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2.
Immunity ; 54(9): 2042-2056.e8, 2021 09 14.
Artigo em Inglês | MEDLINE | ID: mdl-34407391

RESUMO

Recruitment of immune cells to the site of inflammation by the chemokine CCL1 is important in the pathology of inflammatory diseases. Here, we examined the role of CCL1 in pulmonary fibrosis (PF). Bronchoalveolar lavage fluid from PF mouse models contained high amounts of CCL1, as did lung biopsies from PF patients. Immunofluorescence analyses revealed that alveolar macrophages and CD4+ T cells were major producers of CCL1 and targeted deletion of Ccl1 in these cells blunted pathology. Deletion of the CCL1 receptor Ccr8 in fibroblasts limited migration, but not activation, in response to CCL1. Mass spectrometry analyses of CCL1 complexes identified AMFR as a CCL1 receptor, and deletion of Amfr impaired fibroblast activation. Mechanistically, CCL1 binding triggered ubiquitination of the ERK inhibitor Spry1 by AMFR, thus activating Ras-mediated profibrotic protein synthesis. Antibody blockade of CCL1 ameliorated PF pathology, supporting the therapeutic potential of targeting this pathway for treating fibroproliferative lung diseases.


Assuntos
Quimiocina CCL1/metabolismo , Fibroblastos/metabolismo , Proteínas de Membrana/metabolismo , Miofibroblastos/metabolismo , Fosfoproteínas/metabolismo , Fibrose Pulmonar/metabolismo , Receptores do Fator Autócrino de Motilidade/metabolismo , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Animais , Diferenciação Celular/fisiologia , Fibroblastos/patologia , Humanos , Camundongos , Miofibroblastos/patologia , Fibrose Pulmonar/patologia , Transdução de Sinais/fisiologia
3.
Zool Res ; 42(5): 548-561, 2021 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-34327887

RESUMO

The genetic adaptations of various organisms to heterogeneous environments in the northwestern Pacific remain poorly understood. Heterogeneous genomic divergence among populations may reflect environmental selection. Advancing our understanding of the mechanisms by which organisms adapt to different temperatures in response to climate change and predicting the adaptive potential and ecological consequences of anthropogenic global warming are critical. We sequenced the whole genomes of Japanese whiting ( Sillago japonica) specimens collected from different latitudinal locations along the coastal waters of China and Japan to detect possible thermal adaptations. Using population genomics, a total of 5.48 million single nucleotide polymorphisms (SNPs) from five populations revealed a complete genetic break between the Chinese and Japanese groups, which was attributed to both geographic distance and local adaptation. The shared natural selection genes between two isolated populations (i.e., Zhoushan and Ise Bay/Tokyo Bay) indicated possible parallel evolution at the genetic level induced by temperature. These genes also indicated that the process of temperature selection on isolated populations is repeatable. Moreover, we observed natural candidate genes related to membrane fluidity, possibly underlying adaptation to cold environmental stress. These findings advance our understanding of the genetic mechanisms underlying the rapid adaptations of fish species. Species distribution projection models suggested that the Chinese and Japanese groups may have different responses to future climate change, with the former expanding and the latter contracting. The findings of this study enhance our understanding of genetic differentiation and adaptation to changing environments.


Assuntos
Adaptação Fisiológica/genética , Peixes/genética , Peixes/fisiologia , Distribuição Animal , Animais , Evolução Biológica , China , Mudança Climática , Ecossistema , Japão , Oceano Pacífico , Polimorfismo de Nucleotídeo Único , Temperatura , Sequenciamento Completo do Genoma
4.
Front Psychiatry ; 12: 633773, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34093261

RESUMO

Background: In China, intergenerational rearing is a ubiquitous phenomenon based on unique national conditions. This study aimed to explore family dynamics in intergenerational rearing families as well as their correlation with older household members' anxiety and depression. Methods: The elderly from intergenerational (n = 141) and non-intergenerational rearing families (n = 266) were investigated using the following scales: the general information questionnaire, Self-Rating Scale of Systemic Family Dynamics, Geriatric Depression Scale, and Self-Rating Anxiety Scale. Results: Scores from the four dimensions (family atmosphere, system logic, individuation, and the concept of disease) of the structure of family dynamics were computed. The comparison of these dimensions scores and the total scores of grandparents' anxiety and depression for the two groups were not statistically significant (p > 0.05). In Pearson's correlation analysis, no significant correlation between the family atmosphere dimension and the total score of the grandparents' depression and anxiety scales was observed. The system logic aspect was negatively correlated with depression and anxiety scale scores. The individual dimension was positively correlated with the anxiety scale scores. The disease concept dimension was positively correlated with depression and anxiety scale scores. Hence, the results were statistically significant. Conclusion: There were no significant differences in terms of family dynamics and risk of anxiety and depression among grandparents between the two family types. The system logic, individuation, and disease concept dimensions were correlated with their anxiety and depression.

5.
J Int Med Res ; 49(5): 3000605211016138, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34038217

RESUMO

Acute myeloid leukemia (AML) with T lymphoblastic lymphoma (T-LBL) is a hematologic tumor of two origins, myeloid and lymphoblastic, and is relatively rare in the same patient. We report a rare case of AML with T-LBL. After the patient was diagnosed, he received standard chemotherapy, which decreased the primitive bone marrow cell percentage from 84% to 5%; however, the enlarged superficial lymph nodes showed no obvious change in size. Immunohistochemistry revealed the following: cluster of differentiation (CD)3 (+), CD5 (+), CD7 (+), transmission disequilibrium test (TDT) (+), myeloperoxidase (MPO) (-), and lysozyme (Lys) (-). The lymph node morphology and immunohistochemical results indicated T-LBL. Therefore, the final diagnosis was AML with T-LBL, with both diseases occurring independently and concurrently.


Assuntos
Leucemia Mieloide Aguda , Linfoma não Hodgkin , Leucemia-Linfoma Linfoblástico de Células Precursoras , Humanos , Imuno-Histoquímica , Leucemia Mieloide Aguda/tratamento farmacológico , Linfonodos/diagnóstico por imagem , Masculino , Leucemia-Linfoma Linfoblástico de Células Precursoras/tratamento farmacológico
6.
J Ethnopharmacol ; 275: 114045, 2021 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-33831463

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: The Dang-Gui-Si-Ni (DGSN) decoction as a classic prescription has been widely used for thousands of years in the clinical practice of traditional Chinese medicine (TCM). Especially in recent years, the potential efficacy of TCM for the treatment of Raynaud's syndrome has attracted great attention as there are still no specific remedies for this disease. However, the active constituents and underlying mechanisms responsible for the therapeutic benefits are not well understood, which makes it difficult to ensure quality control or to design research and drug development strategies. To identify the potential pharmacodynamic ingredients (PPIs) of TCM will help to achieve suitable process control procedures for industrial production and large-scale manufacturing. AIM OF THE STUDY: In the present study, we propose a multi-dimensional qualitative analysis method combining water-decoction spectra, in-vitro intestinal absorption spectra, in-vivo plasma spectra, and molecular docking of components to quickly identify the PPIs for the DGSN decoction of TCM. MATERIALS AND METHODS: Water-based decoctions of DGSN were prepared in accordance with the clinical use registered in ancient books. Ultra-high-performance liquid chromatography-quadrupole-time of flight mass spectrometry (UHPLC-Q/TOF-MS) coupled with computerized modelling activity screening was used to quickly identify the PPIs of the DGSN decoction. Bioactive compounds absorbed in vitro were identified using the everted intestinal sac model from rats and compounds absorbed in vivo were confirmed in portal vein blood samples obtained following oral administration in rats. Molecular docking validation experiments were adopted to predict the binding activity to coagulation factors I, II, VII, X, and IX. The active components were further confirmed by pharmacodynamics analysis. The anticoagulant activity of the DGSN decoction was verified using rat models. RESULTS: Thirty-one compounds were identified in the DGSN decoction. According to the in vivo experiments, 22 compounds that could be absorbed in vivo were detected by the everted intestinal sac model in rats. This model greatly reduces the scope of PPIs and is easy to perform. Ten compounds were detected in the portal vein blood in rats. The compounds detected in plasma provide stronger evidence supporting the PPIs. Molecular docking in vitro experiments indicated that 7 compounds exhibited better binding activity with coagulation factors I, II, VII, X, and IX. The animal experiments confirmed that the DGSN decoction could improve the microcirculation, providing indirect proof of anticoagulant activity suggested by the molecular docking studies. Finally, based on the multi-dimensional methods, 9 potential compounds present in the DGSN decoction were identified as PPIs (i.e., ferulic acid, paeoniflorin, albiflorin, chlorogenic acid, cryptochlorogenic acid, liquiritin, liquiritin apioside, cinnamaldehyde and glycyrrhizic acid). CONCLUSION: Overall, this study combined the water-decoction spectra, intestinal absorption spectra in vitro, plasma spectra in vivo, and molecular docking studies to establish a multi-dimensional qualitative analysis method of the DGSN decoction. Meanwhile, 9 compounds in DGSN decoction were identified as PPIs using this method, and are proposed for application as quality standards for complex TCM prescriptions.


Assuntos
Medicamentos de Ervas Chinesas/química , Medicamentos de Ervas Chinesas/farmacologia , Administração Oral , Animais , Fatores de Coagulação Sanguínea/química , Modelos Animais de Doenças , Medicamentos de Ervas Chinesas/administração & dosagem , Medicamentos de Ervas Chinesas/metabolismo , Flavonoides/análise , Flavonoides/química , Hidroxibenzoatos/análise , Hidroxibenzoatos/química , Absorção Intestinal , Masculino , Medicina Tradicional Chinesa , Microcirculação/efeitos dos fármacos , Simulação de Acoplamento Molecular , Nucleosídeos/análise , Nucleosídeos/química , Plasma/química , Ratos Sprague-Dawley , Doença de Raynaud/tratamento farmacológico , Terpenos/análise , Terpenos/química
7.
PLoS One ; 16(3): e0248534, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33705481

RESUMO

BACKGROUND: Minimally invasive surgery (MIS) provides a new approach for patients with hilar cholangiocarcinoma (HCCA). However, whether it can achieve similar outcomes to traditional open surgery (OS) remains controversial. METHODS: To assess the safety and feasibility of MIS for HCCA, a systematic review and meta-analysis was performed to compare the outcomes of MIS with OS. Seventeen outcomes were assessed. RESULTS: Nine studies involving 382 patients were included. MIS was comparable in blood transfusion rate, R0 resection rate, lymph nodes received, overall morbidity, severe morbidity (Clavien-Dindo classification > = 3), bile leakage rate, wound infection rate, intra-abdominal infection rate, days until oral feeding, 1-year overall survival, 2-year overall survival and postoperative mortality with OS. Although operation time was longer (mean difference (MD) = 93.51, 95% confidence interval (CI) = 64.10 to 122.91, P < 0.00001) and hospital cost (MD = 0.68, 95% CI = 0.03 to 1.33, P = 0.04) was higher in MIS, MIS was associated with advantages of minimal invasiveness, that was less blood loss (MD = -81.85, 95% CI = -92.09 to -71.62, P < 0.00001), less postoperative pain (MD = -1.21, 95% CI = -1.63 to -0.79, P < 0.00001), and shorter hospital stay (MD = -4.22, 95% CI = -5.65 to -2.80, P < 0.00001). CONCLUSIONS: The safety and feasibility of MIS for HCCA is acceptable in selected patients. MIS is a remarkable alternative to OS for providing comparable outcomes associated with a benefit of minimal invasiveness and its application should be considered more.


Assuntos
Neoplasias dos Ductos Biliares/cirurgia , Tumor de Klatskin/cirurgia , Tempo de Internação , Procedimentos Cirúrgicos Minimamente Invasivos , Procedimentos Cirúrgicos Robóticos , Perda Sanguínea Cirúrgica/prevenção & controle , Humanos , Complicações Pós-Operatórias/prevenção & controle
8.
Sci Transl Med ; 13(586)2021 03 24.
Artigo em Inglês | MEDLINE | ID: mdl-33762435

RESUMO

Most basal-like breast cancers (BLBCs) are triple-negative breast cancers (TNBCs), which have the worst prognosis and distant metastasis-free survival among breast cancer subtypes. Now, no targeted therapies are available for patients with BLBC due to the lack of reliable and effective molecular targets. Here, we performed the BLBC tissue microarray-based immunohistochemical analysis and showed that Faciogenital Dysplasia 5 (FGD5) abundance is associated with poor prognosis in BLBCs. FGD5 deletion decreased the proliferation, invasion, and tumorsphere formation capacity of BLBC cells. Furthermore, genetic inhibition of Fgd5 in mouse mammary epithelial cells attenuated BLBC initiation and progression by reducing the self-renewal ability of tumor-initiating cells. In addition, FGD5 abundance was positively correlated with the abundance of epidermal growth factor receptor (EGFR) in BLBCs. FGD5 ablation decreased EGFR abundance by reducing EGFR stability in TNBC cells in 2D and 3D culture conditions. Mechanistically, FGD5 binds to EGFR and interferes with basal EGFR ubiquitination and degradation induced by the E3 ligase ITCH. Impaired EGFR degradation caused BLBC cell proliferation and promoted invasive properties and self-renewal. To verify the role of the FGD5-EGFR interaction in the regulation of EGFR stability, we screened a cell-penetrating α-helical peptide PER3 binding with FGD5 to disrupt the interaction. Treatment of BLBC patient-derived xenograft-bearing mice with the peptide PER3 disrupting the FGD5-EGFR interaction either with or without chemotherapy reduced BLBC progression. Our study identified FGD5 as a positive modulator of tumor-initiating cells and suggests a potential therapeutic option for the BLBC subtype of breast cancer.


Assuntos
Fatores de Troca do Nucleotídeo Guanina/genética , Células-Tronco Neoplásicas , Neoplasias de Mama Triplo Negativas , Animais , Receptores ErbB , Feminino , Humanos , Camundongos , Neoplasias de Mama Triplo Negativas/genética
9.
J Craniofac Surg ; 32(3): 988-990, 2021 May 01.
Artigo em Inglês | MEDLINE | ID: mdl-33538448

RESUMO

BACKGROUND: Although infantile hemangiomas (IHs) are usually self-limiting, residual elevated appearance may remain. Topical beta-blockers are effective in superficial IHs management, while intralesionally injected diprospan is effective at treating deep, localized IHs. A single application of topical timolol or injected diprospan has obvious limitations. Therefore, for elevated, localized mixed IHs, we applied topical timolol combined with intralesionally injected diprospan, using their respective advantages to maximize benefits. PURPOSE: To evaluate the clinical efficacy and safety of topical timolol combined with intralesionally injected diprospan for the treatment of elevated, localized mixed IHs and identify the optimal injection time. METHODS: Infants with elevated, localized mixed IHs in the proliferative phase were treated with injected diprospan combined with topical timolol between March 2018 and March 2020. The injection was administered only when the tumor surface was higher than that of the surrounding tissue. The patients were asked to return every 4 weeks for a treatment response evaluation, and complications were recorded. RESULTS: Thirty-six patients with elevated, localized mixed IHs (thickness >3 mm on Doppler ultrasound) were recruited. The mean age at treatment initiation was 3.58 ±â€Š1.50 months (range: 1.00-6.00 months). The follow-up period ranged from 9 to 24 months. Considering the size of the IH at the end of treatment, regression was observed in 31 (86.1%) cases, stabilization was observed in 5 (13.9%) cases, and no treatment failure was observed. All the IHs improved in color and height after treatment. CONCLUSION: Topical timolol combined with intralesionally injected diprospan is an effective and safe treatment for elevated, localized mixed IH. The injection is needed only when we forecast the elevated tissue may remain after regression.


Assuntos
Hemangioma , Neoplasias Cutâneas , Administração Tópica , Antagonistas Adrenérgicos beta/uso terapêutico , Betametasona/análogos & derivados , Combinação de Medicamentos , Hemangioma/tratamento farmacológico , Humanos , Lactente , Injeções Intralesionais , Neoplasias Cutâneas/tratamento farmacológico , Timolol/uso terapêutico , Resultado do Tratamento
10.
Sci Total Environ ; 769: 144488, 2021 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-33485203

RESUMO

Methyl halides are important greenhouse gases responsible for the majority of the ozone layer depletion. This study investigated atmospheric and seawater methyl halides (CH3Cl, CH3Br, and CH3I) in the western Pacific Ocean between 2°N and 24°N. Increases in methyl halides in the atmosphere were likely to have originated from Southeast Asian regions. Elevated CH3I concentrations in seawater were mainly produced photochemically from dissolved organic carbon. Maximum methyl halide and chlorophyll a levels in the upper water column (0-200 m) were linked to biological activity and downwelling or upwelling caused by cold and warm eddies. Ship-based incubation experiments showed that nutrient supplementation promoted methyl halide emissions. The elevated methyl halide production was associated with increases in phytoplankton such as diatoms. The mean fluxes of CH3Cl, CH3Br, and CH3I in study area of during the cruise were 82.91, 4.70, and 3.50 nmol m-2 d-1, respectively. The estimated emissions of CH3Cl, CH3Br, and CH3I in the western Pacific Ocean accounted for 0.67%, 0.79% and 0.09% of global oceanic emissions, respectively, indicating that the open sea contribute insignificantly to the global oceanic emissions of these gases.

11.
BMC Surg ; 21(1): 18, 2021 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-33407359

RESUMO

BACKGROUND: Impaction of jujube pits in the upper gastrointestinal (GI) tract is a special clinical condition in the northern Chinese population. Endoscopic removal is the preferred therapy, but there is no consensus on the management strategies. We reported our individualized endoscopic strategies on the jujube pits impacted in the upper GI tract. METHODS: In this retrospective study, we included 191 patients (male: 57; female: 134) who presented to our hospital with ingestion of jujube pits between January 2015 and December 2017. Demographic information, times of hospital visiting, locations of jujube pits, endoscopic procedures, post-extraction endoscopic characteristics were analyzed. Management strategies including sufficient suction, repeated irrigation, jejunal nutrition and gastrointestinal decompression were given based on post-extraction endoscopic characteristics and impacted locations. RESULTS: Peak incidence was in the second quarter of each year (85/191 cases, 44.5%). Among the 191 cases, 169 (88.5%) showed pits impaction in the esophagus, 20 (10.5%) in the prepyloric region and 2 (1.0%) in the duodenal bulb. A total of 185 patients (96.9%) had pits removed with alligator jaw forceps, and 6 (3.1%) underwent suction removal with transparent caps placed over the end of the endoscope to prevent injury on removal of these pits with two sharp painted edges. Post-extraction endoscopic manifestations included mucosal erosion (26.7%), mucosa laceration (24.6%), ulceration with a white coating (18.9%) and penetrating trauma with pus cavity formation (29.8%). All patients received individualized endoscopic and subsequent management strategies and showed good outcomes. CONCLUSIONS: Individualized endoscopic management for impacted jujube pits in the upper GI tract based on post-extraction endoscopic characteristics and impacted locations was safe, effective, and minimally invasive.


Assuntos
Corpos Estranhos , Trato Gastrointestinal Superior , Ziziphus , China , Feminino , Corpos Estranhos/cirurgia , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Trato Gastrointestinal Superior/cirurgia
12.
Nat Commun ; 11(1): 6316, 2020 12 09.
Artigo em Inglês | MEDLINE | ID: mdl-33298911

RESUMO

The transcription factor MYC is deregulated in almost all human cancers, especially in aggressive lymphomas, through chromosomal translocation, amplification, and transcription hyperactivation. Here, we report that high expression of tribbles homologue 3 (TRIB3) positively correlates with elevated MYC expression in lymphoma specimens; TRIB3 deletion attenuates the initiation and progression of MYC-driven lymphoma by reducing MYC expression. Mechanistically, TRIB3 interacts with MYC to suppress E3 ubiquitin ligase UBE3B-mediated MYC ubiquitination and degradation, which enhances MYC transcriptional activity, causing high proliferation and self-renewal of lymphoma cells. Use of a peptide to disturb the TRIB3-MYC interaction together with doxorubicin reduces the tumor burden in MycEµ mice and patient-derived xenografts. The pathophysiological relevance of UBE3B, TRIB3 and MYC is further demonstrated in human lymphoma. Our study highlights a key mechanism for controlling MYC expression and a potential therapeutic option for treating lymphomas with high TRIB3-MYC expression.


Assuntos
Proteínas de Ciclo Celular/metabolismo , Linfoma não Hodgkin/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Proto-Oncogênicas c-myc/metabolismo , Proteínas Repressoras/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antineoplásicos/farmacologia , Antineoplásicos/uso terapêutico , Proteínas de Ciclo Celular/genética , Linhagem Celular Tumoral , Autorrenovação Celular/efeitos dos fármacos , Autorrenovação Celular/genética , Sequenciamento de Cromatina por Imunoprecipitação , Progressão da Doença , Feminino , Regulação Neoplásica da Expressão Gênica , Técnicas de Introdução de Genes , Técnicas de Silenciamento de Genes , Células HEK293 , Humanos , Linfoma não Hodgkin/tratamento farmacológico , Linfoma não Hodgkin/genética , Masculino , Camundongos , Camundongos Knockout , Pessoa de Meia-Idade , Cultura Primária de Células , Complexo de Endopeptidases do Proteassoma/metabolismo , Inibidores de Proteassoma/farmacologia , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Proteólise/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/antagonistas & inibidores , RNA-Seq , Proteínas Repressoras/genética , Ubiquitinação/efeitos dos fármacos , Ubiquitinação/genética , Ensaios Antitumorais Modelo de Xenoenxerto , Adulto Jovem
13.
Technol Cancer Res Treat ; 19: 1533033820977504, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33256552

RESUMO

Lung cancer is one of the leading causes of cancer-related death. In recent years, there has been an increasing interest in the fields of tumor and immunity. This study focused on the possible prognostic value of immune genes in non-small cell lung cancer patients. We used The Cancer Genome Atlas (TCGA) to download gene expression data and clinical information of lung adenocarcinoma (LUAD) and lung squamous cell carcinoma (LUSC). The immune gene list was downloaded from the Immport database. We then constructed immune gene prognostic models on the basis of Cox regression analysis. We further evaluated the clinical significance of the models via survival analysis, receiver operating characteristic (ROC) curves, and independent prognostic factor analysis. Moreover, we analyzed the associations of prognostic models with both mutation burdens and neoantigens. Using the Gene Expression Omnibus (GEO) and Kaplan-Meier plotter databases, we evaluated the validity of the prognostic models. The prognostic model of LUAD included 13 immune genes, and the prognostic model of LUSC contained 10 immune genes. High-risk patients based on prognostic models had a lower 5-year survival rate than did low-risk patients. The ROC curve analysis demonstrated the prediction accuracy of the prognostic models, as the area under the curve (AUC) was 0.742, 0.707, and 0.711 for LUAD, and 0.668, 0.703, and 0.668 for LUSC, when the predicted survival times were 1, 3, and 5 years, respectively. The mutation burden analysis showed that mutation level was associated with the risk score in patients with LUAD. The analysis based on GEO and Kaplan-Meier plotter demonstrated the prognostic validity of the models. Therefore, immune gene-related models of LUAD and LUSC can predict prognosis. Further study of these genes may enable us to better distinguish between LUAD and LUSC and lead to improvement in immunotherapy for lung cancer.

14.
Front Med (Lausanne) ; 7: 556818, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33304910

RESUMO

Background: Coronavirus disease (COVID-19) has swept around the globe and led to a worldwide catastrophe. Studies examining the disease progression of patients with non-severe disease on admission are scarce but of profound importance in the early identification of patients at a high risk of deterioration. Objectives: To elucidate the differences in clinical characteristics between patients with progressive and non-progressive COVID-19 and to determine the risk factors for disease progression. Study design: Clinical data of 365 patients with non-severe COVID-19 from 1 January 2020 to 18 March 2020 were retrospectively collected. Patients were stratified into progressive and non-progressive disease groups. Univariate and multivariate logistic regression analyses were performed to determine the independent risk factors for disease progression. Results: Compared with patients with non-progressive disease, those who progressed to severe COVID-19 were older and had significantly decreased lymphocyte and eosinophil counts; increased neutrophil and platelet counts; lower albumin levels; higher levels of lactate dehydrogenase, C-reactive protein (CRP), creatinine, creatinine kinase, and urea nitrogen; and longer prothrombin times. Hypertension, fever, fatigue, anorexia, bacterial coinfection, bilateral patchy shadowing, antibiotic and corticosteroid administration, and oxygen support had a significantly higher incidence among patients with progressive disease. A significantly longer duration of hospital stay was also observed in patients with progressive disease. Bilateral patchy shadowing (OR = 4.82, 95% CI: 1.33-17.50; P = 0.017) and elevated levels of creatinine (OR =6.24, 95% CI: 1.42-27.40; P = 0.015), and CRP (OR = 7.28, 95% CI: 2.56-20.74; P < 0.001) were independent predictors for disease progression. Conclusion: The clinical characteristics of patients with progressive and non-progressive COVID-19 were significantly different. Bilateral patchy shadowing and increased levels of creatinine, and CRP were independent predictors of disease progression.

15.
J Exp Clin Cancer Res ; 39(1): 229, 2020 Oct 29.
Artigo em Inglês | MEDLINE | ID: mdl-33121524

RESUMO

BACKGROUND: Dysregulation of long non-coding RNAs (lncRNAs) is responsible for cancer initiation and development, positioning lncRNAs as not only biomarkers but also promising therapeutic targets for cancer treatment. A growing number of lncRNAs have been reported in hepatocellular carcinoma (HCC), but their functional and mechanistic roles remain unclear. METHODS: Gene Set Enrichment Analysis was used to investigate the molecular mechanism of UPK1A antisense RNA 1 (UPK1A-AS1). Cell Counting Kit-8 assays, EdU assays, flow cytometry, western blotting, and xenograft assays were used to confirm the role of UPK1A-AS1 in the proliferation of HCC cells in vitro and in vivo. Bioinformatics analyses and quantitative polymerase chain reaction (qRT-PCR) were performed to explore the interplay between UPK1A-AS1 and enhancer of zeste homologue 2 (EZH2). RNA immunoprecipitation (RIP), RNA pull-down assays, western blotting, and qRT-PCR were conducted to confirm the interaction between UPK1A-AS1 and EZH2. The interaction between UPK1A-AS1 and miR-138-5p was examined by luciferase reporter and RIP assays. Finally, the expression level and prognosis value of UPK1A-AS1 in HCC were analyzed using RNA sequencing data from The Cancer Genome Atlas datasets. RESULTS: We showed that UPK1A-AS1, a newly identified lncRNA, promoted cellular proliferation and tumor growth by accelerating cell cycle progression. Cell cycle-related genes, including CCND1, CDK2, CDK4, CCNB1, and CCNB2, were significantly upregulated in HCC cells overexpressing UPK1A-AS1. Furthermore, overexpression of UPK1A-AS1 could protect HCC cells from cis-platinum toxicity. Mechanistically, UPK1A-AS1 interacted with EZH2 to mediate its nuclear translocation and reinforce its binding to SUZ12, leading to increased H27K3 trimethylation. Targeting EZH2 with specific small interfering RNA impaired the UPK1A-AS1-mediated upregulation of proliferation and cell cycle progression-related genes. Moreover, miR-138-5p was identified as a direct target of UPK1A-AS1. Additionally, UPK1A-AS1 was significantly upregulated in HCC, and the upregulation of UPK1A-AS1 predicted poor prognosis for patients with HCC. CONCLUSIONS: Our study revealed that UPK1A-AS1 promotes HCC development by accelerating cell cycle progression through interaction with EZH2 and sponging of miR-138-5p, suggesting that UPK1A-AS1 possesses substantial potential as a novel biomarker for HCC prognosis and therapy.


Assuntos
Carcinoma Hepatocelular/patologia , Proteína Potenciadora do Homólogo 2 de Zeste/metabolismo , Regulação Neoplásica da Expressão Gênica , Neoplasias Hepáticas/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , Uroplaquina Ia/genética , Animais , Apoptose , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Movimento Celular , Proliferação de Células , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Humanos , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Masculino , Camundongos , Camundongos Nus , Prognóstico , RNA Antissenso/genética , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
16.
Front Vet Sci ; 7: 588, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-33005648

RESUMO

Bovine mastitis, an inflammatory disease that occurs frequently in early lactation or the dry period, is primarily caused by bacterial infections. There is growing evidence that Aerococcus viridans (A. viridans) is becoming an important cause of bovine mastitis. The treatment of bovine mastitis is primarily based on antibiotics, which not only leads to a large economic burden but also the development of antibiotic resistance. On the other hand, bacteriophages present a promising alternative treatment strategy. The object of this study was to evaluate the potential of a previously isolated A. viridans phage vB_AviM_AVP (AVP) as an anti-mastitis agent in an experimental A. viridans-induced murine mastitis model. A. viridans N14 was isolated from the milk of clinical bovine mastitis and used to establish a mastitis model in mice. We demonstrated that administration of phage AVP significantly reduced colony formation by A. viridans and alleviated damage to breast tissue. In addition, reduced inflammation was indicated by decreased levels of inflammatory cytokines (TNF-α, IL-1ß, and IL-6) and myeloperoxidase (MPO) activity in the phage-treated group compared to those in the phosphate buffered saline (PBS)-treated group. To the best of our knowledge, this report is the first to show the potential use of phages as a treatment for A. viridans-induced mastitis.

17.
J Cell Mol Med ; 24(21): 12355-12367, 2020 11.
Artigo em Inglês | MEDLINE | ID: mdl-32961025

RESUMO

Diabetes is a disorder of glucose metabolism, and over 90% are type 2 diabetes. Diabetic cardiomyopathy (DCM) is one of the type 2 diabetes complications, usually accompanied by changes in myocardial structure and function, together with cardiomyocyte apoptosis. Our study investigated the effect of curcumin on regulating oxidative stress (OS) and apoptosis in DCM. In vivo, diabetes was induced in an experimental rat model by streptozoticin (STZ) together with high-glucose and high-fat (HG/HF) diet feeding. In vitro, H9c2 cardiomyocytes were cultured with high-glucose and saturated free fatty acid palmitate. Curcumin was orally or directly administered to rats or cells, respectively. Streptozoticin -induced diabetic rats showed metabolism abnormalities and elevated markers of OS (superoxide dismutase [SOD], malondialdehyde [MDA], gp91phox , Cyt-Cyto C), enhanced cell apoptosis (Bax/Bcl-2, Cleaved caspase-3, TUNEL-positive cells), together with reduced Akt phosphorylation and increased Foxo1 acetylation. Curcumin attenuated the myocardial dysfunction, OS and apoptosis in the heart of diabetic rats. Curcumin treatment also enhanced phosphorylation of Akt and inhibited acetylation of Foxo1. These results strongly suggest that apoptosis was increased in the heart of diabetic rats, and curcumin played a role in diabetic cardiomyopathy treatment by modulating the Sirt1-Foxo1 and PI3K-Akt pathways.


Assuntos
Apoptose/efeitos dos fármacos , Curcumina/farmacologia , Cardiomiopatias Diabéticas/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Transdução de Sinais/efeitos dos fármacos , Animais , Glicemia/metabolismo , Sobrevivência Celular , Diabetes Mellitus Experimental , Masculino , Miocárdio/metabolismo , Miócitos Cardíacos/metabolismo , Proteínas do Tecido Nervoso/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/metabolismo , Ratos , Ratos Sprague-Dawley , Sirtuína 1/metabolismo
18.
Biomed Pharmacother ; 131: 110607, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-32841898

RESUMO

Epigenetic mechanisms, such as acetylation, methylation, and succinylation, play pivotal roles in the regulation of multiple normal biological processes, including neuron regulation, hematopoiesis, bone cell maturation, and metabolism. In addition, epigenetic mechanisms are closely associated with the pathological processes of various diseases, such as metabolic diseases, autoimmune diseases and cancers. Epigenetic changes may precede genetic mutation, so research on epigenetic changes and regulation may be important for the early detection and diagnosis of disease. Histone deacetylase11 (HDAC11) is the newest member of the histone deacetylase (HDAC) family and the only class IV histone deacetylase. HDAC11 has different expression levels and biological functions in different systems of the human body and is among the top 1 to 4% of genes overexpressed in cancers, such as breast cancer, hepatocellular carcinoma and renal pelvis urothelial carcinoma. This article analyzes the role and mechanism of HDAC11 in disease, especially in tumorigenesis, in an attempt to provide new ideas for clinical and basic research.


Assuntos
Epigênese Genética/fisiologia , Inibidores de Histona Desacetilases/farmacologia , Histona Desacetilases/genética , Histona Desacetilases/metabolismo , Animais , Epigênese Genética/efeitos dos fármacos , Redes Reguladoras de Genes/efeitos dos fármacos , Redes Reguladoras de Genes/fisiologia , Hematopoese/efeitos dos fármacos , Hematopoese/fisiologia , Inibidores de Histona Desacetilases/uso terapêutico , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/genética , Neoplasias/metabolismo
19.
Nat Commun ; 11(1): 3660, 2020 07 21.
Artigo em Inglês | MEDLINE | ID: mdl-32694521

RESUMO

High expression or aberrant activation of epidermal growth factor receptor (EGFR) is related to tumor progression and therapy resistance across cancer types, including non-small cell lung cancer (NSCLC). EGFR tyrosine kinase inhibitors (TKIs) are first-line therapy for NSCLC. However, patients eventually deteriorate after inevitable acquisition of EGFR TKI-resistant mutations, highlighting the need for therapeutics with alternative mechanisms of action. Here, we report that the elevated tribbles pseudokinase 3 (TRIB3) is positively associated with EGFR stability and NSCLC progression. TRIB3 interacts with EGFR and recruits PKCα to induce a Thr654 phosphorylation and WWP1-induced Lys689 ubiquitination in the EGFR juxtamembrane region, which enhances EGFR recycling, stability, downstream activity, and NSCLC stemness. Disturbing the TRIB3-EGFR interaction with a stapled peptide attenuates NSCLC progression by accelerating EGFR degradation and sensitizes NSCLC cells to chemotherapeutic agents. These findings indicate that targeting EGFR degradation is a previously unappreciated therapeutic option in EGFR-related NSCLC.


Assuntos
Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Proteínas de Ciclo Celular/metabolismo , Neoplasias Pulmonares/patologia , Proteínas Serina-Treonina Quinases/antagonistas & inibidores , Proteínas Repressoras/metabolismo , Adulto , Animais , Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Linhagem Celular Tumoral , Progressão da Doença , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/genética , Receptores ErbB/antagonistas & inibidores , Receptores ErbB/genética , Receptores ErbB/metabolismo , Feminino , Humanos , Estimativa de Kaplan-Meier , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/mortalidade , Masculino , Camundongos , Pessoa de Meia-Idade , Mutação , Fosforilação/efeitos dos fármacos , Proteína Quinase C-alfa/metabolismo , Processamento de Proteína Pós-Traducional/efeitos dos fármacos , Estabilidade Proteica/efeitos dos fármacos , Proteínas Serina-Treonina Quinases/metabolismo , Proteólise/efeitos dos fármacos , Taxa de Sobrevida , Ubiquitinação/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
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