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1.
Bratisl Lek Listy ; 121(2): 159-163, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-32115971

RESUMEN

AIM: In 95 % of Chronic myeloid leukemia (CML) patients, chromosomal translocation resulting in the formation of the Philadelphia (Ph) chromosome (t:9;22) is observed, which in turn leads to the formation of the BCR-ABL fusion gene. MicroRNAs (miRNAs) are a group of small and non-coding RNAs modulating gene expression via binding to the target mRNAs. We aimed to characterize the expression profiles of various miRNAs in different stages of Ph(+) CML patients. METHODS: This case-controlled study was conducted in 75 CML patients and 25 healthy controls. The subjects were categorized into 4 groups; newly diagnosed patients, treatment-response patients, treatment-failure patients, and healthy controls. Expressions of miRNAs was analyzed by RT-PCR. RESULTS: miR-150 expression was downregulated in the treatment failure patients compared to the control group (p = 0.003212) while miRNA 148b expression up-regulated in the treatment failure patients than the control group (p = 0.038016). miR-10a expression was up-regulated in newly diagnosed and treatment response patients compared to control group (p = 0.003934, p = 0.000292, respectively). It was found that miR-10a expression increased 11.17- fold in newly diagnosed patients and 9.82-fold in treatment response patients than in the control group. CONCLUSION: Our data suggest that expression profiles of miR-10a, miR-150, and miRNA 148b were correlated as biomarker and therapeutic tool in Turkish patients with CML (Tab. 2, Fig. 1, Ref. 30).


Asunto(s)
Biomarcadores , Leucemia Mielógena Crónica BCR-ABL Positiva , MicroARNs , Biomarcadores/metabolismo , Estudios de Casos y Controles , Proteínas de Fusión bcr-abl , Humanos , Leucemia Mielógena Crónica BCR-ABL Positiva/diagnóstico , MicroARNs/análisis , ARN Mensajero , Transcriptoma
3.
J Korean Med Sci ; 35(10): e73, 2020 Mar 16.
Artículo en Inglés | MEDLINE | ID: mdl-32174066

RESUMEN

BACKGROUND: Twin-to-twin transfusion syndrome (TTTS) is a serious complication of monochorionic twin pregnancies. It results from disproportionate blood supply to each fetus caused by abnormal vascular anastomosis within the placenta. Amniotic fluid (AF) is an indicator reflecting the various conditions of the fetus, and an imbalance in AF volume is essential for the antenatal diagnosis of TTTS by ultrasound. In this study, two different mass spectrometry quantitative approaches were performed to identify differentially expressed proteins (DEPs) within matched pairs of AF samples. METHODS: We characterized the AF proteome in pooled AF samples collected from donor and recipient twin pairs (n = 5 each) with TTTS by a global proteomics profiling approach and then preformed the statistical analysis to determine the DEPs between the two groups. Next, we carried out a targeted proteomic approach (multiple reaction monitoring) with DEPs to achieve high-confident TTTS-associated AF proteins. RESULTS: A total of 103 AF proteins that were significantly altered in their abundances between donor and recipient fetuses. The majority of upregulated proteins identified in the recipient twins (including carbonic anhydrase 1, fibrinogen alpha chain, aminopeptidase N, alpha-fetoprotein, fibrinogen gamma chain, and basement membrane-specific heparan sulfate proteoglycan core protein) have been associated with cardiac or dermatologic disease, which is often seen in recipient twins as a result of volume overload. In contrast, proteins significantly upregulated in AF collected from donor twins (including IgGFc-binding protein, apolipoprotein C-I, complement C1q subcomponent subunit B, apolipoprotein C-III, apolipoprotein A-II, decorin, alpha-2-macroglobulin, apolipoprotein A-I, and fibronectin) were those previously shown to be associated with inflammation, ischemic cardiovascular complications or renal disease. CONCLUSION: In this study, we identified proteomic biomarkers in AF collected from donor and recipient twins in pregnancies complicated by TTTS that appear to reflect underlying functional and pathophysiological challenges faced by each of the fetuses.


Asunto(s)
Líquido Amniótico/metabolismo , Transfusión Feto-Fetal/diagnóstico , Proteómica , Biomarcadores/metabolismo , Femenino , Humanos , Recién Nacido , Placenta/metabolismo , Embarazo , Embarazo Gemelar , Diagnóstico Prenatal , Proteoma
4.
Medicine (Baltimore) ; 99(11): e19509, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32176096

RESUMEN

Transthyretin amyloid (ATTR) amyloidosis is a rare systemic disorder characterized by amyloid deposits formed by misfolded monomers of the transthyretin. Gastrointestinal (GI) manifestations are common in ATTR amyloidosis; however, their pathogenesis is not fully elucidated. In the present study, we aim to evaluate the diagnostic role of fecal calprotectin (FC) in ATTR amyloidosis patients with GI manifestations.We recruited 21 consecutive ATTR amyloidosis patients and 42 sex and age-matched healthy controls. The presentation of GI symptoms and the severity of peripheral neuropathy were evaluated. Colonoscopy and FC assessment were performed in all subjects.Mean levels of FC in ATTR amyloidosis patients (184 µg/g [30-430]) were significantly higher thаn those of controls (40 µg/g [30-70]), P < .001. Receiver operating characteristic curve analysis indicated a FC cut-off level of 71 µg/g, which differentiates ATTR amyloidosis with GI manifestations from healthy subjects with 91% sensitivity, 100% specificity, 100% positive predictive value, 95% negative predictive value and 97% overall accuracy. FC values were significantly associated with the presence of neutrophilic granulocytic infiltration in the colonic mucosa (P = .002), with the presence of amyloid deposits in rectal mucosa (P = .007) and the presence of diarrhea (P = .046).FC levels are elevated in patients with ATTR amyloidosis with GI manifestations, which suggests an inflammatory component in the pathogenesis of the disease. The presence of elevated FC concentrations could help gastroenterologists to include ATTR amyloidosis in their diagnostic work-up.


Asunto(s)
Neuropatías Amiloides Familiares/diagnóstico , Enfermedades Gastrointestinales/diagnóstico , Complejo de Antígeno L1 de Leucocito/metabolismo , Adulto , Anciano , Neuropatías Amiloides Familiares/metabolismo , Biomarcadores/metabolismo , Estudios de Casos y Controles , Colonoscopía , Heces/química , Femenino , Enfermedades Gastrointestinales/metabolismo , Humanos , Masculino , Persona de Mediana Edad , Valor Predictivo de las Pruebas , Estudios Prospectivos
5.
BMC Med Genet ; 21(1): 34, 2020 02 14.
Artículo en Inglés | MEDLINE | ID: mdl-32059710

RESUMEN

BACKGROUND: Epigenetics could facilitate greater understanding of disparities in the emergence of childhood obesity. While blood is a common tissue used in human epigenetic studies, saliva is a promising tissue. Our prior findings in non-obese preschool-aged Hispanic children identified 17 CpG dinucleotides for which differential methylation in saliva at baseline was associated with maternal obesity status. The current study investigated to what extent baseline DNA methylation in salivary samples in these 3-5-year-old Hispanic children predicted the incidence of childhood obesity in a 3-year prospective cohort. METHODS: We examined a subsample (n = 92) of Growing Right Onto Wellness (GROW) trial participants who were randomly selected at baseline, prior to randomization, based on maternal phenotype (obese or non-obese). Baseline saliva samples were collected using the Oragene DNA saliva kit. Objective data were collected on child height and weight at baseline and 36 months later. Methylation arrays were processed using standard protocol. Associations between child obesity at 36 months and baseline salivary methylation at the previously identified 17 CpG dinucleotides were evaluated using multivariable logistic regression models. RESULTS: Among the n = 75 children eligible for analysis, baseline methylation of Cg1307483 (NRF1) was significantly associated with emerging childhood obesity at 36-month follow-up (OR = 2.98, p = 0.04), after adjusting for child age, gender, child baseline BMI-Z, and adult baseline BMI. This translates to a model-estimated 48% chance of child obesity at 36-month follow-up for a child at the 75th percentile of NRF1 baseline methylation versus only a 30% chance of obesity for a similar child at the 25th percentile. Consistent with other studies, a higher baseline child BMI-Z during the preschool period was associated with the emergence of obesity 3 years later, but baseline methylation of NRF1 was associated with later obesity even after adjusting for child baseline BMI-Z. CONCLUSIONS: Saliva offers a non-invasive means of DNA collection and epigenetic analysis. Our proof of principle study provides sound empirical evidence supporting DNA methylation in salivary tissue as a potential predictor of subsequent childhood obesity for Hispanic children. NFR1 could be a target for further exploration of obesity in this population.


Asunto(s)
Biomarcadores/metabolismo , Metilación de ADN/genética , Epigénesis Genética , Obesidad Pediátrica/genética , Adulto , Índice de Masa Corporal , Preescolar , Islas de CpG/genética , Femenino , Humanos , Masculino , Obesidad Pediátrica/diagnóstico , Obesidad Pediátrica/fisiopatología , Embarazo , Saliva/metabolismo
6.
J Agric Food Chem ; 68(8): 2597-2605, 2020 Feb 26.
Artículo en Inglés | MEDLINE | ID: mdl-32040302

RESUMEN

The world's coffee supply is threatened by the coffee berry borer, Hypothenemus hampei, the most destructive pest affecting coffee production and quality. This study hypothesized that coffee berry borer infestation induces distinct metabolic responses in the green coffee seeds of Coffea arabica and Coffea canephora (robusta). A targeted metabolomics approach was conducted using liquid chromatography tandem mass spectrometry to quantify intracellular metabolites in infested and uninfested arabica and robusta green seeds. In parallel, the seed biomass content and composition were assessed for the same conditions. Coffee berry borer attack induced increases in the levels of chlorogenic acids in arabica seeds, whereas organic acids and sugar alcohols were more abundant in infested robusta seeds. Most importantly, a set of compounds was identified as biomarkers differentiating the metabolic response of these taxa to the coffee berry borer.


Asunto(s)
Coffea/metabolismo , Enfermedades de las Plantas/parasitología , Semillas/química , Gorgojos/fisiología , Animales , Biomarcadores/análisis , Biomarcadores/metabolismo , Ácido Clorogénico/análisis , Ácido Clorogénico/metabolismo , Cromatografía Líquida de Alta Presión , Coffea/química , Coffea/parasitología , Espectrometría de Masas , Semillas/metabolismo , Semillas/parasitología , Alcoholes del Azúcar/análisis , Alcoholes del Azúcar/metabolismo
7.
Zhonghua Gan Zang Bing Za Zhi ; 28(1): 47-52, 2020 Jan 20.
Artículo en Chino | MEDLINE | ID: mdl-32023699

RESUMEN

Objective: To establish and evaluate diagnostic efficacy and applicability of serum Golgi protein (GP) 73 based non-invasive diagnostic model with other conventional serological indicators for compensated stage hepatitis B cirrhosis. Methods: 666 cases with chronic hepatitis B (CHB) who had visited to the Fifth Medical Center of People's Liberation Army General Hospital from January 2010 to December 2017 were selected as the study subjects, and were classified according to compensated stage cirrhosis into clinical and pathological diagnosis group based on whether or not the liver histological examination was performed. A diagnostic model of compensated stage hepatitis B cirrhosis in the clinical diagnosis group was established. The current clinically used diagnostic model of liver cirrhosis, aspartate aminotransferase/platelet ratio index (APRI), fibrosis index (FIB)-4 and liver stiffness measurement (LSM) were compared. Eventually, the diagnostic model was verified step by step by pathological diagnosis group. Results: The area under the receiver operating characteristic curve (AUC) of GP73 and APRI, FIB-4, and LSM for cirrhosis patients in the clinical diagnosis group were 0.842, 0.857, 0.864, and 0.832, respectively. The diagnostic efficiency of the four indicators were of similar (P value > 0.05). A diagnostic model of compensated stage hepatitis B cirrhosis (GAPA) using logistic regression analysis was established: LogitP = 1/ [1 + exp (1.614-0.054 × GP73-0.045 × Age + 0.030 × PLT-0.015 × ALP)]. The AUC of the model was as high as 0.940 and the optimal cut-off value were 0.41. The corresponding diagnostic sensitivity and specificity were 0.92 and 0.82, respectively. The diagnostic efficiency was better than that of APRI, FIB-4, LSM and GP73 alone (P < 0.05). The AUC of GAPA was 0.877 in the pathological diagnosis group, which was similar to the diagnostic efficacy of LSM (0.891) and FIB-4 (0.847) (P > 0.1), but still superior to that of APRI (0.811) and GP73 alone (0.780) (P < 0.001). Conclusion: GAPA, a diagnostic model for compensated stage hepatitis B cirrhosis established in this study, has a good diagnostic efficacy in both the clinical and pathological diagnosis group, and has certain auxiliary diagnostic value in the areas where resources are relatively scarce or where LSM has not been developed.


Asunto(s)
Biomarcadores/metabolismo , Cirrosis Hepática/diagnóstico , Hígado/metabolismo , Proteínas de la Membrana/metabolismo , Aspartato Aminotransferasas/metabolismo , Biopsia , Fibrosis , Hepatitis B , Humanos , Hígado/patología , Proteínas de la Membrana/sangre , Curva ROC , Índice de Severidad de la Enfermedad
8.
Angiology ; 71(4): 366-371, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-32000500

RESUMEN

Contrast-induced nephropathy (CIN) accounts for about 10% of all hospital-acquired acute kidney injury. We aimed to assess the role of the combination of 2 inflammatory biomarkers, the C-reactive protein (CRP)/albumin ratio (CAR), in the development of CIN after percutaneous coronary intervention (PCI) in patients with non-ST-elevation myocardial infarction (NSTEMI). Patients with NSTEMI (n = 205) treated by PCI were classified according to the development of CIN. Both groups were compared according to clinical, laboratory, and demographic characteristics, including inflammatory biomarkers and specifically, CAR. Contrast-induced nephropathy was observed in 10.2% of patients. More advanced age, the presence of diabetes and dyslipidemia, left ventricular ejection fraction, and CAR correlated with the development of CIN. Analysis also showed a significant association between CAR and the development of CIN (CAR in CIN (+): 8.54 ± 8.48, range: 0.7-32, median: 7.13 vs CAR in CIN (-): 2.36 ± 3.01, range: 0.1-24, median: 1.33, P < .001). Multivariate logistic regression analysis showed the impact of CAR on the development of CIN (odds ratio: 1.244, 95% confidence interval: 1.102; 1.392, P < .01). We conclude that CAR, as a combination of 2 inflammatory biomarkers, is a more accurate predictor of CIN development compared with the single-marker assessment of albumin and CRP in the context of NSTEMI.


Asunto(s)
Lesión Renal Aguda/inducido químicamente , Albúminas/metabolismo , Proteína C-Reactiva/metabolismo , Medios de Contraste/efectos adversos , Infarto del Miocardio sin Elevación del ST/sangre , Adulto , Anciano , Anciano de 80 o más Años , Biomarcadores/metabolismo , Estudios Transversales , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio sin Elevación del ST/cirugía , Intervención Coronaria Percutánea , Valor Predictivo de las Pruebas , Estudios Prospectivos
9.
Medicine (Baltimore) ; 99(8): e18973, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-32080075

RESUMEN

This study investigated the relationship between angiographic complexities of coronary artery disease (CAD) assessed by SYNTAX Score synergy between percutaneous coronary intervention with taxus and cardiac surgery score (SYNTAX Score) and cardiac biomarker elevation after revascularization procedures.This is a post-hoc analysis of the medicine, angioplasty or surgery study V study of patients with stable CAD. High-sensitivity troponin 1 (hs-TnI) and creatinine kinase-muscle/brain (CK-MB) were assessed before and after cardiovascular procedures. Baselines SYNTAX Scores (SXScores) were calculated by blinded investigators to patient characteristics.Of the 202 patients studied, the mean SXScore was 21.25 ±â€Š9.24; 40.10 ±â€Š7.09 in the high SXScore group and 19.06 ±â€Š6.61 in low/mid SXscore group (P < .0001). Positive correlations existed between SXScore and median peaks after procedural hs-TnI (r = 0.18, P = .009) and CK-MB (r = 0.24, P = .001) levels. In patients with high SXScores (≥33), the median peaks of post-procedural hs-TnI (P = .034)and CK-MB (P = .004) levels were higher than in low/mid SXScore group (<33).The release of hs-TnI at 6 (P = .002), 12 (P = .008), and 24 hours (P = .039) was higher in high SXScore group than in low/mid SXscore group (<33) as was the release of CK-MB at 6 (P < .0001), 12 (P < .0001), 24 (P = .001), 36 (P = .007), 48 (P = .008), and 72 hours (P = .023). After multivariable analysis, high SXScore was a significant independent predictor of release of CK-MB and hs-TnI peaks higher than the median.The increase in release of cardiac biomarkers was significantly associated with the extent of atherosclerosis identified by the SYNTAX Score.


Asunto(s)
Biomarcadores/metabolismo , Angiografía Coronaria/métodos , Enfermedad de la Arteria Coronaria/sangre , Enfermedad de la Arteria Coronaria/cirugía , Anciano , Angioplastia/métodos , Aterosclerosis/metabolismo , Aterosclerosis/patología , Procedimientos Quirúrgicos Cardíacos/métodos , Angiografía Coronaria/tendencias , Puente de Arteria Coronaria/métodos , Enfermedad de la Arteria Coronaria/diagnóstico por imagen , Enfermedad de la Arteria Coronaria/patología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Infarto del Miocardio/diagnóstico , Infarto del Miocardio/metabolismo , Infarto del Miocardio/terapia , Intervención Coronaria Percutánea/métodos , Estudios Prospectivos , Troponina I/metabolismo
10.
Lancet ; 395(10221): 371-383, 2020 02 01.
Artículo en Inglés | MEDLINE | ID: mdl-32007172

RESUMEN

Asthma is a disease of reversible airflow obstruction characterised clinically by wheezing, shortness of breath, and coughing. Increases in airway type 2 cytokine activity, including interleukin-4 (IL-4), IL-5, and IL-13, are now established biological mechanisms in asthma. Inhaled corticosteroids have been the foundation for asthma treatment, in a large part because they decrease airway type 2 inflammation. However, inhaled or systemic corticosteroids are ineffective treatments in many patients with asthma and few treatment options exist for patients with steroid resistant asthma. Although mechanisms for corticosteroid refractory asthma are likely to be numerous, the development of a new class of biologic agents that target airway type 2 inflammation has provided a new model for treating some patients with corticosteroid refractory asthma. The objective of this Therapeutic paper is to summarise the new type 2 therapeutics, with an emphasis on the biological rationale and clinical efficacy of this new class of asthma therapeutics.


Asunto(s)
Antiasmáticos/uso terapéutico , Anticuerpos Monoclonales Humanizados/uso terapéutico , Asma/tratamiento farmacológico , Productos Biológicos/uso terapéutico , Adulto , Biomarcadores/metabolismo , Ensayos Clínicos Fase III como Asunto , Citocinas/antagonistas & inhibidores , Citocinas/fisiología , Eosinófilos/fisiología , Predicción , Humanos , Ácidos Indolacéticos/uso terapéutico , Interleucina-4/antagonistas & inhibidores , Interleucina-5/antagonistas & inhibidores , Omalizumab/uso terapéutico , Piridinas/uso terapéutico , Células Th2/fisiología , Resultado del Tratamiento
11.
Life Sci ; 248: 117468, 2020 May 01.
Artículo en Inglés | MEDLINE | ID: mdl-32105705

RESUMEN

AIMS: Treatment with 5-fluorouracil (5-FU) can cause impairment to adult hippocampal neurogenesis, resulting in cognitive deficits. As melatonin has been shown to enhance memory and hippocampal neurogenesis in animal models, this research investigated the neuroprotective effects of melatonin against spatial memory and hippocampal neurogenesis impairment in 5-fluorouracil (5-FU)-treated rats. MATERIALS AND METHODS: Four-Five weeks old male Spraque-Dawley rats weighing between 180 and 200 g were used. Animals were maintained under standard laboratory conditions with 25 °C and 12 h light/dark cycle. Animal were administered intravenous (i.v.) injections of 5-FU (25 mg/kg) 5 times every 3 days starting on day 9 of the experiment. The rats were divided into preventive, recovery, and throughout groups and co-treated with melatonin (8 mg/kg, i.p.) once daily (at 7.00 pm) for 21 days prior to, after, and throughout 5-FU treatment, respectively. Spatial memory was assessed using a novel object location (NOL) test. Hippocampal neurogenesis was then examined using Ki67, bromodeoxyuridine (BrdU), and doublecortin (DCX) immunohistochemistry staining. KEY FINDINGS: Melatonin administration was able to both protect the subjects from and reverse spatial memory deficits. 5-FU was also found to reduce the generation of hippocampal newborn neurons. However, co-treatment with melatonin ameliorated the reductions in neurogenesis caused by 5-FU. SIGNIFICANCE: These findings suggest that melatonin administration was able to ameliorate the 5-FU-induced spatial memory deficits associated with neurogenesis. The present work will be valuable for patients who suffer memory deficits from 5-FU chemotherapy.


Asunto(s)
Disfunción Cognitiva/tratamiento farmacológico , Fluorouracilo/antagonistas & inhibidores , Melatonina/farmacología , Trastornos de la Memoria/tratamiento farmacológico , Neurogénesis/efectos de los fármacos , Fármacos Neuroprotectores/farmacología , Memoria Espacial/efectos de los fármacos , Animales , Antimetabolitos/efectos adversos , Biomarcadores/metabolismo , Proliferación Celular/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/fisiopatología , Giro Dentado/efectos de los fármacos , Giro Dentado/metabolismo , Giro Dentado/patología , Esquema de Medicación , Fluorouracilo/efectos adversos , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Inyecciones Intravenosas , Antígeno Ki-67/genética , Antígeno Ki-67/metabolismo , Masculino , Trastornos de la Memoria/metabolismo , Trastornos de la Memoria/fisiopatología , Proteínas Asociadas a Microtúbulos/genética , Proteínas Asociadas a Microtúbulos/metabolismo , Neurogénesis/genética , Neuronas/efectos de los fármacos , Neuronas/metabolismo , Neuronas/patología , Neuropéptidos/genética , Neuropéptidos/metabolismo , Ratas , Ratas Sprague-Dawley , Memoria Espacial/fisiología
14.
Cancer Treat Rev ; 84: 101977, 2020 Mar.
Artículo en Inglés | MEDLINE | ID: mdl-32018128

RESUMEN

Preclinical data suggest that head and neck squamous cell carcinoma (HNSCC) is a profoundly immunosuppressive disease, characterized by abnormal secretion of proinflammatory cytokines and dysfunction of immune effector cells. Based on landmark phase III trials, two anti-Programmed Cell Death-1 (PD-1) antibodies, pembrolizumab and nivolumab have been approved for HNSCC by FDA and EMEA in the recurrent/metastatic setting; in addition, pembrolizumab has recently received FDA and EMEA approval as first line treatment. In clinical practice, only a minority of patients with HNSCC derive benefit from immunotherapy and the need for the discovery of novel biomarkers to optimize treatment strategies is becoming increasingly more relevant. Although currently only PD-L1 is widely used as a predictive biomarker for response to immune checkpoint inhibitors in HNSCC, there are many ongoing trials focusing on the identification of new biomarkers. This review will summarize current data on emerging biomarkers for response to immunotherapy in HNSCC.


Asunto(s)
Antineoplásicos/uso terapéutico , Biomarcadores/metabolismo , Neoplasias de Cabeza y Cuello/patología , Inmunoterapia/métodos , Terapia Molecular Dirigida , Neoplasias de Cabeza y Cuello/tratamiento farmacológico , Neoplasias de Cabeza y Cuello/inmunología , Neoplasias de Cabeza y Cuello/metabolismo , Humanos , Pronóstico
15.
Life Sci ; 244: 117324, 2020 Mar 01.
Artículo en Inglés | MEDLINE | ID: mdl-31958420

RESUMEN

AIMS: The aim of the present study was to evaluate the possible antioxidant role of oleic acid (OA) against Cd-induced injuries in the heart and liver tissues of male Wistar rats. MAIN METHODS: Rats were treated with either vehicle (control), or OA (10 mg/kg b.w., fed orally), or Cd (0.44 mg/kg b.w., s.c.), or both (OA + Cd) for 15 days. Following completion of the treatment period, biomarkers of organ damage and oxidative stress including ROS, activities of antioxidant enzymes and their level, activities of Krebs cycle enzymes and respiratory chain enzymes were measured. Levels of interleukins (IL-1ß, IL-6, IL-10), tumor necrosis factor (TNF-α) and nuclear factor kappa B (NFκB) were estimated to evaluate the state of inflammation. In addition, changes in mitochondrial membrane potential and status of cytochrome c (Cyt c) were also studied. KEY FINDINGS: Pre-treatment of rats with OA significantly protected against Cd-induced detrimental changes possibly by decreasing endogenous ROS through regulation of antioxidant defense system, inflammatory responses and activities of metabolic enzymes. Moreover, OA was also found to restore mitochondrial membrane potential possibly by regulating Cyt c leakage thereby increasing mitochondrial viability. SIGNIFICANCE: Our results for the first time demonstrated systematically that OA provided protection against Cd-induced oxidative stress mediated injuries in rat heart and liver tissues through its antioxidant mechanism. The results raise the possibility of using OA singly or in combination with other antioxidants or diet in the treatment of situations arising due to oxidative stress and may have future therapeutic relevance.


Asunto(s)
Ácido Oléico/metabolismo , Ácido Oléico/farmacología , Animales , Antioxidantes/farmacología , Biomarcadores/metabolismo , Cadmio/efectos adversos , Enfermedad Hepática Inducida por Sustancias y Drogas/prevención & control , Corazón/efectos de los fármacos , Lesiones Cardíacas/prevención & control , Inflamación/patología , Hígado/efectos de los fármacos , Hígado/metabolismo , Masculino , Miocardio/metabolismo , Miocardio/patología , Estrés Oxidativo/efectos de los fármacos , Ratas , Ratas Wistar
16.
High Blood Press Cardiovasc Prev ; 27(1): 1-8, 2020 Feb.
Artículo en Inglés | MEDLINE | ID: mdl-31925708

RESUMEN

Lipids and endothelium are pivotal players on the scene of atherosclerosis and their interaction is crucial for the establishment of the pathological processes. The endothelium is not only the border of the arterial wall: it plays a key role in regulating circulating fatty acids and lipoproteins and vice versa it is regulated by these lipidic molecules thereby promoting atherosclerosis. Inflammation is another important element in the relationship between lipids and endothelium. Recently, proprotein convertase subtilisin/kexin type 9 (PCSK9) has been recognized as a fundamental regulator of LDL-C and anti-PCSK9 monoclonal antibodies have been approved for therapeutic use in hypercholesterolemia, with the promise to subvert the natural history of the disease. Moreover, growing experimental and clinical evidence is enlarging our understanding of the mechanisms through which this protein may facilitate the genesis of atherosclerosis, independently of its impact on lipid metabolism. In addition, environmental stimuli may affect the post-transcriptional regulation of genes through micro-RNAs, which in turn play a key role in orchestrating the crosstalk between endothelium and cholesterol. Advances in experimental research, with development of high throughput techniques, have led, over the last century, to a tremendous progress in the understanding and fine tuning of the molecular mechanisms leading to atherosclerosis. Identification of pivotal keystone molecules bridging lipid metabolism, endothelial dysfunction and atherogenesis will provide the mechanistic substrate to test valuable targets for prediction, prevention and treatment of atherosclerosis-related disease.


Asunto(s)
Aterosclerosis/metabolismo , Colesterol/metabolismo , Dislipidemias/metabolismo , Endotelio Vascular/metabolismo , MicroARNs/metabolismo , Proproteína Convertasa 9/metabolismo , Animales , Aterosclerosis/enzimología , Aterosclerosis/genética , Biomarcadores/metabolismo , Dislipidemias/enzimología , Dislipidemias/genética , Endotelio Vascular/enzimología , Endotelio Vascular/patología , Regulación de la Expresión Génica , Humanos , Mediadores de Inflamación/metabolismo , MicroARNs/genética , Placa Aterosclerótica , Transducción de Señal
17.
BMC Bioinformatics ; 21(1): 11, 2020 Jan 09.
Artículo en Inglés | MEDLINE | ID: mdl-31918658

RESUMEN

BACKGROUND: Metabolomics time-course experiments provide the opportunity to understand the changes to an organism by observing the evolution of metabolic profiles in response to internal or external stimuli. Along with other omic longitudinal profiling technologies, these techniques have great potential to uncover complex relations between variations across diverse omic variables and provide unique insights into the underlying biology of the system. However, many statistical methods currently used to analyse short time-series omic data are i) prone to overfitting, ii) do not fully take into account the experimental design or iii) do not make full use of the multivariate information intrinsic to the data or iv) are unable to uncover multiple associations between different omic data. The model we propose is an attempt to i) overcome overfitting by using a weakly informative Bayesian model, ii) capture experimental design conditions through a mixed-effects model, iii) model interdependencies between variables by augmenting the mixed-effects model with a conditional auto-regressive (CAR) component and iv) identify potential associations between heterogeneous omic variables by using a horseshoe prior. RESULTS: We assess the performance of our model on synthetic and real datasets and show that it can outperform comparable models for metabolomic longitudinal data analysis. In addition, our proposed method provides the analyst with new insights on the data as it is able to identify metabolic biomarkers related to treatment, infer perturbed pathways as a result of treatment and find significant associations with additional omic variables. We also show through simulation that our model is fairly robust against inaccuracies in metabolite assignments. On real data, we demonstrate that the number of profiled metabolites slightly affects the predictive ability of the model. CONCLUSIONS: Our single model approach to longitudinal analysis of metabolomics data provides an approach simultaneously for integrative analysis and biomarker discovery. In addition, it lends better interpretation by allowing analysis at the pathway level. An accompanying R package for the model has been developed using the probabilistic programming language Stan. The package offers user-friendly functions for simulating data, fitting the model, assessing model fit and postprocessing the results. The main aim of the R package is to offer freely accessible resources for integrative longitudinal analysis for metabolomics scientists and various visualization functions easy-to-use for applied researchers to interpret results.


Asunto(s)
Biomarcadores/metabolismo , Metabolómica/métodos , Modelos Teóricos , Bacterias/metabolismo , Teorema de Bayes , Metaboloma
18.
Adv Clin Chem ; 94: xi, 2020.
Artículo en Inglés | MEDLINE | ID: mdl-31952576
19.
Angiology ; 71(4): 360-365, 2020 Apr.
Artículo en Inglés | MEDLINE | ID: mdl-31888345

RESUMEN

Several laboratory parameters have been used to assess inflammatory process and determine cardiovascular risk. The C-reactive protein to albumin ratio (CAR) is a novel marker of inflammation and its clinical importance has not been clearly elucidated in coronary artery disease (CAD). We compared the diagnostic value of CAR with other inflammatory parameters in detecting significant CAD. Patients (n = 421) with stable angina pectoris who underwent coronary angiography for the suspected CAD were included. Neutrophil to lymphocyte ratio (NLR), monocyte to lymphocyte ratio (MLR), platelet to lymphocyte ratio, uric acid, monocyte to high-density cholesterol (HDL-C) ratio, mean platelet volume to lymphocyte ratio (MPVLR), and platelet to mean corpuscular volume (MCV) ratio were measured. Patients with significant CAD had a significantly higher NLR (P = .043), MLR (P = .004), uric acid (P < .001), monocyte to HDL-C ratio (P = .004), and CAR (P < .001) compared to patients without significant CAD. However, MPVLR and platelet to MCV ratio weren't different between 2 groups. The area under the curve (AUC) of CAR was the highest AUC among all inflammatory parameters for predicting significant CAD. Multivariate analysis showed that age (odds ratio [OR]: 1.046, 95% confidence interval [CI], 1.020-1.072, P < .001) and CAR (OR: 1.175, 95% CI, 1.126-1.226, P < .001) were the only independent predictors of significant CAD. In conclusion, CAR had the strongest diagnostic value in detecting significant CAD among the inflammatory parameters evaluated in this study.


Asunto(s)
Albúminas/metabolismo , Angina Estable/diagnóstico , Angina Estable/metabolismo , Proteína C-Reactiva/metabolismo , Enfermedad de la Arteria Coronaria/metabolismo , Biomarcadores/metabolismo , Angiografía Coronaria , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sensibilidad y Especificidad
20.
Mar Pollut Bull ; 150: 110766, 2020 Jan.
Artículo en Inglés | MEDLINE | ID: mdl-31910521

RESUMEN

The present study is an attempt to assess the effects of contamination of several sites in the Red Sea coasts of Saudi Arabia using bivalves as a biomonitoring tool. Oxidative stress biomarkers (including reduced glutathione level (GSH), glutathione-S-transferase activity (GST), Malondialdehyde level (MDA) and Catalase activity (CAT)), neurotoxicity acetylcholinesterase activity (ACHE), and genotoxicity micronucleus rate (MN) were measured in three distinct tissues - digestive glands, gills and mantle - of specimens of the giant clam Tridacna maxima, collected from five sites in Saudi Arabian Red Sea coast (Al-Khuraybah, Al-Wajh, Yanbu, Rabigh and Thuwal). Our results demonstrated that T. maxima showed differential biomarker responses according to the nature of pollutants and human activity that affect the coast. This study can be considered as the first one using biomarkers to assess the state of the Red Sea coast in Saudi Arabia which must be followed by periodic studies for surveillance of aquatic pollution.


Asunto(s)
/métodos , Bivalvos/fisiología , Contaminantes Químicos del Agua/metabolismo , Animales , Biomarcadores/metabolismo , Catalasa/metabolismo , Glutatión Transferasa/metabolismo , Océano Índico , Estrés Oxidativo , Arabia Saudita , Contaminantes Químicos del Agua/toxicidad
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