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1.
Curr Issues Mol Biol ; 46(7): 7065-7085, 2024 Jul 05.
Artículo en Inglés | MEDLINE | ID: mdl-39057062

RESUMEN

Micro-RNAs (miRNAs) are non-coding RNAs with importance in the development of cancer. They are involved in both tumor development and immune processes in tumors. The present study aims to characterize the behavior of two miRNAs, the proinflammatory miR-326-5p and the anti-inflammatory miR-146a-5p, in colorectal cancer (CRC), to decipher the mechanisms that regulate their expression, and to study potential applications. Tissue levels of miR-326-5p and miR-146a-5p were determined by qrt-PCR (real-time quantitative reverse transcription polymerase chain reaction) in 45 patients with colorectal cancer in tumoral and normal adjacent tissue. Subsequent bioinformatic analysis was performed to characterize the transcriptional networks that control the expression of the two miRNAs. The biomarker potential of miRNAs was assessed. The expression of miR-325-5p and miR-146a-5p was decreased in tumors compared to normal tissue. The two miRNAs are regulated through a transcriptional network, which originates in the inflammatory and proliferative pathways and regulates a set of cellular functions related to immunity, proliferation, and differentiation. The miRNAs coordinate distinct modules in the network. There is good biomarker potential of miR-326 with an AUC (Area under the curve) of 0.827, 0.911 sensitivity (Sn), and 0.689 specificity (Sp), and of the combination miR-326-miR-146a, with an AUC of 0.845, Sn of 0.75, and Sp of 0.89. The miRNAs are downregulated in the tumor tissue. They are regulated by a transcriptional network in which they coordinate distinct modules. The structure of the network highlights possible therapeutic approaches. MiR-326 and the combination of the two miRNAs may serve as biomarkers in CRC.

2.
Curr Issues Mol Biol ; 45(2): 975-989, 2023 Jan 20.
Artículo en Inglés | MEDLINE | ID: mdl-36826008

RESUMEN

MicroRNAs (miRNAs) are molecules with a role in the post-transcriptional regulation of messenger RNA, being involved in a wide range of biological and pathological processes. In the present study, we aim to characterize the behavior of a few miRNAs with roles in the cell cycle and differentiation of colon cancer (CC) cells. The present work considers miRNAs as reflections of the complex cellular processes in which they are generated, their observed variations being used to characterize the molecular networks in which they are part and through which cell proliferation is achieved. Tumoral and adjacent normal tissue samples were obtained from 40 CC patients, and the expression of miR-29a, miR-146a, miR-215 and miR-449 were determined by qRT-PCR analysis. Subsequent bioinformatic analysis was performed to highlight the transcription factors (TFs) network that regulate the miRNAs and functionally characterizes this network. There was a significant decrease in the expression of all miRNAs in tumor tissue. All miRNAs were positively correlated with each other. The analysis of the TF network showed tightly connected functional modules related to the cell cycle and associated processes. The four miRNAs are downregulated in CC; they are strongly correlated, showing coherence within the cellular network that regulates them and highlighting possible approach strategies.

3.
Medicina (Kaunas) ; 57(4)2021 Mar 24.
Artículo en Inglés | MEDLINE | ID: mdl-33804963

RESUMEN

Background: Establishing the diagnosis of COVID-19 and Pneumocystisjirovecii pulmonary coinfection is difficult due to clinical and radiological similarities that exist between the two disorders. For the moment, fungal coinfections are underestimated in COVID-19 patients. Case presentation: We report the case of a 52-year-old male patient, who presented to the emergency department for severe dyspnea and died 17 h later. The RT-PCR test performed at his admission was negative for SARS-CoV-2. Retesting of lung fragments collected during autopsy revealed a positive result for SARS-CoV-2. Histopathological examination showed preexisting lesions, due to comorbidities, as well as recent lesions: massive lung thromboses, alveolar exudate rich in foam cells, suprapleural and intra-alveolar Pneumocystisjirovecii cystic forms, and bilateral adrenal hemorrhage. Conclusion: COVID-19 and P.jirovecii coinfection should be considered, particularly in critically ill patients, and we recommend the systematic search for P. jirovecii in respiratory samples.


Asunto(s)
COVID-19/patología , Pulmón/patología , Neumonía por Pneumocystis/patología , Insuficiencia Respiratoria/patología , Trombosis/patología , Lesión Renal Aguda/complicaciones , Insuficiencia Hepática Crónica Agudizada/complicaciones , Enfermedades de las Glándulas Suprarrenales/complicaciones , Enfermedades de las Glándulas Suprarrenales/patología , Autopsia , COVID-19/complicaciones , Coinfección/patología , Exudados y Transudados , Resultado Fatal , Fibrosis , Células Espumosas/patología , Hemorragia/complicaciones , Hemorragia/patología , Humanos , Hipertensión/complicaciones , Hepatopatías Alcohólicas/complicaciones , Masculino , Persona de Mediana Edad , Isquemia Miocárdica/complicaciones , Neumonía por Pneumocystis/complicaciones , Arteria Pulmonar/patología , Venas Pulmonares/patología , Insuficiencia Respiratoria/etiología , SARS-CoV-2 , Trombosis/etiología
4.
Molecules ; 25(20)2020 Oct 14.
Artículo en Inglés | MEDLINE | ID: mdl-33066472

RESUMEN

Metals are considered to be one of the most hazardous substances due to their potential for accumulation, magnification, persistence, and wide distribution in water, sediments, and aquatic organisms. Demersal fish species, such as turbot (Psetta maxima maeotica), are accepted by the scientific communities as suitable bioindicators of heavy metal pollution in the aquatic environment. The present study uses a machine learning approach, which is based on multiple linear and non-linear models, in order to effectively estimate the concentrations of heavy metals in both turbot muscle and liver tissues. For multiple linear regression (MLR) models, the stepwise method was used, while non-linear models were developed by applying random forest (RF) algorithm. The models were based on data that were provided from scientific literature, attributed to 11 heavy metals (As, Ca, Cd, Cu, Fe, K, Mg, Mn, Na, Ni, Zn) from both muscle and liver tissues of turbot exemplars. Significant MLR models were recorded for Ca, Fe, Mg, and Na in muscle tissue and K, Cu, Zn, and Na in turbot liver tissue. The non-linear tree-based RF prediction models (over 70% prediction accuracy) were identified for As, Cd, Cu, K, Mg, and Zn in muscle tissue and As, Ca, Cd, Mg, and Fe in turbot liver tissue. Both machine learning MLR and non-linear tree-based RF prediction models were identified to be suitable for predicting the heavy metal concentration from both turbot muscle and liver tissues. The models can be used for improving the knowledge and economic efficiency of linked heavy metals food safety and environment pollution studies.


Asunto(s)
Peces Planos , Aprendizaje Automático , Metales Pesados/análisis , Metales Pesados/farmacocinética , Contaminantes Químicos del Agua/análisis , Animales , Bioacumulación , Biomarcadores Ambientales , Monitoreo del Ambiente/métodos , Europa (Continente) , Modelos Lineales , Hígado/efectos de los fármacos , Hígado/metabolismo , Músculo Esquelético/efectos de los fármacos , Músculo Esquelético/metabolismo , Dinámicas no Lineales , Contaminantes Químicos del Agua/farmacocinética
5.
Immunol Invest ; 43(3): 267-77, 2014.
Artículo en Inglés | MEDLINE | ID: mdl-24354887

RESUMEN

BACKGROUND: Oral tolerance is the biological process explaining the non-responsiveness of gut lymphoid tissue to intestinal content. Our study tested a new approach for the enhancement of oral tolerance to a multiple sclerosis-triggering auto-antigen-myelin basic protein, by its oral administration with the Staphylococcal enterotoxin A. METHODS: Immune tolerance thus stimulated was assessed in adult BALB/c mice, by measuring different cytokines from the supernatant of mesenteric lymph nodes cells (IFN-γ, IL-4, IL-10, IL-17, and TGF-ß), and in a SJL/E mouse model of experimental autoimmune encephalomyelitis, by evaluating the development of regulatory T cells in mesenteric lymph nodes and the clinical outcome of the intervention. RESULTS: We obtained a significant rise in the levels of IL-10 and TGF-ß compared with control and a significant decrease of IFN-γ, IL-4 (p < 0.05). Regulatory T cells were increased compared with control (p < 0.05). These results were attributable both to myelin basic protein and to Staphylococcal enterotoxin A. The clinical outcome of experimental autoimmune encephalomyelitis was influenced only by the administration of myelin basic protein. CONCLUSION: In our experiment, Staphylococcal enterotoxin A enhanced the immune tolerance to myelin basic protein in the gut mucosa, but had no impact on the clinical evolution of experimental autoimmune encephalomyelitis.


Asunto(s)
Encefalomielitis Autoinmune Experimental/inmunología , Enterotoxinas/inmunología , Ganglios Linfáticos/inmunología , Subgrupos de Linfocitos T/inmunología , Linfocitos T Reguladores/inmunología , Administración Oral , Animales , Células Cultivadas , Citocinas/metabolismo , Progresión de la Enfermedad , Tolerancia Inmunológica , Inmunomodulación , Recuento de Linfocitos , Ratones , Ratones Endogámicos BALB C , Proteína Básica de Mielina/inmunología
6.
Cancers (Basel) ; 16(4)2024 Feb 10.
Artículo en Inglés | MEDLINE | ID: mdl-38398137

RESUMEN

This research investigated the serum levels of three interleukins (IL8, IL17A, and IL33) and the possible relationships between them in healthy people and colon cancer patients at different stages. This study involved 82 participants, 42 of whom had colon cancer and 40 were healthy individuals. The cancer patients were classified into four groups according to the TNM staging classification of colon and rectal cancer. Serum levels of the interleukins were measured by the ELISA test. The data were analyzed statistically to compare the demographic characteristics, the interleukin levels across cancer stages, and the correlation between interleukins in both groups. The results showed that women had more early-stage colon cancer diagnoses, while men had more advanced-stage cancer diagnoses. Stage two colon cancer was more common in older people. Younger people, men, and those with early-stage colon cancer had higher levels of interleukins. The levels of IL8 and IL17A were higher in the cancer group, while the level of IL33 was higher in the healthy group. There was a strong correlation between IL8 and IL17A levels in both groups (p = 0.001). IL17A influenced the level of IL33 in the cancer group (p = 0.007). This study suggested that cytokine variation profiles could be useful for detecting colon cancer and predicting its outcome.

7.
Cancers (Basel) ; 16(12)2024 Jun 20.
Artículo en Inglés | MEDLINE | ID: mdl-38927989

RESUMEN

Early diagnosis and prognosis of cancer progression through biomarker profiling are crucial in managing colon cancer patients. Our research aimed to investigate the expression of miR-101-3p, miR-106a-5p, and miR-326 in tumor and adjacent healthy tissues of colon cancer patients and determine their potential diagnostic utility. This study included 40 patients divided into four groups according to the TNM staging classification. MiRNA expression was analyzed using qRT-PCR. The results showed that miR-101-3p, miR-106a-5p, and miR-326 are overexpressed in adjacent healthy tissues but decrease in advanced cancer stages. MiR-106a-5p and miR-326 are strongly correlated with colon cancer severity. These findings suggest that miRNA profiling could be useful for early diagnosis and prognosis in colon cancer management.

8.
Oncol Lett ; 24(3): 323, 2022 Sep.
Artículo en Inglés | MEDLINE | ID: mdl-35949613

RESUMEN

Colorectal cancer (CRC) remains a major cause of cancer-related mortality. Consequently, new diagnostic and therapeutic approaches are being investigated including the serum levels of cytokines and other molecules, although the results are often inconclusive. Thus, the present study aimed to determine whether serum level of cytokines, cell adhesion molecules or matrix metalloproteinases (MMPs), alone or in combination, may contribute to the non-invasive diagnosis of CRC. The serum levels of nine cytokines [ILs; IL-1ß, IL-4, IL-6, IL-8, IL-10, IL-17, IL-22 and IL-33, and interferon (IFN)-γ], two cell adhesion molecules (intercellular adhesion molecule-1 and P-selectin) and an MMP-7 were measured by ELISA in 33 patients with CRC and 35 healthy controls. Combined capacity of all molecules to detect the presence of CRC was assessed by logistic regression. Molecules and molecule combinations were tested for all stages and tumor grades. A significant increase was identified for IL-8 in patients compared with healthy controls; IL-10 was found to be significantly decreased. The biomarker potential of each significantly modified molecule was tested: IL-8 had a sensitivity of 0.865, a specificity of 0.600 and an area under the curve (AUC) of 0.777; for IL-10, sensitivity was 0.65, specificity was 0.69, with an AUC of 0.689. Logistic regression determined the best discriminative potential between patients and control groups for the combination IL-4 + IL-6 + IL-8 + IFN-γ, with 0.97 sensitivity and 0.58 specificity. For the early stages of CRC, the combination IL-6 + IL-8 + IL-22 showed good performance. It was concluded that increased IL-8 had potential as single biomarker in CRC. Cytokine combinations are superior to single cytokine analysis in showing the presence of CRC.

9.
Clin Chem Lab Med ; 50(1): 125-8, 2011 Sep 17.
Artículo en Inglés | MEDLINE | ID: mdl-21923476

RESUMEN

BACKGROUND: Matrix Gla-protein (MGP) is a calcification inhibitor produced by cartilage and vessel walls. Arthritis is defined by inflammation, cartilage and bone destruction/formation and articular calcifications. Our objectives were to evaluate ucMGP levels in synovial fluid (SF) in arthritis patients and to investigate the relationship between local and circulating ucMGP and their association with age and inflammation. METHODS: Arthritis patients (n=26) with knee joint effusion and controls (n=30) underwent an ultrasonographic knee examination for articular calcifications assessment. Patients were divided into inflammatory and non-inflammatory groups. ucMGP levels were determined in serum and SF using a competitive ELISA assay. RESULTS: Within the arthritis patients, the inflammatory group had the lowest ucMGP serum levels, and the highest levels of synovial ucMGP. Furthermore, the inflammatory group had significantly (p<0.05) higher RucMGP (synovial ucMGP/serum ucMGP*100) than the non-inflammatory group [36 (17-69) vs. 24 (5-55)], and this parameter positively correlated (r=0.4; p<0.05) with the erythrocyte sedimentation rate (ESR). No correlation was found between age and local or circulating ucMGP in patients and controls. CONCLUSIONS: The ucMGP assay can be used for determination of MGP in SF, and combined assessment of ucMGP in serum and SF could potentially serve as a joint inflammatory marker in arthritis patients.


Asunto(s)
Artritis/sangre , Proteínas de Unión al Calcio/análisis , Proteínas de la Matriz Extracelular/análisis , Líquido Sinovial/química , Adulto , Factores de Edad , Anciano , Artritis Reumatoide/sangre , Artritis Reumatoide/inmunología , Biomarcadores/sangre , Proteínas de Unión al Calcio/sangre , Estudios Transversales , Proteínas de la Matriz Extracelular/sangre , Femenino , Humanos , Inflamación/sangre , Masculino , Persona de Mediana Edad , Enfermedades Musculoesqueléticas/sangre , Proteína Gla de la Matriz
10.
Clin Lab ; 57(9-10): 695-701, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22029184

RESUMEN

BACKGROUND: According to the 2008 celiac disease working group run by Dr. A. Fassano under the auspices of the Federation of International Societies of Pediatric Gastroenterology, Hepatology and Nutrition, celiac disease is a chronic immune-mediated enteropathy characterized by gluten sensitivity, which can affect any organ or system, having a wide range of clinical manifestations of variable severity. The serological diagnosis of celiac disease is based on high sensitivity and specificity tests. The measurement of IgA anti-tissue transglutaminase antibodies by ELISA is universally accepted in the screening of celiac disease. METHODS: Using the gold standard represented by IgA anti-endomysium antibodies in a group of 890 children investigated during 2008-2009, we aimed to evaluate IgA anti-tissue transglutaminase antibodies (tTG IgA), as well as to establish their prevalence in associated diseases. RESULTS: Following the measurement of tTG IgA in the entire group, we obtained: sensitivity 773%, positive predictive value 55.2%, specificity 93.1%, negative predictive value 973%, p = 0.000, and in tTG IgA associations we obtained the value 0.51 for the ROC curve area. We found associations of tTG IgA with type 1 diabetes mellitus (235% prevalence), protein-calorie malnutrition (0.89% prevalence), and intestinal malabsorption (0.56% prevalence). CONCLUSIONS: Our results have a high specificity and sensitivity in the screening of celiac disease, while requiring a second method of confirmation.


Asunto(s)
Enfermedad Celíaca/diagnóstico , Transglutaminasas/inmunología , Área Bajo la Curva , Autoanticuerpos/análisis , Enfermedad Celíaca/sangre , Enfermedad Celíaca/epidemiología , Niño , Trastornos de la Nutrición del Niño/sangre , Trastornos de la Nutrición del Niño/diagnóstico , Trastornos de la Nutrición del Niño/epidemiología , Comorbilidad , Diabetes Mellitus Tipo 1/sangre , Diabetes Mellitus Tipo 1/diagnóstico , Diabetes Mellitus Tipo 1/epidemiología , Ensayo de Inmunoadsorción Enzimática , Femenino , Humanos , Inmunoglobulina A/análisis , Síndromes de Malabsorción/sangre , Síndromes de Malabsorción/diagnóstico , Síndromes de Malabsorción/epidemiología , Masculino , Tamizaje Masivo/métodos , Valor Predictivo de las Pruebas , Prevalencia , Desnutrición Proteico-Calórica/sangre , Desnutrición Proteico-Calórica/diagnóstico , Desnutrición Proteico-Calórica/epidemiología , Curva ROC , Rumanía
11.
Roum Arch Microbiol Immunol ; 70(3): 97-100, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22570921

RESUMEN

Worldwide, viral hepatitis chronic infections are a serious health problem and a very interesting topic for both clinicians and researchers. Viral hepatitis has a variety of clinical forms: mild, inactive or severe and with a slow evolution, whose architectural structure of the hepatic tissue evolves towards cirrhosis or hepatocellular carcinoma. Sometimes, the virally induced hepatic injury evolves spectacularly and rapidly leads to exitus. The factors that generate this evolution pattern depend on the immune response of the host and equally on the viral survival and immune surveillance avoidance strategies. This paper aims to resume new discoveries in the field of immunology of the B and C viral hepatitis infection, from the perspective of the complex interactions between virus and host.


Asunto(s)
Hepatitis B/inmunología , Hepatitis C/inmunología , Biomarcadores , Moléculas de Adhesión Celular/análisis , Progresión de la Enfermedad , Humanos , Metaloproteinasas de la Matriz/análisis
12.
Roum Arch Microbiol Immunol ; 70(3): 124-8, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22570926

RESUMEN

The importance of chronic inflammation in atherogenesis and cytokine involvement in all stages of atherosclerotic plaque development is now obvious. Our approach of the significant cytokines involved in atherogenesis or cardiovascular diseases is based on a correlation between clinical research and experiments on animal models. The contribution of IL-17 in atherogenesis remains controversial. In this study we investigated the role of IL-17 in cardiovascular diseases and in atherosclerosis associated with pathological aging. We performed a case-control study, enrolling subjects aged over 65 years in both groups. We included 40 patients with cardiovascular disorders and 10 healthy volunteers. IL-17 levels were measured in the serum of patients and healthy controls, along with serum total cholesterol and triglycerides. Significantly higher levels of IL-17 were obtained in patients compared to healthy controls (p<0.001). The level of this biomarker correlated significantly with two biochemical parameters - serum total cholesterol and triglycerides (the Pearson coefficient showed statistical significance, p=0.033, respectively p=0.043). We did not find any correlation between IL-17 and these two parameters in the control group. Our study is useful in understanding the physiopathological implications of IL-17 in the atherogenesis process. This could represent a starting point for future studies, including research regarding the therapeutic potential of IL-17 in pathological aging.


Asunto(s)
Aterosclerosis/etiología , Interleucina-17/fisiología , Anciano , Anciano de 80 o más Años , Aterosclerosis/sangre , Biomarcadores/sangre , Estudios de Casos y Controles , Femenino , Humanos , Interleucina-17/sangre , Masculino
13.
Roum Arch Microbiol Immunol ; 70(4): 178-85, 2011.
Artículo en Inglés | MEDLINE | ID: mdl-22568266

RESUMEN

Last consensus in celiac disease in 2008 conducted under the aegis of the European Society of Pediatric Gastroenterology, Hepatology and Nutrition jointly with North American Society of Pediatric Gastroenterology, Hepatology and Nutrition reveals the following: "celiac disease is a chronic immune-mediated enteropathy characterized by sensitization to gluten. That can affect any organ or system, with a wide range of clinical manifestations of variable severity". Thus, in recent years, clinical picture of celiac disease has changed the old paradigm--bowel disease with villous atrophy and malnutrition, being replaced with the new paradigm--multi-organ autoimmune disease, affecting many organs and systems throughout but with more less specific symptoms, which undiagnosed leads to delayed diagnosis, at a late-onset disease and long-term major complications as the risk of cancer. According to this consensus "the serological diagnosis of celiac disease is based on high sensitivity and specificity tests", but in line with changing clinical features of celiac disease, its diagnosis has undergone significant changes in recent years. These changes in the diagnosis of celiac disease, we have decided to analyze them.


Asunto(s)
Enfermedad Celíaca/diagnóstico , Enfermedad Celíaca/etiología , Enfermedad Celíaca/inmunología , Enfermedad Celíaca/metabolismo , Dermatitis Herpetiforme/diagnóstico , Diabetes Mellitus Tipo 1/complicaciones , Prueba de Histocompatibilidad , Humanos , Rumanía , Pruebas Serológicas
14.
Exp Ther Med ; 21(1): 96, 2021 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-33363607

RESUMEN

For a long period, cancer has been believed to be a gene disease, in which oncogenic and suppressor mutations accumulate gradually, finally leading to the malignant transformation of cells. This vision has changed in the last few years, the involvement of the tumor microenvironment, the non-malignant part of the tumors, as an important contributor to the malignant growth being now largely recognized. There is a consensus according to which the understanding of the tumor microenvironment is important as a means to develop new approaches in the therapy of cancer. In this context, the present study is a review of the different types of non-malignant cells that can be found in tumors, with their pro or antitumoral actions, presence in tumors and therapeutic targeting. These cells establish complex relations between them, through cytokines, exosomes, cell adhesion, co-stimulation and co-inhibition; these relations will also be examined in the present work.

15.
Roum Arch Microbiol Immunol ; 69(4): 183-9, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21462832

RESUMEN

Pancreatic cancer is a highly lethal disease, being one of the five leading death causes among oncologic patients. It is usually diagnosed late due to the paucity of clinical signs, and the current therapy means have limited success. One of the documented risk factors for developing pancreatic adenocarcinoma is chronic pancreatitis. It is postulated that a chronic inflammatory disease has a potential of evolving toward neoplasia, a fact that could account for a percentage of the pancreatic cancers. Starting from this assumption, we intended to analyze the serum reflection of some molecules with proinflammatory roles, and compare them in healthy individuals, in patients with chronic pancreatitis and with pancreatic adenocarcinoma. Additionally, we performed a biochemical and hematological assessment of the study groups, and compared the results with the immunological parameters analyzed in the same subjects. We found significantly higher levels of Tumor Necrosis Factor-alpha and Interleukin 6 in chronic pancreatitis and pancreatic adenocarcinoma sera (with higher levels in the pancreatitis group than in the cancer group), compared to healthy controls. Additionally, we found significantly higher levels of interleukin 8 and Macrophage Inflammatory Protein-3 alpha in pancreatic cancer, compared to chronic pancreatitis and controls. We also identified numerous correlations between the abovementioned cytokines/chemokines and biochemical parameters, not very much studied before. Our results plead for a pathogenic role of chronic inflammation in pancreatic carcinogenesis, thus offering a potential tool for earliy diagnose or targets for therapy.


Asunto(s)
Citocinas/sangre , Mediadores de Inflamación/sangre , Neoplasias Pancreáticas/sangre , Adenocarcinoma/sangre , Adenocarcinoma/etiología , Estudios de Casos y Controles , Quimiocina CCL20/sangre , Humanos , Interleucina-6/sangre , Interleucina-8/sangre , Neoplasias Pancreáticas/etiología , Pancreatitis Crónica/sangre , Pancreatitis Crónica/complicaciones , Factores de Riesgo , Factor de Necrosis Tumoral alfa/sangre
16.
Roum Arch Microbiol Immunol ; 69(4): 177-82, 2010.
Artículo en Inglés | MEDLINE | ID: mdl-21462831

RESUMEN

Anti-actin antibodies are found in 52-85% of patients with autoimmune hepatitis or chronic active hepatitis and in 22% of patients with primary biliary cirrhosis. In patients with celiac disease, anti-actin antibodies correlate with the degree of villous atrophy. Studies on their involvement in celiac disease and dermatitis herpetiformis in Romania have not been done. The purpose of this study was to evaluate of the quality of IgG anti-F-actin antibodies (IgG-AAA) tests compared with IgA tissue transglutaminase antibodies (IgA-TgA) having IgA endomysial antibody (IgA-EmA) as gold standard in celiac disease and dermatitis herpetiformis and to see if there is any relationship between them. The study included 70 pediatric patients with celiac disease under gluten-free diets and 10 adult patients with dermatitis herpetiformis, during 2010. The IgG-AAA antibodies levels were determined by ELISA. Assessing the qualities of IgG-AAA compared to IgA-TgA, we obtained the following values sensitivity (Se) 27.8%, specificity (Sp) 79.4%, respectively Se 88.9%, Sp 79.4% in celiac disease and Se 33.3%, Sp 100%, respectively Se 100%, Sp 100% in dermatitis herpetiformis. Also, there was a prevalence of 24.3% and 30% of IgG-AAA in the two groups of patients, but no statistically significant associations were found. Therefore, we concluded that IgG-AAA can not replace IgA-TgA in children patients with celiac disease under gluten-free diets and in adult patients with dermatitis herpetiformis. AAA-IgG serum activity in both diseases exist, but without a relationship of association with them.


Asunto(s)
Actinas/inmunología , Autoanticuerpos/sangre , Enfermedad Celíaca/inmunología , Dermatitis Herpetiforme/inmunología , Adolescente , Adulto , Niño , Preescolar , Femenino , Humanos , Inmunoglobulina A/sangre , Inmunoglobulina G/sangre , Masculino , Persona de Mediana Edad , Rumanía , Transglutaminasas/inmunología , Adulto Joven
17.
Clin Epigenetics ; 9: 122, 2017.
Artículo en Inglés | MEDLINE | ID: mdl-29209431

RESUMEN

Background: Both defective DNA methylation and active DNA demethylation processes are emerging as important risk factors in chronic lymphocytic leukemia (CLL). However, associations between 5-cytosine epigenetic markers and the most frequent chromosomal abnormalities detected in CLL remain to be established. Methods: CLL patients were retrospectively classified into a cytogenetic low-risk group (isolated 13q deletion), an intermediate-risk group (normal karyotype or trisomy 12), and a high-risk group (11q deletion, 17p deletion, or complex karyotype [≥ 3 breakpoints]). The two 5-cytosine derivatives, 5-methylcytosine (5-mCyt) and 5-hydroxymethylcytosine (5-hmCyt), were tested by ELISA (n = 60), while real-time quantitative PCR was used for determining transcriptional expression levels of DNMT and TET (n = 24). Results: By using global DNA methylation/demethylation levels, in the low-risk disease group, two subgroups with significantly different clinical outcomes have been identified (median treatment-free survival [TFS] 45 versus > 120 months for 5-mCyt, p = 0.0008, and 63 versus > 120 months for 5-hmCyt, p = 0.04). A defective 5-mCyt status was further associated with a higher percentage of 13q deleted nuclei (> 80%), thus suggesting an acquired process. When considering the cytogenetic intermediate/high-risk disease groups, an association of 5-mCyt status with lymphocytosis (p = 0.0008) and the lymphocyte doubling time (p = 0.04) but not with TFS was observed, as well as a reduction of DNMT3A, TET1, and TET2 transcripts. Conclusions: Combining cytogenetic studies with 5-mCyt assessment adds accuracy to CLL patients' prognoses and particularly for those with 13q deletion as a sole cytogenetic abnormality.


Asunto(s)
Deleción Cromosómica , Cromosomas Humanos Par 13/genética , Análisis Citogenético/métodos , Epigenómica/métodos , Hibridación Fluorescente in Situ/métodos , Leucemia Linfocítica Crónica de Células B/genética , 5-Metilcitosina/análogos & derivados , 5-Metilcitosina/metabolismo , Anciano , Anciano de 80 o más Años , ADN (Citosina-5-)-Metiltransferasas/genética , ADN Metiltransferasa 3A , Proteínas de Unión al ADN/genética , Dioxigenasas , Progresión de la Enfermedad , Femenino , Humanos , Leucemia Linfocítica Crónica de Células B/metabolismo , Masculino , Persona de Mediana Edad , Oxigenasas de Función Mixta/genética , Pronóstico , Proteínas Proto-Oncogénicas/genética , Estudios Retrospectivos
18.
Oncotarget ; 8(39): 65699-65716, 2017 Sep 12.
Artículo en Inglés | MEDLINE | ID: mdl-29029465

RESUMEN

Cytosine derivative dysregulations represent important epigenetic modifications whose impact on the clinical outcome in chronic lymphocytic leukemia (CLL) is incompletely understood. Hence, global levels of 5-methylcytosine (5-mCyt), 5-hydroxymethylcytosine (5-hmCyt), 5-carboxylcytosine (5-CaCyt) and 5-hydroxymethyluracil were tested in purified B cells from CLL patients (n = 55) and controls (n = 17). The DNA methylation 'writers' (DNA methyltransferases [DNMT1/3A/3B]), 'readers' (methyl-CpG-binding domain [MBD2/4]), 'editors' (ten-eleven translocation [TET1/2/3]) and 'modulators' (SAT1) were also evaluated. Accordingly, patients were stratified into three subgroups. First, a subgroup with a global deficit in cytosine derivatives characterized by hyperlymphocytosis, reduced median progression free survival (PFS = 52 months) and shorter treatment free survival (TFS = 112 months) was identified. In this subgroup, major epigenetic modifications were highlighted including a reduction of 5-mCyt, 5-hmCyt, 5-CaCyt associated with DNMT3A, MBD2/4 and TET1/2 downregulation. Second, the cytosine derivative analysis revealed a subgroup with a partial deficit (PFS = 84, TFS = 120 months), mainly affecting DNA demethylation (5-hmCyt reduction, SAT1 induction). Third, a subgroup epigenetically similar to controls was identified (PFS and TFS > 120 months). The prognostic impact of stratifying CLL patients within three epigenetic subgroups was confirmed in a validation cohort. In conclusion, our results suggest that dysregulations of cytosine derivative regulators represent major events acquired during CLL progression and are independent from IGHV mutational status.

19.
Immunotherapy ; 8(5): 569-81, 2016 05.
Artículo en Inglés | MEDLINE | ID: mdl-27140410

RESUMEN

Over the last two decades, anti-CD20 monoclonal antibody (mAb) therapy has improved patient outcome in B-cell malignancies, and confirmed CD20 as an important target in chronic lymphocytic leukemia (CLL). Until recently, the gold standard was based on the utilization of rituximab combined with chemotherapy (fludarabine and cyclophosphamide), but patients often relapse. Next, with our better understanding of mAb engineering, anti-CD20 mAb therapy has evolved with the development of new mAb permitting significant clinical responses by improving pharmacokinetics, safety, activity and immunogenicity. Last but not least, the development of key tumoral tyrosine kinase inhibitors and their association with anti-CD20 mAb is a work in progress with promising results.


Asunto(s)
Anticuerpos Monoclonales Humanizados/uso terapéutico , Linfocitos B/inmunología , Inmunoterapia/métodos , Leucemia Linfocítica Crónica de Células B/terapia , Rituximab/uso terapéutico , Animales , Antígenos CD20/inmunología , Antineoplásicos/uso terapéutico , Terapia Combinada , Humanos , Leucemia Linfocítica Crónica de Células B/inmunología , Ingeniería de Proteínas , Inhibidores de Proteínas Quinasas/uso terapéutico
20.
J Crit Care Med (Targu Mures) ; 2(1): 44-50, 2016 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-29967836

RESUMEN

INTRODUCTION: It has been reported that as compared with total intravenous anesthesia (TIVA), inhalation anesthesia is increasing the postoperative level of proinflammatory interleukins.The aim of the study is to investigate if there is an in-vivo relationship between proinflammatory cytokines, Interleukin-32 (IL-32) and Tumour necrosis factor - α (TNF-α), in patients undergoing laparoscopic cholecystectomies with two different anesthetic techniques, TIVA or inhalation anesthesia. MATERIAL AND METHODS: Twenty two consecutive patients undergoing laparoscopic cholecystectomies were prospectively randomized into two groups: Group 1: TIVA with target-controlled infusion (TIVA-TCI) (n=11) and Group 2: isoflurane anesthesia (ISO) (n=11). IL-32 and TNF-α were determined before the induction of anesthesia (T1), before incision (T2) and at 2h (T3) and 24h (T4) postoperatively. Our primary outcome was to compare plasma levels of IL-32 and TNF-α concentrations (expressed as area-under-the-curve) over 24 hours between study groups. Our secondary outcome was to establish whether there is a correlation between plasma levels of IL-32 and of TNF-α at each time point between the two groups. RESULTS: Area-under-the-curve (AUC) of IL-32 plasma concentration was 7.53 in Group 1 (TIVA) versus 3.80 in Group 2 (ISO), p= 1. For TNF-α, AUC of plasma concentration was 733.9 in Group 1 (TIVA) and 668.7 in Group 2 (ISO), p=0.066. There were no significant differences in plasma concentrations of both IL-32 and TNF-α between the groups. CONCLUSIONS: IL-32 expression in response to minor surgery is very low. There were no significant difference between plasma levels of TNF-α and IL-32 after TIVA versus inhalation anesthesia during the first 24 hours postoperatively. Further studies are needed on larger groups to investigate whether there can be a correlation between these interleukins after 2 different anesthetic techniques and the impact of this correlation on postoperative outcome.

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