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1.
Curr Top Med Chem ; 24(1): 31-44, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-37929725

RESUMO

Bacterial proteins targeting the appropriate subcellular sites are the base for their proper function. Several studies have shown that the anionic phospholipid cardiolipin (CL), a conical lipid preferring negative membrane curvature, modulates the lipid bilayers' structure, which impacts the activity of their resident proteins. Due to the favor of negative membrane curvature, CL is not randomly distributed in the bacterial plasma membrane. In contrast, it gathers in particular parts of the cell membrane to form microdomains, in which many functional membrane proteins are accumulated and carry out diverse physiological processes of bacteria, such as cell division, metabolism, infection, and antibiotic residence. In addition, CL has a unique structure that carries two negative charges, which makes it play a pivotal role in protein assembly, interaction, and location. These characteristics of CL make it closely related to many crucial physiological functions of bacteria. Here, we have reviewed the mechanism of protein dynamics mediated by CL initiated on the bacterial membrane. Furthermore, we studied the effect of CL on bacterial infection and antibiotic residence. Finally, the CL-targeting therapeutic agents for antibacterial therapy are also examined.


Assuntos
Cardiolipinas , Proteínas de Membrana , Cardiolipinas/análise , Cardiolipinas/química , Cardiolipinas/metabolismo , Membrana Celular/química , Proteínas de Membrana/metabolismo , Bactérias/metabolismo , Antibacterianos/farmacologia , Antibacterianos/metabolismo
2.
Front Immunol ; 14: 1295684, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-38035068

RESUMO

Tumor-associated macrophages (TAMs) are integral to the tumor microenvironment (TME), influencing cancer progression significantly. Attracted by cancer cell signals, TAMs exhibit unparalleled adaptability, aligning with the dynamic tumor milieu. Their roles span from promoting tumor growth and angiogenesis to modulating metastasis. While substantial research has explored the fundamentals of TAMs, comprehending their adaptive behavior, and leveraging it for novel treatments remains challenging. This review delves into TAM polarization, metabolic shifts, and the complex orchestration of cytokines and chemokines determining their functions. We highlight the complexities of TAM-targeted research focusing on their adaptability and potential variability in therapeutic outcomes. Moreover, we discuss the synergy of integrating TAM-focused strategies with established cancer treatments, such as chemotherapy, and immunotherapy. Emphasis is laid on pioneering methods like TAM reprogramming for cancer immunotherapy and the adoption of single-cell technologies for precision intervention. This synthesis seeks to shed light on TAMs' multifaceted roles in cancer, pinpointing prospective pathways for transformative research and enhancing therapeutic modalities in oncology.


Assuntos
Neoplasias , Macrófagos Associados a Tumor , Humanos , Macrófagos Associados a Tumor/patologia , Estudos Prospectivos , Macrófagos/metabolismo , Neoplasias/metabolismo , Imunoterapia , Microambiente Tumoral
3.
Biomed Rep ; 19(4): 69, 2023 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-37719680

RESUMO

Breast cancer (BC) has become a threat to women's health. In addition, patients with triple-negative BC (TNBC) have the worst prognosis among all patients with BC. Furthermore, long non-coding RNA ABHD11-AS1 is aberrantly highly expressed in TNBC, suggesting that RNA ABHD11-AS1 may serve as an important role in the progression of TNBC. However, the detailed function of ABHD11-AS1 in TNBC remains largely unknown. The levels of ABHD11-AS1 in MDA-MB-231 cells were assessed by reverse transcription-quantitative PCR. To investigate the effect of ABHD11-AS1 on the progression of TNBC, a xenograft animal model was established. Knockdown of ABHD11-AS1 inhibited the epithelial-mesenchymal transition and migration of TNBC cells. In addition, ABHD11-AS1 promoted the viability and migration of TNBC cells by upregulating microRNA (miR)-199a-5p. Furthermore, knockdown of ABHD11-AS1 suppressed TNBC tumor growth in vivo by upregulating miR-199a-5p. In conclusion, knockdown of ABHD11-AS1 suppressed the progression of TNBC via upregulation of miR-199a-5p. The data of the present study may provide novel directions and a theoretical basis for TNBC treatment.

4.
Anatol J Cardiol ; 27(5): 240-248, 2023 05.
Artigo em Inglês | MEDLINE | ID: mdl-37119184

RESUMO

BACKGROUND: Several studies have shown that malnutrition helps to predict the occurrence of adverse outcomes after transcatheter aortic valve replacement. However, there is still controversy and uncertainty regarding the prevalence and consequences of malnutrition. We performed a systematic review and meta-analysis to assess the relationship between malnutrition and poor postoperative outcomes in transcatheter aortic valve replacement. METHODS: Observational studies were searched in PubMed, EMBASE, Cochrane Library, Web of Science, and MEDLINE regarding the relationship between malnutrition and adverse outcomes after transcatheter aortic valve replacement, with the primary end-point being all-cause mortality and secondary outcomes such as cardiovascular complications and readmission rates. This meta-analysis was registered in PROSPERO (number CRD42022310139). RESULTS: A total of 10 studies involving 5936 subjects were included in the systematic review and meta-analysis. The results showed that malnourished patients had an increased risk of all-cause mortality after transcatheter aortic valve replacement compared with non-malnourished patients (hazard ratios [HR] = 1.32, 95% CI [1.13, 1.53], P <.01). Subgroup analysis showed that in Asia, postoperative all-cause mortality was significantly higher in malnourished transcatheter aortic valve replacement patients than in non-malnourished transcatheter aortic valve replacement patients (P <.01), and in addition, sample size and follow-up time may have contributed to the large heterogeneity. CONCLUSION: Malnutrition increases the risk of all-cause mortality in such patients and may predict the occurrence of adverse postoperative outcomes.


Assuntos
Estenose da Valva Aórtica , Desnutrição , Substituição da Valva Aórtica Transcateter , Humanos , Substituição da Valva Aórtica Transcateter/efeitos adversos , Estenose da Valva Aórtica/complicações , Estenose da Valva Aórtica/cirurgia , Fatores de Risco , Desnutrição/complicações , Desnutrição/epidemiologia , Valva Aórtica/cirurgia , Resultado do Tratamento , Estudos Observacionais como Assunto
5.
Gynecol Obstet Invest ; 87(1): 12-21, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35081534

RESUMO

OBJECTIVES: Endometrial carcinoma (EC) is one of the leading causes of death from gynecological cancer due to the high recurrence rate. However, the molecular mechanisms of EC progression are not well understood. This study aimed to identify critical genes and miRNAs associated with the progression and prognosis of EC and find the potential mRNA-miRNA regulatory relationship. DESIGN: The mRNA and miRNA data were downloaded from The Cancer Genome Atlas (TCGA) database. Next, differentially expressed genes (DEGs) were identified. Subsequently, prognosis-related genes and miRNAs were identified, followed by co-expression analysis of these mRNAs and miRNAs. Materials, Setting, and Methods: Samples in the mRNA microarray were divided into normal (n = 35), early stage (n = 385), and advanced stage (n = 153). Next, DEGs in normal versus early stage and early stage versus advanced stage were, respectively, identified, followed by Venn analysis to screen overlapping DEGs in 2 comparison groups. Based on the expression level of these DEGs, univariate Cox regression analysis and Kaplan-Meier method were performed to obtain prognosis-related genes. Moreover, genes-related miRNAs were predicted, and miRNA-mRNA co-expressed pairs were identified. Then, survival analysis of co-expressed miRNA was performed. Finally, co-expressed genes of key genes were identified, and then functional enrichment analysis was conducted. RESULTS: After integrating analysis, 326 overlapping (309 upregulated and 17 downregulated) DEGs were obtained. Univariate Cox regression analysis showed that 44 mRNAs and 8 miRNAs were associated with the prognosis of EC. Combined with the co-expressed analysis, only one prognosis-related hsa-miR-326/ELFN2 axis was obtained. In addition, functional enrichment analysis showed that co-expressed genes of ELFN2 were mainly involved in the PI3K-Akt signaling pathway. LIMITATIONS: These findings were obtained via bioinformatics analysis, and thus further experimental studies are urgently demanded to validate our results. CONCLUSIONS: One key miRNA-mRNA regulatory pair (hsa-miR-326-ELFN2) was screened. This study provided a bioinformatics basis for the molecular mechanism of EC progression and might contribute to the identification of novel therapeutic targets.


Assuntos
Neoplasias do Endométrio , MicroRNAs , RNA Mensageiro , Biomarcadores Tumorais/genética , Progressão da Doença , Neoplasias do Endométrio/genética , Feminino , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Redes Reguladoras de Genes , Humanos , MicroRNAs/genética , Prognóstico , RNA Mensageiro/genética , Transdução de Sinais
6.
PLoS One ; 16(5): e0252430, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-34043723

RESUMO

BACKGROUND: Specific personality traits may affect the ability of nurses to deal with patient death. The relationship between personality and death coping self-efficacy (DCS) has rarely been investigated in the palliative care setting. In this study, we explored the associations between different personality profiles and DCS in clinical nurses from general wards and ICU. METHODS: A cross-sectional survey of 572 Chinese nurses was conducted between August and September 2020, by way of a self-administered questionnaire. RESULTS: Among the Big Five Personality Traits, in nurses the score was highest for conscientiousness and lowest for neuroticism. With regard to DCS, nurses scored highly on the intention of hospice care. The Big Five Personality Traits were found to explain 20.2% of the overall variation in DCS. Openness, agreeableness and conscientiousness were significantly associated with DCS in nurses. CONCLUSIONS: Nursing managers should pay attention to differences in personality characteristics and provide personalized and targeted nursing education. This should improve nurses' DCS, enrich their professional development and promote high quality palliative care for patients and their families.


Assuntos
Adaptação Psicológica , Enfermeiras e Enfermeiros/psicologia , Personalidade , Autoeficácia , Adulto , Estudos Transversais , Morte , Feminino , Humanos , Unidades de Terapia Intensiva , Masculino , Neuroticismo , Inventário de Personalidade , Inquéritos e Questionários
7.
Am J Rhinol Allergy ; 35(6): 809-816, 2021 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33726554

RESUMO

BACKGROUND: Histamine H1 receptor (H1R) antagonists are the first-line drugs for the treatment of allergic rhinitis (AR) at present. Emerging evidence supports an important role of histamine H4 receptor (H4R) in allergic diseases. However, information regarding the effects of combined treatment with H1 and H4 receptor antagonists in AR is limited. OBJECTIVES: We aimed to assess the effects of combined treatment with H1R and H4R antagonists on Th2 inflammatory responses in the nasal mucosa of AR rats. METHODS: Sprague Dawley rats were sensitized with ovalbumin and treated with H1R antagonist desloratadine or/and H4R antagonist JNJ7777120. Western blotting was used to assay the phenotypic markers of mature dendritic cells in the nasal mucosa, including major histocompatibility complex class II (MHC-II) and co-stimulatory molecules CD80, CD86 and OX40 ligand (OX40L). Th2 inflammatory cytokines including interleukin-4, 5 and 13 in nasal lavage fluids were determined by using enzyme-linked immunoassay. RESULTS: The treatment with desloratadine alone down-regulated the CD86 expression, and decreased the production of Th2 cytokines, but had no impact on the expression of MHC-II, CD80 and OX40L. The administration of NJ7777120 alone reduced the levels of CD86, OX40L and Th2 cytokines, whereas MHC-II and CD80 expression was unaffected. The combination of desloratadine and JNJ7777120 showed more significant synergistic therapeutic effects than monotherapy. CONCLUSION: H4R antagonist acted synergistically with H1R antagonist to reduce Th2 inflammatory responses by down-regulating CD86 and OX40L expression in the nasal mucosa of AR rats. The combination with H1R and H4R antagonists might be a new strategy for AR treatment.


Assuntos
Antagonistas dos Receptores Histamínicos/uso terapêutico , Receptores Histamínicos H4/antagonistas & inibidores , Rinite Alérgica , Células Th2/imunologia , Animais , Modelos Animais de Doenças , Mucosa Nasal/imunologia , Ratos , Ratos Sprague-Dawley , Receptores Histamínicos H3 , Rinite Alérgica/tratamento farmacológico , Rinite Alérgica/imunologia
8.
J Med Virol ; 92(12): 3534-3544, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32568409

RESUMO

CD8+ T cells play multiple and complex immunological roles including antiviral, regulatory, and exhaustive effects in hepatitis C virus (HCV) infected patients. Some CD8+ T-cell subsets were confirmed to be closely related to HCV infection such as TCM , TEM , TEM RA, Tc17, and CD8+ Treg. Herein, we report a new subset of interleukin (IL)-17/interferon (IFN)-γ producing CD8+ T (Tc17/IFN-γ) cells that markedly correlate with CD28+ CD244+ cells, IL-17 levels, and HCV RNA in HCV patients. During early treatment with peg-IFN-a2a plus ribavirin, the imbalance of these Tc17/IFN-γ cells could be partially restored, together with normalized serum alanine aminotransferase but not aspartate transaminase. Also, we analyzed the dynamic change of the percentage of this T cells subset in patients with different outcome after 4-week course of treatment with peg-IFN-a2a plus ribavirin and found that the percentage of CD8+ CD28+ CD244+ T cells significantly decreased in recovered patients but not in nonrecovered patients. In vitro, CD28+ CD244+ T cells were the only CD8+ T-cell group that secreted both IL-17 and IFN-γ in this axis and blockade with anti-CD244 antibodies significantly reduced cytokine production. Taken together, this study demonstrates that the frequency and regulatory functions of CD28+ CD244+ Tc17/IFN-γ cells may play an important role in persistent HCV infection.

9.
Clin Lab ; 65(10)2019 Oct 01.
Artigo em Inglês | MEDLINE | ID: mdl-31625354

RESUMO

BACKGROUND: Heat shock protein 60 has been reported to have a high diagnostic value for digestive system cancers. We sought to systematically evaluate the diagnostic value of HSP60 in patients with gastric cancer (GC), colorectal cancer (CRC), and hepatocellular carcinoma (HCC). METHODS: Relevant literature was adopted from the online databases. The pooled sensitivity, specificity, and diagnostic odds ratio (DOR) were pooled using random effects models. Summary receiver operating characteristic curve and the area under the curve (AUC) were used to express the overall test performance. Statistical analysis was performed by STATA 14.0 and Meta-DiSc 1.4 software. RESULTS: We merged 12 studies in a meta-analysis, including 1 GC, 5 CRC, and 6 HCC. Overall, the pooled sensitivity, specificity, and DOR to predict GC/CRC/HCC patients were 70%, 71%, and 8.49, respectively, corresponding to an AUC of 0.81. In subgroup analysis, the 82% specificity prompted a more advanced diagnostic accuracy for diagnosing CRC than HCC. CONCLUSIONS: HSP60 was an advanced biomarker for digestive system cancers and its abnormal expression might have implications for early diagnosis in screening of GC/CRC/HCC.


Assuntos
Biomarcadores Tumorais/metabolismo , Chaperonina 60/análise , Neoplasias do Sistema Digestório/metabolismo , Trato Gastrointestinal/metabolismo , Proteínas Mitocondriais/análise , Neoplasias do Sistema Digestório/diagnóstico , Trato Gastrointestinal/patologia , Humanos , Razão de Chances , Curva ROC , Sensibilidade e Especificidade
10.
Cancer Res ; 79(7): 1305-1317, 2019 04 01.
Artigo em Inglês | MEDLINE | ID: mdl-30718359

RESUMO

Long noncoding RNAs (lncRNA) play critical roles in the development of cancer, including hepatocellular carcinoma (HCC). However, the mechanisms underlying their deregulation remain largely unexplored. In this study, we report that two lncRNAs frequently downregulated in HCC function as tumor suppressors and are epigenetically silenced by histone methyltransferase EZH2. lncRNAs TCAM1P-004 and RP11-598D14.1 were inhibited by EZH-mediated trimethylation of H3K27me3 at their promoters. Downregulation of TCAM1P-004 and RP11-598D14.1 was frequently observed in HCC tumors compared with adjacent normal tissues. Both lncRNAs inhibited cell growth, cell survival, and transformation in HCC cells in vitro as well as tumor formation in vivo. Using RNA pull-down and mass spectrometry, we demonstrated that TCAM1P-004 bound IGF2BP1 and HIST1H1C, whereas RP11-598D14.1 bound IGF2BP1 and STAU1. These lncRNA-protein interactions were critical in regulating p53, MAPK, and HIF1α pathways that promoted cell proliferation in HCC. Overexpression of EZH2 was critical in repressing TCAM1P-004 and RP11-598D14.1, and EZH2-TCAM1P-004/RP11-598D14.1-regulated pathways were prevalent in human HCC. Aberrant suppression of TCAM1P-004 and RP11-598D14.1 led to loss of their tumor-suppressive effects by disrupting the interaction with IGF2BP1, HIST1H1C, and STAU1, which in turn promoted HCC development and progression. Collectively, these findings demonstrate the role of TCAMP1P-004 and RP11-598D14.1 in suppressing tumor growth and suggest that EZH2 may serve as a therapeutic target in HCC. SIGNIFICANCE: EZH2-mediated loss of lncRNAs TCAM1P-004 and RP11-598D14.1 hinders the formation of tumor suppressor lncRNA-protein complexes and subsequently promotes HCC growth.


Assuntos
Carcinoma Hepatocelular/genética , Proteína Potenciadora do Homólogo 2 de Zeste/genética , Epigênese Genética , Inativação Gênica , Genoma Humano , Neoplasias Hepáticas/genética , RNA Longo não Codificante/genética , Carcinoma Hepatocelular/patologia , Linhagem Celular Tumoral , Proliferação de Células/fisiologia , Genes Supressores de Tumor , Histonas/fisiologia , Humanos , Neoplasias Hepáticas/patologia , Metilação , Proteínas de Ligação a RNA/fisiologia
11.
Cancer Biol Ther ; 20(6): 866-876, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30786815

RESUMO

Most of gastric carcinoma (GC) is attributed to infection by Helicobacter pylori (H. pylori) but there is increasing evidence that the positive H. pylori status correlates with better prognosis in GC. The H. pylori-induced cellular immune response may suppress cancer and in this work, recombinant pcDNA3 plasmids encoding various fragments of H. pylori virulence genes of cagA, vacA and babA are constructed and combined into groups to immunize BALB/c mice. The activated splenic CD3+ T cells are purified and the anticancer effects are investigated in vitro and in vivo. The H. pylori DNA vaccines induce a shift in the response from Th1 to Th2 that mimicks the immune status in patients of GC with chronic H. pylori infection. The stimulated CD3+ T cells inhibit the growth of human GC cells in vitro and adoptive transfusions of the CD3+ T cells suppress the growth of GC xenograft in vivo. The effects may be caused by the larger ratios of infiltrated CD8+/CD4+ T cells, reduced infiltration of regulatory FOXP3+ T cells, and enhanced apoptosis induced by upregulation of Caspase-9/Caspase-3 and downregulation of Survivin. Our results reveal the potential immunotherapeutic value of H. pylori vaccine-activated CD3+ T cells in those with advanced GC.


Assuntos
Vacinas Bacterianas/imunologia , Helicobacter pylori/imunologia , Ativação Linfocitária/imunologia , Subpopulações de Linfócitos T/imunologia , Vacinas de DNA/imunologia , Animais , Apoptose/genética , Apoptose/imunologia , Proteínas de Bactérias/genética , Proteínas de Bactérias/imunologia , Vacinas Bacterianas/administração & dosagem , Infecções por Helicobacter/imunologia , Infecções por Helicobacter/prevenção & controle , Helicobacter pylori/genética , Interações Hospedeiro-Patógeno/imunologia , Humanos , Imunoterapia/métodos , Linfócitos do Interstício Tumoral/imunologia , Linfócitos do Interstício Tumoral/metabolismo , Camundongos , Neoplasias Gástricas/etiologia , Neoplasias Gástricas/terapia , Subpopulações de Linfócitos T/metabolismo , Vacinas de DNA/administração & dosagem
12.
Clin Lab ; 64(4): 569-576, 2018 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-29739083

RESUMO

BACKGROUND: Renal cell carcinoma (RCC) is the most common neoplasm of the adult kidney. miR-210 was a known oncogene with tumor-promoting effects in many types of cancer. This meta-analysis aimed to evaluate the potential diagnostic value of circulating miR-210. METHODS: Relevant literature was collected from PubMed and Embase. Sensitivity, specificity, and diagnostic odds ratio (DOR) for miR-210 in the diagnosis of RCC were pooled using random effects models. Summary receiver operating characteristic (SROC) curve analysis and the area under the curve (AUC) were used to estimate the overall test performance. RESULTS: This meta-analysis included seven studies with a total of 570 RCC patients and 415 healthy controls. For miR-210, the pooled sensitivity, specificity, and DOR to predict RCC patients were 0.74 (95% confidence interval [CI]: 0.70 - 0.77), 0.76 (95% CI: 0.71 - 0.80) and 8.81 (95% CI: 5.31 - 14.57), respectively. In addition, the AUC of miR-210 for the diagnosis of RCC is 0.81. CONCLUSIONS: MiR-210 might be a potential novel biomarker in the diagnosis of renal cell carcinoma.


Assuntos
Biomarcadores Tumorais/genética , Carcinoma de Células Renais/genética , Neoplasias Renais/genética , MicroRNAs/genética , Adulto , Biomarcadores Tumorais/sangue , Carcinoma de Células Renais/sangue , Carcinoma de Células Renais/diagnóstico , Humanos , Neoplasias Renais/sangue , Neoplasias Renais/diagnóstico , MicroRNAs/sangue , Pessoa de Meia-Idade , Curva ROC
13.
Biomed Res Int ; 2017: 4378627, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28904958

RESUMO

Adaptation to changes in the environment is crucial for the viability of all organisms. Although the importance of calcineurin in the stress response has been highlighted in filamentous fungi, little is known about the involvement of ion-responsive genes and pathways in conferring salt tolerance without calcium signaling. In this study, high-throughput RNA-seq was used to investigate salt stress-induced genes in the parent, ΔcnaB, and ΔcnaBΔcchA strains of Aspergillus nidulans, which differ greatly in salt adaption. In total, 2,884 differentially expressed genes including 1,382 up- and 1,502 downregulated genes were identified. Secondary transporters, which were upregulated to a greater extent in ΔcnaBΔcchA than in the parent or ΔcnaB strains, are likely to play important roles in response to salt stress. Furthermore, 36 genes were exclusively upregulated in the ΔcnaBΔcchA under salt stress. Functional analysis of differentially expressed genes revealed that genes involved in transport, heat shock protein binding, and cell division processes were exclusively activated in ΔcnaBΔcchA. Overall, our findings reveal that secondary transporters and stress-responsive genes may play crucial roles in salt tolerance to bypass the requirement for the CchA-calcineurin pathway, contributing to a deeper understanding of the mechanisms that influence fungal salt stress adaption in Aspergillus.


Assuntos
Aspergillus nidulans/genética , Calcineurina/genética , Tolerância ao Sal/genética , Aspergillus nidulans/crescimento & desenvolvimento , Sinalização do Cálcio/genética , Perfilação da Expressão Gênica/métodos , Regulação Fúngica da Expressão Gênica , Proteínas de Choque Térmico/genética , Sequenciamento de Nucleotídeos em Larga Escala/métodos , Estresse Fisiológico/genética , Transcriptoma/genética
14.
Immunology ; 152(3): 462-471, 2017 11.
Artigo em Inglês | MEDLINE | ID: mdl-28664991

RESUMO

Peptide recognition through the MHC class I molecule by cytotoxic T lymphocytes (CTLs) leads to the killing of cancer cells. A potential challenge for T-cell immunotherapy is that dendritic cells (DCs) are exposed to the MHC class I-peptide complex for an insufficient amount of time. To improve tumour antigen presentation to T cells and thereby initiate a more effective T-cell response, we generated artificial antigen-presenting cells (aAPCs) by incubating human immature DCs (imDCs) with poly(lactic-co-glycolic) acid nanoparticles (PLGA-NPs) encapsulating tumour antigenic peptides, followed by maturation with lipopolysaccharide. Tumour antigen-specific CTLs were then induced using either peptide-loaded mature DCs (mDCs) or aAPCs, and their activities were analysed using both ELISpot and cytotoxicity assays. We found that the aAPCs induced significantly stronger tumour antigen-specific CTL responses than the controls, which included both mDCs and aAPCs loaded with empty nanoparticles. Moreover, frozen CTLs that were generated by exposure to aAPCs retained the capability to eradicate HLA-A2-positive tumour antigen-bearing cancer cells. These results indicated that aAPCs are superior to DCs when inducing the CTL response because the former are capable of continuously presenting tumour antigens to T cells in a sustained manner. The development of aAPCs with PLGA-NPs encapsulating tumour antigenic peptides is a promising approach for the generation of effective CTL responses in vitro and warrants further assessments in clinical trials.


Assuntos
Apresentação de Antígeno , Vacinas Anticâncer/farmacologia , Citotoxicidade Imunológica/efeitos dos fármacos , Células Dendríticas/efeitos dos fármacos , Proteínas Inibidoras de Apoptose/farmacologia , Ácido Láctico/química , Lipopolissacarídeos/farmacologia , Antígeno MART-1/farmacologia , Nanopartículas , Neoplasias/terapia , Fragmentos de Peptídeos/farmacologia , Ácido Poliglicólico/química , Linfócitos T Citotóxicos/efeitos dos fármacos , Vacinas Anticâncer/química , Vacinas Anticâncer/imunologia , Sobrevivência Celular/efeitos dos fármacos , Preparações de Ação Retardada , Células Dendríticas/imunologia , Células Dendríticas/metabolismo , Composição de Medicamentos , Liberação Controlada de Fármacos , Humanos , Proteínas Inibidoras de Apoptose/química , Proteínas Inibidoras de Apoptose/imunologia , Cinética , Lipopolissacarídeos/imunologia , Antígeno MART-1/química , Antígeno MART-1/imunologia , Células MCF-7 , Neoplasias/imunologia , Neoplasias/metabolismo , Neoplasias/patologia , Fragmentos de Peptídeos/química , Fragmentos de Peptídeos/imunologia , Copolímero de Ácido Poliláctico e Ácido Poliglicólico , Solubilidade , Survivina , Linfócitos T Citotóxicos/imunologia , Linfócitos T Citotóxicos/metabolismo
15.
Bull Cancer ; 104(7-8): 675-682, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28587766

RESUMO

BACKGROUND: Previous studies suggested a possible influence of circulating 25-hydroxyvitamin D [25(OH)D] level on the prognosis of lung cancer patients, but conflicting findings were reported. A systematic review and meta-analysis was thus conducted to comprehensively assess the influence of circulating 25(OH)D level on the prognosis of lung cancer patients. METHODS: Prospective or retrospective cohort studies assessing the influence of circulating 25(OH)D level on the prognosis of lung cancer patients were considered eligible. Hazard Ratios (HR) were pooled using meta-analysis. RESULTS: Eight studies with 2166 lung cancer patients were included. Meta-analysis of unadjusted HRs from four studies showed low circulating 25(OH)D level was significantly correlated with poor overall survival in lung cancer (HR=1.30, 95%CI 1.08-1.55, P=0.004). Meta-analysis of adjusted HRs from eight studies suggested that low circulating 25(OH)D level was not significantly correlated with poor overall survival (HR=1.25; P=0.13). However, sensitivity analysis suggested an obvious change in the pooled HRs when excluding single study by turns. When the study by Liu et al. was omitted, low circulating 25(OH)D level was significantly correlated with poor overall survival (HR=1.34; P=0.04). CONCLUSION: The present systematic review and meta-analysis suggested a correlation between low circulating 25(OH)D level and poor overall survival in lung cancer. More studies are needed to further validate the finding above.


Assuntos
Neoplasias Pulmonares/sangue , Neoplasias Pulmonares/mortalidade , Vitamina D/análogos & derivados , Biomarcadores Tumorais/sangue , Humanos , Prognóstico , Estudos Prospectivos , Estudos Retrospectivos , Sensibilidade e Especificidade , Vitamina D/sangue
16.
Int Immunopharmacol ; 47: 159-165, 2017 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28410529

RESUMO

Cytotoxic T lymphocytes (CTLs) are a key player in cancer immunotherapies, and MHC class I molecules on the cell surface are crucial for cellular recognition. However, the aberrant expression of MHC class I molecules is frequently found in various malignancies. IFNγ has dual functions in cancer progression, and its effect on tumor immunity is controversial. To investigate whether IFNγ can enhance cytotoxic efficiency of the tumor antigen-specific CTLs, we generated the CTLs using modified human dendritic cells as antigen presenting cells, then studied the activities of CTLs on human leukocyte antigen (HLA)-A2 positive glioma cells treated with, or without IFNγ. The results from both ELISpot and cytotoxicity assays demonstrated that the CTLs recognized and eliminated the HLA-A2 positive glioma cells treated with IFNγ more effectively when compared to the glioma cells deprived of IFNγ treatment. In addition, in vitro experiments showed that the levels of MHC class I molecules were upregulated in all of the HLA-A2 positive glioma cells. Using the publicly accessed TCGA data of low-grade glioma, we found significantly positive associations between IFNγ and both MHC class I molecules and CD8+ T cell activation score (p<0.0001). Furthermore, we found a significantly reduced risk of death in the glioma patients with high T cell activation score in comparison to those with low score (p=0.022). These findings suggest that a clinical application of IFNγ treatment may have potential benefits.


Assuntos
Células Dendríticas/imunologia , Glioma/imunologia , Antígeno HLA-A2/metabolismo , Imunoterapia Adotiva/métodos , Interferon gama/metabolismo , Linfócitos T Citotóxicos/imunologia , Apresentação de Antígeno , Antígenos de Neoplasias/imunologia , Linhagem Celular Tumoral , Citotoxicidade Imunológica , ELISPOT , Regulação Neoplásica da Expressão Gênica , Humanos , Ativação Linfocitária , Regulação para Cima
17.
J Huazhong Univ Sci Technolog Med Sci ; 36(5): 752-757, 2016 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-27752895

RESUMO

This study aimed to conduct measurement uncertainty assessment of a new method for determination of Sudan colorants (Sudan I, II, III and IV) in food by high performance liquid chromatography (HPLC). Samples were extracted with organic solvents (hexane, 20% acetone) and first purified by magnesium trisilicate (2MgO·3SiO2). The Sudan colorants (Sudan I-IV) were also initially separated on C8 by gradient elution using acetonitrile and 0.1% (v/v) formic acid aqueous solution as the mobile phases and detected with diode-array detector (DAD). The uncertainty of mathematical model of Sudan I, II, III and IV is based on EURACHEM guidelines. The sources and components of uncertainty were calculated. The experiment gave a good linear relationship over the concentration from 0.4 to 4.0 µg/mL and spiked recoveries were from 74.0% to 97.5%. The limits of determination (LOD) were 48, 61, 36, 58 µg/kg for the four analytes, respectively. The total uncertainty of Sudan colorants (Sudan I, II, III and IV) was 810±30.8, 790±28.4, 750±27.0, 730±50.0 µg/kg, respectively. The recovery uncertainty was the most significant factor contributing to the total uncertainty. The developed method is simple, rapid, and highly sensitive. It can be used for the determination of trace Sudan dyes in food samples. The sources of uncertainty have been identified and uncertainty components have been simplified and considered.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Análise de Alimentos/métodos , Corantes de Alimentos/isolamento & purificação , Silicatos de Magnésio/química , Compostos Azo/química , Compostos Azo/isolamento & purificação , Corantes de Alimentos/química , Humanos , Limite de Detecção , Naftóis/química , Naftóis/isolamento & purificação
18.
Int Forum Allergy Rhinol ; 6(3): 264-70, 2016 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-26574733

RESUMO

BACKGROUND: Mucin 5 subtype B (MUC5B) is 1 of the major mucins secreted by airway epithelial cells. We sought to determine the effect of histamine on MUC5B expression in human nasal epithelial cells. METHODS: Human nasal epithelial cells from allergic rhinitis patients were cultured, and stimulated with 4 concentrations of histamine, or pretreated with a specific nuclear factor-kappa B (NF-κB) inhibitor (Bay11-7082) before histamine stimulation. Immunocytochemistry and Western blotting were used to detect phosphorylated inhibitor of kappa B alpha (p-IκBα), NF-κBp65 and MUC5B protein. MUC5B content in supernatants was assayed by enzyme-linked immunosorbent assay (ELISA). RESULTS: Histamine promoted IκBα phosphorylation and NF-κBp65 nuclear translocation. A concentration-dependent histamine-induced increase of MUC5B protein was observed, and its content in supernatants was upregulated in a concentration-dependent fashion, but these effects were attenuated by Bay11-7082. CONCLUSION: Histamine activated the IκBα/NF-κB pathway by promoting IκBα phosphorylation and inducing NF-κBp65 nuclear translocation, contributing to MUC5B overproduction and secretion.


Assuntos
Histamina/imunologia , Mucina-5B/metabolismo , NF-kappa B/metabolismo , Mucosa Nasal/imunologia , Rinite Alérgica/imunologia , Adolescente , Adulto , Células Cultivadas , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Mucina-5B/genética , Inibidor de NF-kappaB alfa/metabolismo , NF-kappa B/antagonistas & inibidores , Mucosa Nasal/efeitos dos fármacos , Nitrilas/farmacologia , Fosforilação/efeitos dos fármacos , Fosforilação/imunologia , Transporte Proteico/efeitos dos fármacos , Transporte Proteico/imunologia , Sulfonas/farmacologia , Regulação para Cima/efeitos dos fármacos , Regulação para Cima/imunologia , Adulto Jovem
19.
Artigo em Chinês | MEDLINE | ID: mdl-26510370

RESUMO

Medical parasitology education has been facing some difficulties, because it is a course of wide range, lacking clinical cases and concerned specimens of parasites currently. In addition, its relationship with life is not closely enough. All these reasons may impact the effect of class education negatively. Therefore, it is important to increase the vitality of parasitology education and diversify the instructional mode by using the resources from Internet. In recent years, the Discovery Channel has uploaded a documentary Monsters Inside Me online. This documentary is high professional and closely linked with parasitology. It maintains numbers of clinical cases about parasitic diseases. Each episode is about 3 minutes and shortly enough to be introduced into class teaching. However, this resource has not been fully used in domestic temporally. We found that direct introduction of the documentary into class teaching can enrich teaching forms to attract learning interest of students, and finally improve the teaching effect of class. Above that, another popular documentary A Bite of China involves many related knowledge points of parasitology. The appropriate usage of the knowledge can build up close linkage between book and life, which is extremely helpful to give students a deep impression of parasitology. In brief, it is our strong recommendation to introduce the documentary Monsters Inside Me into class.


Assuntos
Documentação , Parasitologia/educação , Ensino
20.
J Huazhong Univ Sci Technolog Med Sci ; 35(2): 188-191, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25877350

RESUMO

A new, simple and sensitive method was developed for the determination of silicon tetrahydride in the air of workplace in this study. The alkaline resin-based spherical activated carbon was used to collect sample of silicon tetrahydride at workplace. Silicon tetrahydride was then desorbed from active carbon in 100°C hot water. After reacting with ammonium molybdate, oxalic acid and 1,2,4-trichlorobenzene alpha-naphthol amino sulfonic acid under acid condition, silicon tetrahydride was transformed into silicon molybdenum blue. The absorbance of silicon molybdenum blue was quantitatively measured at the wavelength of 680 nm. The results showed that the average sampling efficiency and desorption efficiency were 97.53% and 94.94%, respectively by this method. Detection limits were 0.054 µg/mL for the spectrophotometric method and 0.14 mg/m(3) for the determination of silicon tetrahydride in the air of workplace (sampling volume was 7.5 L). The conversion rate of silicon tetrahydride gradually decreased when storage time of samples was extended. The descent rate of sample was less than 10% when the sample was sealed for 7 days in the room temperature. It was concluded that this spectrophotometric method can be successfully used to determine silicon tetrahydride in the worksites.


Assuntos
Poluentes Ocupacionais do Ar/análise , Silanos/análise , Espectrofotometria/métodos , Local de Trabalho , Humanos , Limite de Detecção , Reprodutibilidade dos Testes
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