasificación del Tumor , Pronóstico , Tasa de Supervivencia , Células Tumorales CultivadasRESUMEN
Neuropathic pain, caused by a lesion or dysfunction of the somatosensory nervous system, is a severe debilitating condition with which clinical treatment remains challenging. Jun activation domain-binding protein (JAB1) is a multifunctional protein that participates in several signaling pathways, controlling cell proliferation and apoptosis. However, the expression and possible function of JAB1 in the pathogenesis of neuropathic pain has not been elucidated. This study aimed to investigate the possible involvement of JAB1. Here, employing a neuropathic pain model induced by chronic constriction injury (CCI) on rats, we reported the role of JAB1 in the maintenance of neuropathic pain. By western blot, we found that CCI markedly up-regulated JAB1 expression in the dorsal root ganglion (DRG) and spinal cord. Immunofluorescent assay demonstrated that JAB1 was extensively localized in IB4-, CGRP- and NF200-positive neurons in the injured L5 DRG, and mainly co-localized with NeuN in spinal cord. In addition, we showed that CCI induced phosphorylation of p65 and JNK in vivo. Intrathecal injection of JAB1 siRNA significantly attenuated the CCI-induced JNK and p65 phosphorylation and alleviated both mechanical allodynia and heat hyperalgesia in rats. Taken together, these results suggested that JAB1 promotes neuropathic pain via positively regulating JNK and NF-κB activation.
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Proteínas Quinasas JNK Activadas por Mitógenos/metabolismo , FN-kappa B/metabolismo , Neuralgia/metabolismo , Proteínas/metabolismo , Animales , Complejo del Señalosoma COP9 , Constricción Patológica/complicaciones , Activación Enzimática , Ganglios Espinales/metabolismo , Calor , Hiperalgesia/metabolismo , Hiperalgesia/fisiopatología , Péptidos y Proteínas de Señalización Intracelular , Masculino , Neuralgia/etiología , Neuralgia/fisiopatología , Estimulación Física , Ratas Sprague-Dawley , Nervio Ciático/lesiones , Médula Espinal/metabolismo , TactoRESUMEN
BACKGROUND: Hepatocellular carcinoma (HCC) is the third leading cause of cancer-related deaths worldwide. It is indispensable to understanding molecular mechanisms of HCC progression and to developing clinically useful biomarkers for this disease. AIM: In this article, we examined whether HOXC8 was associated with the poor prognosis of hepatocellular carcinoma and explored the possible underlying mechanism. METHODS: The HOXC8 and Ki67 expression levels in 86 patients with hepatocellular carcinoma were examined using immunohistochemistry. HOXC8 levels in HCC cells were downregulated by siRNA transfection. The cycle progression and cell proliferation status of HCC cells and the oxaliplatin effectiveness were evaluated by flow cytometry and CCK-8 assay. HOXC8, CyclinD1, PCNA, Nkd2, and cleaved caspase-3 levels were detected by western blot. RESULTS: HOXC8 was upregulated in HCC tissues, compared with adjacent non-tumor ones. HOXC8 expression levels in 86 patients with hepatocellular carcinoma were positively correlated with histological grade. Univariate and multivariate survival analysis revealed that HOXC8 was a significant predictor for overall survival of HCC patients. HOXC8 siRNA knockdown delayed the G1-S phase transition, inhibited cell proliferation, and attenuated resistance to oxaliplatin. CONCLUSIONS: HOXC8 promoted HCC proliferation and predicted poor prognosis. Furthermore, upregulated HOXC8 expression was associated with oxaliplatin resistance in hepatocellular carcinoma.
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Antineoplásicos/uso terapéutico , Carcinoma Hepatocelular/tratamiento farmacológico , Resistencia a Antineoplásicos , Proteínas de Homeodominio/metabolismo , Neoplasias Hepáticas/tratamiento farmacológico , Compuestos Organoplatinos/uso terapéutico , Proteínas Adaptadoras Transductoras de Señales , Adulto , Anciano , Proteínas de Unión al Calcio , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/mortalidad , Carcinoma Hepatocelular/patología , Proteínas Portadoras/metabolismo , Caspasa 3/metabolismo , Proliferación Celular/efectos de los fármacos , Ciclina D1/metabolismo , Femenino , Regulación Neoplásica de la Expresión Génica , Células Hep G2 , Proteínas de Homeodominio/genética , Humanos , Estimación de Kaplan-Meier , Antígeno Ki-67/metabolismo , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/mortalidad , Neoplasias Hepáticas/patología , Masculino , Persona de Mediana Edad , Análisis Multivariante , Clasificación del Tumor , Oxaliplatino , Antígeno Nuclear de Célula en Proliferación/metabolismo , Modelos de Riesgos Proporcionales , Interferencia de ARN , Transducción de Señal/efectos de los fármacos , Factores de Tiempo , Transfección , Resultado del Tratamiento , Regulación hacia Arriba , Adulto JovenRESUMEN
The mammalian airways are sensitive to inhaled stimuli, and airway diseases are characterized by hypersensitivity to volatile stimuli, such as perfumes, industrial solvents, and others. However, the identity and function of the cells in the airway that can sense volatile chemicals remain uncertain, particularly in humans. Here, we show that solitary pulmonary neuroendocrine cells (PNECs), which are morphologically distinct and physiologically undefined, might serve as chemosensory cells in human airways. This conclusion is based on our finding that some human PNECs expressed members of the olfactory receptor (OR) family in vivo and in primary cell culture, and are anatomically positioned in the airway epithelium to respond to inhaled volatile chemicals. Furthermore, apical exposure of primary-culture human airway epithelial cells to volatile chemicals decreased levels of serotonin in PNECs, and the led to the release of the neuropeptide calcitonin gene-related peptide (CGRP) to the basal medium. These data suggest that volatile stimulation of PNECs can lead to the secretion of factors that are capable of stimulating the corresponding receptors in the lung epithelium. We also found that the distribution of serotonin and neuropeptide receptors may change in chronic obstructive pulmonary disease, suggesting that increased PNEC-dependent chemoresponsiveness might contribute to the altered sensitivity to volatile stimuli in this disease. Together, these data indicate that human airway epithelia harbor specialized cells that respond to volatile chemical stimuli, and may help to explain clinical observations of odorant-induced airway reactions.
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Células Quimiorreceptoras/metabolismo , Células Epiteliales/metabolismo , Pulmón/inervación , Odorantes , Transducción de Señal , Animales , Biomarcadores/metabolismo , Péptido Relacionado con Gen de Calcitonina/metabolismo , Estudios de Casos y Controles , Células Cultivadas , Medios de Cultivo Condicionados/metabolismo , Hurones , Humanos , Macaca mulatta , Ratones , Fenotipo , Enfermedad Pulmonar Obstructiva Crónica/metabolismo , Ratas , Receptores Odorantes/genética , Receptores Odorantes/metabolismo , Serotonina/metabolismo , VolatilizaciónRESUMEN
Adenylate cyclase-associated protein 1 (CAP1) is a conserved protein that was found to be up-regulated in breast cancer and related to the migration of breast cancer. We verified its roles in breast cancer specimens and cell lines. In our results, 71 of 100 specimens of breast cancer showed high levels of CAP1 by immunohistochemistry. Associated with statistical analysis, we saw that CAP1 was related to the grade of breast cancer. In MDA-MB-231, the expression of CAP1 was the highest and by knocking down the expression of CAP1 in MDA-MB-231, its ability for proliferating and migrating apparently decreased and induced changes in morphology, which were related to the arrangement of F-actin. Therefore, CAP1 might be a potential molecular targeted therapy for surgery and immune treatment.
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Neoplasias de la Mama/genética , Proteínas de Ciclo Celular/genética , Movimiento Celular/genética , Proliferación Celular , Proteínas del Citoesqueleto/genética , Proteínas de Ciclo Celular/biosíntesis , Línea Celular Tumoral , Proteínas del Citoesqueleto/biosíntesis , Femenino , Regulación Neoplásica de la Expresión Génica , Técnicas de Silenciamiento del Gen , Humanos , Terapia Molecular DirigidaRESUMEN
Exacerbations of chronic obstructive pulmonary disease (COPD) lead to substantial morbidity and mortality. Viral infections could be an important cause of acute exacerbations of COPD (AECOPD) and only a few studies report the prevalence of respiratory viruses on this disease. We aimed to update the review on the prevalence of respiratory viral infection in patients with AECOPD with a meta-analysis. We reviewed the prevalence of respiratory viruses on this disease by searching PubMed systematically to identify primary studies published from Jan 1990 to March 2012. Studies met with seven criteria were extracted for meta-analysis. A total of 17 studies were eligible for the meta-analysis. Weighted overall prevalence of respiratory viruses in patients with AECOPD was 39.3% (95% CI 36.9-41.6) with a high degree of a heterogeneity (I (2) > 75%). In contrast, the rate in stable COPD patients from four studies was 13.6% (95% CI 9.0-18.2) without any apparent heterogeneity. Pooled risk ratio for respiratory viral infection was 4.1 (95% CI 2.0-8.5) for AECOPD as compared with stable COPD. Rhinovirus was the most common virus and with a weighted prevalence of 14.8% (95% CI 13.3-16.5). Respiratory viruses probably are important etiological agents in patients with AECOPD as compared with the stable COPD patients. This result would help to provide better strategies for management of AECOPD and health-care planning.
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Gripe Humana/epidemiología , Infecciones por Picornaviridae/epidemiología , Enfermedad Pulmonar Obstructiva Crónica/epidemiología , Infecciones por Virus Sincitial Respiratorio/epidemiología , Infecciones del Sistema Respiratorio/epidemiología , Progresión de la Enfermedad , Femenino , Humanos , Gripe Humana/complicaciones , Gripe Humana/virología , Masculino , Infecciones por Picornaviridae/complicaciones , Infecciones por Picornaviridae/virología , Prevalencia , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Enfermedad Pulmonar Obstructiva Crónica/virología , Infecciones por Virus Sincitial Respiratorio/complicaciones , Infecciones por Virus Sincitial Respiratorio/virología , Infecciones del Sistema Respiratorio/complicaciones , Infecciones del Sistema Respiratorio/virología , RiesgoRESUMEN
INTRODUCTION: Comprehensively evaluating the efficacy and safety of high-frequency oscillatory ventilation (HFOV) is important to allow clinicians who are using or considering this intervention to make appropriate decisions. METHODS: To find randomized controlled trials (RCTs) comparing HFOV with conventional mechanical ventilation (CMV) as an initial treatment for adult ARDS patients, we searched electronic databases (including PubMed, MedLine, Springer Link, Elsevier Science Direct, ISI web of knowledge, and EMBASE) with the following terms: "acute respiratory distress syndrome", "acute lung injury", and "high frequency oscillation ventilation". Additional sources included reference lists from the identified primary studies and relevant meta-analyses. Two investigators independently screened articles and extracted data. Meta-analysis was conducted using random-effects models. RESULTS: We included 6 RCTs with a total of 1,608 patients in this meta-analysis. Compared with CMV, HFOV did not significantly reduce the mortality at 30 or 28 days. The pooled relative risk (RR) was 1.051 (95% confidence interval (CI) 0.813 to 1.358). ICU mortality was also not significantly reduced in HFOV group, with a pooled RR of 1.218 (95% CI 0.925 to 1.604). The pooled effect sizes of HFOV for oxygenation failure, ventilation failure and duration of mechanical ventilation were 0.557 (95% CI 0.351 to 0.884), 0.892 (95% CI 0.435 to 1.829) and 0.079 (95% CI -0.045 to 0.203), respectively. The risk of barotrauma and hypotension were similar between the CMV group and HFOV group, with a RR of 1.205 (95% CI 0.834 to 1.742) and a RR of 1.326 (95% CI 0.271 to 6.476), respectively. CONCLUSIONS: Although HFOV seems not to increase the risk of barotrauma or hypotension, and reduces the risk of oxygenation failure, it does not improve survival in adult acute respiratory distress syndrome patients.
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Ventilación de Alta Frecuencia/métodos , Ensayos Clínicos Controlados Aleatorios como Asunto/métodos , Síndrome de Dificultad Respiratoria/diagnóstico , Síndrome de Dificultad Respiratoria/terapia , Adulto , Ventilación de Alta Frecuencia/efectos adversos , Humanos , Unidades de Cuidados Intensivos/tendencias , Mortalidad/tendencias , Ensayos Clínicos Controlados Aleatorios como Asunto/mortalidad , Respiración Artificial/efectos adversos , Respiración Artificial/métodos , Síndrome de Dificultad Respiratoria/mortalidad , Resultado del TratamientoRESUMEN
The aggregation and prion-like propagation of tau are the hallmarks of Alzheimer's disease (AD) and other tauopathies. However, the molecular mechanisms underlying the assembly and spread of tau pathology remain elusive. Epidemiological data show that exposure to fine particulate matter (PM2.5) is associated with an increased risk of AD. However, the molecular mechanisms remain unknown. Here, we showed that PM2.5 triggered the aggregation of tau and promoted the formation of tau fibrils. Injection of PM2.5-induced tau preformed fibrils (PFFs) into the hippocampus of tau P301S transgenic mice promoted the aggregation of tau and induced cognitive deficits and synaptic dysfunction. Furthermore, intranasal administration of PM2.5 exacerbated tau pathology and induced cognitive impairment in tau P301S mice. In conclusion, our results indicated that PM2.5 exposure promoted tau pathology and induced cognitive impairments. These results provide mechanistic insight into how PM2.5 increases the risk of AD.
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Modelos Animales de Enfermedad , Hipocampo , Ratones Transgénicos , Material Particulado , Tauopatías , Proteínas tau , Animales , Material Particulado/toxicidad , Proteínas tau/metabolismo , Ratones , Tauopatías/metabolismo , Tauopatías/patología , Hipocampo/metabolismo , Hipocampo/patología , Hipocampo/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/patología , Enfermedad de Alzheimer/metabolismo , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/inducido químicamente , Enfermedad de Alzheimer/etiología , Agregación Patológica de Proteínas/metabolismo , Humanos , MasculinoRESUMEN
Cisplatin resistance significantly impacts the antitumor efficacy of cisplatin chemotherapy and contributes to poor prognosis, including metastasis. In this study, we present the utilization of metal-organic framework (MOF) nanoparticles as the therapeutic component and drug loading scaffold for implementing a ternary combination therapeutic strategy to combat cisplatin-resistant lung cancer and metastasis. Specifically, by engineering MOFs (Cis@MOF-siVEGF) through the self-assembly of THPP as photosensitizer for photodynamic therapy (PDT), along with the incorporation of cisplatin (DDP) and VEGF siRNA (siVEGF), we propose the leverage of photodynamic-induced oxidative damage and gene silencing of the angiogenic factor to reverse cisplatin resistance and sensitize therapeutic potency. Our findings demonstrated that the chemo/photodynamic/antiangiogenic triple combination therapy via Cis@MOF-siVEGF under irradiation effectively inhibits cisplatin-resistant tumor growth and induces abscopal effects. Importantly, molecular mechanistic exploration suggested that MUC4 exerted regulatory effects on governing cancer metastasis, thus representing a potential immunotherapeutic target for cancer intervention. Overall, our study creates a MOFs-based multicomponent delivery platform for complementary therapeutic modules with synergistically enhanced antitumor efficacy and sheds light on potential regulatory mechanisms on cisplatin-resistance cancers.
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Carcinoma de Pulmón de Células no Pequeñas , Cisplatino , Resistencia a Antineoplásicos , Neoplasias Pulmonares , Estructuras Metalorgánicas , ARN Interferente Pequeño , Factor A de Crecimiento Endotelial Vascular , Cisplatino/farmacología , Cisplatino/química , Estructuras Metalorgánicas/química , Estructuras Metalorgánicas/farmacología , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/terapia , Humanos , ARN Interferente Pequeño/química , ARN Interferente Pequeño/farmacología , Factor A de Crecimiento Endotelial Vascular/metabolismo , Resistencia a Antineoplásicos/efectos de los fármacos , Animales , Ratones , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/terapia , Mucina 4/metabolismo , Fotoquimioterapia , Antineoplásicos/química , Antineoplásicos/farmacología , Línea Celular Tumoral , Fármacos Fotosensibilizantes/química , Fármacos Fotosensibilizantes/farmacología , Fármacos Fotosensibilizantes/uso terapéutico , Metástasis de la Neoplasia , Ratones Desnudos , Ratones Endogámicos BALB CRESUMEN
Metal-organic framework (MOF) glasses are an emerging class of glasses which complement traditional inorganic, organic and metallic counterparts due to their hybrid nature. Although a few zeolitic imidazolate frameworks have been made into glasses, how to melt and quench the largest subclass of MOFs, metal carboxylate frameworks, into glasses remains challenging. Here, we develop a strategy by grafting the zwitterions on the carboxylate ligands and incorporating organic acids in the framework channels to enable the glass formation. The charge delocalization of zwitterion-acid subsystem and the densely filled channels facilitate the coordination bonding mismatch and thus reduce the melting temperature. Following melt-quenching realizes the glass formation of a family of carboxylate MOFs (UiO-67, UiO-68 and DUT-5), which are usually believed to be un-meltable. Our work opens up an avenue for melt-quenching porous molecular solids into glasses.
RESUMEN
BACKGROUND: Neutrophil to lymphocyte ratio (NLR) has been shown to be a prognosis indicator in different types of cancer. We aimed to investigate the association between NLR and therapy response, progression free survival (PFS) and overall survival (OS) in advanced non-small cell lung cancer (NSCLC) patients treated with first-line platinum-based chemotherapy. METHODS: Patients who were hospitalized between January 2007 and December 2010 were enrolled and eliminated according to the inclusion and exclusion criteria. The NLR was defined as the absolute neutrophil count divided by the absolute lymphocyte count. Logistic regression analysis was applied for response rate and Cox regression analysis was adopted for PFS and OS. A P value of ≤0.05 was considered to be statistically significant. RESULTS: A total of 182 patients were enrolled in the current study. The median PFS was 164.5 days and median OS was 439.5 days. The statistical analysis data indicated that low pretreatment NLR (≤ 2.63) (OR = 2.043, P = 0.043), decreased posttreatment NLR (OR = 2.368, P = 0.013), well and moderate differentiation (OR = 2.773, P = 0.021) and normal CEA level (≤ 9.6 ng/ml) (OR = 2.090, P = 0.046) were associated with response to first-line platinum-based chemotherapy. A high pretreatment NLR (HR = 1.807, P = 0.018 for PFS, HR = 1.761, P = 0.020 for OS) and distant metastasis (HR = 2.118, P = 0.008 for PFS, HR = 2.753, P = 0.000 for OS) were independent prognostic factors for PFS and OS. CONCLUSION: Elevated pretreatment NLR might be a potential biomarker of worse response to first-line platinum-based chemotherapy and shorter PFS and OS for advanced NSCLC patients. To confirm these findings, larger, prospective and randomized studies are needed.
Asunto(s)
Carcinoma de Pulmón de Células no Pequeñas/inmunología , Neoplasias Pulmonares/inmunología , Recuento de Linfocitos , Linfocitos/inmunología , Neutrófilos/inmunología , Anciano , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Carcinoma de Pulmón de Células no Pequeñas/tratamiento farmacológico , Carcinoma de Pulmón de Células no Pequeñas/mortalidad , Cisplatino/uso terapéutico , Supervivencia sin Enfermedad , Femenino , Humanos , Recuento de Leucocitos , Neoplasias Pulmonares/tratamiento farmacológico , Neoplasias Pulmonares/mortalidad , Masculino , Persona de Mediana Edad , Pronóstico , Resultado del TratamientoRESUMEN
BACKGROUND: Infertility is caused by heterogeneous risks, but most of them are unexplained. The sperm DNA Fragmentation Index (DFI) was increasingly acknowledged as a parameter for the evaluation of male infertility. This study aimed to investigate the association between sperm DFI and laboratory and clinical outcomes in a population with unexplained infertility. METHODS: The clinical data of an infertile population was collected for the selection of reproductive patients with unexplained infertility. The authors classified the patients with normal sperm parameters in a control group (DFI < 25%) and an observation group (DFI ≥ 25%) and compared the difference in basal characteristics, laboratory, and clinical outcomes between the two groups. The authors conducted a correlation analysis to examine the relationship between DFI and the number of D3 good-quality embryos, as well as the clinical pregnancy rate and live birth rate. A total of 176 cases were enrolled in the retrospective study. RESULTS: The observation group (n = 88) showed advanced male age, lower sperm concentration, progressive motility, and morphology assessment than the control group. In addition, lower No. of D3 good-quality embryos, clinical pregnancy rate, and the live birth rate were shown in the observation group. A negative correlation between the DFI and No. of D3 good-quality embryos (rs = -0.347, p < 0.001) or live birth rate (rs = -0.185, p = 0.028) was shown. CONCLUSIONS: Sperm DFI was a good indicator for the prediction of D3 good-quality embryos in unexplained infertility couples, but it did not provide sufficient information regarding clinical pregnancy outcome but live pregnancy outcome.
Asunto(s)
Infertilidad Masculina , Semen , Femenino , Humanos , Masculino , Embarazo , Fragmentación del ADN , Estudios Retrospectivos , Fertilización In Vitro , Espermatozoides , Infertilidad Masculina/genética , Resultado del EmbarazoRESUMEN
Background: Immunotherapy has greatly increased the survival time of patients with extensive-stage small cell lung cancer (ES-SCLC), and is now a standard first-line treatment for these patients. Increasing evidence suggests a possible synergistic effect between immunotherapy and radiotherapy, yet there is a paucity of evidence regarding the efficacy and safety of thoracic radiotherapy (TRT) combined with chemo-immunotherapy for ES-SCLC. Methods: The medical records of 78 consecutive patients with ES-SCLC who received TRT in combination with chemo-immunotherapy at Jinling Hospital and Jiangsu Cancer Hospital from January 2019 to January 2023 were retrospectively reviewed. The median overall survival (mOS) time and median progression-free survival (mPFS) time were used to evaluate efficacy, and the incidence of adverse events (AEs) was used to evaluate safety. Results: The median follow-up time was 31.9 months, the objective response rate (ORR) was 59%, and the disease control rate (DCR) was 89.8%. The mOS time was 20.0 months, and the 6-month OS rate was 95%. The mPFS time was 9.2 months, and the 6-month PFS rate was 78%. There were no treatment-related deaths. The incidence of pneumonitis was 23.1%, the incidence of radiation esophagitis was 5.1%, and 2 patients experienced high-grade pneumonitis. Primary liver metastasis was a predictor of poor OS and PFS. Patients who received consolidative TRT after chemo-immunotherapy experienced more benefit than those who received TRT as palliative or salvage treatment for superior vena cava syndrome or disease progression. Conclusions: TRT is a feasible treatment for patients who receive chemo-immunotherapy for the management of ES-SCLC in consideration of its considerable efficacy and tolerable safety risk. This treatment is especially useful for patients without primary liver metastasis and who receive consolidative TRT after chemo-immunotherapy. Large-scale prospective studies are needed to confirm the efficacy and safety of this treatment modality.