RESUMEN
Melanoma differentiation-associated gene-7 (MDA-7)/interleukin-24 (IL-24) is a pleiotropic member of the IL-10 family of cytokines, and is involved in multiple biological processes, including cell proliferation, cell differentiation, tissue fibrosis, the inflammatory response, and antitumor activity. MDA-7/IL-24 can regulate epithelial integrity, homeostasis, mucosal immunity and host resistance to various pathogens by enhancing immune and inflammatory responses. Our recent study revealed the mechanism of MDA-7/IL-24 in promoting airway inflammation and airway remodeling through activating the JAK/STAT3 and ERK signaling pathways in bronchial epithelial cells. Herein, we summarize the cellular sources, inducers, target cells, signaling pathways, and biological effects of MDA-7/IL-24 in several allergic and autoimmune diseases. This review also synopsizes recent advances in clinical research targeting MDA-7/IL-24 or its receptors. Based on these advancements, we emphasize its potential as a target for immunotherapy and discuss the challenges of developing immunotherapeutic drugs targeting MDA-7/IL-24 or its receptors in autoimmune and inflammatory disorders.
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Enfermedades Autoinmunes , Inflamación , Interleucinas , Humanos , Interleucinas/inmunología , Interleucinas/metabolismo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/terapia , Enfermedades Autoinmunes/tratamiento farmacológico , Inflamación/inmunología , Animales , Transducción de Señal , Inmunoterapia/métodosRESUMEN
BACKGROUND: Chronic obstructive pulmonary disease (COPD) is underdiagnosed with the current gold standard measure pulmonary function test (PFT). A more sensitive and simple option for early detection and severity evaluation of COPD could benefit practitioners and patients. METHODS: In this multicenter retrospective study, frontal chest X-ray (CXR) images and related clinical information of 1055 participants were collected and processed. Different deep learning algorithms and transfer learning models were trained to classify COPD based on clinical data and CXR images from 666 subjects, and validated in internal test set based on 284 participants. External test including 105 participants was also performed to verify the generalization ability of the learning algorithms in diagnosing COPD. Meanwhile, the model was further used to evaluate disease severity of COPD by predicting different grads. RESULTS: The Ensemble model showed an AUC of 0.969 in distinguishing COPD by simultaneously extracting fusion features of clinical parameters and CXR images in internal test, better than models that used clinical parameters (AUC = 0.963) or images (AUC = 0.946) only. For the external test set, the AUC slightly declined to 0.934 in predicting COPD based on clinical parameters and CXR images. When applying the Ensemble model to determine disease severity of COPD, the AUC reached 0.894 for three-classification and 0.852 for five-classification respectively. CONCLUSION: The present study used DL algorithms to screen COPD and predict disease severity based on CXR imaging and clinical parameters. The models showed good performance and the approach might be an effective case-finding tool with low radiation dose for COPD diagnosis and staging.
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Aprendizaje Profundo , Enfermedad Pulmonar Obstructiva Crónica , Humanos , Estudios Retrospectivos , Rayos X , TóraxRESUMEN
Airway remodeling is a major feature of asthma. Interleukin (IL)-36γ is significantly upregulated and promotes airway hyper-responsiveness (AHR) in asthma, but its role in airway remodeling is unknown. Here, we aimed to investigate the role of IL-36γ in airway remodeling, and whether IL-38 can alleviate airway remodeling in chronic asthma by blocking the effects of IL-36γ. IL-36γ was quantified in mice inhaled with house dust mite (HDM). Extracellular matrix (ECM) deposition in lung tissues and AHR were assessed following IL-36γ administration to mice. Airway inflammation, AHR, and remodeling were evaluated after IL-38 or blocking IL-36 receptor (IL-36R) treatment in asthmatic mice. The effects of lung fibroblasts stimulated with IL-36γ and IL-38 were quantified in vitro. Increased expression of IL-36γ was detected in lung tissues of HDM-induced asthmatic mice. The intratracheal instillation of IL-36γ to mice significantly enhanced the ECM deposition, AHR, and the number of activated lung fibroblasts around the airways. IL-38 or blocking IL-36R treated asthmatic mice showed a significant alleviation in the airway inflammation, AHR, airway remodeling, and number of activated fibroblasts around airways as compared with the HDM group. In vitro, IL-36γ promoted the activation and migration of human lung fibroblasts (HFL-1). The administration of IL-38 can counteract these biological processes induced by IL-36γ in HFL-1cells. The results indicated that IL-38 can mitigate airway remodeling by blocking the profibrotic effects of IL-36γ in chronic asthma. IL-36γ may be a new therapeutic target, and IL-38 is a potential candidate agent for inhibiting airway remodeling in asthma.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma , Animales , Humanos , Ratones , Asma/metabolismo , Interleucinas/metabolismo , Pulmón/metabolismo , Inflamación/metabolismo , Modelos Animales de Enfermedad , Pyroglyphidae , Ratones Endogámicos BALB CRESUMEN
Tobacco smoke exposure is a major environmental risk factor that facilitates the development and progression of asthma. Our previous study showed that CpG oligodeoxynucleotide (CpG-ODN) inhibits thymic stromal lymphopoietin (TSLP)-dendritic cells (DCs) to reduce Th2/Th17-related inflammatory response in smoke-related asthma. However, the mechanism underlying CpG-ODN -downregulated TSLP remains unclear. A combined house dust mite (HDM)/cigarette smoke extract (CSE) model was used to assess the effects of CpG-ODN on airway inflammation, Th2/Th17 immune response, and amount of IL-33/ST2 and TSLP in mice with smoke-related asthma induced by adoptive transfer of bone-marrow-derived dendritic cells (BMDCs) and in the cultured human bronchial epithelium (HBE) cells administered anti-ST2, HDM, and/or CSE. In vivo, compared to the HDM alone model, the combined HDM/CSE model had aggravated inflammatory responses, while CpG-ODN attenuated airway inflammation, airway collagen deposition, and goblet cell hyperplasia and reduced the levels of IL-33/ST2, TSLP, and Th2/Th17-cytokines in the combined model. In vitro, IL-33/ST2 pathway activation promoted TSLP production in HBE cells, which could be inhibited by CpG-ODN. CpG-ODN administration alleviated Th2/Th17 inflammatory response, decreased the infiltration of inflammatory cells into the airway, and improved the remodeling of smoke-related asthma. The underlying mechanism may be that CpG-ODN inhibits the TSLP-DCs pathway by downregulating the IL-33/ST2 axis.
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Asma , Interleucina-33 , Animales , Humanos , Ratones , Traslado Adoptivo , Alérgenos , Asma/metabolismo , Citocinas/metabolismo , Células Dendríticas , Inflamación , Interleucina-33/metabolismo , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/farmacología , Células Th2 , Linfopoyetina del Estroma Tímico , Células Th17RESUMEN
This study aims to explore the effects of Shenqi Dihuang Decoction on high-glucose induced ferroptosis and the nuclear factor erythroid 2-related factor 2(Nrf2)/heme oxygenase-1(HO-1)/glutathione peroxidase 4(GPX4) axis in human renal tubular epithelial cells(HK-2) and to clarify the underlying mechanism. The cell injury model was established by exposing HK-2 to high glucose, and the Shenqi Dihuang Decoction-medicated serum was prepared. The optimal concentration and intervention time of Shenqi Dihuang Decoction were determined. HK-2 were divided into normal, high glucose, and low-, medium-, and high-dose Shenqi Dihuang Decoction groups. After interventions, the cell proliferation rate in each group was determined and the cell morphology and mitochondrial ultrastructure were observed. Then, the levels of intracellular reactive oxygen species(ROS), ferrous ion(Fe~(2+)), glutathione(GSH), and malondialdehyde(MDA) and the protein levels of Nrf2, HO-1, GPX4, and xCT were measured. The optimal concentration and intervention time of Shenqi Dihuang Decoction-medicated serum were determined to be 10% and 24 h, respectively. Compared with the high glucose group, high-dose Shenqi Dihuang Decoction promoted the proliferation of HK-2. The cells in the low-, medium-, and high-dose Shenqi Dihuang Decoction groups presented tight arrangement, an increased cell count, improved morphology from a spindle-fiber shape to a cobblestone shape, and improved morphology and structure of mitochondrial membrane and cristae, compared with those in the high glucose group. Meanwhile, all the doses of Shenqi Dihuang Decoction inhibited ROS elevation to mitigate the peroxidation damage, lowered the Fe~(2+) and MDA levels and elevated the GSH level to inhibit lipid peroxidation, and activated the antioxidant pathway to upregulate the protein levels of Nrf2, HO-1, xCT, and GPX4. In conclusion, Shenqi Dihuang Decoction-medicated serum can inhibit high-glucose induced ferroptosis of HK-2 in vitro, which involves the antioxidant effect and the activation of the Nrf2/HO-1/GPX4 pathway.
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Ferroptosis , Humanos , Factor 2 Relacionado con NF-E2/genética , Especies Reactivas de Oxígeno , Células Epiteliales , Antioxidantes , Glutatión , GlucosaRESUMEN
BACKGROUND: Epithelial-mesenchymal transition (EMT) is one of the mechanisms of airway remodeling in chronic asthma. Interleukin (IL)-24 has been implicated in the promotion of tissue fibrosis, and increased IL-24 levels have been observed in the nasal secretions and sputum of asthmatic patients. However, the role of IL-24 in asthmatic airway remodeling, especially in EMT, remains largely unknown. We aimed to explore the effect and mechanism of IL-24 on EMT and to verify whether IL-37 could alleviate IL-24-induced EMT in chronic asthma. METHODS: BEAS-2B cells were exposed to IL-24, and cell migration was assessed by wound healing and Transwell assays. The expression of EMT-related biomarkers (E-cadherin, vimentin, and α-SMA) was evaluated after the cells were stimulated with IL-24 with or without IL-37. A murine asthma model was established by intranasal administration of house dust mite (HDM) extracts for 5 weeks, and the effects of IL-24 and IL-37 on EMT and airway remodeling were investigated by intranasal administration of si-IL-24 and rhIL-37. RESULTS: We observed that IL-24 significantly enhanced the migration of BEAS-2B cells in vitro. IL-24 promoted the expression of the EMT biomarkers vimentin and α-SMA via the STAT3 and ERK1/2 pathways. In addition, we found that IL-37 partially reversed IL-24-induced EMT in BEAS-2B cells by blocking the ERK1/2 and STAT3 pathways. Similarly, the in vivo results showed that IL-24 was overexpressed in the airway epithelium of an HDM-induced chronic asthma model, and IL-24 silencing or IL-37 treatment could reverse EMT biomarker expression. CONCLUSIONS: Overall, these findings indicated that IL-37 mitigated HDM-induced airway remodeling by inhibiting IL-24-mediated EMT via the ERK1/2 and STAT3 pathways, thereby providing experimental evidence for IL-24 as a novel therapeutic target and IL-37 as a promising agent for treating severe asthma.
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Remodelación de las Vías Aéreas (Respiratorias) , Asma , Interleucina-1/farmacología , Animales , Asma/metabolismo , Asma/prevención & control , Bronquios/metabolismo , Transición Epitelial-Mesenquimal , Humanos , Interleucinas/metabolismo , Interleucinas/farmacología , Ratones , Pyroglyphidae/metabolismo , Transducción de Señal , Vimentina/metabolismoRESUMEN
Interleukin (IL)-37 has been described as a negative regulator of immune responses and is critical for asthma pathogenesis, but the mechanisms behind the protective role of IL-37 against allergic asthma are less well understood. We show here that IL-37 administered intranasally inhibited house dust mite (HDM)-induced chronic airway eosinophilic inflammation, goblet cell hyperplasia, peribronchial collagen deposition and airway hyperresponsiveness (AHR) to methacholine. In contrast to a weakened Th2 response in the lung that was characterized by the downregulation of Th2-associated cytokines and chemokines in IL-37-treated mice, IL-37 has no effect on relevant markers of systemic Th2 immune including serum immunoglobulins expression and in vitro production of Th2-associated cytokines by splenocytes on HDM recall. We demonstrated that the production of thymic stromal lymphopoietin (TSLP) in the lung tissue was associated with IL-37. Importantly, compared with IL-37 alone, TSLP coadministration with IL-37 restored HDM-induced airway inflammation and structural alterations, increased AHR to methacholine and promoted Th2-associated cytokine production. We further found that IL-37 inhibited the induction of TSLP expression by the main antigen of house dust mite, Der p1, by suppressing NF-κB and extracellular signal regulated kinase 1/2 (ERK1/2) activation in human bronchial epithelial (16-HBE) cells in vitro. These data highlight the importance of TSLP in IL-37-mediated protective role in asthma. IL-37 might represent a useful innovative and alternative therapy to control TSLP production in the airway.
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Asma/tratamiento farmacológico , Citocinas/metabolismo , Hipersensibilidad/dietoterapia , Interleucina-1/uso terapéutico , Sistema de Señalización de MAP Quinasas , FN-kappa B/metabolismo , Pyroglyphidae/fisiología , Remodelación de las Vías Aéreas (Respiratorias)/efectos de los fármacos , Animales , Asma/complicaciones , Asma/inmunología , Asma/fisiopatología , Línea Celular , Enfermedad Crónica , Citocinas/administración & dosificación , Células Epiteliales/efectos de los fármacos , Células Epiteliales/inmunología , Células Epiteliales/parasitología , Femenino , Humanos , Hipersensibilidad/complicaciones , Hipersensibilidad/inmunología , Hipersensibilidad/fisiopatología , Interleucina-1/farmacología , Sistema de Señalización de MAP Quinasas/efectos de los fármacos , Ratones Endogámicos BALB C , Pyroglyphidae/efectos de los fármacos , Hipersensibilidad Respiratoria/complicaciones , Hipersensibilidad Respiratoria/inmunología , Hipersensibilidad Respiratoria/fisiopatología , Células Th2/efectos de los fármacos , Células Th2/inmunología , Linfopoyetina del Estroma TímicoRESUMEN
BACKGROUND: Lung involvement is rare in peripheral T cell lymphoma, and there is a lack of sufficient clinical study. The authors describe a rare case of lung involvement in a 40-year-old male patient with peripheral T cell lymphoma. METHODS: Hematological investigation, bone marrow aspirate, and lung biopsy were performed. RESULTS: The patient received 4 courses of CHOP regimen chemotherapy. He achieved partial response (PR) at the 2nd course, but showed disease progressive (PD) at the 4th course. Then he received 2 courses of GDP regimen chemotherapy. Unfortunately, the patient died of tumor overload with hyper-lactacidemia 6 months after the onset of the disease. CONCLUSIONS: Lung biopsy is important to confirm a diagnosis of primary pulmonary lymphoma. Lung involvement in peripheral T cell lymphoma as a prognostic factor needs further studies.
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Neoplasias Pulmonares/patología , Pulmón/patología , Linfoma de Células T Periférico/patología , Acidosis Láctica/inducido químicamente , Acidosis Láctica/complicaciones , Acidosis Láctica/diagnóstico , Adulto , Protocolos de Quimioterapia Combinada Antineoplásica/efectos adversos , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapéutico , Biopsia , Ciclofosfamida/administración & dosificación , Ciclofosfamida/efectos adversos , Doxorrubicina/administración & dosificación , Doxorrubicina/efectos adversos , Resultado Fatal , Humanos , Ácido Láctico/sangre , Pulmón/efectos de los fármacos , Neoplasias Pulmonares/complicaciones , Neoplasias Pulmonares/tratamiento farmacológico , Linfoma de Células T Periférico/complicaciones , Linfoma de Células T Periférico/tratamiento farmacológico , Masculino , Prednisolona/administración & dosificación , Prednisolona/efectos adversos , Vincristina/administración & dosificación , Vincristina/efectos adversosRESUMEN
BACKGROUND As a common nosocomial infection, ventilator-associated pneumonia (VAP) often has high mortality. This study aimed to assess the risk factor for mortality owing to VAP. MATERIAL AND METHODS This retrospective clinical audit study screened medical records between the period of January 2014 and December 2017. All patients under mechanical ventilation MV) for ≥72 hours were screened against previously reported diagnostic criteria for VAP. The medical records were obtained for cases of documented diagnosis of VAP. RESULTS In all, 145 patients (5.0%) diagnosed with VAP were included in the study; the morbidity of VAP was 19.5 episodes per 1000 days of MV. The 30-day mortality rate was 42.8%. Univariate logistic analysis showed that elevated neutrophil-to-lymphocyte ratio (NLR), high blood urea nitrogen/albumin (BUN/ALB) ratio, Multidrug-resistant organism infection, and a higher sequential organ failure assessment (SOFA) score were risk factors for mortality caused by VAP. In the second multivariate analysis, elevated NLR levels (P=0.038), high BUN/ALB ratio (P=0.016), multidrug-resistant organism infections (P=0.036), and a higher SOFA score (P<0.001) were still associated with the 30-day mortality rate. CONCLUSIONS The 30-day mortality rate of VAP was high. Blood NLR and BUN/ALB levels can be used as risk factors to assess the 30-day VAP-related mortality to help clinicians improve the prognosis of VAP.
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Hospitales , Neumonía Asociada al Ventilador/mortalidad , Anciano , China/epidemiología , Femenino , Humanos , Incidencia , Modelos Logísticos , Masculino , Mortalidad , Neumonía Asociada al Ventilador/epidemiología , Estudios Retrospectivos , Factores de RiesgoRESUMEN
This study aimed to evaluate the factors that affect 30-day mortality of patients with HAP. The data used in this study were collected from all HAP occurred in our hospital between January 2014 and December 2017. A total of 1158 cases were included. 150 (13.0%) of whom died within 30 days. This reported mortality identified by the univariate Cox regression analysis is found to have been affected by the following factors: age greater than 70 years, presence of diabetes mellitus and chronic obstructive pulmonary disease, gastric tube intubation, administration of proton-pump inhibitor, blood albumin level less than 30 g/l, elevated neutrophil-to-lymphocyte ratio, antibiotics therapy in the preceding 90 days, intensive care unit (ICU) admission, blood lymphocyte count less than 0.8 × 109/L, elevated blood urea nitrogen/albumin (BUN/ALB) level, and presence of multidrug-resistant (MDR) pathogens. In the second multivariate analysis, administration of proton-pump inhibitor, administration of antibiotics in the preceding 90 days, ICU admission, blood lymphocyte count less than 0.8 × 109/L, elevated BUN/ALB level, and presence of MDR pathogens were still associated with 30-day mortality. The area under the receiver operating characteristic curves in the BUN/ALB predicting 30-day mortality due to HAP was 0.685. A high BUN/ALB was significantly associated with a worse survival than a low BUN/ALB (P < 0.001). Therefore, an elevated BUN/ALB level is a risk factor for mortality on patients with HAP.
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Objective: Fibrocyte localization to the airways and thymic stromal lymphopoietin (TSLP) overexpression in the lung are features of severe asthma. The aim of this study was to determine whether TSLP contributes to fibrocyte trafficking and airway remodeling in a mouse model of allergic asthma. Methods: We established a chronic asthma animal model by administering house dust mite (HDM) extracts intranasally for up to 5 consecutive weeks. Mouse anti-TSLP monoclonal antibody (mAb) was given intraperitoneally starting the 4th week. Fluorescence-labeled CD34/collagen I (Col I)-dual-positive fibrocytes were examined by confocal microscopy. The level of TGF-ß1 in the bronchoalveolar lavage (BAL) fluid was determined by ELISA. Results: We found significantly increased levels of TSLP and TGF-ß1 in the lung of the mice subjected to repeated allergen exposure, which was accompanied by increased number of fibrocytes in the sub-epithelial zone and the BAL fluid. However, blocking TSLP markedly decreased the production of TGF-ß1, reduced the number of fibrocytes and subsequently prevented alterations of both airway and vascular structures. Conclusions: Our data suggested that TSLP might function in airway remodeling by promoting circulating fibrocyte recruitment to the lung in the mice subjected to chronic allergen exposure. These results provide a better rationale for targeting the interaction between TSLP and fibrocytes as a therapeutic approach for chronic allergic asthma.
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Remodelación de las Vías Aéreas (Respiratorias)/fisiología , Asma/fisiopatología , Citocinas/biosíntesis , Factor de Crecimiento Transformador beta1/biosíntesis , Animales , Líquido del Lavado Bronquioalveolar/inmunología , Enfermedad Crónica , Células del Tejido Conectivo , Modelos Animales de Enfermedad , Femenino , Pulmón/fisiopatología , Ratones , Ratones Endogámicos BALB C , Imagen Óptica , Pyroglyphidae/inmunología , Linfopoyetina del Estroma TímicoRESUMEN
OBJECTIVE: To investigate the effects and the underlying mechanisms of ShenFu Injection on paclitaxel-induced peripheral neuropathy. METHODS: Twenty-eight adult male Wister rats were randomized into 4 groups (n=7) : control group, paclitaxel group, paclitaxel combined with low or high dose of ShenFu Injection groups. Rats were intraperitoneally injected with paclitaxel 8 mg/kg every 4 d for a total of 4 doses except control group. From Day 1 of the experiment (injection),low dose (4 mL/kg) and high dose (8 mL/kg) of Shenfu Injection were intraperitoneally injected daily in the combination groups for a total of 21 d respectively,while normal saline (NS) was injected in control group in the same way instead. Mechanical withdraw threshold (MWT) and thermal withdraw latency (TWL) of rats' hind paw were measured before (0 d) and after the first injection (6 d,14 d). The level of nerve growth factor (NGF) in the serum was measured at 22 d before the euthanasia,and the ultrastructure of the sciatic nerve was observed with transmission electron microscope. RESULTS: The MWT and TWL of 14 d in paclitaxel group significantly increased compared with those of 0 d and control group ( P<0.05). The combination of paclitaxel with ShenFu Injection,especially the high dose ( P<0.05),significantly reduced the MWT and TWL when compared to paclitaxel group at 14 d. Compared with simultaneous control group,there was no remarkably increased MWT and TWL in the low and high dose of ShenFu Injection (P>0.05) . Compared with control group,the serum NGF level significantly decreased ( P<0.05) in paclitaxel group,while the serum NGF level in low and high dose of ShenFu Injection groups were higher than paclitaxel group,particularly in the high dose group ( P<0.05). When compared to control group,the sciatic nerve fiber structure in the paclitaxel group was generally damaged,including myelin sheath swelling,fragmentation and vacuolization,endoplasmic reticulum swelling and matrix structure disorder in Schwann cells. The structural damages were mitigated in the low dose and high dose groups,especially the latter one,when compared to the paclitaxel group. CONCLUSION: Shenfu Injection can reduce the peripheral neurotoxicity of paclitaxel by promoting the expression of NGF in serum.
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Medicamentos Herbarios Chinos/farmacología , Paclitaxel/efectos adversos , Nervio Ciático/efectos de los fármacos , Animales , Masculino , Neurotoxinas/efectos adversos , Distribución Aleatoria , Ratas , Ratas Sprague-Dawley , Nervio Ciático/ultraestructuraRESUMEN
PURPOSE: Thymic stromal lymphopoietin (TSLP) is a critical regulator of immune responses associated with Th2 cytokine-mediated inflammation. Intranasal administration of oligodeoxynucleotides with CpG motifs (CpG-ODNs) might improve lower airway outcomes of combined allergic rhinitis and asthma syndrome (CARAS), but the inherent mechanisms of CpG-ODNs are not well defined. This study investigated whether CpG-ODNs treated to upper airway could reduce lower airway TSLP expression as well as whether this reduction could contribute to the alleviation of lower allergic inflammation and airway hyper-reactivity (AHR) in CARAS mice. MATERIALS AND METHODS: Ovalbumin (OVA)-sensitized BALB/c mice were intranasal OVA exposure three times a week for 3 weeks. CpG-ODNs or an anti-TSLP mAb was administered to a subset of these mice 1 hour after intranasal OVA challenge, followed by 5 days of OVA aerosol challenge. The resulting immunological variables, nasal symptoms, and nasal mucosa and lung tissues pathology were evaluated. TSLP production in the lung tissues and bronchoalveolar lavage fluid (BALF) were determined by RT-PCR, western blotting or enzyme-linked immunosorbent assay. RESULTS: The CARAS mice exhibited overexpression of TSLP in the lung tissues and BALF, and also demonstrated significant increases in BALF and splenocyte Th2-associated cytokine production, serum OVA-specific IgE, nose and lung pathologies, and AHR. Intranasal administration of CpG-ODNs restored TSLP in the lower airway, and it significantly reduced the following parameters: Th2-type cytokine production levels; the percentage of eosinophils in the BALF; IL-4 and IL-5 concentrations in the supernatants of cultured splenic lymphocytes; serum OVA-specific IgE; peribronchial inflammation score in the lungs; and nose pathology and nasal symptoms. Similar results were obtained when the CARAS mice were treated with an anti-TSLP mAb to block intranasal TSLP activity. CONCLUSIONS: Treatment with intranasal CpG-ODNs improves lower airway immunological variable outcomes in the CARAS model via a mechanism that possibly involves in suppressing pulmonary TSLP-triggered allergic inflammation.
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Asma/tratamiento farmacológico , Citocinas/metabolismo , Pulmón/efectos de los fármacos , Oligodesoxirribonucleótidos/uso terapéutico , Rinitis Alérgica/tratamiento farmacológico , Administración Intranasal , Animales , Asma/metabolismo , Islas de CpG , Evaluación Preclínica de Medicamentos , Femenino , Pulmón/metabolismo , Ratones Endogámicos BALB C , Oligodesoxirribonucleótidos/farmacología , Rinitis Alérgica/metabolismo , Linfopoyetina del Estroma TímicoRESUMEN
We retrospectively analyzed the medical records and clinical characteristics of 15 patients diagnosed with Penicilliosis marneffei (PSM) between January 1, 1993, and December 31, 2012, at the Third Affiliated Hospital of Sun Yat-sen University. The most common symptoms of PSM were fever (14/15, 93 %), cough (13/15, 87 %), and sputum production (6/15, 40 %), weight loss (14/15, 60 %), lymph node enlargement (9/15, 60 %), hepatosplenomegaly (7/15, 47 %), anemia (7/15, 47 %), and hemoptysis (4/15, 26 %). The most common underlying diseases in patients diagnosed with PSM were AIDS (9/15, 60 %), post-organ transplantation (3/15, 20 %), rheumatic autoimmune disease (2/15, 13 %), and hematological malignancy (1/15, 7 %). All patients, except those with AIDS, were treated with immunosuppressant drugs. White blood cell counts were increased in 10/15 (67 %) patients, while hemoglobin concentrations were decreased in 8/15 (53 %) patients. The ratios of CD4(+)/total T lymphocytes and CD4(+)/CD8(+) T lymphocytes declined in all the 11 test cases. Nodular lesions or masses were the most common anomalies detected during computed tomography scans, but disseminated inflammation and interstitial changes were also seen. Clinical samples with positive culture results were obtained from sputum or secretions obtained by bronchoscopy, venous blood, percutaneous pulmonary puncture, bone marrow, or skin lesions. Between 1993 and 2003, only four cases of PSM, all connected with AIDS, were diagnosed, while 11 cases of PSM, with or without concurrent AIDS, were diagnosed between 2003 and 2012. Amphotericin B was used to control the disease in some cases. In conclusion, the occurrence of PSM, especially in patients without concurrent AIDS, has increased. The early culture of Penicillium marneffei from clinical samples is critical for correct diagnosis of PSM, and amphotericin B is recommended as the first choice for treatment.
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Micosis/microbiología , Penicillium/aislamiento & purificación , Adulto , Anciano , Anfotericina B/uso terapéutico , Antifúngicos/uso terapéutico , China , Femenino , Hospitales , Humanos , Masculino , Persona de Mediana Edad , Micosis/diagnóstico , Micosis/tratamiento farmacológico , Micosis/inmunología , Penicillium/efectos de los fármacos , Penicillium/genética , Estudios Retrospectivos , Adulto JovenRESUMEN
Cigarette smoke (CS) facilitates adverse effects on the airway inflammation and treatment of asthma. Here, we investigated the mechanisms by which CS exacerbates asthma. The roles of IL-33 and IL-35 in asthma development were examined by treatment with IL-33 knockout (IL-33 KO) or transfection of adenovirus encoding IL-35 (Ad-IL-35) in a murine model of cigarette smoke-exposure asthma. Furthermore, the involvement of IL-33 and IL-35 in regulating DCs and Th2/Th17 cells was examined in a coculture system of DCs with CD4+ T cells. Additionally, we observed the effect of CpG-ODNs on the balance of IL-33 and IL-35. We show that CS and house dust mite (HDM) exposure induced IL-33 and suppressed IL-35 levels in cigarette smoke-exposure asthma in vivo and in vitro. Treatment with IL-33 KO or Ad-IL-35 significantly attenuated airway hyperreactivity, goblet hyperplasia, airway remodelling, and eosinophil and neutrophil infiltration in the lung tissues from asthmatic mice. Furthermore, we demonstrated reciprocal regulation between CS and HDM-modulated IL-33 and IL-35. Mechanistically, IL-33 KO (or anti-ST2) and Ad-IL-35 attenuated Th2- and Th17-associated inflammation by downregulating TSLP-DC signalling. Finally, administration of CpG-ODNs suppressed the expression of IL-33/ST2 and elevated the levels of IL-35, which is mainly derived from CD4+Foxp+ Tregs, to alleviate Th2- and Th17-associated inflammation by inhibiting the activation of BMDCs. Taken together, the IL-33/ST2 pathway drives the DC-Th2 and Th17 responses of cigarette smoke-exposure asthma, while IL-35 has the opposite effect. CpG-ODNs represent a potential therapeutic strategy for modulating the balance of IL-33 and IL-35 to suppress allergic airway inflammation.
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Asma , Fumar Cigarrillos , Animales , Ratones , Pyroglyphidae/metabolismo , Proteína 1 Similar al Receptor de Interleucina-1/metabolismo , Células Th17/metabolismo , Interleucina-33/metabolismo , Fumar Cigarrillos/efectos adversos , Citocinas/metabolismo , Asma/metabolismo , Células Th2/metabolismo , Inflamación/metabolismo , Modelos Animales de Enfermedad , Ratones Endogámicos BALB CRESUMEN
BACKGROUND: Chronic hyperglycemia in diabetes induces oxidative stress, leading to damage to the vascular system. In this study, we aimed to evaluate the effects and mechanisms of AS-IV-Exos in alleviating endothelial oxidative stress and dysfunction caused by high glucose (HG). METHODS: Histopathological changes were observed using HE staining, and CD31 expression was assessed through immunohistochemistry (IHC). Cell proliferation was evaluated through CCK8 and EDU assays. The levels of ROS, SOD, and GSH-Px in the skin tissues of each group were measured using ELISA. Cell adhesion, migration, and tube formation abilities were assessed using adhesion, Transwell, and tube formation experiments. ROS levels in HUVEC cells were measured using flow cytometry. The levels of miR-210 and Nox2 were determined through quantitative reverse transcription-polymerase chain reaction (qRT-PCR). The expression of Nox2, SOD, GSH-Px, CD63, and CD81 was confirmed using WB. RESULTS: The level of miR-210 was reduced in diabetes-induced skin damage, while the levels of Nox2 and ROS increased. Treatment with AS-IV increased the level of miR-210 in EPC-Exos. Compared to Exos, AS-IV-Exos significantly reduced the proliferation rate, adhesion number, migration speed, and tube-forming ability of HGdamaged HUVEC cells. AS-IV-Exos also significantly decreased the levels of SOD and GSH-Px in HG-treated HUVEC cells and reduced the levels of Nox2 and GSH-Px. However, ROS levels and Nox2 could reverse this effect. CONCLUSION: AS-IV-Exos effectively alleviated endothelial oxidative stress and dysfunction induced by HG through the miR-210/Nox2/ROS pathway.
RESUMEN
A Gram-positive, non-motile, non-spore-forming, rod-shaped bacterium, strain 7087(T), was isolated from rhizosphere of maize in China. The strain grew at 4-50 °C and at pH 4-10, with optima of 37 °C and pH 7.0, respectively. Phylogenetic analysis based on the full-length 16S rRNA gene sequence revealed that strain 7087(T) was a member of the genus Microbacterium. High levels of 16S rRNA gene similarities were found between strain 7087(T) and Microbacterium binotii DSM 19164(T) (99.8 %). However, the DNA-DNA hybridization value between strain 7087(T) and Microbacterium binotii DSM 19164(T) was 24.2 %. The DNA G+C content of strain 7087(T) was 69.9 mol%. The major fatty acids were anteiso-C(17 : 0) (36.45 %), anteiso-C(15 : 0) (36.08 %) and iso-C(16 : 0) (16.11 %). The predominant menaquinones were MK-10 (28.1 %), MK-11 (54.8 %) and MK-12 (17.1 %). The diagnostic diamino acid in the cell-wall peptidoglycan was ornithine. The major polar lipids are diphosphatidylglycerol, unknown phospholipids, an unknown glycolipid and unknown amino lipids. On the basis of these results, strain 7087(T) is considered to represent a novel species of the genus Microbacterium, for which the name Microbacterium neimengense sp. nov. is proposed. The type strain is 7087(T) ( = ACCC 03008(T) = DSM 24985(T)).
Asunto(s)
Actinomycetales/clasificación , Filogenia , Rizosfera , Microbiología del Suelo , Zea mays/microbiología , Actinomycetales/genética , Actinomycetales/aislamiento & purificación , Técnicas de Tipificación Bacteriana , Composición de Base , China , ADN Bacteriano/genética , Ácidos Grasos/análisis , Datos de Secuencia Molecular , Hibridación de Ácido Nucleico , Peptidoglicano/análisis , ARN Ribosómico 16S/genética , Análisis de Secuencia de ADN , Vitamina K 2/análisisRESUMEN
INTRODUCTION: The pathogenesis of non-cystic fibrosis bronchiectasis has not been clearly clarified. This study aimed to investigate the expression of ciliary regulating protein forkhead box protein j1 (Foxj1) on airway epithelium in non-cystic fibrosis bronchiectasis and its association with airway cilia structure disorder and disease severity. METHODS: Lung tissue sections excised from 47 patients with non-cystic fibrosis bronchiectasis were included between January 2018 and June 2021. Specimens from 26 subjects who underwent a lobectomy due to lung nodule were chosen as controls. Clinical information was collected, and pathologic analysis was performed to assess the epithelial structure and expression of ciliary regulating Foxj1. RESULTS: Of the 47 patients with non-cystic fibrosis bronchiectasis, 25 were considered as mild, 12 were moderate whereas the remaining 10 cases were severe according to the bronchiectasis severity index score evaluation. Epithelial hyperplasia, hyperplasia of goblet cells and inflammatory cell infiltration were observed in non-cystic fibrosis bronchiectasis, compared with control subjects. Cilia length in non-cystic fibrosis bronchiectasis patients were shorter than that in the control group, (5.34 ± 0.89) µm versus (7.34 ± 0.71) µm, respectively (P = 0.002). The expression of Foxj1 was (2.69 ± 1.09) × 106 in non-cystic fibrosis bronchiectasis, compared with (6.67 ± 1.15) × 106 in the control group (P = 0.001). Moreover, patients with lower expression of Foxj1 showed shorter airway cilia and worse in disease severity. CONCLUSION: Foxj1 declined in the airway epithelium of patients with non-cystic fibrosis bronchiectasis, positively correlated to cilia length and might imply worse disease severity.
Asunto(s)
Bronquiectasia , Cilios , Factores de Transcripción Forkhead , Humanos , Bronquiectasia/patología , Epitelio/metabolismo , Factores de Transcripción Forkhead/metabolismo , Hiperplasia/metabolismo , Hiperplasia/patología , Pulmón/patología , Gravedad del PacienteRESUMEN
Here, the complete chloroplast genome sequence of Zingiber teres is described using MGI paired-end sequencing. The genome is 163,428 bp in length and contains a small single-copy region (SSC) of 15,782 bp, a large single-copy region (LSC) of 88,142 bp, and two inverted repeat (IR) regions of 29,752 bp. The overall GC content is 36.1%, and the GC content of the IR regions is 41.1%, which is higher than that of both the LSC region (33.8%) and SSC region (29.5%). The genome of Z. teres contains 133 complete genes, including 88 protein-coding genes (79 protein-coding gene species), 38 tRNA genes (28 tRNA species), and 8 rRNA genes (four rRNA species). Maximum likelihood phylogenetic analysis yielded a well-resolved tree of the genus Zingiber, and Z. teres and Zingiber mioga were sister species in this tree. The development of DNA barcodes could aid the identification of Zingiber species.
RESUMEN
OBJECTIVE: We explore the effects of endothelial progenitor cell (EPC)-derived exosomes (EPCexos) and of astragaloside IV (ASIV)-stimulated EPCexos (ASIV-EPCexos) on type I diabetic-wound healing, and determine the basic molecular mechanisms of action. METHODS: EPCs were exposed to different concentrations of ASIV to generate ASIV-EPCexos. A chronic-wound healing model involving streptozotocin-stimulated diabetic rats was established. These rats were treated with EPCexos, ASIV-EPCexos, rapamycin, and wortmannin. Wound healing was evaluated by direct photographic observation, hematoxylin and eosin staining, and Masson's trichrome staining. RESULTS: ASIV treatment increased the abilities of EPCs (e.g., proliferation), as well as exosome secretion. EPCexo showed a "cup holder" like structure. Treatment with ASIV-EPCexos increased the wound-healing rate, collagen-deposition area, bromodeoxyuridine uptake, VEGF expression, and the number of CD31- and αSMA- positive cells, whereas decreased epidermal thickness and CD45 expression. The expression of the PI3K/AKT/mTOR pathway increased, whereas the expression of inflammatory factor decreased. However, rapamycin and wortmannin reversed these changes. CONCLUSIONS: ASIV-EPCexos may accelerate type I diabetic-wound healing via the PI3K/AKT/mTOR pathway. This study may lay the foundation for new clinical treatment options for patients with type I diabetic wounds.