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1.
Discov Oncol ; 15(1): 148, 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38720149

RESUMO

INTRODUCTION: As proteins that promote immune cell differentiation, chemokines have attracted great interest regarding their role in anti-tumor immune responses within the cancer environment. However, the exact role of CXCL10, a chemokine, in bladder cancer (BLCA) is still not fully elucidated. METHOD: In the present study, we employed bioinformatics approaches to examine the expression pattern, prognostic value, and immune infiltration of CXCL10 in BLCA. Furthermore, we focused on examining the impact of CXCL10 on immune therapy in BLCA. Additionally, we validated the expression of CXCL10 in various BLCA cell lines using PCR techniques. RESULTS: We observed an upregulation of CXCL10 in BLCA tissues as well as in different cell lines. Additionally, upregulation of CXCL10 indicates a better prognosis for BLCA patients. ESTIMATE and CIBERSORT algorithms suggest that CXCL10 is closely associated with the immune microenvironment of BLCA. Through multiple immune therapy cohorts, we also identified that CXCL10 has shown promising predictive value for assessing the efficacy of immune therapy in in BLCA. CONCLUSION: Our study indicates that CXCL10 has the potential to serve as a favorable prognostic factor and is strongly associated with immune infiltration in BLCA.

2.
Br J Haematol ; 204(1): 56-67, 2024 01.
Artigo em Inglês | MEDLINE | ID: mdl-38083878

RESUMO

Cyclic thrombocytopenia (CTP) is characterized by periodic platelet oscillation with substantial amplitude. Most CTP cases have a thrombocytopenic background and are often misdiagnosed as immune thrombocytopenia with erratically effective treatment choices. CTP also occurs during hydroxyurea treatment in patients with myeloproliferative diseases. While the aetiology of CTP remains uncertain, here we evaluate historical, theoretical and clinical findings to provide a framework for understanding CTP pathophysiology. CTP retains the intrinsic oscillatory factors defined by the homeostatic regulation of platelet count, presenting as reciprocal platelet/thrombopoietin oscillations and stable oscillation periodicity. Moreover, CTP patients possess pathogenic factors destabilizing the platelet homeostatic system thereby creating opportunities for external perturbations to initiate and sustain the exaggerated platelet oscillations. Beyond humoral and cell-mediated autoimmunity, we propose recently uncovered germline and somatic genetic variants, such as those of MPL, STAT3 or DNMT3A, as pathogenic factors in thrombocytopenia-related CTP. Likewise, the JAK2 V617F or BCR::ABL1 translocation that drives underlying myeloproliferative diseases may also play a pathogenic role in hydroxyurea-induced CTP, where hydroxyurea treatment can serve as both a trigger and a pathogenic factor of platelet oscillation. Elucidating the pathogenic landscape of CTP provides an opportunity for targeted therapeutic approaches in the future.


Assuntos
Neoplasias da Medula Óssea , Transtornos Mieloproliferativos , Trombocitopenia , Humanos , Hidroxiureia/uso terapêutico , Trombocitopenia/etiologia , Trombocitopenia/genética , Contagem de Plaquetas , Plaquetas , Transtornos Mieloproliferativos/genética
3.
Sci Total Environ ; 904: 166473, 2023 Dec 15.
Artigo em Inglês | MEDLINE | ID: mdl-37659565

RESUMO

In this study, a combination of property analysis and high-throughput sequencing was used to investigate the microbial colonization ability and their community structures and functions in polypropylene microplastics (PPMPs), polystyrene microplastics (PSMPs) and montmorillonite (MMT), respectively as the representatives of artificial and natural substrates in aerobic sludge treatment. After 45 d of incubation, the surface properties of substrates were altered with the increased oxygen functional groups and surface roughness, indicating microbial settlement. Moreover, MPs had different microbial structures from that of MMT, and PSMPs exhibited higher microbial diversity and abundance than PPMPs and MMT. Also, these substrates changed the inherent ecological niche in sludge. Especially, the abundance of some pathogens (e.g., Pseudomonas, Klebsiella and Flavobacterium) was increased in MPs, and the disease risk of Kyoto Encyclopedia of Genes and Genomes metabolic pathway (e.g., Infectious diseases: Bacterial, Infectious diseases: Parasitic and Immune diseases) was higher. Also, the presence of MPs inhibited the decomposition of organic matter including soluble chemical oxygen demand and protein compared to natural substrates. The findings revealed the crucial vector role of MPs for microbes and the effect on aerobic sludge treatment, highlighting the necessity of MP removal in sludge.


Assuntos
Doenças Transmissíveis , Microplásticos , Humanos , Plásticos , Esgotos , Argila , Polipropilenos , Poliestirenos
4.
J Hazard Mater ; 460: 132350, 2023 10 15.
Artigo em Inglês | MEDLINE | ID: mdl-37619279

RESUMO

Microplastics (MPs) in the environment are always colonized by microbes, which may have implications for carrying effect of pollutants and exposure risk in organisms. We present the crucial impacts and mechanisms of microbial colonization on the bioaccessibility and toxicity of Pb(II) loaded in disposable box-derived polypropylene (PP) and polystyrene (PS) MPs and montmorillonite (MMT) clay particles. After 45 d incubation, higher biomass measured by crystal violet staining were detected in MMT (1.23) than in PP and PS (0.400 and 0.721) indicating preferential colonization of microbes in clay particles. Microbial colonization further enhanced the sorption ability toward Pb(II), but inhibited the desorption and bioaccessibility of enriched Pb(II) in zebrafish and decreased the toxicity to gastric epithelial cells in an order of MMT > PS ≈ PP. The crucial effects were mainly because microbe-colonized substrates possessed higher oxygen functional groups and specific surface area and exhibited stronger interactions with Pb(II) and digestive component (i.e., pepsin) than pure substrates. This decreased the available soluble pepsin for complexing with sorbed Pb(II). The findings highlight the role of microbial colonization in modulating the exposure risks of artificial and natural substrate-associated pollutants and suggest that the risks of MPs may be overestimated compared to clay particles.


Assuntos
Bentonita , Poluentes Ambientais , Animais , Bentonita/toxicidade , Argila , Chumbo/toxicidade , Microplásticos/toxicidade , Pepsina A , Plásticos , Peixe-Zebra , Polipropilenos , Poliestirenos/toxicidade
5.
Cancer Control ; 30: 10732748231198749, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37632208

RESUMO

BACKGROUND: Lung cancer is one of the most common malignant tumors in the world. It has become an increasingly important public health problem in China. In this study, we systematically assessed the lung cancer situation in China from 1990 to 2019 and provided an epidemiological knowledge base for the revision of health policies. The relevant data were extracted from the Global Burden of Disease (GBD) database. METHODS: Based on GBD 2019 data, we evaluated the incidence, prevalence, and death rates of lung cancer in China and their change trends from 1990 to 2019, making comparisons by gender and age. RESULTS: The age-standardized incidence and death rates (ASIR and ASDR, respectively) of lung cancer in China were higher than the average levels in Asia, Africa, Europe, and Oceania and also higher than those of neighboring Asian countries. Lung cancer rose from the seventh leading cause of death in 1990 to the fourth leading one in 2019, indicating that the disease burden of lung cancer is increasing. In 2019, the incidence, prevalence, and death rates of lung cancer were all higher in men than in women across all age groups. All three indices were lower in men and women <50 years old than in men and women >50 years. From 1990 to 2019, the ASIR, age-standardized prevalence rate (ASPR), and ASDR showed trends of increase (P < .05), and the rise in the ASPR (average annual percentage change [AAPC] = 1.9) was greater than those in the ASIR (AAPC = 1) and ASDR (AAPC = .8). CONCLUSIONS: From 1990 to 2019, the incidence, prevalence, and death rates of lung cancer continued to increase in China. To reduce this burden, prevention and management of known risk factors should be promoted through national policies.


Assuntos
Neoplasias Pulmonares , Masculino , Feminino , Humanos , Pessoa de Meia-Idade , Neoplasias Pulmonares/epidemiologia , Carga Global da Doença , China/epidemiologia , Efeitos Psicossociais da Doença , Análise por Conglomerados , Incidência
6.
Front Immunol ; 14: 1202825, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37409118

RESUMO

Background: Stem cells play an important role in acute myeloid leukemia (AML). However, their precise effect on AML tumorigenesis and progression remains unclear. Methods: The present study aimed to characterize stem cell-related gene expression and identify stemness biomarker genes in AML. We calculated the stemness index (mRNAsi) based on transcription data using the one-class logistic regression (OCLR) algorithm for patients in the training set. According to the mRNAsi score, we performed consensus clustering and identified two stemness subgroups. Eight stemness-related genes were identified as stemness biomarkers through gene selection by three machine learning methods. Results: We found that patients in stemness subgroup I had a poor prognosis and benefited from nilotinib, MK-2206 and axitinib treatment. In addition, the mutation profiles of these two stemness subgroups were different, which suggested that patients in different subgroups had different biological processes. There was a strong significant negative correlation between mRNAsi and the immune score (r= -0.43, p<0.001). Furthermore, we identified eight stemness-related genes that have potential to be biomarkers, including SLC43A2, CYBB, CFP, GRN, CST3, TIMP1, CFD and IGLL1. These genes, except IGLL1, had a negative correlation with mRNAsi. SLC43A2 is expected to be a potential stemness-related biomarker in AML. Conclusion: Overall, we established a novel stemness classification using the mRNAsi score and eight stemness-related genes that may be biomarkers. Clinical decision-making should be guided by this new signature in prospective studies.


Assuntos
Genes Reguladores , Leucemia Mieloide Aguda , Humanos , Estudos Prospectivos , Células-Tronco Neoplásicas , Biomarcadores , Leucemia Mieloide Aguda/genética
7.
Heliyon ; 9(6): e16874, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-37342584

RESUMO

The combination of Sintilimab with pemetrexed/platinum has become the first-line treatment for non-squamous non-small-cell lung carcinoma (NSCLC). Here, we report a patient with metastatic large cell neuroendocrine carcinoma (LCNEC) treated with Sintilimab for five cycles who developed shortness of breath after activity. The level of creatine kinase (CK), creatine kinase-MB (CK-MB) and cardiac troponin T (cTnT) were significantly increased. The cardiac MR suggested that heart function was slightly decreased. Considering that the patient did not take any illicit drugs, without history of autoimmune disease, coronary heart disease, arrhythmia, or chronic heart failure, we diagnosed the patient with Sintilimab-induced myocarditis. The symptoms alleviated after rapid use of glucocorticoids. Myocarditis is a rare immune-related adverse events (irAEs), especially myocarditis induced by programmed cell death receptor-1 (PD-1) inhibitor in the treatment of LCNEC.

8.
Blood ; 141(20): 2417-2429, 2023 05 18.
Artigo em Inglês | MEDLINE | ID: mdl-36749920

RESUMO

Immune thrombocytopenia (ITP) is traditionally considered an antibody-mediated disease. However, a number of features suggest alternative mechanisms of platelet destruction. In this study, we use a multidimensional approach to explore the role of cytotoxic CD8+ T cells in ITP. We characterized patients with ITP and compared them with age-matched controls using immunophenotyping, next-generation sequencing of T-cell receptor (TCR) genes, single-cell RNA sequencing, and functional T-cell and platelet assays. We found that adults with chronic ITP have increased polyfunctional, terminally differentiated effector memory CD8+ T cells (CD45RA+CD62L-) expressing intracellular interferon gamma, tumor necrosis factor α, and granzyme B, defining them as TEMRA cells. These TEMRA cells expand when the platelet count falls and show no evidence of physiological exhaustion. Deep sequencing of the TCR showed expanded T-cell clones in patients with ITP. T-cell clones persisted over many years, were more prominent in patients with refractory disease, and expanded when the platelet count was low. Combined single-cell RNA and TCR sequencing of CD8+ T cells confirmed that the expanded clones are TEMRA cells. Using in vitro model systems, we show that CD8+ T cells from patients with ITP form aggregates with autologous platelets, release interferon gamma, and trigger platelet activation and apoptosis via the TCR-mediated release of cytotoxic granules. These findings of clonally expanded CD8+ T cells causing platelet activation and apoptosis provide an antibody-independent mechanism of platelet destruction, indicating that targeting specific T-cell clones could be a novel therapeutic approach for patients with refractory ITP.


Assuntos
Púrpura Trombocitopênica Idiopática , Adulto , Humanos , Interferon gama , Linfócitos T CD8-Positivos , Células Clonais/patologia , Receptores de Antígenos de Linfócitos T
9.
Blood Adv ; 7(1): 190-194, 2023 01 10.
Artigo em Inglês | MEDLINE | ID: mdl-35381066

RESUMO

Cyclic thrombocytopenia (CTP) is a rare disease of periodic platelet count oscillations. The pathogenesis of CTP remains elusive. To study the underlying pathophysiology and genetic and cellular associations with CTP, we applied systems biology approaches to 2 patients with stable platelet cycling and reciprocal thrombopoietin (TPO) cycling at multiple time points through 2 cycles. Blood transcriptome analysis revealed cycling of platelet-specific genes, which are in parallel with and precede platelet count oscillation, indicating that cyclical platelet production leads platelet count cycling in both patients. Additionally, neutrophil and erythrocyte-specific genes also showed fluctuations correlating with platelet count changes, consistent with TPO effects on hematopoietic progenitors. Moreover, we found novel genetic associations with CTP. One patient had a novel germline heterozygous loss-of-function (LOF) thrombopoietin receptor (MPL) c.1210G>A mutation, and both had pathogenic somatic gain-of-function (GOF) variants in signal transducer and activator of transcription 3 (STAT3). In addition, both patients had clonal T-cell populations that remained stable throughout platelet count cycles. These mutations and clonal T cells may potentially involve in the pathogenic baseline in these patients, rendering exaggerated persistent thrombopoiesis oscillations of their intrinsic rhythm upon homeostatic perturbations. This work provides new insights into the pathophysiology of CTP and possible therapies.


Assuntos
Receptores de Trombopoetina , Trombocitopenia , Humanos , Receptores de Trombopoetina/genética , Trombocitopenia/etiologia , Fator de Transcrição STAT3/genética , Estudos Longitudinais , Mutação
10.
Biol Trace Elem Res ; 201(8): 4191-4201, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-36441496

RESUMO

In this paper, five C and N metabolites and eighteen mineral elements were used to identify the cigar's geographical origin on a country scale (Dominica, Indonesia, and China) and on a prefecture scale (Yuxi, Puer, and Lincang in China). The results show that the best origin traceability method is the combination of C and N metabolites and mineral elements method. Its. Its accuracy of cross-validation can achieve 95% on a country scale and 94% on a prefecture scale. Determination accuracy is ranked as identification by combination > mineral elements > C and N metabolites. For geo-origin determination of cigars, mineral element identification is better than that metabolite identification. The algorithm and factors for origin determination are selected. The results can be used to guide cigar agricultural practices and monitor and regulate the cigar in production and circulation.


Assuntos
Quimiometria , Produtos do Tabaco , Minerais/análise , Geografia , China
11.
J Pediatr Hematol Oncol ; 45(2): e180-e187, 2023 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-36524840

RESUMO

Primitive neuroectodermal tumors (PNET) are rare malignant tumors, but the mortality rate of the patients is extremely high. The aim of this study was to identify the hub genes and pathways involved in the pathogenesis of PNET and to screen the potential small molecule drugs for PNET. We extracted gene expression profiles from the Gene Expression Omnibus database and identified differentially expressed genes (DEGs) through Limma package in R. Two expression profiles (GSE14295 and GSE74195) were downloaded, including 33 and 5 cases separately. Four hundred sixty-eight DEGs (161 upregulated; 307 downregulated) were identified. Functional annotation and KEGG pathway enrichment of the DEGs were performed using DAVID and Kobas. Gene Ontology analysis showed the significantly enriched Gene Ontology terms included but not limited to mitosis, nuclear division, cytoskeleton, synaptic vesicle, syntaxin binding, and GABA A receptor activity. Cancer-related signaling pathways, such as DNA replication, cell cycle, and synaptic vesicle cycle, were found to be associated with these genes. Subsequently, the STRING database and Cytoscape were utilized to construct a protein-protein interaction and screen the hub genes, and we identified 5 hub genes (including CCNB1, CDC20, KIF11, KIF2C, and MAD2L1) as the key biomarkers for PNET. Finally, we identified potential small molecule drugs through CMap. Seven small molecule compounds, including trichostatin A, luteolin, repaglinide, clomipramine, lorglumide, vorinostat, and resveratrol may become potential candidates for PNET drugs.


Assuntos
Biomarcadores Tumorais , Perfilação da Expressão Gênica , Humanos , Biomarcadores Tumorais/genética , Biomarcadores Tumorais/metabolismo , Transcriptoma , Proteínas de Ciclo Celular/genética , Biologia Computacional
12.
Front Cardiovasc Med ; 10: 1295146, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38235290

RESUMO

Bicuspid aortic valve (BAV) is a common congenital heart condition that can lead to some valve-related complications, such as aortic stenosis and/or regurgitation, and is often associated with aortic root dilation. With the development and refinement of BAV repair techniques over the past three decades, surgical repair of BAV has emerged as an effective treatment option, offering symptomatic relief and improved outcomes. This review aims to summarize the current techniques, outcomes, and challenges of BAV repair, and to provide potential future perspectives in the field.

13.
Front Nutr ; 9: 962720, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36386943

RESUMO

With global prevalence, metabolic diseases, represented by obesity and type 2 diabetes mellitus (T2DM), have a huge burden on human health and medical expenses. It is estimated that obese population has doubled in recent 40 years, and population with diabetes will increase 1.5 times in next 25 years, which has inspired the pursuit of economical and effective prevention and treatment methods. Natural polyphenols are emerging as a class of natural bioactive compounds with potential beneficial effects on the alleviation of obesity and T2DM. In this review, we investigated the network interaction mechanism of "gut microbial disturbance, metabolic disorder, and immune imbalance" in both obesity and T2DM and systemically summarized their multiple targets in the treatment of obesity and T2DM, including enrichment of the beneficial gut microbiota (genera Bifidobacterium, Akkermansia, and Lactobacillus) and upregulation of the levels of gut microbiota-derived metabolites [short-chain fatty acids (SCFAs)] and bile acids (BAs). Moreover, we explored their effect on host glucolipid metabolism, the AMPK pathway, and immune modulation via the inhibition of pro-inflammatory immune cells (M1-like Mϕs, Th1, and Th17 cells); proliferation, recruitment, differentiation, and function; and related cytokines (TNF-α, IL-1ß, IL-6, IL-17, and MCP-1). We hope to provide evidence to promote the clinical application of natural polyphenols in the management of obesity and T2DM.

14.
Acta Pharmacol Sin ; 43(4): 840-849, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34267346

RESUMO

Luteolin is a flavonoid in a variety of fruits, vegetables, and herbs, which has shown anti-inflammatory, antioxidant, and anti-cancer neuroprotective activities. In this study, we investigated the potential beneficial effects of luteolin on memory deficits and neuroinflammation in a triple-transgenic mouse model of Alzheimer's disease (AD) (3 × Tg-AD). The mice were treated with luteolin (20, 40 mg · kg-1 · d-1, ip) for 3 weeks. We showed that luteolin treatment dose-dependently improved spatial learning, ameliorated memory deficits in 3 × Tg-AD mice, accompanied by inhibiting astrocyte overactivation (GFAP) and neuroinflammation (TNF-α, IL-1ß, IL-6, NO, COX-2, and iNOS protein), and decreasing the expression of endoplasmic reticulum (ER) stress markers GRP78 and IRE1α in brain tissues. In rat C6 glioma cells, treatment with luteolin (1, 10 µM) dose-dependently inhibited LPS-induced cell proliferation, excessive release of inflammatory cytokines, and increase of ER stress marker GRP78. In conclusion, luteolin is an effective agent in the treatment of learning and memory deficits in 3 × Tg-AD mice, which may be attributable to the inhibition of ER stress in astrocytes and subsequent neuroinflammation. These results provide the experimental basis for further research and development of luteolin as a therapeutic agent for AD.


Assuntos
Doença de Alzheimer , Disfunção Cognitiva , Doença de Alzheimer/tratamento farmacológico , Animais , Disfunção Cognitiva/tratamento farmacológico , Modelos Animais de Doenças , Estresse do Retículo Endoplasmático , Endorribonucleases/farmacologia , Endorribonucleases/uso terapêutico , Luteolina/farmacologia , Luteolina/uso terapêutico , Camundongos , Camundongos Transgênicos , Doenças Neuroinflamatórias , Proteínas Serina-Treonina Quinases , Ratos
15.
Bioeng Transl Med ; 6(1): e10193, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33532592

RESUMO

Intraplaque hemorrhage (IPH) plays a major role in the aggressive progression of vulnerable plaque, leading to acute cardiovascular events. We previously demonstrated that sonodynamic therapy (SDT) inhibits atherosclerotic plaque progression. In this study, we investigated whether SDT could also be applied to treat more advanced hemorrhagic plaque and addressed the underlying mechanism. SDT decreased atherosclerotic burden, positively altered atherosclerotic lesion composition, and alleviated iron retention in rabbit hemorrhagic plaques. Furthermore, SDT reduced iron retention by stimulating ferroportin 1 (Fpn1) expression in apolipoprotein E (ApoE)-/- mouse plaques with high susceptibility to IPH. Subsequently, SDT inhibited iron-overload-induced foam-cell formation and pro-inflammatory cytokines secretion in vitro. Moreover, SDT reduced levels of the labile iron pool and ferritin expression via the reactive oxygen species (ROS)-nuclear factor erythroid 2-related factor 2 (Nrf2)-FPN1 pathway. SDT exerted therapeutic effects on hemorrhagic plaques and reduced iron retention via the ROS-Nrf2-FPN1 pathway in macrophages, thereby suggesting that it is a potential translational strategy for patients with advanced atherosclerosis in clinical practice.

16.
Platelets ; 32(1): 120-129, 2021 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-32090650

RESUMO

Current guidelines favor dual anti-platelet therapy with ticagrelor 90 mg BID (T90BID) over clopidogrel 75 mg QD (C75QD) in addition to aspirin for acute coronary syndrome. However, an increased risk of ticagrelor-related adverse events prompted the evaluation of low-dose regimens. This study (NCT03381742) retrospectively analyzed the data from 11 hospitals on 3,043 patients with coronary artery disease, who received C75QD, T90BID, ticagrelor 45 mg BID (T45BID), or ticagrelor 90 mg QD (T90QD). Compared with C75QD, both T45BID and T90QD showed significantly higher inhibition of platelet aggregation (P < .0001) and lower platelet-fibrin clot strength (P < .0001) induced by adenosine diphosphate. Furthermore, compared with T90BID, two low-dose regimens had a much lower minor bleeding rate and a significantly higher proportion of patients within the therapeutic window for P2Y12 receptor reactivity. There were no significant differences between T45BID and T90QD in the trough plasma concentrations of ticagrelor and its active metabolite. Similar efficacy and safety outcomes were observed in the propensity score-matched analysis. In conclusion, the low-dose ticagrelor regimen, either T45BID or T90QD, may provide a more attractive benefit-risk profile than C75QD or T90BID.


Assuntos
Clopidogrel/uso terapêutico , Doença da Artéria Coronariana/tratamento farmacológico , Inibidores da Agregação Plaquetária/uso terapêutico , Ticagrelor/uso terapêutico , Idoso , Clopidogrel/farmacologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Inibidores da Agregação Plaquetária/farmacologia , Estudos Retrospectivos , Ticagrelor/farmacologia
17.
Neurochem Int ; 141: 104860, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-33022312

RESUMO

Cerebral ischemia-reperfusion injury induces a secondary immune inflammatory reaction that exacerbates brain injury and clinical prognosis. Dendritic cells (DCs) and microglia are both important regulators of neuroinflammation. Studies have confirmed that a large number of cells express the DC surface marker CD11c in the ischemic area, and some of these cells also express microglial markers. However, the specific mechanism of transformation between microglia and DCs and their roles in the process of cerebral ischemia-reperfusion injury are still not clear. In this study, we established a mouse model and flow cytometry was used to detect the expression of mature DC surface molecules in activated microglia. IFN-γ knockout mice were used to determine the regulatory effect of IFN-γ on microglial transformation. We found that CD11c+ cells were derived from microglia after ischemia-reperfusion injury, and this group of cells highly expressed MHC-II molecules and other costimulatory molecules, such as CD80 and CD86, which were regulated by IFN-γ and its downstream signaling molecules ERK/c-myc. In summary, our results showed in cerebral ischemia-reperfusion injury, IFN-γ regulates the transformation of microglia to DC-like cells. Microglial-derived DC-like cells possess the ability to present antigens and activate naïve T cells which is regulated by the ERK/c-myc signaling pathway.


Assuntos
Dendritos/efeitos dos fármacos , Interferon gama/genética , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Microglia/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-myc/efeitos dos fármacos , Traumatismo por Reperfusão/patologia , Animais , Antígenos CD11/metabolismo , Dendritos/patologia , Genes MHC da Classe II , Interferon gama/fisiologia , Ativação Linfocitária , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Microglia/patologia , Cultura Primária de Células , Receptores de Interferon/biossíntese , Linfócitos T
18.
Arch Biochem Biophys ; 684: 108334, 2020 05 15.
Artigo em Inglês | MEDLINE | ID: mdl-32173334

RESUMO

Emerging evidence shows that histone modification and its related regulators are involved in the progression and chemoresistance of ovarian cancer (OC) cells. Our present study found that the expression of Jumonji C domain-containing 2A (JMJD2A), while not JMJD2B or JMJD2C, is increased in OC cells and tissues as compared with that in their corresponding controls. Knockdown of JMJD2A can decrease proliferation while increase cisplatin (CDDP) sensitivity of OC cells. By screening the expression of cytokines involved in the progression of ovarian cancer, we found that knockdown of JMJD2A can inhibit the expression of interleukin-6 (IL-6) and IL-8 in ovarian cancer cells. Recombinant IL-6 (rIL-6) and rIL-8 can attenuate si-JMJD2A-suppressed malignancy of OC cells. Mechanistically, JMJD2A can directly bind with the promoter of IL-6 to trigger its transcription. For IL-8, JMJD2A can increase it mRNA stability in OC cells. Collectively, we revealed that JMJD2A can trigger the malignancy of OC cells via upregulation of IL-6 and IL-8. It suggested that JMJD2A might be a potential target for OC treatment and therapy.


Assuntos
Interleucina-6/metabolismo , Interleucina-8/metabolismo , Histona Desmetilases com o Domínio Jumonji/metabolismo , Neoplasias Ovarianas/metabolismo , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Feminino , Regulação Neoplásica da Expressão Gênica/fisiologia , Técnicas de Silenciamento de Genes , Humanos , Interleucina-6/genética , Interleucina-8/genética , Histona Desmetilases com o Domínio Jumonji/genética , Estabilidade de RNA/genética , RNA Mensageiro/metabolismo , Transcrição Gênica/fisiologia , Regulação para Cima
19.
Aging (Albany NY) ; 12(2): 1171-1185, 2020 01 24.
Artigo em Inglês | MEDLINE | ID: mdl-31977318

RESUMO

Hepatocellular carcinoma (HCC) is a common malignancy with a dismal prognosis. It is of great importance to identify biomarkers for the prediction of patients' survival.The mRNA expression level of deoxyribonuclease 1 like 3 (DNASE1L3) and its correlation with survival were accessed in 424 samples from The Cancer Genome Atlas database. Its expression level was confirmed by real-time quantitative polymerase chain reaction and western blotting in 20 pairs of postsurgical specimens. In addition, immunohistochemistry staining of DNASE1L3 was also performed in 113 postoperative samples, using a histochemistry score system. The relationship between patients' survival and DNASE1L3 expression level was evaluated by the Kaplan-Meier method.DNASE1L3 is downregulated in both mRNA and protein levels in HCC tissues, compared with adjacent normal tissues. 52 of 113 HCC specimens showed positive DNASE1L3 protein expression. Patients with positive DNASE1L3 expression had significantly longer overall survival, compared with patients with negative expression (p = 0.023). However, the DNASE1L3 fails to discriminate progression-free survival (p = 0.134). Multivariate COX analysis revealed that positive DNASE1L3 expression and higher differentiation were significantly associated with better overall survival.This study demonstrated that positive DNASE1L3 expression is an independent prognostic factor for better survival in HCC patients following radical resection.


Assuntos
Biomarcadores Tumorais , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/mortalidade , Endodesoxirribonucleases/genética , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/mortalidade , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Hepatocelular/patologia , Carcinoma Hepatocelular/cirurgia , Biologia Computacional/métodos , Feminino , Regulação Neoplásica da Expressão Gênica , Hepatectomia , Humanos , Imuno-Histoquímica , Neoplasias Hepáticas/patologia , Neoplasias Hepáticas/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Análise de Sobrevida , Transcriptoma , Carga Tumoral
20.
Cancer Med ; 9(5): 1790-1797, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31918459

RESUMO

Diffuse large B-cell lymphoma (DLBCL) is the most common subtype of non-Hodgkin lymphoma (NHL) and is a clinical, pathological, and molecular heterogeneous disease with highly variable clinical outcomes. Currently, valid prognostic biomarkers in DLBCL are still lacking. To optimize targeted therapy and improve the prognosis of DLBCL, the performance of proposed biomarkers needs to be evaluated in multiple cohorts, and new biomarkers need to be investigated in large datasets. Here, we developed a consensus Online Survival analysis web server for Diffuse Large B-Cell Lymphoma, abbreviated OSdlbcl, to assess the prognostic value of individual gene. To build OSdlbcl, we collected 1100 samples with gene expression profiles and clinical follow-up information from The Cancer Genome Atlas (TCGA) and Gene Expression Omnibus (GEO) databases. In addition, DNA mutation data were also collected from the TCGA database. Overall survival (OS), progression-free survival (PFS), disease-specific survival (DSS), disease-free interval (DFI), and progression-free interval (PFI) are important endpoints to reflect the survival rate in OSdlbcl. Moreover, clinical features were integrated into OSdlbcl to allow data stratifications according to the user's special needs. By inputting an official gene symbol and selecting desired criteria, the survival analysis results can be graphically presented by the Kaplan-Meier (KM) plot with hazard ratio (HR) and log-rank p value. As a proof-of-concept demonstration, the prognostic value of 23 previously reported survival associated biomarkers, such as transcription factors FOXP1 and BCL2, was evaluated in OSdlbcl and found to be significantly associated with survival as reported (HR = 1.73, P < .01; HR = 1.47, P = .03, respectively). In conclusion, OSdlbcl is a new web server that integrates public gene expression, gene mutation data, and clinical follow-up information to provide prognosis evaluations for biomarker development for DLBCL. The OSdlbcl web server is available at https://bioinfo.henu.edu.cn/DLBCL/DLBCLList.jsp.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Linfoma Difuso de Grandes Células B/mortalidade , Idoso , Consenso , Conjuntos de Dados como Assunto , Intervalo Livre de Doença , Feminino , Seguimentos , Fatores de Transcrição Forkhead/genética , Humanos , Internet , Linfoma Difuso de Grandes Células B/tratamento farmacológico , Linfoma Difuso de Grandes Células B/genética , Masculino , Pessoa de Meia-Idade , Mutação , Valor Preditivo dos Testes , Prognóstico , Intervalo Livre de Progressão , Estudo de Prova de Conceito , Proteínas Proto-Oncogênicas c-bcl-2/genética , RNA-Seq , Proteínas Repressoras/genética , Medição de Risco/métodos , Análise de Sobrevida
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