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1.
Biomed Khim ; 66(1): 83-88, 2020 Jan.
Artigo em Russo | MEDLINE | ID: mdl-32116230

RESUMO

The relationship between the content of supernatant cytokines and the expression of non-specific type of markers of epithelial-mesenchymal transition markers in the presence (group II) and the absence of lymphogenous metastasis (group I) were studied in biopsy specimens of mammary invasive breast carcinoma. The concentrations of TNF-α, IFN-γ, G-CSF, GM-CSF, VEGF, MCP-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-17, IL-18, IL-1ß and IL-1Ra, as well as the expression of immunohistochemical (IHC) markers of the epithelial-mesenchymal transition - cadherin-E (CDH1), ß-1 integrin (CD29) and type II collagen (CII) were assayed. Results have shown that patients of these groups statistically significantly differed in spontaneous production of IL-18 and G-CSF, in terms of the index of the effect of the polyclonal activator on G-CSF production. There was a correlation between the parameter of CII expression in tumor tissue and the production of cytokines by tumor biopsy specimens; it was characteristic of all patients with invasive carcinoma of a non-specific type, and correlations, both direct and reverse between the expression indices of CDH1, CD29 and cytokine production varied depending on the presence or the absence of lymphogenous metastasis. The study revealed the features of the correlation between the production of cytokines by the tumor, its microenvironment and the expression of IHC markers of the epithelial-mesenchymal transition in patients with invasive non-specific breast carcinoma in the presence and absence of lymphogenous metastasis.


Assuntos
Neoplasias da Mama/patologia , Carcinoma/patologia , Citocinas/análise , Transição Epitelial-Mesenquimal , Antígenos CD/análise , Biomarcadores Tumorais/análise , Caderinas/análise , Colágeno Tipo II/análise , Feminino , Humanos , Integrina beta1/análise , Microambiente Tumoral
3.
Georgian Med News ; (294): 123-128, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31687963

RESUMO

Microenvironment plays central role in the development of cervical precancerous and cancerous lesions. Cervical intraepithelial neoplasia (CIN) represents a group of precancerous lesions, divided into three degrees. We investigated the distribution of intraepithelial lymphocytes and macrophages in different grades of CIN. We analysed lymphocyte marker CD103, macrophage marker CD68 and proliferation marker Ki67 using standard immunohistochemistry. In addition, we investigated the distribution of lymphocytes using standard haematoxylin and eosin method. The results of our study indicated thatgrade I CIN which subsequently progressed into grade II CIN was characterised with low lymphocytic infiltration, low lympho-epithelial index and low lymphocyte proliferation index. Similar results were seen in cases of CINII which were later progressed into CINIII or in carcinoma. Therefore, we would like to recommend the analysis of microenvironment alterations in CIN lesions, in order to assess their progression potential.


Assuntos
Antígenos CD/metabolismo , Biomarcadores Tumorais/análise , Transformação Celular Neoplásica/patologia , Neoplasia Intraepitelial Cervical/patologia , Linfócitos Intraepiteliais/patologia , Antígeno Ki-67/metabolismo , Macrófagos/patologia , Microambiente Tumoral , Neoplasias do Colo do Útero/patologia , Antígenos CD/análise , Neoplasia Intraepitelial Cervical/metabolismo , Progressão da Doença , Feminino , Humanos , Imuno-Histoquímica/métodos , Antígeno Ki-67/análise , Gradação de Tumores , Neoplasias do Colo do Útero/metabolismo
4.
BMC Infect Dis ; 19(1): 1006, 2019 Nov 28.
Artigo em Inglês | MEDLINE | ID: mdl-31779590

RESUMO

BACKGROUND: Monocytes are the predominant innate immune cells at the early stage of Mycobacterium tuberculosis (M. tb) infection as the host defense against intracellular pathogens. Understanding the profile of different monocyte subpopulations and the dynamics of monocyte-related biomarkers may be useful for the diagnosis and prognosis of tuberculosis. METHODS: We enrolled 129 individuals comprising patients with pulmonary tuberculosis (PTB) (n = 39), tuberculous pleurisy (TBP) (n = 28), malignant pleural effusion (MPE) (n = 21), latent tuberculosis infection (LTBI) (n = 20), and healthy controls (HC) (n = 21). Surface expression of CD14, CD16, and CD163 on monocytes was detected using flow cytometry. In addition, soluble CD163 (sCD163) was determined by enzyme linked immunosorbent assay. RESULTS: Higher frequency of CD14+CD16+ (15.7% vs 7.8%, P < 0.0001) and CD14-CD16+ (5.3% vs 2.5%, P = 0.0011) monocytes and a decreased percentage of CD14+CD16- (51.0% vs 70.4%, P = 0.0110) cells was observed in PTB patients than in HCs. Moreover, PTB patients displayed a higher frequency of CD163+ cells in CD16+ monocytes than those in the HC group (40.4% vs 11.3%, P < 0.0001). The level of sCD163 was elevated in TBP patients and was higher in pleural effusion than in plasma (2116.0 ng/ml vs 1236.0 ng/ml, P < 0.0001). sCD163 levels in pleural effusion and plasma could be used to distinguish TBP from MPE patients (cut-off values: 1950.0 and 934.7 ng/ml, respectively; AUCs: 0.8418 and 0.8136, respectively). Importantly, plasma sCD163 levels in TBP patients decreased significantly after anti-TB treatment. CONCLUSIONS: Higher expression of membrane and soluble CD163 in active tuberculosis patients might provide insights regarding the pathogenesis of tuberculosis, and sCD163 may be a novel biomarker to distinguish TBP from MPE and to predict disease severity.


Assuntos
Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Monócitos/metabolismo , Receptores de Superfície Celular/análise , Tuberculose/diagnóstico , Adulto , Idoso , Antígenos CD/sangue , Antígenos CD/metabolismo , Antígenos de Diferenciação Mielomonocítica/sangue , Antígenos de Diferenciação Mielomonocítica/metabolismo , Área Sob a Curva , Estudos de Casos e Controles , Feminino , Humanos , Imunidade Inata , Receptores de Lipopolissacarídeos/metabolismo , Masculino , Pessoa de Meia-Idade , Monócitos/citologia , Monócitos/imunologia , Prognóstico , Curva ROC , Receptores de Superfície Celular/sangue , Receptores de Superfície Celular/metabolismo , Receptores de IgG/metabolismo , Índice de Gravidade de Doença , Tuberculose/imunologia , Tuberculose/patologia , Tuberculose Pleural/imunologia , Tuberculose Pleural/patologia , Tuberculose Pulmonar/imunologia , Tuberculose Pulmonar/patologia
5.
Wiad Lek ; 72(9 cz 2): 1791-1794, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31622268

RESUMO

OBJECTIVE: Introduction: At present biocomposite materials are used in the surgical treatment of frontal bone fracture. They improve osteogenesis, reduce the number of complications. Immunologic aspects of application of these materials are studied insufficiently, therefore this report presents the results of immunoassay of patients with frontal bone fracture in the proximate posttraumatic period before implanting preparation "Syntekost". The aim: To define the role of immune mechanisms in the realization of the biocomposite material's positive influence on the development of effective posstraumatic rehabilitation schemes. PATIENTS AND METHODS: Materials and methods: 16 patients with frontal bone fracture (FBF) were examined on admission to the Otolaryngology Clinics of Vinnitsa Region Hospital. Additionally, 10 patients of the similar age were examined as a control group. The content of cells with markers of surface antigens-CD3,14,16,20,25, concentration of immunoglobulins of classes M,G,A,E, С4 complement component and lactoferrin was determined in blood. Immunoenzyme methods were applied. Nonparametric Wilcoxon - Mann - Whitney test, computer programme WIN Pepi were used for statistical measurements. RESULTS: Results: A decrease in the level of IgM in comparison with practically healthy donors and an increase in the concentration of lactoferrin were identified as humoral immunity factors of patients with frontal basilar trauma. The most significant deviation in the peripheral blood cellular makeup in CD-markers was an increase in cells with markers CD14 and CD16. CONCLUSION: Conclusions: The level of cells and prodefensin-lactoferrin that maintain inborn immunity increases and the concentration of coarse defensive protein decreases in the initial period after frontal bone fracture, which must be taken into consideration during post-surgical treatment.


Assuntos
Osso Frontal/lesões , Imunidade Celular , Imunidade Humoral , Antígenos CD/análise , Humanos , Imunoglobulinas/sangue , Lactoferrina/sangue
6.
Cardiovasc Pathol ; 43: 107148, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31518915

RESUMO

BACKGROUND: Immune checkpoint inhibition (ICI) has emerged as a promising new approach to treat malignancy. Such therapies can result in autoimmune-related complications such as myocarditis and hepatitis. The impact of ICI on sites of preexisting chronic inflammation has been less clear. Atherosclerosis is a chronic vascular disease with a significant inflammatory component. METHODS: To determine the effect of ICI on the inflammatory infiltrate in coronary artery atherosclerotic plaques, 11 patients who had recently been treated with ICI and subsequently underwent autopsy were matched with 11 cancer patients who had not received ICI treatment. The amount of CD3+ T-lymphocytes, CD8+ cytotoxic T-lymphocytes, and CD68+ macrophages and the ratios of the various cell types in the coronary artery atherosclerotic plaques were compared. RESULTS: There was no significant difference in the absolute numbers of CD3+, CD8+, or CD68+ cells in the atherosclerotic plaques. In the plaques of the ICI-treated patients, there was a significant increase in the ratio of CD3+ cells to CD68+ cells (CD3/CD68) (P=.002) and a trend towards an increased CD8/CD68 ratio. The increased CD3/CD68 ratio in the ICI-treated patients resulted in 6 of the 11 patients having lymphocyte-predominate inflammation in contrast to the macrophage-predominate inflammation typically found in atherosclerotic plaques. CONCLUSIONS: These findings indicate that ICI alters the inflammatory composition of human atherosclerotic plaque and, thus, may influence plaque progression and/or clinical coronary events. SUMMARY: In cancer patients, treatment with immune checkpoint inhibition is associated with an altered inflammatory cell composition in coronary artery atherosclerotic plaques with an increased ratio of CD3+ T cells to CD68+ macrophages. Thus, immune checkpoint inhibition may influence plaque progression and/or clinical coronary events.


Assuntos
Antineoplásicos Imunológicos/uso terapêutico , Doença da Artéria Coronariana/imunologia , Vasos Coronários/efeitos dos fármacos , Macrófagos/efeitos dos fármacos , Neoplasias/tratamento farmacológico , Placa Aterosclerótica , Linfócitos T/efeitos dos fármacos , Idoso , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Autopsia , Complexo CD3/análise , Antígenos CD8/análise , Doença da Artéria Coronariana/patologia , Vasos Coronários/imunologia , Vasos Coronários/patologia , Progressão da Doença , Feminino , Humanos , Macrófagos/imunologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Neoplasias/imunologia , Neoplasias/patologia , Estudos Retrospectivos , Linfócitos T/imunologia , Linfócitos T/patologia , Resultado do Tratamento
7.
Oncology ; 97(5): 311-318, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31550723

RESUMO

INTRODUCTION: Human epidermal growth factor 2 (HER2) gene overexpression in breast carcinoma cell lines has been shown to drive mammary carcinogenesis and tumor growth and invasion through its effects on mammary stem cells. OBJECTIVE: Therefore, we investigated the mechanism by which HER2 regulates cancer stem cell (CSC) activity in gastric cancer cells. METHODS: HER2 was transfected into MKN28 gastric cancer cells, and its role in regulating CSC activity was determined by characterizing the HER2-overexpressing cells. RESULTS: The sphere formation assay revealed that the sphere sizes and frequency of sphere formation were significantly greater for the HER2-overexpressing cells than for the MKN28 control cells. The CSC markers Oct-4 and BMI1 were more highly expressed in the HER2-overexpressing cells, as were the EMT markers. This was accompanied by a significant enhancement in cellular invasion of the Matrigel and migration. The E-cadherin level was significantly downregulated, and the mesenchymal marker Snail upregulated, in the HER2-transfected cells. HER2 overexpression activated the well-characterized CSC-associated Wnt/ß-catenin signaling pathway, as shown by the luciferase assay. After treatment of these cells with the Wnt signal inhibitor PRI-724, the BMI1 and Oct-4 levels were decreased for 24 h and Snail was also downregulated. Immunofluorescence staining revealed the significant restoration of E-cadherin levels in the HER2-transfected cells after PRI-724 treatment. CONCLUSIONS: These results established a role for HER2 in regulating gastric CSC activity, with Wnt/ß-catenin signaling being mediated via a HER2-dependent pathway. In summary, HER2-overexpressing gastric cancer cells exhibited increased stemness and invasiveness and were regulated by Wnt/ß-catenin signaling.


Assuntos
Células-Tronco Neoplásicas/fisiologia , Receptor ErbB-2/fisiologia , Neoplasias Gástricas/patologia , Via de Sinalização Wnt/fisiologia , Antígenos CD/análise , Caderinas/análise , Linhagem Celular Tumoral , Humanos , Invasividade Neoplásica , Fator 3 de Transcrição de Octâmero/análise , Complexo Repressor Polycomb 1/análise , Receptor ErbB-2/análise , Neoplasias Gástricas/química , beta Catenina/análise
9.
Acta Med Port ; 32(9): 617-620, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31493367

RESUMO

Langerhans cell histiocytosis remains an enigmatic disease with a very heterogeneous presentation. We describe a rare case of orbital Langerhans cell histiocytosis in a 39-year-old female patient who presented right orbital pain and edema of the upper right eyelid. Surgery showed a friable lesion and underlying bone irregularity. Morphological aspects and immunohistochemical profile favored the diagnosis of Langerhans cell histiocytosis, which was confirmed with evidence of Langerin expression. The staging tests did not reveal any organ involvement, so we decided to follow the algorithm proposed by Euro Histio Net: in case of unifocal disease and in a single organ, clinical surveillance was preferred. This case aims to raise awareness of a manifestation of Langerhans cell histiocytosis, which should always be considered as a differential diagnosis in adults with osteolytic orbital lesions.


Assuntos
Histiocitose de Células de Langerhans/diagnóstico , Doenças Orbitárias/diagnóstico , Adulto , Antígenos CD/análise , Biomarcadores/análise , Blefarite/etiologia , Feminino , Histiocitose de Células de Langerhans/patologia , Humanos , Lectinas Tipo C/análise , Espectroscopia de Ressonância Magnética , Lectinas de Ligação a Manose/análise , Doenças Orbitárias/patologia
10.
Med Hypotheses ; 131: 109281, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31443770

RESUMO

The data of literature are discordant about the role of mast cells in different types of neoplasms. In this paper the authors propose the hypothesis that tumor-associated mast cells may switch to different polarization states, conditioning the immunogenic capacities of the different neoplasms. Anti-inflammatory polarized mast cells should express cytokines such as interleukin-10 (IL-10) and then mast cells number should be inversely related to the intensity of inflammatory infiltrate. On the contrary, when mast cells do not express anti-inflammatory cytokines their number should be directly related to the intensity of the inflammatory infiltrate. In this paper we briefly argue around feasible approaches, based on the retrospective studies of tumor tissue samples from neoplasms considered "immunologically hot" and neoplasms considered "immunologically cold", through immunohistochemistry and immunofluorescence techniques (confocal microscopy). The establishment of the actual existence of a polarization interchange of mast cells, could lead to a new vision in prognostic terms, useful to contrive new approaches in immunotherapy of tumors.


Assuntos
Citocinas/biossíntese , Mastócitos/imunologia , Modelos Imunológicos , Neoplasias/imunologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Antígenos de Neoplasias/análise , Contagem de Células , Regulação Neoplásica da Expressão Gênica/imunologia , Humanos , Imunoquímica , Inflamação , Linfócitos do Interstício Tumoral/química , Macrófagos/química , Mastócitos/metabolismo , Mastócitos/ultraestrutura , Microscopia Confocal , Neoplasias/química , Neoplasias/ultraestrutura , Inclusão em Parafina , Proteínas Proto-Oncogênicas c-kit/análise , Receptores de Superfície Celular/análise , Projetos de Pesquisa , Estudos Retrospectivos
11.
PLoS Negl Trop Dis ; 13(8): e0007623, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31425508

RESUMO

BACKGROUND: Susceptibility to HIV has been linked to systemic CD4+ T cell activation in cohorts of seronegative individuals with high HIV-exposure risk. We recently described an increased risk of HIV transmission in individuals infected with Wuchereria bancrofti, the causative agent for lymphatic filariasis, in a prospective cohort study. However, the reason for this phenomenon needs further investigation. METHODOLOGY/PRINCIPAL FINDINGS: Two-hundred and thirty-five HIV negative adults were tested using Trop Bio ELISA for detection of W. bancrofti infection and Kato Katz urine filtration and stool based RT-PCR for detection of soil transmitted helminths and schistosomiasis. FACS analysis of the fresh peripheral whole blood was used to measure T cell activation markers (HLA-DR, CD38), differentiation markers (CD45, CD27), markers for regulatory T cells (FoxP3, CD25) and the HIV entry receptor CCR5. Frequencies of activated HLA-DRpos CD4 T cells were significantly increased in subjects with W. bancrofti infection (n = 33 median: 10.71%) compared to subjects without any helminth infection (n = 42, median 6.97%, p = 0.011) or those with other helminths (Schistosoma haematobium, S. mansoni, Trichuris trichiura, Ascaris lumbricoides, hookworm) (n = 151, median 7.38%, p = 0.009). Similarly, a significant increase in HLA-DRposCD38pos CD4 T cells and effector memory cells CD4 T cells (CD45ROposCD27neg) was observed in filarial infected participants. Multivariable analyses further confirmed a link between W. bancrofti infection and systemic activation of CD4 T cells independent of age, fever, gender or other helminth infections. CONCLUSIONS/SIGNIFICANCE: W. bancrofti infection is linked to systemic CD4 T cell activation, which may contribute to the increased susceptibility of W. bancrofti infected individuals to HIV infection.


Assuntos
Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Filariose Linfática/patologia , Ativação Linfocitária , Subpopulações de Linfócitos T/imunologia , Wuchereria bancrofti/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Animais , Antígenos CD/análise , Linfócitos T CD4-Positivos/química , Linfócitos T CD8-Positivos/química , Filariose Linfática/imunologia , Feminino , Citometria de Fluxo , Antígenos HLA-DR/análise , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Subpopulações de Linfócitos T/química , Adulto Jovem
12.
Biosens Bioelectron ; 141: 111209, 2019 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-31357174

RESUMO

Enhancing the efficiency of antibody protein immobilized on a silicon nanowire-based chip for their antigens detection is reported. An external electric field (EEF) is applied to direct the orientation of antibodies during their immobilization on a chip. Atomic force microscopy (AFM) is used to measure the binding forces between immobilized antibody and targeting antigen under the influence of EEF at different angles. The maximum binding force under a specific angle (optimal angle; oa) of EEF (maxEEFoa) implies the optimal orientation of the antibodies on the chip. In this report, two different cancer carcinoembryonic antigen (CEA)-related cell adhesion molecules 5 (CEACAM5) & 1 (CEACAM1) were used for the examples of disease antigen detection. maxEEFoa of anti-CEACAM5 or anti-CEACAM1 immobilized on a general chip was firstly determined. Spectroscopy of AFM revealed that both binding forces were the largest ones with their antigens when maxEEFoa was applied as compared with no or other angles of EEF. These antibody proteins accompanied with the application of EEF were secondly immobilized on silicon-nanowires (n = 1000) and the field effects were measured (∆I) as their target antigens were approached. Results showed that ∆I was the largest ones when maxEEFoas (225°/270° and 135°/180° for anti-CEACAM5 and anti-CEACAM1, respectively) were applied as compared with other angles of EEF. These observations imply that the silicon nanowires together with the application of maxEEFoa as detection tools could be applied for the cancer diagnostics in the future.


Assuntos
Anticorpos Imobilizados/química , Antígenos CD/análise , Técnicas Biossensoriais/instrumentação , Antígeno Carcinoembrionário/análise , Moléculas de Adesão Celular/análise , Nanofios/química , Silício/química , Desenho de Equipamento , Proteínas Ligadas por GPI/análise , Humanos , Análise Serial de Proteínas/instrumentação
13.
Clin Exp Nephrol ; 23(10): 1202-1210, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31240503

RESUMO

INTRODUCTION: In sarcoidosis, renal involvement includes hypercalcemia-related nephrocalcinosis and granulomatous tubulointerstitial nephritis. Hypercalcemia is thought to be due to increased production of 1,25 dihydroxyvitamin D (1-25D), but 1-25D levels have not been evaluated in sarcoidosis patients with renal dysfunction. MATERIALS AND METHODS: We enrolled 9 sarcoidosis patients who underwent renal biopsy, and compared the serum 1-25D concentration and eGFR with those in 428 non-sarcoidosis patients who had renal dysfunction (stage 2 or higher CKD with an estimated glomerular filtration rate < 90). RESULTS: Serum calcium and 1-25D levels were significantly higher in the sarcoidosis patients than in the non-sarcoidosis patients (p < 0.01 and p = 0.01, respectively). There was a positive correlation between 1-25D and eGFR in the patients without sarcoidosis (r = 0.693; p < 0.01). As the renal function of sarcoidosis patients was improved by steroid therapy, the serum 1-25D and adjusted serum calcium levels decreased to near the median values in non-sarcoidosis patients. On renal biopsy, CD68 staining was positive for tissue macrophages in all 8 patients who had tubulointerstitial nephritis (with or without typical granulomas), while Von Kossa staining showed calcification of tubules near or inside granulomas in 6 of these 8 patients. CONCLUSION: While tissue macrophages promote development of tubulointerstitial nephritis and 1-25D overproduction in renal sarcoidosis, hypercalcemia secondary to elevation of 1-25D may be related to renal calcification and granuloma formation.


Assuntos
24,25-Di-Hidroxivitamina D 3/sangue , Hipercalcemia/sangue , Nefropatias/sangue , Sarcoidose/sangue , Adulto , Idoso , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Biópsia , Cálcio/sangue , Estudos de Coortes , Feminino , Taxa de Filtração Glomerular , Humanos , Hipercalcemia/etiologia , Rim/patologia , Nefropatias/complicações , Nefropatias/patologia , Macrófagos/patologia , Masculino , Pessoa de Meia-Idade , Nefrite Intersticial/sangue , Nefrite Intersticial/patologia , Estudos Retrospectivos , Sarcoidose/complicações , Sarcoidose/tratamento farmacológico , Esteroides/uso terapêutico , Adulto Jovem
14.
Virchows Arch ; 475(3): 357-364, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31218404

RESUMO

Chronic intervillositis of unknown etiology (CIUE) is a rare placental lesion associated with infiltration of mononuclear inflammatory cells into the intervillous space, poor perinatal outcomes (intrauterine fetal demise or fetal growth restriction), and high rates of recurrence. CD39 is the ectonucleotidase that protects tissues from inflammatory stress and cell injury, which is localized on the surface of villi in normal placentas; however, its expression and role in CIUE are unknown. The aims of this retrospective study were to determine the expression of CD39 in CIUE and its significance in pregnancy outcomes. We compared the number of CD68- and CD3-positive cells, CD39 expression, and complement 4d (C4d) and fibrin deposition in placental tissues from patients with CIUE (n = 22) and gestational age-matched controls (n = 20), and between CIUE pregnancies with poor and good outcomes. The numbers of CD68- or CD3-positive cells were significantly higher (P < 0.0001), whereas CD39 expression on the surface of villi and endothelial cells of the stem villi was significantly lower in the CIUE group than that in controls (45% vs. 95%, P < 0.0001 and 77% vs. 96%, P < 0.001, respectively). C4d and fibrin deposition were also significantly increased in CIUE compared with those of controls. Furthermore, CD39 downregulation and the number of CD68 cells were strongly associated with poor pregnancy outcomes (P < 0.01 and P < 0.05, respectively), but other histological parameters (CD3, C4d, and fibrin) did not show this association. Our study suggests that CD39 downregulation is a useful marker of CIUE and is associated with poor pregnancy outcomes in patients with CIUE.


Assuntos
Apirase/metabolismo , Doenças Placentárias/patologia , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Apirase/fisiologia , Complexo CD3/análise , Vilosidades Coriônicas/patologia , Regulação para Baixo , Células Endoteliais/patologia , Feminino , Retardo do Crescimento Fetal/patologia , Humanos , Placenta/patologia , Doenças Placentárias/metabolismo , Gravidez , Resultado da Gravidez/epidemiologia , Recidiva , Estudos Retrospectivos
15.
Mol Med Rep ; 20(1): 633-639, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31180542

RESUMO

Mesenchymal stem cells (MSCs) are derived from the mesoderm and have the self­renewal capacity and multi­directional differentiation potential of adult stem cells. Stem cells from different sources have different molecular and growth characteristics; therefore, the mechanisms and effects of stem cell­mediated repair and tissue regeneration may be different. The aim of the present study was to compare the biological characteristics of MSCs derived from the umbilical cord (UC­MSCs) and MSCs derived from the decidua parietalis (DP­MSCs), and to provide new evidence for the selection of seed cells in regenerative medicine. Growth curves, cell doubling times, colony formation rates, immunophenotypes, differentiation capacities and secretion­factor levels of MSCs derived from the two sources were analysed. UC­MSCs and DP­MSCs exhibited similar properties with regards to morphology, spiral growth, immunophenotype, and potential to differentiate into osteoblasts and adipocytes. For each cell type, the positive rates of the cell surface markers CD73, CD90 and CD105 were >95%, whereas CD34 and CD45 positive rates were <1%. Analyses of in vitro growth kinetics revealed shorter cell­doubling times, and higher proliferative rates and colony formation rates of UC­MSCs compared with DP­MSCs (P<0.05). The concentration of basic fibroblast growth factor in the supernatant from UC­MSCs was higher compared with that from DP­MSCs (P<0.05). However, UC­MSC supernatants exhibited lower levels of of keratinocyte growth factor, vascular endothelial growth factor and stem cell factor compared with DP­MSCs (P<0.05). In conclusion, in vitro characterization of MSCs from these tissue sources revealed a number of common biological properties. However, the results also demonstrated clear biological distinctions and suggested that UC­MSCs may have more effective application prospects.


Assuntos
Decídua/citologia , Células-Tronco Mesenquimais/citologia , Cordão Umbilical/citologia , Adipogenia , Antígenos CD/análise , Proliferação de Células , Células Cultivadas , Citocinas/análise , Feminino , Humanos , Imunofenotipagem , Osteogênese
16.
Acta Histochem ; 121(5): 657-663, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31153587

RESUMO

The prognostic significance and clinical implications of resident CD103+CD8+T cells in human colorectal cancer tissues still remains largely unexplored. In our present study, we aimed to characterize the resident CD8+T cells in human colorectal cancer tissues by using double staining of CD103 and CD8, and further evaluated the prognostic significance of resident CD8+T cells in colorectal cancer. We found that the OS rate of the colorectal cancer patients with higher infiltration of CD8+T cells, or with higher numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues was significantly better than that of the patients with lower infiltration of CD8+T cells, or with lower numbers of resident CD103+CD8+T cells, or with higher ratio of CD103+CD8+T cells over total CD8+T cells in cancer tissues, respectively. Moreover, higher infiltration of CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with advanced TNM stage. Higher numbers of resident CD103+CD8+T cells in colorectal cancer tissues were significantly and inversely correlated with distant metastasis status. Higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues was significantly and inversely correlated with age status. The COX model analysis demonstrated that higher infiltration of CD8+T cells, higher numbers of resident CD103+CD8+T cells, or higher ratio of CD103+CD8+T cells over total CD8+T cells in colorectal cancer tissues, could serve as independent prognostic predictors for colorectal cancer patients. Taken together, our present study demonstrated the density of tumor infiltrating CD8+T cells or the numbers of resident CD103+CD8+T cells in colorectal tissues could be used as an important prognostic predictor for this malignancy.


Assuntos
Antígenos CD/análise , Linfócitos T CD8-Positivos , Neoplasias Colorretais/mortalidade , Cadeias alfa de Integrinas/análise , Linfócitos do Interstício Tumoral , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD/metabolismo , Antígenos CD8/metabolismo , Neoplasias Colorretais/imunologia , Neoplasias Colorretais/patologia , Feminino , Humanos , Cadeias alfa de Integrinas/metabolismo , Masculino , Pessoa de Meia-Idade , Taxa de Sobrevida , Subpopulações de Linfócitos T
17.
Cells ; 8(5)2019 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-31035565

RESUMO

Nucleated teleost red blood cells (RBCs) are known to express molecules from the major histocompatibility complex and peptide-generating processes such as autophagy and proteasomes, but the role of RBCs in antigen presentation of viruses have not been studied yet. In this study, RBCs exposed ex vivo to viral hemorrhagic septicemia virus (VHSV) were evaluated by means of transcriptomic and proteomic approaches. Genes and proteins related to antigen presentation molecules, proteasome degradation, and autophagy were up-regulated. VHSV induced accumulation of ubiquitinated proteins in ex vivo VHSV-exposed RBCs and showed at the same time a decrease of proteasome activity. Furthermore, induction of autophagy was detected by evaluating LC3 protein levels. Sequestosome-1/p62 underwent degradation early after VHSV exposure, and it may be a link between ubiquitination and autophagy activation. Inhibition of autophagosome degradation with niclosamide resulted in intracellular detection of N protein of VHSV (NVHSV) and p62 accumulation. In addition, antigen presentation cell markers, such as major histocompatibility complex (MHC) class I & II, CD83, and CD86, increased at the transcriptional and translational level in rainbow trout RBCs exposed to VHSV. In summary, we show that nucleated rainbow trout RBCs can degrade VHSV while displaying an antigen-presenting cell (APC)-like profile.


Assuntos
Apresentação do Antígeno/imunologia , Eritroblastos/imunologia , Eritroblastos/virologia , Septicemia Hemorrágica Viral/imunologia , Septicemia Hemorrágica Viral/virologia , Novirhabdovirus/imunologia , Oncorhynchus mykiss/imunologia , Oncorhynchus mykiss/virologia , Animais , Apresentação do Antígeno/genética , Células Apresentadoras de Antígenos/citologia , Células Apresentadoras de Antígenos/imunologia , Antígenos CD/análise , Antígenos CD/imunologia , Autofagossomos/efeitos dos fármacos , Autofagossomos/imunologia , Autofagossomos/virologia , Autofagia/efeitos dos fármacos , Autofagia/imunologia , Antígeno B7-2/análise , Antígeno B7-2/imunologia , Biomarcadores/análise , Septicemia Hemorrágica Viral/genética , Antígenos de Histocompatibilidade Classe I/análise , Antígenos de Histocompatibilidade Classe I/imunologia , Antígenos de Histocompatibilidade Classe II/análise , Antígenos de Histocompatibilidade Classe II/imunologia , Imunoglobulinas/análise , Imunoglobulinas/imunologia , Glicoproteínas de Membrana/análise , Glicoproteínas de Membrana/imunologia , Niclosamida/farmacologia , Proteínas do Nucleocapsídeo , Complexo de Endopeptidases do Proteassoma/efeitos dos fármacos , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteólise , Proteômica , Proteína Sequestossoma-1/metabolismo
18.
Braz Oral Res ; 33: e047, 2019 May 27.
Artigo em Inglês | MEDLINE | ID: mdl-31141038

RESUMO

The aim of this study was to evaluate macrophage M1 and M2 subpopulations in radicular cysts (RCs) and periapical granulomas (PGs) and relate them to clinical and morphological aspects. M1 macrophages were evaluated by the percentage of CD68 immunostaining associated with the inflammatory cytokine TNF-α, and M2 macrophages, by its specific CD163 antibody. The CD68+/CD163+ ratio was adopted to distinguish between the two macrophage subpopulations. Clinical, radiographic, symptomatology, treatment, and morphological parameters of lesions were collected and a significance level of p = 0.05 was adopted for statistical analysis. The results showed that the CD68+/CD163+ ratio was higher in the RCs (median = 1.22, p = 0.002), and the highest TNF-α immunostaining scores were found in RCs (p = 0.018); in PGs, the CD68+/CD163+ ratio was lower and associated with a greater CD163+ immunostaining (median = 1.02, p <0.001). The TNF-α in cyst epithelium had a score of 3 in 10 cases and predominance of M1 macrophages by CD68+/CD163+ (median = 2.23). In addition, CD68+ cells had higher percentage of immunostaining in smaller RCs (p = 0.034). Our findings suggest that increased CD68 immunostaining associated with TNF-α cytokine in RCs results in a greater differentiation of the M1 phenotype. The higher CD163 immunostaining in PGs results in greater differentiation of the M2 phenotype. Therefore, the inflammatory state promoted by M1 macrophages is related to growth and progression of RCs; on the other hand, the immunomodulatory state of M2 macrophages is related to maintenance of PGs.


Assuntos
Macrófagos/patologia , Granuloma Periapical/patologia , Cisto Radicular/patologia , Adulto , Antígenos CD/análise , Antígenos de Diferenciação Mielomonocítica/análise , Doença Crônica , Feminino , Humanos , Imuno-Histoquímica , Masculino , Pessoa de Meia-Idade , Receptores de Superfície Celular/análise , Valores de Referência , Estatísticas não Paramétricas , Fator de Necrose Tumoral alfa/análise
19.
Thromb Res ; 180: 1-9, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31146120

RESUMO

BACKGROUND: Immune thrombocytopenia (ITP) is an immune-mediated bleeding disorder in children. Activated T cells have been shown to play important roles in ITP. The aims of this study were to evaluate whether these T cell activation markers could be used as indicators to differentiate ITP patients from controls, and to assess whether they could be used as predictors of IVIG response in ITP patients. METHODS: A cohort of 92 hospitalized ITP patients, 49 unrelated healthy children, and 48 thrombocytosis patients were enrolled in this retrospective study between February 2013 and September 2018. Expression of CD25, HLA-DR, and CD69 on the surfaces of CD4+ and CD8+ T cells were detected by flow cytometry. All statistical analyses were performed using SPSS 20.0 software. RESULTS: Compared to the healthy controls, ITP patients had higher percentages of CD4 + CD25+ T cells, CD4 + HLA-DR+ T cells, CD8 + HLA-DR+ T cells, and CD8 + CD69+ T cells. Compared to the thrombocytosis patients, ITP patients had higher percentages of CD4 + HLA-DR+ T cells and CD8 + HLA-DR+ T cells, and lower CD4 + CD69+ T cells and CD8 + CD69+ T cells. Platelet count at admission had a negative correlation with CD4 + CD25+ T cells in ITP. CD4 + CD69+ T cells were decreased in chronic compared to the newly diagnosed and persistent ITP patients. Activated T cell markers had no predictive value for IVIG response in ITP patients. CONCLUSIONS: T cell activation markers were excessively expressed in pediatric ITP, and those markers had no predictive value for IVIG response in ITP patients.


Assuntos
Ativação Linfocitária , Púrpura Trombocitopênica Idiopática/imunologia , Linfócitos T/imunologia , Adolescente , Antígenos CD/análise , Antígenos de Diferenciação de Linfócitos T/análise , Antígenos CD4/análise , Criança , Pré-Escolar , Doença Crônica , Feminino , Antígenos HLA-DR/análise , Humanos , Imunoglobulinas Intravenosas/uso terapêutico , Lactente , Lectinas Tipo C/análise , Masculino , Púrpura Trombocitopênica Idiopática/diagnóstico , Púrpura Trombocitopênica Idiopática/terapia , Linfócitos T/patologia , Trombocitose/diagnóstico , Trombocitose/imunologia
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