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Bone marrow-derived mesenchymal stem cells (BM-MSCs) are considered a novel regenerative therapy that holds much potential. This study aimed to examine and compare the ameliorative effects of BM-MSCs compared to α-tocopherol (α-Toc) on apoptosis, autophagy, and ß-cell function in a rat model of streptozotocin (STZ)-induced diabetes and further analyzed the implications and interrelations of the entero-insular axis, and type I phosphoinositide 3-kinase (PI3K)/Akt signaling. Forty adult male albino rats were categorized into four groups (n = 10, in each): control group, STZ-induced diabetic group (single i.p. injection of STZ 45 mg/kg), diabetic and treated with BM-MSCs injection, diabetic and treatment with α-Toc p.o. The serum glucose, insulin, nitric oxide (NO), and catalase (CAT) were measured. Histopathological examination of the pancreas, the expression levels of insulin, CD44, caspase-3, autophagy markers, P13K/Akt, and pancreas/duodenum homeobox protein 1, in pancreatic tissue, and glucose-dependent insulinotropic polypeptide (GIP) in the duodenum were detected by hematoxylin and eosin staining, immunofluorescence labeling, and by quantitative real-time polymerase chain reaction. The diabetic rats showed reduced insulin, hyperglycemia, nitrosative stress (NO, CAT), augmented apoptosis (caspase 3), impaired autophagy (p62/SQSTM1, LC3), downregulated PI3K/Akt pathway and increased GIP expression, and degeneration of pancreatic islets. Treatment with either BM-MSCs or α-Toc suppressed the nitrosative stress, reduced apoptosis, recovered autophagy, upregulated PI3K/Akt pathway, and subsequently increased insulin levels, decreased blood glucose, and downregulated GIP expression with partial restoration of pancreatic islets. Based on our findings, the cytoprotective effects of BM-MSCs and α-Toc in type 1-induced diabetes appeared to be related to repaired autophagy and recovered PI3K/Akt signaling. Moreover, we reported their novel effects on reversing intestinal GIP expression level. The effect of BM-MSCs was notably superior to that of α-Toc.
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Diabetes Mellitus Experimental , Células Madre Mesenquimatosas , Ratas , Masculino , Animales , Proteínas Proto-Oncogénicas c-akt/metabolismo , Fosfatidilinositol 3-Quinasas/metabolismo , Estreptozocina/farmacología , alfa-Tocoferol/metabolismo , alfa-Tocoferol/farmacología , Fosfatidilinositol 3-Quinasa/metabolismo , Diabetes Mellitus Experimental/inducido químicamente , Diabetes Mellitus Experimental/terapia , Diabetes Mellitus Experimental/metabolismo , Transducción de Señal , Apoptosis , Insulina/metabolismo , Autofagia , Glucosa/metabolismo , Células Madre Mesenquimatosas/metabolismoRESUMEN
Hepatocellular carcinoma (HCC) is one of the most critical cancers; thus, novel therapeutical regimens are of great need. In this study, we investigated the effects of umbilical cord mesenchymal stem cells (UC-MSCs) derived exosomes on HepG2 cell line, and the underlying mechanism to control HCC proliferation, to identify the potential clinical role of exosomes as a novel molecular therapeutic target. Proliferation, apoptosis, and angiogenesis effects were assessed together with the cell viability evaluation by MTT assay in HepG2 cells at 24/48 h. with or without UC-MSCs-derived exosomes. Gene expressions of TNF-α, caspase-3, VEGF, stromal cell-derived factor-1 (SDF-1), and CX chemokine receptor-4 (CXCR-4) were measured by quantitative real-time PCR technique. Expression of sirtuin-1 (SIRT-1) protein was detected by western blot. Treatment of HepG2 cells with UC-MSCs-derived exosomes for 24 and 48 h. demonstrated a significant reduction of cells survival compared to the control group (p < 0.05). The SIRT-1 protein, and VEGF, SDF-1, CXCR-4 expression levels were significantly lower, TNF-α and caspase-3 expression levels were significantly higher in exosomal-treated HepG2 cells for 24 and 48 h. than those in the control group. Moreover, our findings documented that the anti-proliferative, apoptotic, and anti-angiogenic effects were achieved in a time-dependent manner in which more effects were determined after 48 h supplementation compared to 24 h (p < 0.05). UC-MSCs-derived exosomes exert anticarcinogenic molecular effects on HepG2 cells through the involvement of SIRT-1, SDF-1, and CXCR-4. Hence, exosomes would be a potential novel therapy regimen against HCC. Large-scale studies are recommended to verify this conclusion.
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Carcinoma Hepatocelular , Exosomas , Neoplasias Hepáticas , Células Madre Mesenquimatosas , Humanos , Carcinoma Hepatocelular/tratamiento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Caspasa 3/genética , Caspasa 3/metabolismo , Factor de Necrosis Tumoral alfa/metabolismo , Exosomas/genética , Exosomas/metabolismo , Factor A de Crecimiento Endotelial Vascular/genética , Neoplasias Hepáticas/tratamiento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Apoptosis , Cordón Umbilical , Células Madre Mesenquimatosas/metabolismoRESUMEN
Communication between amino acids (AAs) and heart failure (HF) is unclear. We evaluate the plasma metabolomic profile of AAs in HF and its subgroups and association with clinical features. This is a case-control study in which 90 patients with HF, 63 with reduced ejection fraction (HFrEF) and 27 with preserved ejection fraction (HFpEF), were compared with 60 controls. The quantitative measurement of plasma concentrations of AA metabolites was performed using an AA analyzer. Compared with controls, HF patients had significantly higher levels of nine AAs and significantly lower levels of seven AAs. Leu, phenylalanine (Phe), and methionine (Met) were the independent predictors of HF that remained significant after adjustment for confounding factors in multivariate analysis. There was a significant difference in 10 AAs and some clinical features between HFpEF and HFrEF. The plasma levels of six AAs were significantly increased across the different New York Heart Association (NYHA) classes, (class II, class III, class IV) but they were not predictor of reduced EF and NYHA in multivariate regression analysis. There were significant associations between Leu, Phe, and Met with cardiovascular risk variables and prognosis. In conclusion, plasma Leu, Phe, and Met provide early prediction and prognostic values of HF. The plasma AAs could have significant impact on the risk-stratifying HFrEF and HFpEF and NYHA functional class but do not predict them.
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Aminoácidos/sangre , Insuficiencia Cardíaca , Metaboloma/fisiología , Adulto , Aminoácidos/metabolismo , Estudios de Casos y Controles , Femenino , Insuficiencia Cardíaca/sangre , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/metabolismo , Insuficiencia Cardíaca/fisiopatología , Humanos , Masculino , Persona de Mediana Edad , Pronóstico , Sensibilidad y Especificidad , Volumen Sistólico/fisiologíaRESUMEN
BACKGROUND: Vitiligo is a chronic depigmentary skin disorder, characterised clinically by the development of white macules and or patches caused by loss of epidermal melanocytes. S100B is a dual function protein released from epidermal melanocytes in response to injury. It considered a possible marker of disease activity in both malignant melanoma and vitiligo. AIM OF THE STUDY: To estimate the serum level of S100B level in vitiligo patients and correlate its level with disease activity and various disease parameters. PATIENTS AND METHODS: Sixty vitiligo patients and 60 healthy volunteers as controls were included in the study. Vitiligo Area Severity Index (VASI) and Vitiligo Disease Activity (VIDA) scores were estimated for each patient. Quantitative assessment of S100B level using ELISA technique was done for all participants. RESULTS: S100B level was significantly correlated with the presence of vitiligo (P = 0.01), while it showed no correlation with the disease activity using VASI or VIDA scores. As regards the receiver operating characteristic (ROC) curve analysis of S100B for diagnosis and discrimination of vitiligo, serum S100B showed area under the curve (AUC) of 0.781 with 73.3% sensitivity and 80% specificity. CONCLUSION: The serum level of S100B was related to the presence of vitiligo, but its level did not show any relation to the disease activity using either VASI and VIDA scores or various disease parameters.
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Subunidad beta de la Proteína de Unión al Calcio S100/sangre , Vitíligo/sangre , Adolescente , Adulto , Biomarcadores/sangre , Estudios de Casos y Controles , Niño , Femenino , Humanos , Masculino , Persona de Mediana Edad , Estudios Prospectivos , Sensibilidad y Especificidad , Índice de Severidad de la Enfermedad , Vitíligo/diagnóstico , Adulto JovenRESUMEN
BACKGROUND: Heart failure (HF) is a global growing health threat. This case-control clinical trial aimed to detect the predictive value and difference in aldosterone level between right side heart failure, heart failure with decreased ejection fraction (HFrEF) and heart failure with preserved ejection fraction (HFpEF) and compare the efficacy and safety of adding mineralocorticoid receptor antagonist (MRA) for treatment. PATIENTS AND METHODS: We recruited 151 participants, 135 HF patients divided equally into 45 patients in each group:(1) right side HF (2) HFrEF and (3) HFpEF and 16 healthy controls. Serum aldosterone, troponin and echocardiography were evaluated at the beginning of the study, three and six months after administration of MRA. RESULTS: Aldosterone level was significantly greater in HF patients relative to controls. Aldosterone level can detect HF with excellent accuracy. There were significantly lower levels of aldosterone in right side HF compared to left side HF. There was a significant decrease in right ventricle dimensions, pulmonary artery systolic pressure and pulmonary artery size and significant increase in tricuspid annular plane systolic excursion after treatment in patients with right side HF. In the HFrEF group, there was a significant decrease in left ventricular end diastolic dimension and a significant increase in left ventricular EF after treatment. In the HFpEF group, there was a significant decrease in E/A and E/e' after treatment. CONCLUSIONS: Aldosterone may have pathogenic role in HF. Measuring and follow-up of aldosterone levels should be considered in HF patients. MRA treatment gives a significant improvement in right side HF group.
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Insuficiencia Cardíaca , Humanos , Aldosterona/farmacología , Aldosterona/uso terapéutico , Estudios de Casos y Controles , Insuficiencia Cardíaca/diagnóstico , Insuficiencia Cardíaca/tratamiento farmacológico , Antagonistas de Receptores de Mineralocorticoides/efectos adversos , Pronóstico , Volumen Sistólico , Función Ventricular IzquierdaRESUMEN
BACKGROUND: Acute pancreatitis (AP) ranges in severity from mild to severe with high mortality. Severe AP, similar to other critical illnesses, is associated with changes in cortisol level. Early increase of high-sensitivity C-reactive protein (hs-CRP) as an inflammatory marker could be an indicator of AP progression. We aimed to assess the level of cortisol and hs-CRP on initial diagnosis of AP and identify their prognostic value. METHODS: This case-control study included patients with AP and a control group of healthy subjects. Laboratory tests such as liver profile, kidney functions, blood picture, lactate dehydrogenase, blood glucose, and lipogram were evaluated, the severity of AP was determined, the duration of hospitalization, complications, and outcomes were identified, and the serum levels of cortisol and hs-CRP were assessed. RESULTS: There were 90 patients with AP and 60 controls with a higher percent of females in both groups. Serum cortisol and hs-CRP were significantly higher in AP relative to controls and were higher in severe AP relative to mild AP. Significant positive correlation was present between high cortisol and severity of AP (r = 0.520 and p<0.001) and negatively with pancreatic necrosis (r= - 0.303 and p = 0.007) and morality (r= - 0.432, p = 0.005) while hs-CRP did not show significant correlation. CONCLUSIONS: Different levels of serum cortisol in early AP should be considered on initial diagnosis. High cortisol level was a good prognostic indicator for AP with low mortality. This could have further implications on the appropriate initiation of steroid therapy to prevent necrotizing pancreatitis and lower the mortality. Meanwhile, hs-CRP has a low prognostic value in early AP.
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Proteína C-Reactiva , Hidrocortisona , Pancreatitis Aguda Necrotizante , Enfermedad Aguda , Biomarcadores , Proteína C-Reactiva/análisis , Estudios de Casos y Controles , Femenino , Humanos , Hidrocortisona/análisis , Masculino , Pancreatitis Aguda Necrotizante/diagnóstico , Pronóstico , Índice de Severidad de la EnfermedadRESUMEN
INTRODUCTION AND OBJECTIVES: Erectile dysfunction (ED) is one of the main threats in diabetic patients. This research aimed to assess the relationship between glycated hemoglobin (HbA1c) level and pharmacopenile duplex ultrasonography (PPDU) indices in diabetic patients with ED. MATERIALS AND METHODS: A total of 130 males with ED were recruited (100 had diabetes mellitus (DM) and 30 did not as control). The International Index of Erectile Function (IIEF) was used to evaluate patients for ED. Measurement of HbA1c, lipid profile and assessment of erectile function using PPDU were performed. All participants were assessed to take the medical history. RESULTS: The mean age±SD was 53.8±8.9 and 53.6±2.8 years for patients and controls, respectively. Patients had variable grades of ED: mild in 20%, mild to moderate in 32.3%, moderate in 35.3%, and severe in 12.3%. A significant association was found between the existence of DM and a deprived response to intracorporeal injection (ICI), rising end-diastolic velocity (EDV), and reducing resistance index (RI) values. Comparing all diabetic groups according to HbA1c with controls, a significant relationship was found in; severity of IIEF-5 score, poor response to ICI, decreased peak systolic velocity (PSV) at 10min, increased EDV at 10, 20min and decreased RI at 10, 20min. A significant relationship was found between smoking, dyslipidaemia, and decreased PSV at 10, 20min and decreased increment ratio. However, a non-significant relationship was observed between age, type of DM and PPDU parameters. CONCLUSION: Poor glycaemic control of DM is associated with an increase in EDV and decrease in RI, and PSV of PPDU.
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Diabetes Mellitus , Disfunción Eréctil , Adulto , Disfunción Eréctil/diagnóstico por imagen , Disfunción Eréctil/etiología , Hemoglobina Glucada , Humanos , Masculino , Persona de Mediana Edad , Pene/diagnóstico por imagen , UltrasonografíaRESUMEN
BACKGROUND: Heart failure (HF) is a serious public health concern resulting in death. An individual predisposition to HF is determined by relationship between genetic and environmental variables. The macrophage migration inhibitory factor (MIF) is a significant mediator that involved in a variety of inflammatory and cardiovascular diseases. To reveal contribution of MIF rs755622 G173C gene variants in the promoter region towards HF pathogenesis and investigate association between recognized genotype and clinical characteristics. PATIENTS AND METHODS: We recruited 90 patients with HF, 63 with preserved ejection fraction (HFpEF) and 27 with reduced ejection fraction (HFrEF), and 60 age- and sex- matched controls. MIF rs755622 (G>C) single-nucleotide polymorphism was genotyped by PCR-RFLP method. RESULTS: The GG genotype of MIF rs755622 gene polymorphism was more frequent in HF patients than in controls which increased the risk of HF by about 4.25 times (p<0.05). The distribution of the GG, GC and CC genotypes of MIF were 42%, 21% and 0.0% among HFrEF, and 33.3%, 55.6% and 11.1% among HFpEF respectively. Higher frequency of MIF rs755622 G allele among HFrEF (100%) compared to HFpEF (88.9%) (p = 0.007). MIF-GG genotype variant had significantly lower LVEF. In multivariate analysis, MIF-GG genotype was independent risk predictor among HF (OR 4.6). CONCLUSION: MIF rs755622 (GG) could be considered as a probable genotypic risk factor for HF, especially in those with HFrEF which increases the possibility that MIF contribute to HF progression. MIF genotype assay may serve as early predictor and help to recognize those at great risk of developing HF.
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Insuficiencia Cardíaca , Factores Inhibidores de la Migración de Macrófagos , Estudios de Casos y Controles , Ecocardiografía , Predisposición Genética a la Enfermedad , Insuficiencia Cardíaca/genética , Humanos , Oxidorreductasas Intramoleculares/genética , Factores Inhibidores de la Migración de Macrófagos/genética , Regiones Promotoras Genéticas , Índice de Severidad de la Enfermedad , Volumen SistólicoRESUMEN
Breast cancer (BC) is a major concern to female health worldwide. We assessed the circulating osteocyte-related biomarkers, hepcidin, and oxidative stress status among early-stage BC patients in aspects of clinical severity and impact on the outcome. The study incorporated 73 patients categorized into 57 early-stage BC and 16 benign breast diseases and 30 healthy controls. Serum 25-hydroxyvitamin D [25(OH)D], sclerostin (SOST), dickkopf-1(DKK1), and hepcidin were measured using ELISA, while, serum oxidative stress markers were assessed by spectrophotometry. Our results show that patients with BC showed significant increase in the mean levels of DKK1, SOST, hepcidin, and LPER and significant decrease in the mean levels of 25(OH)D, SOD, GPx, and Hb when compared with controls and benign breast diseases. Significantly higher DKK1, hepcidin, and SOD levels among benign breast diseases were found in comparison to control group. There were significantly lower levels of 25(OH)D, SOD, and Hb and significantly higher levels of SOST, DKK1, hepcidin, No, and LPER with advanced grade. Lower levels of 25(OH)D, SOD and higher levels of SOST, hepcidin were observed with increasing the malignant stage. Reduced levels of 25(OH)D, and SOD were significantly associated with poor prognosis and were strong predictors among BC. There were significant negative correlations between 25(OH)D with LPER, SOST, and hepicidin. We conclude that low 25(OH)D, high SOST, DKK1, and hepcidin, and dysregulated oxidative stress could be helpful in early detection and assessment of BC. 25(OH)D, and SOD were the most relevant to tumor progression and prognosis which indicate a significant role in the BC pathogenesis and could be promising targets in management. Our research paves the way to disrupt vicious circle between these biomarkers to obtain the best care of BC.
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Proteínas Adaptadoras Transductoras de Señales/sangre , Neoplasias de la Mama/sangre , Hepcidinas/sangre , Péptidos y Proteínas de Señalización Intercelular/sangre , Vitamina D/sangre , Vitaminas/sangre , Adulto , Anciano , Biomarcadores/sangre , Estudios de Casos y Controles , Progresión de la Enfermedad , Femenino , Humanos , Persona de Mediana Edad , Osteocitos , Estrés OxidativoRESUMEN
Ketamine, a dissociative anesthetic, recently has spread as a recreational drug. Its abuse lead to neurobehavioral disturbance in addition to toxic effects on other body organs. To evaluate the toxic effects of chronic administration of low ketamine doses on the memory, testicles, and erection, explore its pathophysiology through oxidative stress mechanism and examine the ameliorating effect of N-acetyl cysteine (NAC). A total of 40 male albino rats were assigned to control, vehicle, ketamine only I.P. (10 mg/kg), and ketamine (10 mg/kg) + NAC (150 mg/kg) groups. Assessment of memory affection and erectile function by Passive Avoidance, Novel Object Recognition, and copulatory tests were performed. Estimation of malondialdehyde (MDA), catalase (CAT), and total antioxidant capacity (TAC) in serum and prefrontal & hippocampal homogenate, and luteinizing hormone (LH), testosterone in serum were done. Prefrontal cortex, hippocampus, and testes were collected for histopathology. Chronic ketamine administration induced significant memory deficits (P < 0.05), reduced erectile function (P < 0.05), severe hypospermatogenesis, increased MDA, reduced CAT, TAC levels in serum, and tissue homogenate (P < 0.05) and reduction of LH, and testosterone (P < 0.05). Treatment with NAC resulted in significant improvement of memory function, improved erectile function, and decrease in oxidative injury in both serum and tissue homogenates. Testosterone and LH levels exhibited significant difference between treatment groups and controls (P < 0.05). NAC reduced the deleterious histopathological changes. These data suggest that long-term ketamine affects short and long memory, induces erectile and testicular dysfunction through oxidative stress. Co-administration with NAC ameliorates these toxic effects.
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Acetilcisteína/uso terapéutico , Analgésicos/toxicidad , Disfunción Cognitiva/inducido químicamente , Disfunción Cognitiva/tratamiento farmacológico , Disfunción Eréctil/inducido químicamente , Disfunción Eréctil/tratamiento farmacológico , Ketamina/toxicidad , Testículo/efectos de los fármacos , Acetilcisteína/farmacología , Animales , Antioxidantes/metabolismo , Conducta Animal/efectos de los fármacos , Disfunción Cognitiva/metabolismo , Disfunción Cognitiva/patología , Disfunción Eréctil/metabolismo , Disfunción Eréctil/patología , Femenino , Hipocampo/efectos de los fármacos , Hipocampo/metabolismo , Hipocampo/patología , Hormona Luteinizante/sangre , Masculino , Corteza Prefrontal/efectos de los fármacos , Corteza Prefrontal/metabolismo , Corteza Prefrontal/patología , Ratas , Recuento de Espermatozoides , Motilidad Espermática/efectos de los fármacos , Testículo/patología , Testosterona/sangreRESUMEN
BACKGROUND/PURPOSE: This work aimed to assess the impact of different etiologies of acute pancreatitis (AP) and vitamin D receptor (VDR) TaqI rs731236 gene polymorphism on the severity of AP. METHODS: This case-control study included 70 patients with AP and 40 healthy controls. Etiologies of AP were identified by imaging, ANA, cytomegalovirus (CMV) IgM, coxsackie B virus IgM, and IgG4. Genotyping of VDR TaqI rs731236 polymorphism, Laboratory tests and severity scores using Ranson, BISAP, Atlanta and APACHE II scores were determined. RESULTS: The age in AP patients was 36.03 ± 10.76, and females were 85.7%. The etiologies of AP were as follows: biliary (51.4%), coxsackievirus (22.9%), autoimmune (14.3%), post-ERCP (8.6%) and 2.9% were idiopathic. The TT genotype of VDR polymorphism was significantly more common in AP than control (P = .001) and allele T dominated in AP group (OR = 2; 95% CI: 0.665-5.64). Most cases showed low severity scores with significant differences among etiologies and VDR genotypes. Biliary pancreatitis showed highest percentages of severe AP. However, etiologies and VDR polymorphism were not predictors of severity. CONCLUSION: Etiology of AP could have impact on the disease severity. VDR gene polymorphism increases the risk of AP. Neither the etiology nor VDR gene polymorphism could predict AP severity.
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Pancreatitis , Receptores de Calcitriol , Enfermedad Aguda , Estudios de Casos y Controles , Femenino , Predisposición Genética a la Enfermedad , Humanos , Pancreatitis/genética , Polimorfismo Genético , Receptores de Calcitriol/genéticaRESUMEN
Despite advances in the management of cardiovascular diseases, acute coronary syndrome (ACS) remains the leading cause of death worldwide. ACS is associated with an imbalance between coronary blood supply and metabolic requirements. Lipid peroxidation and production of reactive oxygen species (ROS) damage the cardiac cell membrane. A total of 130 subjects, 65 ACS patients (45 with ST segment elevation (STE-ACS), 20 non-STE-ACS), and 65 healthy controls were recruited. Measurement of serum zinc, total antioxidant capacity (TAC) and malondialdehyde (MDA) by spectrophotometric methods 24 h after onset of ACS, and relations between the studied biochemical parameters and risk factors were performed. MDA levels were significantly increased; TAC and zinc levels were significantly decreased in ACS patients compared to the controls (P < 0.001 for each). No significant difference was detected between the different types of ACS and each of the oxidative stress parameters, cardiac biomarkers, lipogram, and risk factors. Only serum zinc in STE-ACS patients was significantly lower compared with NSTE-ACS patients (P < 0.001). Serum zinc showed the greatest AUC (area under the ROC curve) of 0.926 with 76.92% sensitivity and 95.38% specificity. Negative and positive correlations between MDA and zinc and between TAC and zinc levels respectively (P < 0.01) were found in ACS. Week negative correlation was observed between serum zinc and SYNTAX score (r = - 0.434, P = 0.049). Our results indicate that deficient serum zinc concentration strongly associated with the etiopathogenesis of ACS.
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Síndrome Coronario Agudo/metabolismo , Antioxidantes/metabolismo , Peróxidos Lipídicos/metabolismo , Infarto del Miocardio con Elevación del ST/metabolismo , Zinc/sangre , Síndrome Coronario Agudo/sangre , Anciano , Estudios de Casos y Controles , Femenino , Humanos , Peroxidación de Lípido , Masculino , Malondialdehído/metabolismo , Persona de Mediana Edad , Pronóstico , Infarto del Miocardio con Elevación del ST/sangreRESUMEN
Background: Lung cancer is one of the main human health threats. Survival of lung cancer patients depends on the timely detection and diagnosis. Among the genetic irregularities that control cancer development and progression, there are microRNAs (miRNAs). This study aimed to assess the plasma level of circulating miRNA-17 and miRNA-222 as non-invasive markers in non-small-cell lung cancer (NSCLC) patients. Patients and methods: A total of 40 patients with NSCLC and 20 healthy controls who were matched in terms of age and sex with the patient group were included in this case-control study.. Estimation of miRNA-17 and miRNA-222 expression profiles in the plasma was done using quantitative real-time PCR (qRT-PCR). The relationship between both markers and their clinicopathological features were also determined. Receiver operating characteristic (ROC) curve analysis was done to evaluate the role of these microRNAs in NSCLC diagnosis and follow-up. Results: MiRNA-17 and miRNA-222 levels were significantly upregulated in NSCLC patients compared with controls (48.32±12.35 vs 1.16±0.19 and 34.53±3.1 vs 1.22±0.14) (P=0.000). Plasma miRNA-17 level was increased, and the miRNA-222 level was decreased across different stages of the disease; however, these differences d were not statistically significant (P=0.4, P=0.5, respectively). The miRNA-17 levels were higher in the lung cancer patients with metastasis , but miRNA-222 levels were lower patients without metastasis. We found no statistically significant difference in this regard(P=0.4 vs P=0.3, respectively). ROC curve analysis showed that the sensi¬tivity and specificity of miRNA-17 were 77.78% and 87.50% , and of miRNA-222 were 50% and 88.89%. Conclusion: MiRNA-17 and miRNA-222 can be considered as non-invasive biomarkers for detection of early lung carcinogenesis and metastasis in patients with NSCLC, hence providing a basis for the development of novel therapeutic approaches.
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Adenocarcinoma/sangre , Biomarcadores de Tumor/genética , Carcinoma de Células Grandes/sangre , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Células Escamosas/sangre , Neoplasias Pulmonares/sangre , MicroARNs/genética , Adenocarcinoma/genética , Adenocarcinoma/secundario , Adenocarcinoma/cirugía , Biomarcadores de Tumor/sangre , Carcinoma de Células Grandes/genética , Carcinoma de Células Grandes/secundario , Carcinoma de Células Grandes/cirugía , Carcinoma de Pulmón de Células no Pequeñas/genética , Carcinoma de Pulmón de Células no Pequeñas/patología , Carcinoma de Pulmón de Células no Pequeñas/cirugía , Carcinoma de Células Escamosas/genética , Carcinoma de Células Escamosas/secundario , Carcinoma de Células Escamosas/cirugía , Estudios de Casos y Controles , Egipto , Femenino , Estudios de Seguimiento , Regulación Neoplásica de la Expresión Génica , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patología , Neoplasias Pulmonares/cirugía , Masculino , MicroARNs/sangre , Persona de Mediana Edad , Pronóstico , Curva ROCRESUMEN
BACKGROUND AND AIM: Lung Cancer (LC) is a major cancer killer worldwide, and 5-yr survival is extremely poor (≤15%), accentuating the need for more effective diagnostic and therapeutic strategies. Studies have shown cell-free microRNAs (miRNAs) circulating in the serum and plasma with specific expression in cancer, indicating the potential of using miRNAs as biomarkers for cancer diagnosis and therapy. This study aimed to identify differentially-expressed two miRNAs in the plasma of Non-Small Cell Lung Cancer (NSCLC) patients that might be a clinically useful tool for lung cancer early detection. miRNA-21 is one of the most abundant oncomirs. miRNA-23a functions as an oncogene in several human cancers, however, its clinical value has not been investigated in NSCLC. MATERIALS AND METHODS: A case-control study was conducted in Assiut University Hospital, Egypt, from 2017 to 2018. Plasma samples were obtained from 45 NSCLC patients. The expression level of miR-21 and miRNA-23a was detected by qRT-PCR and compared to 40 healthy control subjects. The relation between both miRNAs and clinicopathological parameters was evaluated. RESULTS: The expression level of miR-21 and miRNA-23a was significantly up-regulated (36.9 ± 18.7 vs. 1.12 ± 0.84 and 24.7 ± 19.09 vs. 1.16 ± 0.45) in NSCLC compared to matched controls (P<0.0001each). There was a significant difference in the level of plasma miRNA-21 and miRNA- 23a expression between the different grades of the disease (P = 0.032 and P = 0.001, respectively). The plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with distant metastasis (n = 20) were significantly higher than those in the patients without metastasis (n = 25) (P<0.0001 each), the expression of miR-21 and miRNA-23a was significantly associated with tumor size (P = 0.001, P = 0.0001, respectively), but not significantly related to lymph node metastasis (P = 0.687 and 0.696, respectively). A positive correlation was observed between miRNA-21 and miRNA-23a (r = 0.784, P<0.01), There was no significant difference in the plasma miRNA-21 and miRNA-23a levels in the lung cancer patients with different histopathological types. CONCLUSION: miR-21 and miR-23a might play an oncogenic role in LC and is a poor prognostic factor. Switching off miRNA-21 and miRNA-23a may improve the treatment of LC. Our results must be verified by large-scale prospective studies with standardized methodology.
Asunto(s)
Biomarcadores de Tumor/sangre , Carcinoma de Pulmón de Células no Pequeñas/diagnóstico , Neoplasias Pulmonares/diagnóstico , MicroARNs/sangre , MicroARNs/genética , Biomarcadores de Tumor/genética , Carcinoma de Pulmón de Células no Pequeñas/sangre , Carcinoma de Pulmón de Células no Pequeñas/genética , Estudios de Casos y Controles , Femenino , Humanos , Neoplasias Pulmonares/sangre , Neoplasias Pulmonares/genética , Masculino , MicroARNs/aislamiento & purificación , Persona de Mediana EdadRESUMEN
Telomere length dysfunction is involved in the generation of genomic rearrangements that drive progression to malignancy. A set of serological markers for telomere dysfunction, namely chitinase and N-acetylglucosaminidase (NAG), DNA damage, and tissue alteration of p53 have been identified. The probability that genomic damage, accumulation of reactive oxygen species, and shorter telomeres may be related to the onset and advancement of gastrointestinal (GI) tumors. A total of 40 patients with GI tumors and 20 healthy controls with matched age and sex were included. Estimation of serum chitinase, NAG, lipid peroxide (LPER), glutathione peroxidase (GPx), superoxide dismutase (SOD), catalase by colorimetric methods, and p53 by ELISA were assessed. Related clinicopathological features were determined. Serological chitinase, NO, LPER, and p53 were significantly increased, SOD was significantly decreased (p Ë 0.001 for each) in GI tumor patients compared with controls and correlated significantly with age. There was a significant correlation between telomere dysfunction indices, p53, oxidative stress indices, and malignant stages of GI cancer patients. Moreover, a significant difference in the mean serum levels of indices between control, malignant, and benign subjects was found. Accordingly, these biomarkers play an important role in the pathogenesis of GI cancer and their estimation may predict the GI tumor behavior.