Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 19 de 19
Filtrar
1.
IEEE Trans Image Process ; 33: 1710-1725, 2024.
Artículo en Inglés | MEDLINE | ID: mdl-38416622

RESUMEN

Deep learning has excelled in single-image super-resolution (SISR) applications, yet the lack of interpretability in most deep learning-based SR networks hinders their applicability, especially in fields like medical imaging that require transparent computation. To address these problems, we present an interpretable frequency division SR network that operates in the image frequency domain. It comprises a frequency division module and a step-wise reconstruction method, which divides the image into different frequencies and performs reconstruction accordingly. We develop a frequency division loss function to ensure that each reconstruction module (ReM) operates solely at one image frequency. These methods establish an interpretable framework for SR networks, visualizing the image reconstruction process and reducing the black box nature of SR networks. Additionally, we revisited the subpixel layer upsampling process by deriving its inverse process and designing a displacement generation module. This interpretable upsampling process incorporates subpixel information and is similar to pre-upsampling frameworks. Furthermore, we develop a new ReM based on interpretable Hessian attention to enhance network performance. Extensive experiments demonstrate that our network, without the frequency division loss, outperforms state-of-the-art methods qualitatively and quantitatively. The inclusion of the frequency division loss enhances the network's interpretability and robustness, and only slightly decreases the PSNR and SSIM metrics by an average of 0.48 dB and 0.0049, respectively.

2.
Int J Infect Dis ; 130: 17-19, 2023 May.
Artículo en Inglés | MEDLINE | ID: mdl-36828236

RESUMEN

A rare case of fungus Arthroderma multifidum infection occurred in a 63-year-old man. The patient had some risk factors, including occupational exposure, immunosuppressive state, and structural basis following pulmonary tuberculosis and pneumothorax surgery. The pathogen was repeatedly isolated from bronchoalveolar lavage fluid and identified by gene sequencing. It is the first report of human infection caused by A. multifidum. Whole genome sequencing and analysis of its genomic characterization are completed. The findings provide us with a key clinical insight that the combination of immune suppression and environmental exposure could create an ideal condition for zoonotic fungal infections.


Asunto(s)
Arthrodermataceae , Neumonía , Masculino , Animales , Humanos , Persona de Mediana Edad , Arthrodermataceae/genética , Pulmón , Zoonosis/diagnóstico , Zoonosis/microbiología , Líquido del Lavado Bronquioalveolar/microbiología
3.
World J Clin Cases ; 10(28): 10186-10192, 2022 Oct 06.
Artículo en Inglés | MEDLINE | ID: mdl-36246838

RESUMEN

BACKGROUND: With programmed death-1 (PD-1) inhibitors becoming the standard treatment for lung cancer, PD-1-related adverse reactions and treatment have gradually become prominent. CASE SUMMARY: First reported case of tislelizumab-related enteritis successfully treated with adalimumab 40mg every 2 wk for 3 times in an advanced lung cancer patient who received first-line tislelizumab/pemetrexed/carboplatin for 4 cycles. The patient continued receiving the treatment of pemetrexed/carboplatin after symptoms, abdominal computed tomography and colonoscopy improved, significant diarrhea was not occurred. CONCLUSION: Adalimumab can be an effective treatment option for patients with PD-1 antibody related enteritis if they do not respond well to glucocorticoid treatment.

4.
Respir Res ; 23(1): 289, 2022 Oct 21.
Artículo en Inglés | MEDLINE | ID: mdl-36271366

RESUMEN

BACKGROUND: Asthma is one of the most common chronic diseases that affects more than 300 million people worldwide. Though most asthma can be well controlled, individuals with severe asthma experience recurrent exacerbations and impose a substantial economic burden on healthcare system. Neutrophil inflammation often occurs in patients with severe asthma who have poor response to glucocorticoids, increasing the difficulty of clinical treatment. METHODS: We established several neutrophil-dominated allergic asthma mouse models, and analyzed the airway hyperresponsiveness, airway inflammation and lung pathological changes. Neutrophil extracellular traps (NETs) formation was analyzed using confocal microscopy and western blot. RESULTS: We found that the ovalbumin (OVA)/complete Freund's adjuvant (CFA)/low-dose lipopolysaccharide (LPS)-induced mouse model best recapitulated the complex alterations in the airways of human severe asthmatic patients. We also observed OVA/CFA/LPS-exposed mice produced large quantities of neutrophil extracellular traps (NETs) in lung tissue and bone marrow neutrophils. Furthermore, we found that reducing the production of NETs or increasing the degradation of NETs can reduce airway inflammation and airway hyperresponsiveness. CONCLUSION: Our findings identify a novel mouse model of neutrophilic asthma. We have also identified NETs play a significant role in neutrophilic asthma models and contribute to neutrophilic asthma pathogenesis. NETs may serve as a promising therapeutic target for neutrophilic asthma.


Asunto(s)
Asma , Hipersensibilidad Respiratoria , Ratones , Humanos , Animales , Ovalbúmina , Lipopolisacáridos/toxicidad , Activación Neutrófila , Adyuvante de Freund/efectos adversos , Modelos Animales de Enfermedad , Glucocorticoides/efectos adversos , Asma/metabolismo , Inflamación/inducido químicamente , Inflamación/patología , Hipersensibilidad Respiratoria/inducido químicamente
5.
Front Med (Lausanne) ; 9: 831213, 2022.
Artículo en Inglés | MEDLINE | ID: mdl-35280885

RESUMEN

Mucormycosis is a rare and invasive fungal infection with high mortality. Cases of invasive pulmonary mucormycosis that involve allergic reactions such as allergic bronchopulmonary mycosis are rarely reported. Herein, we describe a case of invasive pulmonary mucormycosis overlapping with allergic diseases in a patient who presented with eosinophilia and high total plasma immunoglobulin E (IgE). The patient was successfully treated with systemic corticosteroids (initial dose of prednisolone approximately 0.5 mg/kg per day, total duration less than 3 months) combined with posaconazole antifungal therapy. The treatment resulted in recovery of peripheral-blood eosinophil count and total plasma IgE, and significant reduction in lung lesions. A subsequent lobectomy was performed. The findings in this case indicate that systemic corticosteroid therapy may contribute to the treatment of pulmonary mucormycosis combined with allergic factors.

6.
World J Clin Cases ; 9(22): 6435-6442, 2021 Aug 06.
Artículo en Inglés | MEDLINE | ID: mdl-34435009

RESUMEN

BACKGROUND: Antisynthetase syndrome (ASS) is characterized by the presence of antisynthetase antibodies coupled with clinical findings such as fever, polymyositis-dermatomyositis and interstitial lung disease. It is, however, rare to observe ASS association with B cell lymphoma presenting severe pneumonia as the first clinical manifestation. CASE SUMMARY: We evaluated a 59-year-old male patient who presented with cough with sputum, shortness of breath and fever for 13 d. A chest computed tomography radiograph revealed bilateral diffuse ground-glass infiltrates in both upper fields, left lingual lobe and right middle lobe. Initially, the patient was diagnosed with severe community-acquired pneumonia and respiratory failure. He was empirically treated with broad-spectrum antibiotics, without improvement. Further analysis showed an ASS panel with anti-PL7 antibodies. Besides, electromyography evaluation demonstrated a manifestation of myogenic damage, while deltoid muscle biopsy showed irregular muscle fiber bundles especially abnormal lymphocyte infiltration. In addition, bone marrow biopsy revealed high invasive B cell lymphoma. Thus, the patient was diagnosed with a relatively rare anti-PL7 antibody positive ASS associated with B cell lymphoma. CONCLUSION: This case highlights that rapidly progressive lung lesions and acute hypoxemic respiratory failure associated with heliotrope rash and extremely high lactate dehydrogenase level should be considered as the characteristics of non-infectious diseases, especially ASS and B cell lymphoma.

7.
Infect Drug Resist ; 14: 1191-1198, 2021.
Artículo en Inglés | MEDLINE | ID: mdl-33790589

RESUMEN

PURPOSE: Parvimonas micra (P. micra) is a Gram-positive anaerobic bacterium distributed in the oral cavity, with a potential to become pathogenic causing lung abscess. Due to the lack of specificity of symptoms and the difficulty in culture, the diagnosis of lung abscess associated with P. micra is delayed. It is essential to elucidate the clinical characteristics of lung abscess associated with P. micra. METHODS: From January 2019 to July 2020, five patients with chronic lung abscess associated with P. micra diagnosed by pathological biopsy and metagenomic next-generation sequencing (mNGS) were analyzed in this retrospective study. RESULTS: Among the five patients, four had a history of smoking, three had periodontitis, and two had a history of drinking. The average course of the disease was 6.5 months. High-density flake-like or mass shadows with irregular boundaries were observed in the chest computed tomography (CT) images of the five patients, and liquefactive necrosis was detected in the middle of the lesions; however, no gas-liquid plane or cavity was noted, making it difficult to distinguish a lung cancer. The pathological biopsy of the five patients showed chronic inflammation of lung tissue, and P. micra was detected by mNGS in the biopsy or bronchoalveolar lavage fluid samples. Two patients were treated with amoxicillin-clavulanate, two had metronidazole, and one had moxifloxacin. Among them, four recovered after receiving antibiotic treatment, and the remaining one underwent surgical resection due to poor antibiotic treatment effect. CONCLUSION: Chronic lung abscess associated with P. micra, common in elderly male smokers with poor oral hygiene, is often diagnosed in a delayed manner and misdiagnosed as lung cancer. The mNGS technology is beneficial to the rapid determination of P. micra.

8.
J Cancer ; 10(4): 1004-1012, 2019.
Artículo en Inglés | MEDLINE | ID: mdl-30854106

RESUMEN

The tumor-associated inflammatory microenvironment plays a pivotal role in human non-small cell lung cancer (NSCLC) development. FGFR1 and TLR4 involve in the regulation of inflammatory microenvironment of NSCLC.However, the relationship between the FGFR1 and TLR4 signaling and the mechanisms that involved in tumor-associated microenvironment are still unclear. We investigated the expression of FGFR1 and TLR4 in cancerous tissues and noncancerous lung tissues from 60 primary NSCLC patients using immunohistochemical staining. Three cell lines (A549, PC-9 and SK-MES-1) were used for in vitro studies. We demonstrated that the expression of FGFR1 and TLR4 was significantly correlated (r=0.504, p<0.05) in NSCLC tissues. We revealed that activation of FGFR1 and TLR4 pathways by specific signaling agonist increased Akt phosphorylation. Further results showed that FGFR1 and TLR4 regulated cell proliferation and migration and promoted the production of proinflammatory or immunosuppressive cytokines TNF-α and IL-6. Meanwhile, the PI3K inhibitor LY294002 rescued these changes. Taken together, our results indicate that the FGFR1 expression level is positively correlated with TLR4 expression level in human NSCLC tissues. The activation of FGFR1 and TLR4 in cancer cells contributes to inflammatory microenvironment via PI3K/Akt signaling and may make a significant contribution to the progression of human NSCLC.

9.
Cell Death Differ ; 26(10): 2086-2099, 2019 Oct.
Artículo en Inglés | MEDLINE | ID: mdl-30683915

RESUMEN

Glutathione S-transferases P1 (GSTP1) is a phase II detoxifying enzyme and increased expression of GSTP1 has been linked with acquired resistance to anti-cancer drugs. However, most anticancer drugs are not good substrates for GSTP1, suggesting that the contribution of GSTP1 to drug resistances might not be dependent on its capacity to detoxify chemicals or drugs. In the current study, we found a novel mechanism by which GSTP1 protects human breast cancer cells from adriamycin (ADR)-induced cell death and contributes to the drug resistance. GSTP1 protein level is very low in human breast cancer cell line MCF-7 but is high in ADR-resistant MCF-7/ADR cells. Under ADR treatment, MCF-7/ADR cells showed a higher autophagy level than MCF-7 cells. Overexpression of GSTP1 in MCF-7 cells by using the DNA transfection vector enhanced autophagy and down-regulation of GSTP1 through RNA interference in MCF-7/ADR cells decreased autophagy. When autophagy was prevented, GSTP1-induced ADR resistance reduced. We found that GSTP1 enhanced autophagy level in MCF-7 cells through interacting with p110α subunit of phosphatidylinositol-3-kinase (PI3K) and then inhibited PI3K/protein kinase B (AKT)/mechanistic target of rapamycin (mTOR) activity. Proline123, leucine160, and glutamine163, which located in C terminal of GSTP1, are essential for GSTP1 to interact with p110α, and the following autophagy and drug resistance regulation. Taken together, our findings demonstrate that high level of GSTP1 maintains resistance of breast cancer cells to ADR through promoting autophagy. These new molecular insights provide an important contribution to our better understanding the effect of GSTP1 on the resistance of tumors to chemotherapy.


Asunto(s)
Neoplasias de la Mama/tratamiento farmacológico , Neoplasias de la Mama/enzimología , Doxorrubicina/farmacología , Gutatión-S-Transferasa pi/metabolismo , Antibióticos Antineoplásicos/farmacología , Autofagia/efectos de los fármacos , Neoplasias de la Mama/genética , Neoplasias de la Mama/patología , Muerte Celular/efectos de los fármacos , Línea Celular Tumoral , Fosfatidilinositol 3-Quinasa Clase I/metabolismo , Femenino , Humanos , Células MCF-7 , Espectrometría de Masas/métodos , Microscopía Electrónica de Transmisión/métodos , Fosfatidilinositol 3-Quinasas/metabolismo , Proteínas Proto-Oncogénicas c-akt/metabolismo , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Transfección
10.
PLoS One ; 12(11): e0188665, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29190716

RESUMEN

Cancer stem-like cells (CSCs) have been reported to play major roles in tumorigenesis, tumor relapse, and metastasis after therapy against colorectal carcinoma (CRC). Therefore, identification of colorectal CSC regulators could provide promising targets for CRC. Ligand-of-Numb protein X1 (LNX1) is one E3 ubiquitin ligase which mediates the ubiquitination and degradation of Numb. Although several studies indicate LNX1 could be a potential suppressor of cancer diseases, the functions of LNX1 in mediating cancer stemness remain poorly understood. In this study, LNX1 was identified as a negative regulator of cancer stemness in CRC, which was downregulated in colonospheres or side population (SP) cells. Furthermore, the coxsackievirus and adenovirus receptor (CXADR) was found to be one critical downstream mediator of cancer stemness regulated by LNX1. Interestingly, the anti-breast cancer drug tamoxifen was found to be an agonist of LNX1 and suppress cancer stemness in CRC. In sum, this study provided the evidences that LNX1 signaling plays important roles in regulating the stemness of colon cancer cells.


Asunto(s)
Neoplasias Colorrectales/patología , Células Madre Neoplásicas/patología , Ubiquitina-Proteína Ligasas/metabolismo , Regulación hacia Arriba , Línea Celular Tumoral , Neoplasias Colorrectales/metabolismo , Humanos , Células Madre Neoplásicas/metabolismo , Ubiquitina-Proteína Ligasas/antagonistas & inhibidores
11.
Drug Des Devel Ther ; 11: 3065-3075, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29118572

RESUMEN

PURPOSE: Methotrexate is widely used in chemotherapy for a variety of malignancies. However, severe toxicity, poor pharmacokinetics, and narrow safety margin of methotrexate limit its clinical application. The aim of this study was to develop sustained-release methotrexate-loaded implants and evaluate antitumor activity of the implants after intratumoral implantation. MATERIALS AND METHODS: We prepared the implants containing methotrexate, poly(D,L-lactide-co-glycolide), and polyethylene glycol 4000 with the melt-molding technique. The implants were characterized with regards to drug content, morphology, in vitro, and in vivo release profiles. Differential scanning calorimetry (DSC) and Fourier transform infrared spectroscopy (FTIR) were carried out to investigate the physicochemical properties of the implants. Furthermore, the antitumor activity of the implants was tested in a sarcoma 180 mouse model. RESULTS: The implants were prepared as solid rods. Scanning electron microscopy images showed a smooth surface of the implant, suggesting that methotrexate was homogeneously dispersed in the polymeric matrix. The results of DSC and FTIR indicated that no significant interaction between methotrexate and the polymer was observed in the implants. Both in vitro and in vivo release profiles of the implants were characterized by burst release followed by sustained release of methotrexate. Intratumoral implantation of methotrexate-loaded implants could efficiently delay tumor growth. Moreover, an increase in the dose of implants led to a higher tumor suppression rate without additional systemic toxicity. CONCLUSION: These results demonstrate that methotrexate-loaded implants had significant antitumor efficacy in a sarcoma 180 mouse model without dose-limiting side effects, and suggest that the implants could be potentially applied as an intratumoral delivery system to treat cancer.


Asunto(s)
Antineoplásicos/farmacología , Portadores de Fármacos/química , Metotrexato/farmacología , Sarcoma 180/tratamiento farmacológico , Animales , Antineoplásicos/administración & dosificación , Antineoplásicos/toxicidad , Rastreo Diferencial de Calorimetría , Preparaciones de Acción Retardada , Sistemas de Liberación de Medicamentos , Implantes de Medicamentos , Liberación de Fármacos , Femenino , Ácido Láctico/química , Masculino , Metotrexato/administración & dosificación , Metotrexato/toxicidad , Ratones , Microscopía Electrónica de Rastreo , Polietilenglicoles/química , Ácido Poliglicólico/química , Copolímero de Ácido Poliláctico-Ácido Poliglicólico , Ratas , Ratas Wistar , Sarcoma 180/patología
12.
Eur J Pharmacol ; 815: 274-281, 2017 Nov 15.
Artículo en Inglés | MEDLINE | ID: mdl-28943104

RESUMEN

Fructose 1, 6-diphosphate (FDP), a glycolytic intermediate,has been identified to possess antioxidant activities. Here we show the protective effect of FDP against alcohol-induced liver injury in mice and the underlying mechanisms. The in vivo experiments demonstrated that FDP, orally administered to mice, dose-dependently suppressed alcohol (50%, v/v, 12ml/kg)-induced increase of serum activities of alanine aminotransferase (ALT) and aspartate aminotransferase (AST), serum triglyceride (TG) level and hepatic malondialdehyde (MDA) level. FDP also inhibited liver histological lesions induced by seven-day administration of alcohol to mice. In vitro study indicated that FDP inhibited ethanol-induced L02 cell apoptosis via reducing pro-caspase3 protein level and increasing poly ADP-ribose polymerase (PARP) cleavage. The mechanism analysis showed that FDP prevented ethanol-induced decrease of mouse antioxidant capability through inhibiting the reducion of the level of glutathione (GSH) and activities of superoxide dismutase (SOD), catalase (CAT), glutathione reductase (GR) and glutathione peroxidase (GSH-PX) in mouse livers, and suppressing the reducion of GSH level and SOD activity in L02 cells. FDP also enhanced alcohol metabolic rate through increasing alcohol dehydrogenase (ADH) activity and acetaldehyde dehydrogenase (ALDH) protein level, and down-regulating cytochrome p450 2E1 (CYP2E1). These results displayed that FDP protected mice from alcohol-induced liver injury, suggesting the potential activity of FDP in preventing alcoholic liver disease (ALD).


Asunto(s)
Enfermedad Hepática Inducida por Sustancias y Drogas/metabolismo , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Etanol/efectos adversos , Etanol/metabolismo , Fructosadifosfatos/farmacología , Estrés Oxidativo/efectos de los fármacos , Animales , Apoptosis/efectos de los fármacos , Enfermedad Hepática Inducida por Sustancias y Drogas/patología , Hepatocitos/efectos de los fármacos , Hepatocitos/patología , Humanos , Masculino , Ratones , Ratones Endogámicos ICR
13.
Cell Immunol ; 312: 15-24, 2017 02.
Artículo en Inglés | MEDLINE | ID: mdl-27884393

RESUMEN

BACKGROUND: In our previous studies, we have indentified that 1,25-dihydroxyvitamin D3 (1,25(OH)2D3) can alleviate toluene diisocyanate-induced airway epithelial barrier disruption and we also found that vascular endothelial growth factor (VEGF) derived from airway epithelials cells could disrupt epithelial barrier. OBJECTIVE: The study aimed to investigate whether 1,25(OH)2D3 can inhibit house dust mite (HDM) induced airway epithelial barrier dysfunction by regulating the VEGF pathway. METHOD: The 16HBE and BEAS-2B cells were cultured and treated according to the experiment requirement. Trans Epithelial Electric Resistance (TEER), permeability of epithelial layer, and distribution and expression of junction proteins were used to evaluate the cell layer barrier function, Western Blot was used to evaluate the expression of junction proteins and phosphorylated Akt in the cells, RT-PCR and ELISA were used to evaluate the VEGF gene expression and protein release in the cells. Recombinant VEGF165 was used to determine the role of the VEGF pathway in the epithelial barrier function. RESULTS: HDM resulted in a decline in TEER and increase of cell permeability, following abnormal distribution and expression of junction proteins (E-Cadherin and zona occludens (ZO)-1), accompanied by a significant upregulation of VEGF and phosphorylated Akt, which were all partly recovered by treatment with either 1,25(OH)2D3 or PI3K inhibitor LY294002. VEGF165-induced barrier dysfunction was accompanied by disruption of the epithelial E-cadherin and ß-catenin, pretreatment of 1,25(OH)2D3 and LY294002 markedly attenuated VEGF-induced airway barrier disruption in 16HBE cells. CONCLUSION: 1,25(OH)2D3 can alleviate HDM-induced airway epithelial barrier dysfunction by inhibiting PI3K pathway-dependent VEGF release.


Asunto(s)
Antialérgicos/farmacología , Calcitriol/farmacología , Hipersensibilidad/tratamiento farmacológico , Mucosa Respiratoria/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo , Animales , Antígenos Dermatofagoides/inmunología , Cadherinas/metabolismo , Línea Celular , Permeabilidad de la Membrana Celular/efectos de los fármacos , Impedancia Eléctrica , Humanos , Hipersensibilidad/inmunología , Fosfatidilinositol 3-Quinasas/metabolismo , Pyroglyphidae , Mucosa Respiratoria/patología , Transducción de Señal/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/antagonistas & inhibidores , beta Catenina/metabolismo
14.
Mediators Inflamm ; 2015: 587378, 2015.
Artículo en Inglés | MEDLINE | ID: mdl-26273137

RESUMEN

Conventional concept suggests that immediate surgery is the optimal choice for elderly hip fracture patients; however, few studies focus on the adverse effect of immediate surgery. This study aims to examine the adverse effect of immediate surgery, as well as to explore the meaning of mtDNA release after trauma. In the experiment, elderly rats, respectively, received hip fracture operations or hip fracture plus intramedullary nail surgery. After fracture operations, the serum mtDNA levels as well as the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. After immediate surgery, the above variables were further increased. The serum mtDNA levels were significantly related with the serum cytokine (TNF-α and IL-10) levels and pulmonary histological score. In order to identify the meaning of mtDNA release following hip fracture, the elderly rats received injections with mtDNA. After treatment, the related indicators of systemic inflammatory response and lung injury significantly increased in the rats. These results demonstrated that the immediate surgery increased the mtDNA release that could aggravate systemic inflammatory response and lung injury induced by elderly hip fracture; serum mtDNA might serve as a potential biomarker of systemic inflammatory response and lung injury following elderly hip fracture.


Asunto(s)
ADN Mitocondrial/metabolismo , Fijación Intramedular de Fracturas/efectos adversos , Fracturas de Cadera/inmunología , Fracturas de Cadera/cirugía , Inflamación/inmunología , Lesión Pulmonar/inmunología , Animales , ADN Mitocondrial/sangre , Inflamación/etiología , Interleucina-10/sangre , Lesión Pulmonar/etiología , Masculino , Ratas , Ratas Sprague-Dawley , Factores de Tiempo , Factor de Necrosis Tumoral alfa/sangre
15.
Cell Immunol ; 295(2): 137-43, 2015 Jun.
Artículo en Inglés | MEDLINE | ID: mdl-25880105

RESUMEN

Cigarette smoke extracts (CSE) alter calpain-1 expression via ERK signaling pathway in bronchial epithelial cells. 1α,25-dihydroxyvitamin D3 (1,25D3) inhibits cigarette smoke-induced epithelial barrier disruption. This study was aimed to explore whether the 1,25D3 counteracted the CSE effects in a human bronchial epithelial cell line (16HBE). In particular, transepithelial electrical resistance (TER) and permeability, expression and distribution of E-cadherin and ß-catenin, calpain-1 expression, and ERK phosphorylation were assessed in the CSE-stimulated 16HBE cells. The CSE induced the ERK phosphorylation, improved the calpain-1 expression, increased the distribution anomalies and the cleaving of E-cadherin and ß-catenin, and resulted in the TER reduction and the permeability increase. The 1,25D3 reduced these pathological changes. The 1,25D3 mediated effects were associated with a reduced ERK phosphorylation. In conclusion, the present study provides compelling evidences that the 1,25D3 may be considered a possible valid therapeutic option in controlling the cigarette smoke-induced epithelial barrier disruption.


Asunto(s)
Calcitriol/farmacología , Nicotiana/efectos adversos , Mucosa Respiratoria/efectos de los fármacos , Mucosa Respiratoria/inmunología , Humo/efectos adversos , Western Blotting , Cadherinas/inmunología , Calpaína/inmunología , Línea Celular , Impedancia Eléctrica , Células Epiteliales/inmunología , Humanos , Sistema de Señalización de MAP Quinasas/inmunología , Microscopía Fluorescente , beta Catenina/inmunología
16.
Shock ; 44(1): 52-7, 2015 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-25705859

RESUMEN

Acute lung injury is the most serious and fatal complication of the elderly patients with hip fracture, but the mechanisms are unknown. Recent studies demonstrated the mitochondrial DNA (mtDNA) release was associated with lung injury after trauma. This study aimed to examine the differential release of mtDNA between younger and elderly rats suffering from hip fracture and to investigate the possible mechanism of mtDNA in the lung injury induced by hip fracture. In the first part of the study, we investigated the effects of hip fracture on the rats. The elderly and younger rats, respectively, received hip fracture operations. The degree of lung injury was evaluated, toll-like receptor 9 (TLR9) and nuclear factor kappa B (NF-κB) were determined using Western blot, and mtDNA were analyzed by fluorescent quantitative polymerase chain reaction. In the second part of the study, we investigated the effects of mtDNA on the rats. The elderly and younger rats directly received intravenous injections with mtDNA. After 24 h, the specimens were collected and detected as the first part. Hip fracture resulted in significant mtDNA release, TLR9 and NF-κB p65 expression, and lung injury in the rats. Meanwhile, the mtDNA injection could indirectly induce lung injury. Compared to the younger ones, the elderly rats suffered more serious lung injury after hip fracture and mtDNA injection. These results suggest that the lung injury induced by hip fracture may be involved with the mtDNA release and its TLR9/NF-κB pathway.


Asunto(s)
Lesión Pulmonar Aguda/sangre , ADN Mitocondrial/sangre , Fracturas de Cadera/sangre , Transducción de Señal , Receptor Toll-Like 9 , Lesión Pulmonar Aguda/etiología , Lesión Pulmonar Aguda/patología , Animales , Regulación de la Expresión Génica , Fracturas de Cadera/complicaciones , Fracturas de Cadera/patología , Masculino , Ratas , Ratas Sprague-Dawley , Receptor Toll-Like 9/agonistas , Receptor Toll-Like 9/biosíntesis , Factor de Transcripción ReIA/biosíntesis
17.
Oncol Lett ; 6(1): 280-286, 2013 Jul.
Artículo en Inglés | MEDLINE | ID: mdl-23946818

RESUMEN

Apoptosis protease activating factor-1 (Apaf-1) and death-associated protein kinase (DAPK) are p53 pathway-related genes that play significant roles in the activation of caspases, which are involved in mitochondrial-mediated apoptosis. The present study aimed to confirm the role of hyper-methylation of the Apaf-1 and DAPK gene promoter regions in oral squamous cell carcinoma (OSCC) and the effect of the demethylation drug, 5-aza-2'-deoxycytidine (DAC). mRNA from 53 OSCC samples, 23 normal oral mucosa samples and Tca8113 human tongue carcinoma cell lines was detected using semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR). The DNA from each sample was analyzed using methylation-specific PCR (MSP). The Tca8113 cells were demethylated using DAC and the demethylation and re-expression of Apaf-1 and DAPK were analyzed. The Apaf-1 and DAPK mRNA expression index was decreased in 51 (96.23%) and 50 (94.34%) cases, respectively, in the tumor tissues. Hypermethylation of the Apaf-1 and DAPK promoter regions was detected in 46 (86.79%) and 38 (71.69%) cases, respectively. Promoter hypermethylation of the two genes correlated with a decreased mRNA expression in the tumor tissues. Subsequent to being treated with DAC, Apaf-1 and DAPK were demethylated and re-expressed in the Tca8113 cells. Apaf-1 and DAPK promoter hypermethylation may be associated with low gene expression in OSCC. Furthermore, a loss of Apaf-1 and DAPK expression may recover following demethylation. The data provide evidence that methylation exists in OSCC and may play a role in the development of this disease.

18.
Molecules ; 16(7): 5315-32, 2011 Jun 24.
Artículo en Inglés | MEDLINE | ID: mdl-21705972

RESUMEN

The aim of the reported study was to optimize the extraction process for ganoderma triterpenes and to investigate the in vivo inhibitory effect of ganoderma triterpenes on the genesis and progression of oral cancer. Single-factor and orthogonal methods were used to investigate the effects of extraction solvent, solvent amount, extraction time, extraction temperature, and number of extractions, on the extraction rate for ganoderma triterpenes. A golden hamster model with cheek pouch dynamic canceration was established to receive oral treatment of ganoderma triterpenes water solution. Animals were continuously monitored, oral tissue samples were collected for histopathologic examination, and changes in the expression of VEGF (vascular endothelial growth factor) and Caspase-3 were detected by immunohistochemical methods. Optimization of the experimental conditions allowed the identification of the optimal extraction conditions: 90% ethanol as the extraction solvent, a solvent amount by the liquid-material ratio of 35 mL/g, extraction time of 2 h and extraction temperature of 80 °C. Under these conditions, the average extraction rate of ganoderma triterpenes was 1.09%. Tests in golden hamsters showed that compared with the model group during the same period, animals in the treatment group had better conditions, constantly larger number of normal cases shown by histopathologic results (P < 0.01), and consistently smaller numbers of cases with paraplasm (P < 0.05). Immunohistochemical results showed that compared with the model group, the treatment group had significantly lower (P < 0.05) rates of positive VEGF expression in the normal state, simple epithelial hyperplasia, epithelial dysplasia or squamous cell carcinoma disease stages. Caspase-3 expression showed a tendency toward a gradual increase with the worsening of disease severity in each group. Compared with the model group, the treatment group had significantly lower (P < 0.05) rates of positive Caspase-3 in the normal state, simple epithelial hyperplasia, epithelial dysplasia or squamous cell carcinoma disease grades. Using the optimized extraction process, ganoderma triterpenes could be extracted with high efficiency, and the results of animal tests showed inhibitory effects of ganoderma triterpenes on oral mucosa cancer.


Asunto(s)
Antineoplásicos/química , Antineoplásicos/uso terapéutico , Ganoderma/química , Mucosa Bucal/patología , Neoplasias de la Boca/tratamiento farmacológico , Triterpenos/química , Triterpenos/uso terapéutico , Animales , Caspasa 3/metabolismo , Cricetinae , Femenino , Inmunohistoquímica , Masculino , Mesocricetus , Mucosa Bucal/efectos de los fármacos , Mucosa Bucal/metabolismo , Neoplasias de la Boca/metabolismo
19.
Breast Cancer Res Treat ; 96(3): 267-77, 2006 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-16341821

RESUMEN

BACKGROUND: Gene targeting using short interfering RNA(siRNA) has become a common strategy to explore gene function because of its prominent efficacy and specificity. It is proven that the application of siRNA technology to gene therapy is effective. In this study, we constructed a siRNA expression plasmid against gene X-linked inhibitor of apoptosis (XIAP), and then used breast cancer cells MCF-7 to assess its functions. MATERIALS AND METHODS: XIAP siRNA plasmid was constructed using an U6pro vector contained U6 promoter, After the plasmid had been transfected into MCF-7 cells and effected on the cell cycle, the expression change of XIAP was examined by semi-quantitative reverse transcription-polymerase chain reaction (RT-PCR) and Western blot. The apoptosis of the transfected cells was analyzed by flow cytometry, and TUNEL method. The in vitro cellular growth activities were assayed by MTT incorporation. Twenty-four nude mice were randomly divided into 3 equal groups and were inoculated with electroinjection of blank plasmid, scrambled nucleotide control (control siRNA), or siRNA against XIAP subcutaneously respectively, then the appearance and size of tumors were observed. Four weeks later the mice were killed and the volumes of tumor were calculated so as to evaluate the therapeutic effects of siRNA against XIAP. RESULTS: The successful construction of siRNA against XIAP plasmid was identified with sequencing. After the siRNA expression vector was transfected into the MCF-7 cells, the expression of XIAP gene was inhibited significantly (by 90%). The cellular growth activities in the MCF-7 cells transfected with siRNA against XIAP plasmid decreased obviously. The siRNA against XIAP plasmid knocked down XIAP expression in MCF-7 cells obviously, arrested the cell cycle in G1 phase, inhibited cell proliferation significantly, and promoted cell apoptosis in a tendency. TUNEL assay and flow cytometry showed that the classic apoptosis characters of the MCF-7 cells transfected with siRNA against XIAP plasmid manifested an apoptosis rate of 77.2%, significantly higher than those in the control siRNA group and in the blank plasmid group (both p < 0.01). The growth speed and formation rate of xenograft tumor in mice transfected with siRNA against XIAP transfected mice slowed down significantly. By HE staining, a lot of necrotic tissues could be observed in the siRNA against XIAP transfected group, however, there was no similar inhibitive effect in the control siRNA or blank plasmid group. CONCLUSION: This study represents that MCF-7 transfected cells with siRNA against XIAP remarkably suppress tumor growth and induces apoptosis, both in vitro and in vivo. This novel modality may be a promising tool for cancer therapy.


Asunto(s)
Apoptosis , Neoplasias de la Mama/terapia , ARN Interferente Pequeño/administración & dosificación , Proteína Inhibidora de la Apoptosis Ligada a X/antagonistas & inhibidores , Neoplasias de la Mama/patología , Línea Celular Tumoral , Femenino , Humanos , Regiones Promotoras Genéticas , Proteínas Proto-Oncogénicas c-akt/fisiología , Transfección , Proteína Inhibidora de la Apoptosis Ligada a X/genética
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA