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1.
Heliyon ; 9(1): e12713, 2023 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-36685478

RESUMO

The growing economic uncertainty makes consumers realize the importance of financial preparedness and management ability. Based on the U.S. National Financial Capability Study dataset from 2009, 2012, 2015, and 2018, this study explores the nexus between consumer financial knowledge and financial behaviors of credit card use. The results indicate that financial knowledge positively affects consumer credit card ownership and desirable financial behaviors of credit card use, and is negatively related to undesirable credit card behaviors. The results are robust to different regression methods and after removing income outliers. The heterogeneity test shows that financial knowledge cannot enhance desirable credit card behaviors because of the income limitations in the low-income group. Therefore, there are implications for policymakers, financial sectors, and consumers to improve consumers' usage of credit cards and cultivate proper consumption habits by enhancing consumer financial knowledge.

2.
Trends Microbiol ; 2023 Jan 10.
Artigo em Inglês | MEDLINE | ID: mdl-36635162

RESUMO

Respiratory viral infections such as severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and influenza A virus (IAV) trigger distinct clinical outcomes defined by immunity-based viral clearance or disease associated with exaggerated and prolonged inflammation. The important role of T cells in shaping both antiviral immunity and inflammation has revived interest in understanding the host-pathogen interactions that lead to the diverse functions of T cells in respiratory viral infections. Inborn deficiencies and acquired insufficiency in immunity can prolong infection and shift the immune response towards exacerbated inflammation, which results from persistent innate immune activation and bystander T-cell activation that is nonspecific to the pathogen but is often driven by cytokines. This review discusses how virus variants, exposure doses, routes of infection, host genetics, and immune history can modulate the activation and function of T cells, thus influencing clinical outcomes. Knowledge of virus-host interaction can inform strategies to prevent immune dysfunction in respiratory viral infection and help in the treatment of associated diseases.

3.
Elife ; 122023 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-36655976

RESUMO

A defining feature of successful vaccination is the ability to induce long-lived antigen-specific memory cells. T follicular helper (Tfh) cells specialize in providing help to B cells in mounting protective humoral immunity in infection and after vaccination. Memory Tfh cells that retain the CXCR5 expression can confer protection through enhancing humoral response upon antigen re-exposure but how they are maintained is poorly understood. CXCR5+ memory Tfh cells in human blood are divided into Tfh1, Tfh2, and Tfh17 cells by the expression of chemokine receptors CXCR3 and CCR6 associated with Th1 and Th17, respectively. Here, we developed a new method to induce Tfh1, Tfh2, and Tfh17-like (iTfh1, iTfh2, and iTfh17) mouse cells in vitro. Although all three iTfh subsets efficiently support antibody responses in recipient mice with immediate immunization, iTfh17 cells are superior to iTfh1 and iTfh2 cells in supporting antibody response to a later immunization after extended resting in vivo to mimic memory maintenance. Notably, the counterpart human Tfh17 cells are selectively enriched in CCR7+ central memory Tfh cells with survival and proliferative advantages. Furthermore, the analysis of multiple human cohorts that received different vaccines for HBV, influenza virus, tetanus toxin or measles revealed that vaccine-specific Tfh17 cells outcompete Tfh1 or Tfh2 cells for the persistence in memory phase. Therefore, the complementary mouse and human results showing the advantage of Tfh17 cells in maintenance and memory function supports the notion that Tfh17-induced immunization might be preferable in vaccine development to confer long-term protection.


Assuntos
Memória Imunológica , Células T Auxiliares Foliculares , Humanos , Animais , Camundongos , Células Th17/metabolismo , Linfócitos B , Linfócitos T Auxiliares-Indutores
4.
Nat Commun ; 14(1): 378, 2023 Jan 24.
Artigo em Inglês | MEDLINE | ID: mdl-36690674

RESUMO

BRD4-NUT, a driver fusion mutant in rare and highly aggressive NUT carcinoma, acts in aberrant transcription of anti-differentiation genes by recruiting histone acetyltransferase (HAT) p300 and promoting p300-driven histone hyperacetylation and nuclear condensation in chromatin. However, the molecular basis of how BRD4-NUT recruits and activates p300 remains elusive. Here, we report that BRD4-NUT contains two transactivation domains (TADs) in NUT that bind to the TAZ2 domain in p300. Our NMR structures reveal that NUT TADs adopt amphipathic helices when bound to the four-helical bundle TAZ2 domain. The NUT protein forms liquid-like droplets in-vitro that are enhanced by TAZ2 binding in 1:2 stoichiometry. The TAD/TAZ2 bipartite binding in BRD4-NUT/p300 triggers allosteric activation of p300 and acetylation-driven liquid-like condensation on chromatin that comprise histone H3 lysine 27 and 18 acetylation and transcription proteins BRD4L/S, CDK9, MED1, and RNA polymerase II. The BRD4-NUT/p300 chromatin condensation is key for activating transcription of pro-proliferation genes such as ALX1, resulting ALX1/Snail signaling and epithelial-to-mesenchymal transition. Our study provides a previously underappreciated structural mechanism illuminating BRD4-NUT's bipartite p300 recruitment and activation in NUT carcinoma that nucleates a feed-forward loop for propagating histone hyperacetylation and chromatin condensation to sustain aberrant anti-differentiation gene transcription and perpetual tumor cell growth.


Assuntos
Carcinoma , Proteínas de Ciclo Celular , Cromatina , Proteínas de Neoplasias , Proteínas Nucleares , Humanos , Acetilação , Carcinoma/metabolismo , Carcinoma/patologia , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Histonas/metabolismo , Proteínas Nucleares/metabolismo , Fatores de Transcrição/metabolismo , Transcrição Genética , Proteínas de Neoplasias/metabolismo
5.
Food Chem ; 409: 135285, 2023 May 30.
Artigo em Inglês | MEDLINE | ID: mdl-36586248

RESUMO

The variations of volatile organic compounds (VOCs) and microbial communities of three pickles during storage at 4°C for one week were analyzed by headspace-gas chromatography-ion mobility spectrometry (HS-GC-IMS), high-throughput sequencing, and Spearman correlation analysis. A total of 50 VOCs were identified from three pickles. During storage, most alcohols, aldehydes, ketones, and esters decreased, while acids increased, and sulfides, alkenes, and phenols were relatively equal. Firmicutes, Cyanobacteria, and Proteobacteria were the predominant bacterial phyla, and Weissella, Streptophyta, Leuconostoc, Bacillariophyta, and Lactobacillus were the predominant bacterial genera in three pickles. The bacterial diversity level significantly decreased during storage (P < 0.05). Spearman correlation coefficient indicated that Leuconostoc, Lactobacillus, and Weissella were highly correlated with the flavor of pickles, while Bacillariophyta and Streptophyta were highly correlated with the flavor formation of pickles during storage. These results could contribute to a better understanding of the impact of bacteria in flavor formation during pickle storage.


Assuntos
Alimentos Fermentados , Microbiota , Compostos Orgânicos Voláteis , Compostos Orgânicos Voláteis/análise , Cromatografia Gasosa-Espectrometria de Massas/métodos , Alimentos , Bactérias/genética , Alimentos Fermentados/análise
6.
J Am Heart Assoc ; 12(1): e026901, 2023 01 03.
Artigo em Inglês | MEDLINE | ID: mdl-36583428

RESUMO

Background Cerebral small vessel disease is associated with higher ratios of soluble-epoxide hydrolase derived linoleic acid diols (12,13-dihydroxyoctadecenoic acid [DiHOME] and 9,10-DiHOME) to their parent epoxides (12(13)-epoxyoctadecenoic acid [EpOME] and 9(10)-EpOME); however, the relationship has not yet been examined in stroke. Methods and Results Participants with mild to moderate small vessel stroke or large vessel stroke were selected based on clinical and imaging criteria. Metabolites were quantified by ultra-high-performance liquid chromatography-mass spectrometry. Volumes of stroke, lacunes, white matter hyperintensities, magnetic resonance imaging visible perivascular spaces, and free water diffusion were quantified from structural and diffusion magnetic resonance imaging (3 Tesla). Adjusted linear regression models were used for analysis. Compared with participants with large vessel stroke (n=30), participants with small vessel stroke (n=50) had a higher 12,13-DiHOME/12(13)-EpOME ratio (ß=0.251, P=0.023). The 12,13-DiHOME/12(13)-EpOME ratio was associated with more lacunes (ß=0.266, P=0.028) but not with large vessel stroke volumes. Ratios of 12,13-DiHOME/12(13)-EpOME and 9,10-DiHOME/9(10)-EpOME were associated with greater volumes of white matter hyperintensities (ß=0.364, P<0.001; ß=0.362, P<0.001) and white matter MRI-visible perivascular spaces (ß=0.302, P=0.011; ß=0.314, P=0.006). In small vessel stroke, the 12,13-DiHOME/12(13)-EpOME ratio was associated with higher white matter free water diffusion (ß=0.439, P=0.016), which was specific to the temporal lobe in exploratory regional analyses. The 9,10-DiHOME/9(10)-EpOME ratio was associated with temporal lobe atrophy (ß=-0.277, P=0.031). Conclusions Linoleic acid markers of cytochrome P450/soluble-epoxide hydrolase activity were associated with small versus large vessel stroke, with small vessel disease markers consistent with blood brain barrier and neurovascular-glial disruption, and temporal lobe atrophy. The findings may indicate a novel modifiable risk factor for small vessel disease and related neurodegeneration.


Assuntos
Doenças de Pequenos Vasos Cerebrais , Acidente Vascular Cerebral , Humanos , Ácido Linoleico , Oxilipinas , Epóxido Hidrolases , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/patologia , Doenças de Pequenos Vasos Cerebrais/diagnóstico por imagem , Imageamento por Ressonância Magnética , Atrofia , Água
7.
Phytother Res ; 2022 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-36581492

RESUMO

Total saponins of Panax ginseng (TSPG) have antidepressant effects. However, the underlying antidepressant mechanism of TSPG remains not clear. This study aimed to predict the mechanism of TSPG by bioinformatics analysis and to verify it experimentally. Bioinformatics analysis showed that the antidepressant effects of TSPG may be related to inflammation, and CX3CL1/CX3CR1 may play a key mediating role. Wistar rats were exposed to chronic unpredictable mild stress (CUMS) for 6 weeks, and TSPG (50 mg/kg/d, 100 mg/kg/d) was administered throughout the modeling period. It was found that TSPG improves depressive behavior and reduces neuropathic damage in the hippocampus in rats. Meanwhile, TSPG decreased mRNA and protein expression of pro-inflammatory cytokines and CX3CL1/CX3CR1 and inhibited P38 and JNK protein phosphorylation in the hippocampus. Rat astrocytes were employed to explore further the potential mechanism of TSPG in regulating CX3CL1/CX3CR1. The results showed that CX3CL1 small interfering RNA (siRNA-CX3CL1) and CX3CR1 inhibitor (JMS-17-2) had similar effects to TSPG, that is, reduced inflammatory response, reactive oxygen species (ROS), and phosphorylation of P38 and JNK proteins, while overexpression of CX3CL1 (pcDNA-CX3CL1) counteracted the above effects of TSPG. It is suggested that the antidepressant effect of TSPG may be achieved through inhibition of CX3CL1/CX3CR1.

8.
Front Pharmacol ; 13: 1033919, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386126

RESUMO

Overview: In treating pulmonary fibrosis (PF), traditional Chinese medicine (TCM) has received much attention, but its mechanism is unclear. The pharmacological mechanisms of TCM can be explored through network pharmacology. However, due to its virtual screening properties, it still needs to be verified by in vitro or in vivo experiments. Therefore, we investigated the anti-PF mechanism of Yiqi Huayu Decoction (YHD) by combining network pharmacology with in vivo experiments. Methods: Firstly, we used classical bleomycin (BLM)-induced rat model of PF and administrated fibrotic rats with YHD (low-, medium-, and high-dose). We comprehensively assessed the treatment effect of YHD according to body weight, lung coefficient, lung function, and histopathologic examination. Second, we predict the potential targets by ultra-high-performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) combined with network pharmacology. In brief, we obtained the chemical ingredients of YHD based on the UHPLC-MS/MS and TCMSP database. We collected drug targets from TCMSP, HERB, and Swiss target prediction databases based on active ingredients. Disease targets were acquired from drug libraries, Genecards, HERB, and TTD databases. The intersecting targets of drugs and disease were screened out. The STRING database can obtain protein-protein interaction (PPI) networks and hub target proteins. Molecular Complex Detection (MCODE) clustering analysis combined with enrichment analysis can explore the possible biological mechanisms of YHD. Enrichment analyses were conducted through the R package and the David database, including the Kyoto Encyclopedia of Genes and Genomes (KEGG), Gene Ontology (GO), and Reactome. Then, we further validated the target genes and target proteins predicted by network pharmacology. Protein and gene expression detection by immunohistochemistry, Western blot (WB), and real-time quantitative PCR (rt-qPCR). Results: The results showed that high-dose YHD effectively attenuated BLM-induced lung injury and fibrosis in rats, as evidenced by improved lung function, relief of inflammatory response, and reduced collagen deposition. We screened nine core targets and cellular senescence pathways by UHPLC-MS/MS analysis and network pharmacology. We subsequently validated key targets of cellular senescence signaling pathways. WB and rt-qPCR indicated that high-dose YHD decreased protein and gene expression of senescence-related markers, including p53 (TP53), p21 (CDKN1A), and p16 (CDKN2A). Increased reactive oxygen species (ROS) are upstream triggers of the senescence program. The senescence-associated secretory phenotypes (SASPs), containing interleukin 6 (IL-6), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß1 (TGF-ß1), can further exacerbate the progression of senescence. High-dose YHD inhibited ROS production in lung tissue and consistently reduced the SASPs expression in serum. Conclusion: Our study suggests that YHD improves lung pathological injury and lung function in PF rats. This protective effect may be related to the ability of YHD to inhibit cellular senescence.

9.
Front Bioeng Biotechnol ; 10: 1034972, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36394004

RESUMO

The basidiomycetous yeast Rhodosporidium toruloides (R. toruloides) is an excellent producer for neutral lipids, including triacylglycerols (TAG). Partially because genetic tools for this yeast were less developed, limited efforts were shown to explore its capacity for the production of higher-value lipids such as diacylglycerols (DAG). Here, four genes linked to the interconversion between DAG and TAG were manipulated to promote the production of DAG and free fatty acids (FFA). Among them, three TAG synthesis-related genes, DGA1, LRO1, and ARE1, were down-regulated successively via the RNA interference technology, and an endogenous TAG lipase encoded by TGL5 was fused with LDP1 and over-expressed to convert TAG into DAG and FFA. Results showed that those engineered R. toruloides strains grew normally under nutrient-rich conditions but notably slower than the parental strain NP11 in the lipid production stage. When cultivated in nitrogen-limited media, engineered strains were able to produce total lipids with improved contents of DAG and FFA by up to two-fold and three-fold, respectively. Further correlation analysis between lipid composition and cell density indicated that the formation of TAG correlated positively with cell growth; however, other lipids including DAG did negatively. This study offered valuable information and strains to engineer R. toruloides for advanced production of fatty acid derivatives.

10.
Fish Shellfish Immunol ; 131: 682-696, 2022 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-36341871

RESUMO

Aeromonas hydrophila, a Gram-negative bacterium, is one of the major pathogens causing bacterial sepsis in aquatic animals due to drug resistance and pathogenicity, which could cause high mortality and serious economic losses to the aquaculture. Sanguisorba officinalis (called DiYu in Chinese, DY) is well known as herbal medicine, which could inhibit the growth of pathogenic bacteria, hemostasis and regulate the immune response. Moreover, the active ingredients in DY could remarkably reduce drug resistance. In this study, we investigated the effects of probiotic fermentation cultures on A. hydrophila through in vitro and in vivo experiments. Three lactic acid bacteria, including Lactobacillus rhamnosus (LGG), Lactobacillus casei (LC) and Lactobacillus plantarum (LP), were selected to ferment the Chinese herbal medicine DY. The assays of antagonism showed that all three fermented cultures could influence the ability of A. hydrophila growth, among which L. rhamnosus fermented DY cultures appeared to be the strongest inhibitory effect. In addition, the biofilm determination revealed that L. rhamnosus fermented DY cultures could significantly inhibit the biofilm formation of A. hydrophila compared to the other groups. Furthermore, protease, lecithinase and urease activities were found in the three fermentation cultures. Three probiotics fermented DY cultures were orally administration with crucian carp to evaluate the growth performance, immunological parameters and pathogen resistance. The results showed that the three fermentation cultures could promote the growth performance of crucian carp, and the immunoglobulins, antioxidant-related enzymes and immune-related genes were significantly enhanced. Besides, the results showed that crucian carp received L. rhamnosus (60.87%), L. casei (56.09%) and L. plantarum (41.46%) fermented DY cultures had higher survival rates compared with the control group after infection with A. hydrophila. Meanwhile, the pathological tissue results revealed that the probiotic fermented cultures could largely improve the tissues damage caused by the pathogenic bacteria. In conclusion, this study proved that the fermentation cultures of three probiotics could effectively inhibit the growth of A. hydrophila, regulate the level of immune response and improve the survival rate against A. hydrophila in crucian carp. The present data suggest that probiotic fermented Sanguisorba officinalis act as a potential gut-targeted therapy regimens to protecting fish from pathogenic bacteria infection.

11.
JAMA Netw Open ; 5(11): e2241451, 2022 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-36355371

RESUMO

Importance: Primary Sjögren syndrome (pSS) is a systemic autoimmune disease associated with dysregulated immune cells, with no efficient therapy. There is a need to study potential therapeutic approaches. Objective: To investigate the efficacy, safety, and immune response of low-dose interleukin 2 (LD-IL-2) in the treatment of pSS. Design, Setting, and Participants: A double-blind, placebo-controlled randomized clinical trial was conducted with a 2-group superiority design from June 2015 to August 2017. Sixty patients, aged 18 to 70 years, were recruited from Peking University People's Hospital. Efficacy analyses were based on the intention-to-treat (ITT) principle. Data were analyzed from December 2018 to March 2020. Interventions: Patients with pSS were treated with LD-IL-2 or placebo for 12 weeks and accompanied by 12 weeks of follow-up. Main Outcomes and Measures: The primary end point was defined as a 3-point or greater improvement on the European League Against Rheumatism Sjögren's Syndrome Disease Activity Index (ESSDAI) by week 24. The secondary end points included other clinical responses, safety, and changes of immune cell subsets at week 12 and 24. Results: Sixty patients with pSS were recruited, with 30 in the LD-IL-2 group (mean [SD] age, 47.6 [12.8] years; 30 [100%] women) and 30 in the placebo group (mean [SD] age, 51.0 [11.9] years; 30 [100%] women), and 57 completed the trial. More patients in the LD-IL-2 group (20 [66.7%]) achieved ESSDAI score reduction of at least 3 points than in the placebo group (8 [26.7%]) at week 24 (P = .004). There were greater resolutions of dryness, pain, and fatigue in the LD-IL-2 group than placebo group at week 12 (dryness: difference, -18.33 points; 95% CI, -28.46 to -8.21 points; P = .001; pain: difference, -10.33 points; 95% CI, -19.38 to -1.29 points; P = .03; fatigue: difference, -11.67 points; 95% CI, -20.65 to -2.68 points; P = .01). No severe adverse events were observed in either group. In addition, the LD-IL-2 group showed a significant decrease in infection compared with the placebo group (1 [3.3%] vs 9 [30.0%]; P = .006). Immunological analysis revealed that LD-IL-2 promoted an expansion of regulatory T cells and regulatory CD24highCD27+ B cells. Conclusions and Relevance: In this randomized clinical trial, LD-IL-2 was effective and well tolerated in patients with pSS, and it restored immune balance, with enhanced regulatory T cells and CD24highCD27+ B cells. Trial Registration: ClinicalTrials.gov Identifier: NCT02464319.


Assuntos
Síndrome de Sjogren , Humanos , Feminino , Pessoa de Meia-Idade , Masculino , Síndrome de Sjogren/tratamento farmacológico , Síndrome de Sjogren/complicações , Interleucina-2/uso terapêutico , Método Duplo-Cego , Resultado do Tratamento , Fadiga/tratamento farmacológico , Dor/complicações
12.
BMC Cancer ; 22(1): 1229, 2022 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-36443709

RESUMO

BACKGROUND: Dysregulation of inhibitor of differentiation/DNA binding (ID) genes is linked to cancer growth, angiogenesis, invasiveness, metastasis and patient survival. Nevertheless, few investigations have systematically determined the expression and prognostic value of ID genes in acute myeloid leukemia (AML). METHODS: The expression and clinical prognostic value of ID genes in AML were first identified by public databases and further validated by our research cohort. RESULTS: Using public data, the expression of ID1/ID3 was markedly downregulated in AML, and the expression of ID2 was greatly upregulated in AML, whereas ID4 showed no significant difference. Among the ID genes, only ID3 expression may be the most valuable prognostic biomarker in both total AML and cytogenetically normal AML (CN-AML) and especially in CN-AML. Clinically, reduced ID3 expression was greatly associated with higher white blood cell counts, peripheral blood/bone marrow blasts, normal karyotypes and intermediate cytogenetic risk. In addition, low ID3 expression was markedly related to FLT3 and NPM1 mutations as well as wild-type TP53. Despite these associations, multivariate Cox regression analysis revealed that ID3 expression was an independent risk factor affecting overall survival (OS) and disease free survival (DFS) in CN-AML patients. Biologically, a total of 839 mRNAs/lncRNAs and 72 microRNAs were found to be associated with ID3 expression in AML. Importantly, the expression of ID3 with discriminative value in AML was further confirmed in our research cohort. CONCLUSION: The bioinformatics analysis and experimental verification demonstrate that low ID3 expression independently affects OS and DFS in patients with CN-AML, which might be seen as a potential prognostic indicator in CN-AML.


Assuntos
Biologia Computacional , Leucemia Mieloide Aguda , Humanos , Prognóstico , Leucemia Mieloide Aguda/genética , Intervalo Livre de Doença , Intervalo Livre de Progressão , Proteínas de Neoplasias , Proteínas Inibidoras de Diferenciação/genética
13.
Clin Transl Med ; 12(12): e1117, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36447054

RESUMO

BACKGROUND: The aberrant differentiation of T follicular helper (Tfh) cells plays an important role in the pathogenesis of systemic lupus erythematosus (SLE). However, the mechanism of regulating Tfh cells differentiation remains unclear. Long noncoding RNAs (lncRNAs) act as important regulators in the processes of innate and adaptive immune response. Whether lncRNAs are involved in regulating Tfh cell differentiation and autoimmune responses need to be further identified. METHODS: The characters and functions of human IL21-AS1 and its mouse homologous lncRNA (mIl21-AS) were investigated by a series of biochemical assays and cell transfection assay. mIl21-AS1 regulating humoral immune response in vivo was explored by keyhole limpet haemocyanin (KLH) and chronic graft versus host disease (cGVHD) model. RESULTS: Human IL21-AS1 and its mouse homologous lncRNA (mIl21-AS) were identified and cloned. We uncovered that IL21-AS1 was highly expressed in CD4+ T cells of SLE patients and Tfh cells, which promoted differentiation of Tfh cells. Mechanistically, IL21-AS1 bound heterogeneous nuclear ribonucleoprotein U and recruited acetyltransferases CREB-binding protein to the promoter of IL21, leading to the transcriptional activation of IL21 and Tfh cells differentiation through increasing Histone H3 acetylation level on IL21 promoter. Moreover, Tfh proportion and antibodies production were significantly increased in mIl21-AS knock-in mice immunized with KLH. mIl21-AS1 overexpression also exacerbated the lupus-like phenotype in cGVHD mice model. CONCLUSIONS: Our results demonstrate that IL21-AS1 activates IL21 transcription via epigenetic mechanism to promote germinal centre response, adding insight into the molecular regulation of autoimmune pathogenesis and providing a novel target for SLE treatment.


Assuntos
Lúpus Eritematoso Sistêmico , RNA Longo não Codificante , Humanos , Camundongos , Animais , Células T Auxiliares Foliculares , RNA Longo não Codificante/genética , Diferenciação Celular/genética , Lúpus Eritematoso Sistêmico/genética
14.
Cell Tissue Res ; 2022 Nov 30.
Artigo em Inglês | MEDLINE | ID: mdl-36447073

RESUMO

Systemic sclerosis associated with lung interstitial lung disease (SSc-ILD) is the most common cause of death among patients with SSc. Mesenchymal stem cell (MSCs) transplantations had been treated by SSc patients that showed in the previous case report. The therapeutic mechanisms and effects of MSCs on SSc-ILD are still obscure. In this study, we investigated the therapeutic effects and mechanisms of treatment of BM-MSC derived from C57BL/6 on the topoisomerase I (TOPO I) induced SSc-ILD-like mice model. The mice were immunized with a mixture of recombinant human TOPO I in PBS solution (500 U/mL) and completed Freund's adjuvant [CFA; 1:1 (volume/volume)] twice per week for 9 weeks. On week 10, the mice were sacrificed to analyze the related pathological parameters. Lung and skin pathologies were analyzed using histochemical staining. CD4 T-helper (TH) cell differentiation in lung and skin-draining lymph nodes was detected using flow cytometry. Our results revealed that allogeneic and syngeneic MSCs exhibited similar repressive effects on TOPO I-induced IgG1 and IgG2a in the SSc group. After intravascular (IV) treatment with syngeneic or allogeneic MSCs, the dermal thickness and fibrosis dramatically condensed and significantly reduced airway hyperresponsiveness. These findings showed that both allogeneic and syngeneic MSCs have therapeutic potential for SSc-ILD.

15.
World J Clin Cases ; 10(29): 10713-10720, 2022 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-36312484

RESUMO

BACKGROUND: Large abdominal wall defect (LAWD) caused by shotgun wound is rarely reported. CASE SUMMARY: Herein, we describe a case of LAWD caused by a gunshot wound in which the abdominal wall was reconstructed in stages, including debridement, tension-reduced closure (TRC), and reconstruction with mesh and a free musculocutaneous flap. During a 3-year follow-up, the patient recovered well without hernia or other problems. CONCLUSION: TRC is a practical approach for the temporary closure of LAWD, particularly in cases when one-stage abdominal wall restoration is unfeasible due to significant comorbidities.

16.
Food Chem X ; 15: 100440, 2022 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-36211780

RESUMO

Carboxyl compounds have a significant influence on the flavor of Chinese Baijiu. However, because of the structural diversity and low concentration, the deep profiling of carboxyl compounds in Chinese Baijiu is still challenging. In this work, a systematic method for comprehensive analysis of carboxyl compounds in Chinese Baijiu was established. After derivatized under optimized conditions, 197 p-dimethylaminophenacyl bromide-derived carboxylic compounds were annotated by multidimensional information including accurate mass, predicted tR, in-silico MS/MS, and diagnostic ions for the first time. In addition, 48 of the 197 carboxyl compounds were positively identified, and three of them were newly identified in Chinese Baijiu. Moreover, we found the number and the concentration of carboxyl compounds in sauce-flavor Baijiu were more abundant than in strong-flavor Baijiu. This work provides a novel method for the analysis of carboxyl compounds in Baijiu and other complex samples.

17.
Comput Struct Biotechnol J ; 20: 4746-4755, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36147674

RESUMO

The common γ chain family of cytokines and their receptors play fundamental roles in the immune system. Evolutionary studies of γ chain cytokines have elegantly illustrated how the immune system adapts to ever-changing environmental conditions. Indeed, these studies have revealed the uniqueness of cytokine evolution, which exhibits strong positive selection pressure needed to adapt to rapidly evolving threats whilst still conserving their receptor binding capabilities. In this review, we summarise the evolutionary mechanisms that gave rise to the characteristically diverse family of γ chain cytokines. We also speculate on the benefits of studying cytokine evolution, which may provide alternative ways to design novel cytokine therapeutic strategies. Additionally, we discuss current evolutionary models that elucidate the emergence of distinct cytokines (IL-4 and IL-13) and cytokine receptors (IL-2Rα and IL-15Rα). Finally, we address and reflect on the difficulties associated with evolutionary studies of rapidly evolving genes and describe a variety of computational methods that have revealed numerous aspects of cytokine evolution.

18.
Signal Transduct Target Ther ; 7(1): 319, 2022 09 16.
Artigo em Inglês | MEDLINE | ID: mdl-36109504

RESUMO

Interleukin 27 (IL-27), a heterodimeric cytokine composed of Epstein-Barr virus-induced 3 and p28, is a pleiotropic cytokine with both pro-and anti-inflammatory properties. However, the precise role of IL-27 in acute graft-versus-host disease is not yet fully understood. In this study, utilizing mice with IL-27 p28 deficiency in dendritic cells (DCs), we demonstrated that IL-27 p28 deficiency resulted in impaired Treg cell function and enhanced effector T cell responses, corresponding to aggravated aGVHD in mice. In addition, using single-cell RNA sequencing, we found that loss of IL-27 p28 impaired Treg cell generation and promoted IL-1R2+TIGIT+ pathogenic CD4+ T cells in the thymus at a steady state. Mechanistically, IL-27 p28 deficiency promoted STAT1 phosphorylation and Th1 cell responses, leading to the inhibition of Treg cell differentiation and function. Finally, patients with high levels of IL-27 p28 in serum showed a substantially decreased occurrence of grade II-IV aGVHD and more favorable overall survival than those with low levels of IL-27 p28. Thus, our results suggest a protective role of DC-derived IL-27 p28 in the pathogenesis of aGVHD through modulation of the Treg/Teff cell balance during thymic development. IL-27 p28 may be a valuable marker for predicting aGVHD development after transplantation in humans.


Assuntos
Infecções por Vírus Epstein-Barr , Doença Enxerto-Hospedeiro , Interleucina-27 , Interleucinas/metabolismo , Animais , Citocinas , Células Dendríticas/patologia , Infecções por Vírus Epstein-Barr/patologia , Doença Enxerto-Hospedeiro/genética , Herpesvirus Humano 4 , Humanos , Interleucina-27/genética , Camundongos , Receptores Tipo II de Interleucina-1 , Linfócitos T Reguladores , Virulência
19.
Nat Commun ; 13(1): 5413, 2022 09 15.
Artigo em Inglês | MEDLINE | ID: mdl-36109526

RESUMO

Anti-cancer immunity and response to immune therapy is influenced by the metabolic states of the tumours. Immune checkpoint blockade therapy (ICB) is known to involve metabolic adaptation, however, the mechanism is not fully known. Here we show, by metabolic profiling of plasma samples from melanoma-bearing mice undergoing anti-PD1 and anti-CTLA4 combination therapy, that higher levels of purine metabolites, including inosine, mark ICB sensitivity. Metabolic profiles of ICB-treated human cancers confirm the association between inosine levels and ICB sensitivity. In mouse models, inosine supplementation sensitizes tumours to ICB, even if they are intrinsically ICB resistant, by enhancing T cell-mediated cytotoxicity and hence generating an immunologically hotter microenvironment. We find that inosine directly inhibits UBA6 in tumour cells, and lower level of UBA6 makes the tumour more immunogenic and this is reflected in favourable outcome following ICB therapy in human melanomas. Transplanted mouse melanoma and breast cancer cells with genetic ablation of Uba6 show higher sensitivity to ICB than wild type tumours. Thus, we provide evidence of an inosine-regulated UBA6-dependent pathway governing tumour-intrinsic immunogenicity and hence sensitivity to immune checkpoint inhibition, which might provide targets to overcome ICB resistance.


Assuntos
Inibidores de Checkpoint Imunológico , Melanoma , Animais , Terapia Combinada , Humanos , Inosina/farmacologia , Melanoma/patologia , Camundongos , Radioimunoterapia , Microambiente Tumoral , Enzimas Ativadoras de Ubiquitina
20.
World J Clin Cases ; 10(19): 6744-6749, 2022 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-35979286

RESUMO

BACKGROUND: Squamous cell carcinoma (SCC) of the liver is rare, and is more commonly found in the skin, rectum, cervical or inguinal lymph nodes. CASE SUMMARY: A 73-year-old man had been experiencing right upper quadrant discomfort for some weeks. He had a 50-year history of smoking and drinking. On average, he smoked 20 cigarettes and consumed 200 galcoholdaily. He didn't have a history of hepatitis or surgery. Fever, vomiting, jaundice, dysuria, chills, and abdominal distention were not observed at the time of admission. Tenderness in the right upper quadrant was found on physical examination, but there was no palpable abdominal mass. No obvious abnormalities in laboratory tests and tumor markers were found. The plasma retention rate of indocyanine green (ICG) at 15 min was 1.35%. Subsequent abdominal ultrasonography showed a mixed echoic mass approximately 3.8 cm diameter in the left caudate lobe of the liver. Abdominal computed tomography confirmed a 3.0 cm × 3.5 cm irregular mass with inhomogeneous density and moderate delayed enhancement in the left caudate lobe of the liver. Laparoscopic left caudate lobectomy was performed to remove the liver mass. Intra-operative findings confirmed a non-cirrhotic liver, with a 3 cm × 3.5 cm white tumor mass in the left caudate lobe with no tumor rupture and no hemoperitoneum. The resection margin was 1.0 cm in width. CONCLUSION: We describe the first case of SCC in the left caudate lobe of the liver, which was successfully treated by surgical resection and postoperative immunotherapy. No tumor recurrence was observed during the 8-mo follow-up.

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