Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 197
Filtrar
1.
SAGE Open Med Case Rep ; 9: 2050313X211057704, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34777811

RESUMO

Alpha-fetoprotein hardly increased due to nasopharyngeal cancer. In this article, we reported a 57-year-old male nasopharyngeal carcinoma patient who had posttreatment subscapular metastasis with high serum alpha-fetoprotein but negative plasma Epstein-Barr virus DNA. Pathology results indicated that the scapular mass was undifferentiated non-keratinizing carcinoma originated in the nasopharynx. Moreover, no liver lesion was detected by imaging examination. In view of the positive alpha-fetoprotein and alpha-fetoprotein messenger RNA staining result in the right scapular mass fine needle aspiration biopsy sample, we considered the diagnosis of alpha-fetoprotein-producing nasopharyngeal carcinoma that had never been reported before.

2.
Eur J Cancer ; 159: 133-143, 2021 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-34743068

RESUMO

PURPOSE: To compare the prognosis and adverse effects of induction or adjuvant chemotherapy (IC or AC) plus concurrent chemoradiotherapy (CCRT) versus CCRT alone in paediatric nasopharyngeal carcinoma (NPC) patients in the intensity-modulated radiotherapy (IMRT) era. METHODS AND MATERIALS: 549 patients diagnosed from 2005 to 2021 were enrolled. Our primary endpoint was progression-free survival (PFS). The recursive partitioning analysis (RPA) was applied to derive a risk stratification system. Kaplan-Meier survival curves were used to assess the cumulative survival rates, and cox analysis was applied to evaluate the relationship between variables and endpoints. RESULTS: The RPA-based risk stratification identified three different risk groups. In the intermediate-risk (stage IVa and EBV<4000 copies/ml) group, patients who received IC followed by CCRT achieved a significantly better 3-year PFS rate than those treated with CCRT alone (87.35% versus 75.89%; P = 0.04). But survival benefit was not obtained from the additional IC or AC in the low-risk (stage II-III and EBV<4000 copies/ml) or high-risk (stage II-IVa and EBV≥4000 copies/ml) group. The most common grade 3 or 4 adverse events in patients treated with CCRT, IC + CCRT, and CCRT + AC were neutropenia (8.1%, 33.0% versus 36.9%, respectively) and leukopenia (14.1%, 26.8% versus 32.3%, respectively) with statistically significant difference. CONCLUSIONS: Paediatric NPC patients in the intermediate-risk group treated with IC followed by CCRT had significantly better PFS compared with patients treated with CCRT alone. And the overall incidence of acute adverse events in patients treated with IC or AC plus CCRT was higher than in patients treated with CCRT alone.

3.
Front Cell Infect Microbiol ; 11: 729346, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34631603

RESUMO

Irritable bowel syndrome (IBS) is the most common functional bowel disorder worldwide and is associated with visceral hypersensitivity, gut motility, immunomodulation, gut microbiota alterations, and dysfunction of the brain-gut axis; however, its pathophysiology remains poorly understood. Gut microbiota and its metabolites are proposed as possible etiological factors of IBS. The aim of our study was to investigate specific types of microbiota-derived metabolites, especially bile acids, short-chain fatty acids, vitamins, amino acids, serotonin and hypoxanthine, which are all implicated in the pathogenesis of IBS. Metabolites-focused research has identified multiple microbial targets relevant to IBS patients, important roles of microbiota-derived metabolites in the development of IBS symptoms have been established. Thus, we provide an overview of gut microbiota and their metabolites on the different subtypes of IBS (constipation-predominant IBS-C, diarrhea-predominant IBS-D) and present controversial views regarding the role of microbiota in IBS.


Assuntos
Gastroenteropatias , Microbioma Gastrointestinal , Síndrome do Intestino Irritável , Ácidos e Sais Biliares , Ácidos Graxos Voláteis , Humanos
4.
Bioinformatics ; 2021 Oct 12.
Artigo em Inglês | MEDLINE | ID: mdl-34636837

RESUMO

MOTIVATION: Immune cells are important components of the immune system and are crucial for disease initiation, progression, prognosis, and survival. Although several computational methods have been designed for predicting the abundance of immune cells, very few tools are applicable to mouse. Given that mouse is the most widely used animal model in biomedical research, there is an urgent need to develop a precise algorithm for predicting mouse immune cells. RESULTS: We developed a tool named ImmuCellAI-mouse (Immune Cell Abundance Identifier for mouse), for estimating the abundance of 36 immune cell (sub)types from gene expression data in a hierarchical strategy of three layers. Reference expression profile and robust marker gene sets of immune cell types were curated. The abundance of cells in three layers was predicted separately by calculating the ssGSEA enrichment score of the expression deviation profile per cell type. Benchmark results showed high accuracy of ImmuCellAI-mouse in predicting most immune cell types, with correlation coefficients between predicted value and real cell proportion of most cell types being larger than 0.8. We applied ImmuCellAI-mouse to a mouse breast tumor dataset and revealed the dynamic change of immune cell infiltration during treatment, which is consistent with the findings of the original study but with more details. We also constructed an online server for ImmuCellAI-mouse, on which users can upload expression matrices for analysis. ImmuCellAI-mouse will be a useful tool for studying the immune microenvironment, cancer immunology, and immunotherapy in mouse models, providing an indispensable supplement for human disease studies. AVAILABILITY: Software is available at http://bioinfo.life.hust.edu.cn/ImmuCellAI-mouse/. SUPPLEMENTARY INFORMATION: Supplementary data are available at Bioinformatics online.

5.
Artigo em Inglês | MEDLINE | ID: mdl-34704612

RESUMO

PURPOSE: This study aimed to investigate the prevalence and risk factors for myopia and high myopia among Han and Uyghur students in Xinjiang, China. METHODS: This cross-sectional study with a multistage, stratified cluster sampling method was completed in Xinjiang, China. Visual acuity and noncycloplegic refraction were measured. The crude and sex- and age-adjusted prevalence of myopia and high myopia in Han and Uyghur students were compared. Multivariate logistic regression analyses were applied to identify risk factors associated with myopia and high myopia. RESULTS: In total, 84,033 participants were included in the final analysis, comprising 64,110 Han and 19,923 Uyghur participants. The overall age- and sex-adjusted prevalence of myopia and high myopia were 47.70% (95% CI: 47.67-47.74) and 2.55% (95% CI: 2.54-2.56), respectively. Compared to the Uyghur population, the Han population had a higher prevalence of myopia (63.59% vs. 21.34%, p < 0.0001) and high myopia (4.68% vs. 0.6%, p < 0.0001). Han ethnicity, age, female sex, higher education level and living in urban areas were found to be positively associated with myopia and high myopia. Living in northern Xinjiang was found to be positively associated with myopia but negatively associated with high myopia. CONCLUSIONS: Our study investigated the prevalence of myopia and high myopia among Han and Uyghur students aged 4-23 years in Xinjiang, China. The Han population had a higher prevalence of myopia and high myopia than the Uyghur population. However, the prevalence of myopia among the Uyghur population showed a more remarkable increasing trend than that among the Han population in Xinjiang.

6.
Pathogens ; 10(9)2021 Aug 27.
Artigo em Inglês | MEDLINE | ID: mdl-34578126

RESUMO

Pogostemon cablin is one of the well-known Southern Chinese medicinal plants with detoxification, anti-bacterial, anti-inflammatory, and other pharmacological functions. Identification and characterization of phytopathogens on P. cablin are of great significance for the prevention and control of diseases. From spring to summer of 2019 and 2020, a leaf spot disease on Pogostemon cablin was observed in Guangdong Province, South China. The pathogen was isolated and identified based on both morphological and DNA molecular approaches. The molecular identification was conducted using multi-gene sequence analysis of large subunit (LSU), the nuclear ribosomal internal transcribed spacer (ITS), beta-tubulin (ß-tubulin), and RNA polymerase II (rpb2) genes. The causal organism was identified as Stagonosporopsis pogostemonis, a novel fungal species. Pathogenicity of Stagonosporopsis pogostemonis on P. cablin was fulfilled via confining the Koch's postulates, causing leaf spots and stem blight disease. This is the first report of leaf spot diseases on P. cablin caused by Stagonosporopsis species worldwide.

7.
Sci Rep ; 11(1): 18181, 2021 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-34518608

RESUMO

To investigate the effects of ketamine on glucose uptake and glucose transporter (GLUT) expression in depressive-like mice. After HA1800 cells were treated with ketamine, 2-[N-(7-Nitrobenz-2-oxa-1,3-diazol-4-yl)Amino]-2-Deoxyglucose (2-NBDG) was added to the cells to test the effects of ketamine on glucose uptake, production of lactate, and expression levels of GLUT, ERK1/2, AKT, and AMPK. Adult female C57BL/6 mice were subjected to chronic unpredictable mild stress (CUMS), 27 CUMS mice were randomly divided into the depression, ketamine (i.p.10 mg/kg), and FR180204 (ERK1/2 inhibitor, i.p.100 mg/kg) + ketamine group. Three mice randomly selected from each group were injected with 18F-FDG at 6 h after treatment. The brain tissue was collected at 6 h after treatment for p-ERK1/2 and GLUTs. Treatment with ketamine significantly increased glucose uptake, extracellular lactic-acid content, expression levels of GLUT3 and p-ERK in astrocytes and glucose uptake in the prefrontal cortex (P < 0.05), and the immobility time was significantly shortened in depressive-like mice (P < 0.01). An ERK1/2 inhibitor significantly inhibited ketamine-induced increases in the glucose uptake in depressive-like mice (P < 0.05), as well as prolonged the immobility time (P < 0.01). The expression levels of p-ERK1/2 and GLUT3 in depressive-like mice were significantly lower than those in normal control mice (P < 0.01). Ketamine treatment in depressive-like mice significantly increased the expression levels of p-ERK1/2 and GLUT3 in the prefrontal cortex (P < 0.01), whereas an ERK1/2 inhibitor significantly inhibited ketamine-induced increases (P < 0.01).Our present findings demonstrate that ketamine mitigated depressive-like behaviors in female mice by activating the ERK/GLUT3 signal pathway, which further increased glucose uptake in the prefrontal cortex.

8.
J Proteomics ; 248: 104349, 2021 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-34411764

RESUMO

Low temperature in winter was the most crucial abiotic stress that limits the mangrove afforestation northward. Previous study demonstrated that Sonneratia apetala initially transplanted to high latitude area exhibited a stronger plasticity of cold tolerance. To clarify the underlying mechanism, the physiological and proteomic responses to chilling stress were investigated in S. apetala leaves. Our results found that cold-acclimated seedlings had lower relative electrolyte leakage and MDA content than non-acclimated seedlings. On the contrary, higher chlorophyll content and photosynthetic capacity were observed in cold-acclimated seedlings. With proteomic analyses, the differentially accumulated proteins (DAPs) involved in ROS scavenging, photosynthesis and energy metabolism, carbohydrate metabolism, cofactor biosynthesis, and protein folding were suggested to play important roles in enhancing the cold tolerance of S. apetala. However, the down-regulation DAPs were suggested as a tradeoff between plant growth and chilling response. By the protein-protein interaction analyses, translation elongation factor G, chlorophyll A-B binding protein and ascorbate peroxidase 1 were suggested as the important regulators in cold-acclimated S. apetala seedlings under chilling stress. Based on the above results, a schematic diagram describing the mechanism of cold tolerance of exotic mangrove species S. apetala that was achieved by cold acclimation was presented in this study. SIGNIFICANCE: The major environmental factor limits the mangrove afforestation northward is the low temperature in winter. Previous study reported that Sonneratia apetala grew in high latitude exhibited a higher cold tolerance than that in low latitude, which was suggested as a result of cold acclimation. To further understand "how cold acclimation enhance the cold tolerance in S. apetala", the response of S. apetala subjected to chilling stress with or without cold acclimation was investigated in this study at the physiological and proteomic aspects. Our physiological results showed that S. apetala seedlings treated with cold acclimation exhibited a higher tolerance under chilling stress than that without cold acclimation. By using the comparative proteomic approaches and bioinformatic analyses, various biological processes were suggested to play an important role in enhancing the cold tolerance of S. apetala under chilling stress, such as ROS scavenging, photosynthesis and energy metabolism, carbohydrate metabolism, cofactor biosynthesis, and protein folding. Among these differentially accumulated proteins, translation elongation factor G (eEF-G), chlorophyll A-B binding protein (CAB) and ascorbate peroxidase 1 (APX1) were identified as the hub proteins function in coordinated regulating ROS scavenging, photosynthesis and protein biosynthesis in chloroplast and subsequently enhanced the cold tolerance of S. apetala under chilling stress. Our results provided a further understanding of cold acclimation in improving the cold tolerance in exotic mangrove species S. apetala.


Assuntos
Proteoma , Plântula , Aclimatação , Clorofila A , Temperatura Baixa , Proteômica
9.
Radiother Oncol ; 163: 185-191, 2021 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-34453953

RESUMO

BACKGROUND: Unsatisfactory tumor response to induction chemotherapy (IC) is an adverse prognostic factor of locoregionally advanced nasopharyngeal carcinoma (LANPC). A re-induction strategy which applies additional cycles of an alternative IC regimen prior to radiotherapy (RT) has been adopted. METHODS: A total of 419 LANPC patients who attained suboptimal response (stable disease or disease progression) according to the Response Evaluation in Solid Tumors (RECIST) guideline after initial IC were retrospectively included. They were divided into those who received additional cycles of re-induction regimen prior to RT (re-induction group, n = 87) and those who had no additional chemotherapy (direct to RT group, n = 332). Propensity score matching (PSM) was used to adjust for potential confounders. Tumor response and long-term survival were compared between two groups. RESULTS: After receiving a second IC regimen, 39.1% of the patients in re-induction group attained partial response; however, the tumor control of subsequent RT was not significantly improved when compared with direct to RT group (patients attaining complete response after RT 55.2% vs. 52.5%, P = 0.757). Patients who received re-induction therapy showed worse locoregional relapse-free survival (LRFS) and progression-free survival (PFS) than those proceeded directly to RT (3-year LRFS 75.7% vs. 83.1%, P = 0.005; 3-year PFS 62.4% vs. 68.3%, P = 0.037). The increased hematological toxicities were observed in re-induction group that included grade 3-4 anemia, thrombocytopenia and liver enzyme increase. CONCLUSION: Re-induction therapy decreased LRFS and PFS and increased toxicities among patients who attain suboptimal response to initial IC regimen, as compared with direct to RT strategy.

10.
ACS Appl Mater Interfaces ; 13(30): 36080-36088, 2021 Aug 04.
Artigo em Inglês | MEDLINE | ID: mdl-34291893

RESUMO

In this work, three small molecular donors (SMDs) S35, S35-1Si, and S35-2Si, with 3,5-difluorophenyl-substituted benzodithiophene as the central 2-dimensional unit to combine different numbers of siloxane-terminated side chain, were synthesized for all-small-molecule organic solar cells (ASM-OSCs). The three SMDs showed comparable film absorption peaks at 570 nm and optical band gaps of 1.8 eV. Relative to S35 and S35-1Si with symmetric alkyl side chains and asymmetric side chains on the central unit, respectively, the S35-2Si carrying two symmetric siloxane-terminated side chains displayed largely elevated melting and crystalline temperatures, lowered surface energy, and modulated molecular orientation. The three SMDs possessed edge-on dominated molecular orientations of their neat films; however, a big difference was found for their blend films with nonfullerene acceptor Y6. The S35:Y6 and S35-1Si:Y6 blends exhibited edge-on and face-on bimodal orientations but the S35-2Si:Y6 blend showed pure face-on orientation, indicating quite different donor:acceptor intermolecular interactions. Some large domains existed in the S35:Y6 and S35-1Si:Y6 blends, but could be suppressed by the S35-2Si:Y6 blend, leading to a more balanced charge transport. In ASM-OSCs, the two S35:Y6 and S35-1Si:Y6 active layers showed comparable power conversion efficiencies (PCE) of ∼12% but a much higher efficiency of 13.50% could be achieved with the S35-2Si:Y6 active layer. Our results suggest that the siloxane-terminated side chain is promising to regulate crystalline ability of a SMD, paving a way for high performance ASM-OSCs.

11.
Front Neurol ; 12: 700007, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34220696

RESUMO

Background: A growing number of evidences suggest that TMZ applications can generate impressive benefits for APT and PC patients. However, the definite role of TMZ for individuals remains unclarified due to the variation between studies. And the predictive factors to alter its efficacy remain debatable. Objective: To evaluate the long-term effectiveness and safety profile of TMZ in the treatment of pituitary malignancies, and delineate the predictors during its clinical employment. Results: A literature retrieval was conducted from online databases for studies published up to December 31, 2020. Twenty one studies involving 429 patients were identified. TMZ exhibited 41% radiological overall response rate (rORR). The biochemical response rate was determinate in 53% of the functioning subset. Two-year and 4-year survival rate were 79 and 61%, respectively. TMZ prolonged the median PFS and OS as 20.18 and 40.24 months. TMZ-related adverse events occurred in 19% of patients. Regarding predictors of TMZ response, rORR was dramatically improved in patients with low/intermediate MGMT expression than those with high-MGMT (>50%) (p < 0.001). The benefit of TMZ varied according to functioning subtype of patients, with greater antitumor activities in functioning subgroups and fewer activities in non-functioning sets (p < 0.001). Notably, the concomitant therapy of radiotherapy and TMZ significantly increased the rORR (p = 0.007). Conclusion: TMZ elicits clinical benefits with moderate adverse events in APT and PC patients. MGMT expression and clinical subtype of secreting function might be vital predictors of TMZ efficacy. In the future, the combination of radiotherapy with TMZ may further improve the clinical outcomes than TMZ monotherapy.

12.
PLoS Pathog ; 17(7): e1009763, 2021 07.
Artigo em Inglês | MEDLINE | ID: mdl-34283874

RESUMO

Sensing and resisting oxidative stress is critical for Vibrio cholerae to survive in either the aquatic environment or the gastrointestinal tract. Previous studies mainly focused on the mechanisms of oxidative stress response regulation that rely on enzymatic antioxidant systems, while functions of non-enzymatic antioxidants are rarely discussed in V. cholerae. For the first time, we investigated the role of hydrogen sulfide (H2S), the simplest thiol compound, in protecting V. cholerae against oxidative stress. We found that degradation of L-cysteine by putative cystathionine ß-synthase (CBS) is the major source of endogenous H2S in V. cholerae. Our results indicate that intracellular H2S level has a positive correlation with cbs expression, while the enhanced H2S production can render V. cholerae cells less susceptible to H2O2 in vitro. Using proteome analysis and real-time qPCR assay, we found that cbs expression could stimulate the expression of several enzymatic antioxidants, including reactive oxygen species (ROS) detoxifying enzymes SodB, KatG and AhpC, the DNA protective protein DPS and the protein redox regulator Trx1. Assays of ROS detoxification capacities revealed that CBS-derived H2S could promote catalase activity at the post-translational level, especially for KatB, which serves as an important way that endogenous H2S participates in H2O2 detoxification. The enhancement of catalase activity by H2S is achieved through facilitating the uptake of iron. Adult mice experiments showed that cbs mutant has colonization defect, while either complementation of cbs or exogenous supplement of N-Acetyl-L-Cysteine restores its fitness in the host environment. Herein, we proposed that V. cholerae regulates CBS-dependent H2S production for better survival and proliferation under ROS stress.


Assuntos
Cistationina beta-Sintase/metabolismo , Interações Hospedeiro-Patógeno/fisiologia , Sulfeto de Hidrogênio/metabolismo , Cinesina/metabolismo , Vibrio cholerae/metabolismo , Animais , Proteínas de Bactérias/metabolismo , Catalase/metabolismo , Cólera/metabolismo , Camundongos , Estresse Oxidativo/fisiologia , Vibrio cholerae/patogenicidade
13.
Elife ; 102021 07 02.
Artigo em Inglês | MEDLINE | ID: mdl-34212857

RESUMO

Mannose-sensitive hemagglutinin (MSHA) pili and flagellum are critical for the surface attachment of Vibrio cholerae, the first step of V. cholerae colonization on host surfaces. However, the cell landing mechanism remains largely unknown, particularly in viscoelastic environments such as the mucus layers of intestines. Here, combining the cysteine-substitution-based labeling method with single-cell tracking techniques, we quantitatively characterized the landing of V. cholerae by directly observing both pili and flagellum of cells in a viscoelastic non-Newtonian solution consisting of 2% Luria-Bertani and 1% methylcellulose (LB+MC). The results show that MSHA pili are evenly distributed along the cell length and can stick to surfaces at any point along the filament. With such properties, MSHA pili are observed to act as a brake and anchor during cell landing which includes three phases: running, lingering, and attaching. Importantly, loss of MSHA pili results in a more dramatic increase in mean path length in LB+MC than in 2% LB only or in 20% Ficoll solutions, indicating that the role of MSHA pili during cell landing is more apparent in viscoelastic non-Newtonian fluids than viscous Newtonian ones. Our work provides a detailed picture of the landing dynamics of V. cholerae under viscoelastic conditions, which can provide insights into ways to better control V. cholerae infections in a real mucus-like environment.


Assuntos
Proteínas de Fímbrias/fisiologia , Flagelos/fisiologia , Vibrio cholerae/fisiologia , Regulação Bacteriana da Expressão Gênica/fisiologia , Lectina de Ligação a Manose/fisiologia , Movimento , Análise de Célula Única , Substâncias Viscoelásticas
14.
Clin Rheumatol ; 40(8): 3185-3193, 2021 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-34080081

RESUMO

OBJECTIVE: This study systematically compares the efficacy and adverse events of mycophenolate mofetil (MMF) and cyclophosphamide (CYC) in patients with systemic sclerosis-related interstitial lung disease (SSc-ILD). METHODS: The EMBASE and PubMed databases were systematically searched to find all relevant studies. Quality assessment, study selection, and data extraction were independently conducted by two reviewers. The mean changes in forced vital capacity (FVC)% and diffusing capacity for carbon monoxide (DLco)% of the patients were selected to be primary outcome measures. Stata software was used for the pooled analysis. RESULTS: Among 284 titles screened from multiple databases, six studies met the inclusion criteria (one randomized controlled trial, three prospective observational studies, and two retrospective observational studies). The summary weighted mean difference (WMD) of FVC change in the MMF group compared with the CYC group was - 1.17 (95% CI: - 2.713, 0.373; P = 0.137), and the summary WMD of DLco change in the MMF group compared with the CYC group was 2.245 (95% CI: 0.258, 4.232; P = 0.027). Studies enrolled showed that adverse events were less common in the MMF group. CONCLUSIONS: The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events. Key Points • A systematic review and meta-analysis was conducted to compare the efficacy and adverse events of mycophenolate mofetil and cyclophosphamide in patients with systemic sclerosis-related interstitial lung disease. • The efficacy of MMF with respect to FVC and DLco improvement is comparable to that of CYC, and MMF is preferred on the basis of the occurrence of adverse events.


Assuntos
Doenças Pulmonares Intersticiais , Escleroderma Sistêmico , Ciclofosfamida/uso terapêutico , Humanos , Imunossupressores/uso terapêutico , Doenças Pulmonares Intersticiais/tratamento farmacológico , Ácido Micofenólico/uso terapêutico , Estudos Observacionais como Assunto , Estudos Retrospectivos , Escleroderma Sistêmico/complicações , Escleroderma Sistêmico/tratamento farmacológico , Resultado do Tratamento
15.
Biomed Res Int ; 2021: 6663646, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34055993

RESUMO

Background: Vitiligo is a disfiguring skin disease with profound psychosocial impacts, such as anxiety, but the reported effect sizes of associations vary. We aimed to conduct a meta-analysis to quantify the strength of association between anxiety and vitiligo and to estimate the prevalence of anxiety among individuals with vitiligo. Methods: A systematic literature search was performed in five online databases (MEDLINE, Embase, Web of Science, Cochrane Library, and PsycINFO) from inception until March 20, 2020. All of the eligible studies were comprehensively reviewed, and all of the available data were analyzed according to our predefined criteria. Results: Twenty-one studies involving 3259 patients in 11 countries were included in this meta-analysis. Compared with the healthy control group, patients with vitiligo often had concomitant anxiety (OR = 6.14 [95% CI: 3.35-11.24], I 2 = 30.1%). The pooled prevalence of anxiety in female patients was significantly higher than that in males (OR = 2.24 [95% CI: 1.31-3.84], I 2 = 0.0%). Subgroup analysis showed that the pooled prevalence of clinical anxiety disorder and anxiety symptoms was 12% (95% CI: 7%-16%, I 2 = 76.3%) and 34% (95% CI: 21%-46%, I 2 = 94.7%), respectively. No publication bias has been detected by Begg's funnel plot and Egger's test. Conclusion: Patients with vitiligo have high anxiety comorbidity, with female predominance. Dermatologists and psychiatrists should be vigilant to the presence of anxiety, apply appropriate interventions to reduce the psychological impacts in a timely manner, and thus promote recovery in vitiligo patients. However, due to some objective limitations (poor information about the OR and diversity in assessment tools among included studies), findings should be interpreted with caution.


Assuntos
Ansiedade/epidemiologia , Comorbidade , Vitiligo/epidemiologia , Transtornos de Ansiedade/epidemiologia , Bases de Dados Factuais , Depressão , Feminino , Humanos , Masculino , Prevalência
16.
Crit Rev Immunol ; 41(1): 77-87, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33822526

RESUMO

Immunotherapy has emerged as a potent and effective treatment for multiple cancer types. For example, the engineering of T cells through the expression of chimeric antigen receptor (CAR) against tumors has shown remarkable potential. This review outlines clinical applications of CAR-T cell therapy in hematological malignancies and solid tumors, with a focus on the main challenges related to the safety and efficacy of the current CAR-T cell therapy and the promising strategies to maximize antitumor efficacy while minimizing adverse events. Finally, we present the future outlook of CAR-T cell therapy for the treatment against malignancies. We believe that potential problems can be overcome by strategies to further facilitate effective clinical translation and improve the efficacy, especially through the combination of different approaches.


Assuntos
Neoplasias , Receptores de Antígenos Quiméricos , Terapia Baseada em Transplante de Células e Tecidos , Humanos , Imunoterapia , Imunoterapia Adotiva , Neoplasias/terapia , Receptores de Antígenos Quiméricos/genética , Linfócitos T
17.
J Raman Spectrosc ; 2021 Feb 19.
Artigo em Inglês | MEDLINE | ID: mdl-33821082

RESUMO

The outbreak of COVID-19 coronavirus disease around the end of 2019 has become a pandemic. The preferred method for COVID-19 detection is the real-time polymerase chain reaction (RT-PCR)-based technique; however, it also has certain limitations, such as sample-dependent procedures with a relatively high false negative ratio. We propose a safe and efficient method for screening COVID-19 based on Raman spectroscopy. A total of 177 serum samples are collected from 63 confirmed COVID-19 patients, 59 suspected cases, and 55 healthy individuals as a control group. Raman spectroscopy is adopted to analyze these samples, and a machine learning support-vector machine (SVM) method is applied to the spectrum dataset to build a diagnostic algorithm. Furthermore, 20 independent individuals, including 5 asymptomatic COVID-19 patients and 5 symptomatic COVID-19 patients, 5 suspected patients, and 5 healthy patients, were sampled for external validation. In these three groups-confirmed COVID-19, suspected, and healthy individuals-the distribution of statistically significant points of difference showed highly consistency for intergroups after repeated sampling processes. The classification accuracy between the COVID-19 cases and the suspected cases is 0.87 (95% confidence interval [CI]: 0.85-0.88), and the accuracy between the COVID-19 and the healthy controls is 0.90 (95% CI: 0.89-0.91), while the accuracy between the suspected cases and the healthy control group is 0.68 (95% CI: 0.67-0.73). For the independent test dataset, we apply the obtained SVM model to the classification of the independent test dataset to have all the results correctly classified. Our model showed that the serum-level classification results were all correct for independent test dataset. Our results suggest that Raman spectroscopy could be a safe and efficient technique for COVID-19 screening.

18.
Int J Biol Macromol ; 180: 578-589, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33727188

RESUMO

G-quadruplex DNA (G4DNA) structure, which widely exists in the chromosomal telomeric regions and oncogenic promoter regions, plays a pivotal role in extending telomeric DNA with the help of telomerase in human cells. Bloom (BLM) helicase, a crucial member of the family of genome surveillance proteins, plays an essential role in DNA metabolic and repair pathways, including DNA replication, repair, transcription, recombination during chromosome segregation, and assuring telomere stability. The unwinding of G4DNA requires the participation of DNA helicase, which is crucial for maintaining chromosomal stability in cancer cells. Using fluorescence polarization and the electrophoretic mobility shift assay (EMSA), this study aimed to investigate the DNA-binding and unwinding properties of BLM helicase, cloned and purified from prostate cancer cells, toward G4DNA. The results revealed that BLM helicase derived from prostate cancer cells could bind and unwind G4DNA. The molecular affinity of bond between G4DNA and the helicase was dependent on the single-stranded DNA (ssDNA) terminals in G4DNA; the helicase was effectively bound to the G4DNA when the helicase monomer sufficiently covered approximately 10 nucleotides at the 3' or 5' ssDNA tail of G4DNA. For the unwinding of G4DNA, there was an apparent requirement of a 3' ssDNA tail and ATP; a G4DNA with only a 3' ssDNA tail was identified to be the most suitable substrate to be unwound by BLM helicase and required 3' ssDNA tails of at least 10 nt in length for efficient unwinding. Besides, BLM helicase was loosely bound and partly unwound the blunt-ended G4DNA. Although further mechanistic studies are warranted, the experimental results presented in this study are beneficial to further our understanding of the functional implication of BLM helicase in prostate cancer cells.


Assuntos
DNA/química , Quadruplex G , Neoplasias da Próstata/metabolismo , RecQ Helicases/metabolismo , Telômero/metabolismo , DNA/genética , DNA/metabolismo , DNA de Cadeia Simples/química , DNA de Cadeia Simples/genética , DNA de Cadeia Simples/metabolismo , Humanos , Cinética , Masculino , Modelos Moleculares , Conformação de Ácido Nucleico , Células PC-3 , Neoplasias da Próstata/genética , Neoplasias da Próstata/patologia , Ligação Proteica , RecQ Helicases/genética , Especificidade por Substrato , Telômero/genética
19.
Signal Transduct Target Ther ; 6(1): 110, 2021 03 06.
Artigo em Inglês | MEDLINE | ID: mdl-33677468

RESUMO

The 2019 coronavirus disease (COVID-19) outbreak caused by the SARS-CoV-2 virus is an ongoing global health emergency. However, the virus' pathogenesis remains unclear, and there is no cure for the disease. We investigated the dynamic changes of blood immune response in patients with COVID-19 at different stages by using 5' gene expression, T cell receptor (TCR), and B cell receptors (BCR) V(D)J transcriptome analysis at a single-cell resolution. We obtained single-cell mRNA sequencing (scRNA-seq) data of 341,420 peripheral blood mononuclear cells (PBMCs) and 185,430 clonotypic T cells and 28,802 clonotypic B cells from 25 samples of 16 patients with COVID-19 for dynamic studies. In addition, we used three control samples. We found expansion of dendritic cells (DCs), CD14+ monocytes, and megakaryocytes progenitor cells (MP)/platelets and a reduction of naïve CD4+ T lymphocytes in patients with COVID-19, along with a significant decrease of CD8+ T lymphocytes, and natural killer cells (NKs) in patients in critical condition. The type I interferon (IFN-I), mitogen-activated protein kinase (MAPK), and ferroptosis pathways were activated while the disease was active, and recovered gradually after patient conditions improved. Consistent with this finding, the mRNA level of IFN-I signal-induced gene IFI27 was significantly increased in patients with COVID-19 compared with that of the controls in a validation cohort that included 38 patients and 35 controls. The concentration of interferon-α (IFN-α) in the serum of patients with COVID-19 increased significantly compared with that of the controls in an additional cohort of 215 patients with COVID-19 and 106 controls, further suggesting the important role of the IFN-I pathway in the immune response of COVID-19. TCR and BCR sequences analyses indicated that patients with COVID-19 developed specific immune responses against SARS-CoV-2 antigens. Our study reveals a dynamic landscape of human blood immune responses to SARS-CoV-2 infection, providing clues for therapeutic potentials in treating COVID-19.


Assuntos
COVID-19/imunologia , Leucócitos/imunologia , Receptores de Antígenos de Linfócitos B/imunologia , Receptores de Antígenos de Linfócitos T/imunologia , SARS-CoV-2/imunologia , Análise de Célula Única , Adulto , COVID-19/genética , Feminino , Ferroptose/genética , Ferroptose/imunologia , Humanos , Sistema de Sinalização das MAP Quinases/genética , Sistema de Sinalização das MAP Quinases/imunologia , Masculino , Pessoa de Meia-Idade , RNA-Seq , Receptores de Antígenos de Linfócitos B/genética , Receptores de Antígenos de Linfócitos T/genética , SARS-CoV-2/genética
20.
Nat Commun ; 12(1): 1346, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33649323

RESUMO

SARS-CoV-2 is the underlying cause for the COVID-19 pandemic. Like most enveloped RNA viruses, SARS-CoV-2 uses a homotrimeric surface antigen to gain entry into host cells. Here we describe S-Trimer, a native-like trimeric subunit vaccine candidate for COVID-19 based on Trimer-Tag technology. Immunization of S-Trimer with either AS03 (oil-in-water emulsion) or CpG 1018 (TLR9 agonist) plus alum adjuvants induced high-level of neutralizing antibodies and Th1-biased cellular immune responses in animal models. Moreover, rhesus macaques immunized with adjuvanted S-Trimer were protected from SARS-CoV-2 challenge compared to vehicle controls, based on clinical observations and reduction of viral loads in lungs. Trimer-Tag may be an important platform technology for scalable production and rapid development of safe and effective subunit vaccines against current and future emerging RNA viruses.


Assuntos
Vacinas contra COVID-19/uso terapêutico , COVID-19/imunologia , COVID-19/prevenção & controle , SARS-CoV-2/patogenicidade , Animais , Anticorpos Neutralizantes/imunologia , Anticorpos Antivirais/imunologia , Western Blotting , COVID-19/terapia , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imunidade Celular/fisiologia , Imunização Passiva , Imuno-Histoquímica , Macaca mulatta , Camundongos , Camundongos Endogâmicos BALB C , Microscopia Eletrônica , SARS-CoV-2/imunologia
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA
...