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1.
Mol Genet Genomics ; 299(1): 56, 2024 May 24.
Artigo em Inglês | MEDLINE | ID: mdl-38787424

RESUMO

Breast cancer (BC) is a heterogenous disease with multiple pathways implicated in its development, progression, and drug resistance. Autophagy, a cellular process responsible for self-digestion of damaged organelles, had been recognized as eminent player in cancer progression and chemotherapeutic resistance. The haploinsufficiency of Beclin 1 (BECN1), autophagy protein, is believed to contribute to cancer pathogenesis and progression. In our study, we investigated the expression of BECN1 in a BC female Egyptian patient cohort, as well as its prognostic role through evaluating its association with disease free survival (DFS) after 2 years follow up and association of tumor clinicopathological features. Twenty frozen female BC tissue samples and 17 adjacent normal tissue were included and examined for the expression levels of BECN1. Although the tumor tissues showed lower expression 0.73 (0-8.95) than their corresponding normal tissues 1.02 (0.04-19.59), it was not statistically significant, p: 0.463. BECN1 expression was not associated with stage, nodal metastasis or tumor size, p:0.435, 0.541, 0.296, respectively. However, statistically significant negative correlation was found between grade and BECN1 mRNA expression in the studied cases, p:0.028. BECN1 expression had no statistically significant association with DFS, P = 0.944. However, we observed that triple negative (TNBC) cases had significantly lower DFS rate than luminal BC patients, p: 0.022, with mean DFS 19.0 months, while luminal BC patients had mean DFS of 23.41 months. Our study highlights the potential role of BECN1 in BC pathogenesis, showing that BECN1 expression correlates with poorer differentiation of BC, indicating its probable link with disease aggressiveness. DFS two years follow up showed that TNBC subtype remains associated with less favorable prognosis.


Assuntos
Proteína Beclina-1 , Neoplasias da Mama , Gradação de Tumores , RNA Mensageiro , Humanos , Feminino , Proteína Beclina-1/genética , Proteína Beclina-1/metabolismo , Neoplasias da Mama/genética , Neoplasias da Mama/patologia , Pessoa de Meia-Idade , Adulto , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Prognóstico , Regulação Neoplásica da Expressão Gênica , Intervalo Livre de Doença , Biomarcadores Tumorais/genética , Idoso , Egito
2.
Sci Rep ; 13(1): 18330, 2023 10 26.
Artigo em Inglês | MEDLINE | ID: mdl-37884543

RESUMO

Hepatitis C virus (HCV) infection can regulate the number and dynamics of mitochondria, and is associated with a prominent hepatic mitochondrial injury. Mitochondrial distress conveys oxidative damage which is implicated in liver disease progression. The present study was conducted to assess the change of mitochondrial DNA (mtDNA) copy number in patients with HCV-related chronic liver disease and the impact of direct-acting antiviral (DAA) therapy. Whole blood mtDNA copy number was measured using real-time quantitative polymerase chain reaction at baseline and 12 weeks after the end of therapy in 50 treatment-naïve HCV-infected patients who achieved sustained viral response (SVR) after DAA therapy and 20 healthy controls. Whole blood mtDNA copy number appeared significantly lower in HCV-infected patients before therapy compared to healthy subjects (P < 0.001). Post-treatment, there was significant increase of mtDNA copy number in HCV-infected patients at SVR12 compared to the pre-treatment values (P < 0.001), meanwhile it didn't differ significantly between HCV-infected patients after therapy and healthy subjects (P = 0.059). Whole blood mtDNA copy number correlated inversely to the serum bilirubin in HCV-infected patients (P = 0.013), however it didn't correlate significantly to the serum aminotransferases, viral load or fibrosis-4 score (P > 0.05). In conclusion, chronic HCV infection has been associated with a prominent mitochondrial injury which could mediate a progressive liver disease. The improved mtDNA content after DAA therapy highlights a possible potential of these drugs to alleviate mitochondrial damage in HCV-related liver disease.


Assuntos
Hepatite C Crônica , Hepatite C , Humanos , Antivirais/uso terapêutico , Hepacivirus/genética , Hepatite C Crônica/tratamento farmacológico , Hepatite C Crônica/genética , Hepatite C Crônica/complicações , DNA Mitocondrial/genética , DNA Mitocondrial/análise , Variações do Número de Cópias de DNA , Hepatite C/tratamento farmacológico , Mitocôndrias/genética , Mitocôndrias/química
3.
Int J Rheum Dis ; 26(11): 2195-2205, 2023 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-37731289

RESUMO

INTRODUCTION: To investigate the radiological and laboratory features of bone and cartilage losses in premenopausal women with rheumatoid arthritis (RA). METHODS: This case-control study is the continuation of a study that was conducted on 48 women with RA and 48 matched healthy volunteers. All RA patients were previously subjected to clinical examination, disease activity assessment using the 28-joint Disease Activity Score (DAS28) and Clinical Disease Activity Index (CDAI), serological tests, dual-energy X-ray absorptiometry measuring bone mineral density (BMD), and plain X-ray of both hands. Added to these, matrix metalloproteinase 3 (MMP-3) and cartilage oligomeric matrix protein (COMP) were measured by enzyme-linked immunosorbent assay. RESULTS: There were statistically significant differences between patients and controls regarding COMP and MMP-3, being higher in patients (p < .001). COMP and MMP-3 have significant positive correlation with serum levels of anti-cyclic citrullinated peptide (anti-CCP) and anti-carbamylated protein (anti-CarP). The original Sharp erosion score was positively correlated with the serum level of the studied antibodies and disease duration, but no significant correlation was found with either COMP, MMP-3, or DAS-28. Spine BMD and Z score were negatively correlated with disease activity and anti-CarP. There were significant positive relationhsips between indices of local cartilage and bone loss and the indices of systemic bone loss. MMP-3 had no correlation with indices of local cartilage and bone loss and disease activity scores. CONCLUSIONS: The pathogenic mechanism of hand joint damage involved the three studied autoantibodies namely, rheumatoid factor, anti-CCP and anti-CarP antibodies. Anti-CarP antibody was involved in the reduction of BMD of the spine. The association between systemic osteoporosis and hand joint damage pointed to a common pathogenic mechanism.


Assuntos
Artrite Reumatoide , Metaloproteinase 3 da Matriz , Humanos , Feminino , Estudos de Casos e Controles , Anticorpos Antiproteína Citrulinada , Artrite Reumatoide/diagnóstico por imagem , Autoanticorpos , Densidade Óssea , Cartilagem/patologia
4.
J. coloproctol. (Rio J., Impr.) ; 43(3): 166-170, July-sept. 2023. tab, graf, ilus
Artigo em Inglês | LILACS | ID: biblio-1521148

RESUMO

Purpose: Colorectal cancer (CRC) is one of the most fatal tumors worldwide. In Egypt, most CRC cases occur in individuals > 40 years old. TUG1 has been proved to be disrupted in different malignancies and may have a critical role in tumor progression, invasion, and metastasis. However, its role in CRC has not been adequately studied. Materials / Methods: Quantitative real-time polymerase chain reaction (PCR) was used to evaluate the expression levels of long non-coding RNA (LncRNA) taurine upregulated gene 1 (TUG1), in nonmetastatic and metastatic CRC tissues and adjacent noncancerous tissues as control. Results: LncRNA TUG1 expression was significantly upregulated in both nonmetastatic and metastatic CRC tissues, in comparison with the adjacent noncancerous tissue. It was found that TUG1 could have a possible prognostic role in CRC, by comparing the sensitivity and specificity of TUG1 with those of CEA and CA19-9. Conclusion: The results of the current study suggest that the LncRNA TUG1 participates in the malignant behaviors of CRC cells. (AU)


Assuntos
Humanos , Masculino , Feminino , Adulto , Pessoa de Meia-Idade , Idoso , Idoso de 80 Anos ou mais , Adenocarcinoma , Reação em Cadeia da Polimerase Via Transcriptase Reversa , RNA Longo não Codificante , Neoplasias Colorretais/patologia
5.
Arch Dermatol Res ; 315(7): 2107-2118, 2023 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-36961533

RESUMO

Hypoxia-inducible factor-1α (HIF-1α) is the master transcription factor of glycolysis, Th17 cell differentiation and suppression of regulatory T cells. In the skin and serum of patients with psoriasis vulgaris, increased expression of HIF-1α has been reported, whereas HIF-1α expression in the skin and serum of patients with hidradenitis suppurativa (HS) has not yet been studied. The objective of the study is to demonstrate is there a role for HIF-1α in the pathogenesis of hidradenitis suppurativa, and its relation to HS severity. Twenty patients suffering from hidradenitis suppurativa were included in the study. Punch biopsies were taken from lesional skin for the determination of HIF-1α expression by immunohistochemical staining, and HIF-1α gene expression by quantitative reverse transcription real time PCR. Quantification of HIF-1α protein concentration was done by enzyme-linked immunosorbent assay. Twenty socio-demographically cross-matched healthy volunteers served as controls. We found increased serum levels of HIF-1α. Literature-derived evidence indicates that the major clinical triggering factors of HS, obesity, and smoking are associated with hypoxia and enhanced HIF-1α expression. Pro-inflammatory cytokines such as tumor necrosis factor-[Formula: see text] via upregulation of nuclear factor [Formula: see text]B enhance HIF-1α expression. HIF-1α plays an important role for keratinocyte proliferation, especially for keratinocytes of the anagen hair follicle, which requires abundant glycolysis providing sufficient precursors molecules for biosynthetic pathways. Metformin via inhibition of mTORC1 as well as adalimumab attenuate HIF-1α expression, the key mediator between Th17-driven deviated immunity and keratinocyte hyperproliferation. In accordance with psoriasis, our study identifies HS as an HIF-1α-driven inflammatory skin disease and offers a new rationale for the prevention and treatment of HS by targeting HIF-1[Formula: see text] overexpression.


Assuntos
Hidradenite Supurativa , Psoríase , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia , Pele/patologia , Regulação da Expressão Gênica
6.
Arch Dermatol Res ; 315(5): 1355-1365, 2023 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-36585988

RESUMO

The transcriptomic regulation induced by isotretinoin (13-cis retinoic acid) is still a matter of debate as short-term exposures of immortalized sebocytes with isotretinoin produced conflicting results. Based on translational evidence, it has been hypothesized that oral isotretinoin treatment upregulates the expression of the transcription factor p53. Twenty-five patients suffering from acne vulgaris were treated with isotretinoin (0.6 mg/kg body weight) for 6 weeks. Biopsies from back skin were taken before and after isotretinoin treatment for the determination of p53 expression by immunohistochemical staining, quantification of p53 protein concentration by enzyme-linked immunosorbent assay and TP53 gene expression by quantitative reverse transcription real time PCR. Fifteen socio-demographically cross-matched healthy volunteers served as controls. Isotretinoin treatment significantly increased the nuclear expression of p53 in sebaceous glands of treated patients compared to pre-treatment levels and p53 levels of untreated controls. Furthermore, the p53 protein and gene expression significantly increased in the skin after treatment. The magnitude of p53 expression showed an inverse correlation to acne severity score and body mass index. Under clinical conditions, isotretinoin induced the expression of p53, which controls multiple transcription factors involved in the pathogenesis of acne vulgaris including FoxO1, androgen receptor and critical genes involved in the induction of autophagy and apoptosis. Increased p53-FoxO1 signalling enhanced by systemic isotretinoin treatment explains the underlying transcriptomic changes causing sebum suppression but also the adverse effects associated with systemic isotretinoin therapy.


Assuntos
Acne Vulgar , Isotretinoína , Glândulas Sebáceas , Pele , Humanos , Acne Vulgar/tratamento farmacológico , Acne Vulgar/genética , Acne Vulgar/patologia , Isotretinoína/farmacologia , Isotretinoína/uso terapêutico , Glândulas Sebáceas/efeitos dos fármacos , Glândulas Sebáceas/metabolismo , Pele/efeitos dos fármacos , Pele/patologia , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismo
7.
Clin Exp Hepatol ; 8(2): 139-146, 2022 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36092759

RESUMO

Aim of the study: Homeobox transcript antisense intergenic RNA (HOTAIR) is a long non-coding RNA classified as an oncogene and has been implicated in liver cancer initiation and progression. This study investigated the clinical usefulness of serum HOTAIR to predict hepatocellular carcinoma (HCC) and prefigure the tumor stage. Material and methods: This study included 80 patients with de novo HCC divided into 40 late-stage HCC patients (group IA) and 40 early-stage HCC patients (group IB), 40 patients with non-tumorous liver cirrhosis (group II), and 20 healthy controls (group III). Serum HOTAIR was measured using real-time quantitative polymerase chain reaction. Serum α-fetoprotein (AFP) was measured via enzyme-linked immunosorbent assay. Results: Serum HOTAIR was significantly higher in groups IA, IB and II compared to healthy subjects. Serum HOTAIR was significantly higher in group IA than group IB, and in groups IA and IB compared to group II. Serum HOTAIR at cut-off value > 15.45 (AUC = 0.71) showed 66% sensitivity and 78% specificity in discriminating HCC patients of group IB from HCC patients of group IA. When combined with AFP, the discriminative sensitivity and specificity increased to 74% and 90% respectively (AUC = 0.85). Serum HOTAIR at cut-off value > 9.42 (AUC = 0.823) showed 67.5% sensitivity and 93.3% specificity in discriminating HCC patients of group IB from patients with non-tumorous cirrhotic liver. When combined with AFP, the discriminative sensitivity and specificity increased to 80% and 98.3% respectively (AUC = 0.954). Conclusions: Circulating HOTAIR is a potential biomarker which may be used solely, or preferably in combination with AFP, to help HCC detection in cirrhotic liver and prefigure the tumor stage.

8.
Fundam Clin Pharmacol ; 36(4): 731-741, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35106814

RESUMO

Diabetic dyslipidemia is a significant contributor in the pathogenesis of type 2 diabetes (T2D). The study aimed at comparing the effect of dapagliflozin, liraglutide, and atorvastatin alone or their combinations on lipids and inflammatory markers and their vascular impact in T2D rats. There were 56 male albino rats included in the study and divided into two main groups. Group A (8 rats) served as normal control. Group B (48 rats) were streptozotocin-nicotinamide-induced diabetic rats. Subgroups (B-1, B-2, B-3, B-4, B-5, and B-6) received (no medications, dapagliflozin, liraglutide, atorvastatin, dapagliflozin + atorvastatin, and liraglutide + atorvastatin), respectively. Urine albumin/creatinine ratio (UACR), glycosylated hemoglobin (HBA1c), fasting serum glucose (FSG), serum low-density lipoprotein-cholesterol (LDL-C), high-density lipoprotein-cholesterol (HDL-C), TGs, lipoprotein(a) Lp (a), serum thyrotropin (TSH), highly sensitive C-reactive protein (hs-CRP) and advanced glycation end products (AGEs), were assessed. Qualitative and quantitative histological examination of kidneys focused on renal corpuscles. Dapagliflozin improved the studied parameters but with statistically insignificant increase in LDL-C, Lp (a) and significant increase in UACR. Atorvastatin improved the studied parameters but with statistically insignificant increase in FSG and HbA1C. Liraglutide and the combination groups significantly improved all studied parameters. Histologically, liraglutide and atorvastatin produced therapeutic effect, while dapagliflozin depicted nephrotoxic effect. Combination groups resulted in better effects with normalization of most of renal corpuscles. There were positive correlations between LDL-C and hs-CRP, AGEs, TSH and mesangial expansion. Combination of atorvastatin with liraglutide can improve its vasculoprotective effect. Moreover, combination of atorvastatin with dapagliflozin can ameliorate its possible nephrotoxic effect.


Assuntos
Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 2 , Animais , Masculino , Atorvastatina/farmacologia , Atorvastatina/uso terapêutico , Compostos Benzidrílicos , Proteína C-Reativa/metabolismo , LDL-Colesterol/uso terapêutico , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Glucosídeos , Hemoglobinas Glicadas/metabolismo , Hemoglobinas Glicadas/uso terapêutico , Liraglutida/farmacologia , Liraglutida/uso terapêutico , Pirróis , Tireotropina/uso terapêutico , Ratos
9.
Mol Biol Rep ; 48(5): 4351-4360, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-34076790

RESUMO

The search for novel non-invasive biomarkers such as epigenetic molecular markers is new hope for common and burdensome cancers. We aim to assess serum expression of miRNA 27a and miRNA150-5p in endometrial cancer patients. Serum was drawn for 36 un-intervened endometrial cancer patients scheduled for hysterectomy and 35 controls. miRNA 27a and miRNA150-5p were measured by real time reverse transcription polymerase chain reaction. Significant overexpression of both miRNA in patients (p < 0.001). At cutoffs 0.2872 & > 1.02, miRNA 27a showed 100% sensitivity, specificity, positive and negative predictive values. miRNA150-5p showed 88.89% sensitivity, 100% specificity, 100% positive and 78.9% negative predictive values. Areas under curve were 1.0 for miRNA 27a, 0.982 for miRNA 150 performing much better than Ca125. miRNA 27a was significantly associated with type I endometroid endometrial cancer. Conclusion: miRNA 27a and miRNA-150-5P can be suggested as promising biomarkers of endometrial cancer possibly part of a miRNA panel for management.


Assuntos
MicroRNA Circulante/genética , Neoplasias do Endométrio/genética , Regulação Neoplásica da Expressão Gênica , Expressão Gênica , MicroRNAs/genética , Adulto , Idoso , Área Sob a Curva , Biomarcadores Tumorais/sangue , Biomarcadores Tumorais/genética , Antígeno Ca-125/sangue , Estudos de Casos e Controles , MicroRNA Circulante/sangue , Neoplasias do Endométrio/sangue , Feminino , Humanos , MicroRNAs/sangue , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Reação em Cadeia da Polimerase em Tempo Real/métodos , Reação em Cadeia da Polimerase Via Transcriptase Reversa
10.
Parasitol Int ; 80: 102201, 2021 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-33010472

RESUMO

Intestinal schistosomiasis, one of the neglected tropical diseases whose control depends on accurate diagnosis of the disease prevalence. The use of low sensitive Kato Katz (KK) fecal egg detection method as a reference gold standard is not an accurate indication especially in low transmission areas. Latent class analysis frameworks especially the Bayesian could be used instead to compare between different diagnostic tests without the use of a gold standard method as a reference. Thus, this study compared two urine-based tests for the detection of circulating antigen and cell free DNA of Schistosoma mansoni versus KK method using the Bayesian latent class analytical framework and in two models where the trace results of point of contact - assay of circulating cathodic antigen (POC-CCA) were once estimated as positive, and as negative in the other model. The Bayesian framework in the trace CCA positive model showed an estimate of disease prevalence of 26% (95% BCI:0 to 60%). POC-CCA showed the highest sensitivity (74% with BCI: 9 to 91%) and lowest specificity for (20% with BCI: 0% to 37%) and the reverse for KK. For POC-CCA with traces considered negative, it was found that results between the three tests were moderated where the positivity for infection by Schistosoma antigen detection and PCR for cell free DNA approached that estimated by the Bayesian framework (44%), and the specificity for point of contact assay(81%; 95%BCI: 59% to 100%) rose in hand with its sensitivity(77%, 95% BCI:53% to 100%) and with results for PCR test (sensitivity = 80%; 95% BCI: 61% to 100%, specificity = 69%; 95% BIC: 47% to 100%). KK remains with the highest specificity while its sensitivity in the two models never exceeded 22%. Thus, we conclude that the use of a single urine sample could be very sensitive and highly specific in the diagnosis of intestinal schistosomiasis using either the trace negative model of point of contact assay, or conventional PCR, when compared to the fecal egg detection using duplicate KK. However, the use of a single tool restricts the management of the disease in areas of low endemicity.


Assuntos
Testes Diagnósticos de Rotina/métodos , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/diagnóstico , Adulto , Animais , Teorema de Bayes , Egito/epidemiologia , Feminino , Humanos , Masculino , Prevalência , Esquistossomose mansoni/epidemiologia , Esquistossomose mansoni/parasitologia , Esquistossomose mansoni/urina , Sensibilidade e Especificidade , Adulto Jovem
11.
Rheumatology (Oxford) ; 60(3): 1419-1428, 2021 03 02.
Artigo em Inglês | MEDLINE | ID: mdl-32995835

RESUMO

OBJECTIVES: Anti-carbamylated protein antibodies (anti-CarP Abs) are present in patients with RA, however, their association with bone loss is not confirmed. The purpose of this study was to determine the relation between the serum level of anti-CarP Abs in premenopausal RA women and disease activity and bone loss. METHODS: This case-control study was conducted on 48 premenopausal women with RA and 48 matched healthy premenopausal women. All RA women were subjected to clinical examination, disease activity assessment using the 28-joint DAS (DAS28) and Clinical Disease Activity Index (CDAI), functional assessment using the HAQ, physical activity assessment using the International Physical Activity Questionnaire (IPAQ), fatigue assessment using the Modified Fatigue Impact Scale (MFIS), serological tests as well as anti-CarP Abs using ELISA. Moreover, the BMD was measured by DXA and plain X-ray of both hands was done to assess juxta-articular osteopenia and erosions. RESULTS: The anti-CarP Abs level was significantly higher in RA patients than in healthy controls. The serum level of anti-CarP Abs had a significant positive correlation with the RA DAS28, CDAI, HAQ, MFIS and original Sharp score, while a significant negative correlation was present with the IPAQ. Anti-CarP Abs were negatively correlated with either spine BMD or Z-score and positively correlated with the original Sharp score. CONCLUSION: Anti-CarP Abs were higher in premenopausal RA women compared with older and BMI matched healthy women. Anti-CarP Abs are associated with higher RA disease activity, increased disability and fatigability and decreased physical activity. Moreover, anti-CarP Abs are associated with systemic trabecular bone loss as well as local bone loss.


Assuntos
Artrite Reumatoide/patologia , Autoanticorpos/imunologia , Osteoporose/imunologia , Pré-Menopausa/imunologia , Carbamilação de Proteínas/imunologia , Adulto , Artrite Reumatoide/imunologia , Estudos de Casos e Controles , Feminino , Humanos , Pessoa de Meia-Idade , Osteoporose/patologia , Índice de Gravidade de Doença
12.
J Clin Lab Anal ; 34(11): e23397, 2020 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-33161598

RESUMO

Cholangiocarcinoma (CCA) is a rare tumor which requires a multimodality approach for its diagnosis. Carbohydrate antigen 19-9 (CA19-9) is currently the most commonly used tumor marker for CCA; nevertheless, it has certain limitations which need to be considered when using it as a tumor marker. MiRNA-150 altered expression has been linked to the development and tumorigenesis of several cancers including CCA. This work aimed to study the serum level of CA19-9 and miRNA-150 expression in CCA patients and, also, to correlate their levels with tumor staging and different studied clinical and laboratory parameters. This work included 35 patients with CCA who were admitted to Hepatobiliary Unit, Alexandria Main University Hospital (Group I). Also, 35 age- and sex-matched healthy subjects were included as a control group (Group II). All included subjects were submitted to measurement of serum CA19-9 and MiRNA-150 expression levels. Serum CA19-9 levels showed an evident high median among CCA patients, while serum miRNA-150 expression levels were evidently low among those patients. Moreover, combining miRNA-150 with CA19-9 made the accuracy of diagnosis of CCA much more reliable. Thus, miRNA-150 can be considered as a non-invasive, sensitive serum biomarker for the diagnosis of CCA especially when combined with CA 19-9.


Assuntos
Neoplasias dos Ductos Biliares , Colangiocarcinoma , MicroRNA Circulante/sangue , MicroRNAs/sangue , Neoplasias dos Ductos Biliares/sangue , Neoplasias dos Ductos Biliares/diagnóstico , Neoplasias dos Ductos Biliares/epidemiologia , Biomarcadores Tumorais/sangue , Antígeno CA-19-9/sangue , Estudos de Casos e Controles , Colangiocarcinoma/sangue , Colangiocarcinoma/diagnóstico , Colangiocarcinoma/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Fatores de Risco
13.
Int J Rheumatol ; 2020: 6069484, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32831850

RESUMO

Over the last decades, there has been an increasing need to discover new diagnostic RA biomarkers, other than the current serologic biomarkers, which can assist early diagnosis and response to treatment. The purpose of this study was to analyze the serum peptidomic profile in patients with rheumatoid arthritis (RA) by using matrix-assisted laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF-MS). The study included 35 patients with rheumatoid arthritis (RA), 35 patients with primary osteoarthritis (OA) as the disease control (DC), and 35 healthy controls (HC). All participants were subjected to serum peptidomic profile analysis using magnetic bead (MB) separation (MALDI-TOF-MS). The trial showed 113 peaks that discriminated RA from OA and 101 peaks that discriminated RA from HC. Moreover, 95 peaks were identified and discriminated OA from HC; 38 were significant (p < 0.05) and 57 nonsignificant. The genetic algorithm (GA) model showed the best sensitivity and specificity in the three trials (RA versus HC, OA versus HC, and RA versus OA). The present data suggested that the peptidomic pattern is of value for differentiating individuals with RA from OA and healthy controls. We concluded that MALDI-TOF-MS combined with MB is an effective technique to identify novel serum protein biomarkers related to RA.

14.
Andrologia ; 52(3): e13525, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32022285

RESUMO

The pathophysiology of varicocele remains to be unknown. Several genetic factors have been implicated in varicocele etiopathogenesis. We studied the relationship between NOS3 c.894G>T, c.786T>C and 4b/a polymorphisms to varicocele risk and their prognostic value as regards improvement of the post-operative seminal parameters &/or seminal malonaldehyde levels. The three NOS3 polymorphisms were evaluated in 100 patients with varicocele and 100 healthy subjects by RT-PCR. Seminal plasma MDA level was measured pre-operatively and 3 months after varicocelectomy by the thiobarbituric acid method. The GT, TT, TC and bb genotypes of NOS3 polymorphism were more commonly observed in varicocele patients (30%, 9%, 28% and 70% respectively) compared to normal controls (12%, 0%, 10% and 50% respectively). The mean percentage of post-varicocelectomy seminal MDA reduction was highest with the GT genotype (p < .001). Genotypes GT+TT, TC and bb were associated with varicocele occurrence in our patients. The T (c.894G>T), C (c.786T>C) and b (NOS3 intron 4 VNTR) alleles were significantly associated with varicocele occurrence in our cohort of patients. We also report a better response regarding the reduction of seminal MDA after varicocelectomy with the GT and ba genotypes.


Assuntos
Infertilidade Masculina/prevenção & controle , Óxido Nítrico Sintase Tipo III/genética , Procedimentos Cirúrgicos Urológicos Masculinos , Varicocele/genética , Procedimentos Cirúrgicos Vasculares , Adulto , Estudos de Casos e Controles , Predisposição Genética para Doença , Humanos , Incidência , Infertilidade Masculina/genética , Infertilidade Masculina/patologia , Masculino , Malondialdeído/análise , Malondialdeído/metabolismo , Pessoa de Meia-Idade , Estresse Oxidativo/genética , Polimorfismo de Nucleotídeo Único , Prognóstico , Sêmen/metabolismo , Cordão Espermático/irrigação sanguínea , Cordão Espermático/cirurgia , Resultado do Tratamento , Varicocele/epidemiologia , Varicocele/cirurgia
15.
Biomed Chromatogr ; 34(3): e4743, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31715013

RESUMO

Lipotoxicity is defined as deposition of excess fat associated with an inflammatory response. Metabolomic analysis of fatty acids (FAs) can be a marker of silent inflammation. ω3-Enriched diet, celecoxib, and safranal may have a protective anti-inflammatory role. In this work, total FAs extracted from red blood cells and arachidonic acid-to-eicosapentaenoic acid (AA-to-EPA) ratios were assessed using GC-MS assay in single-ion monitoring mode. The study was conducted on 64 male rats divided into eight groups: I, controls; II, rats received high-fat diet (HFD), III, rats received ω-6-enriched HFD; IV, rats received ω-3-enriched HFD; V, rats received celecoxib with HFD; VI, rats received safranal with HFD; VII and VIII, rats received celecoxib and safranal with ω-3 HFD, respectively. GC-MS Gas chromatography Mass spectrometry was performed for analysis of fatty acid methyl ester. Enzyme-linked immunosorbent assay was used to analyze serum interleukin-6 (IL-6) and transforming growth factor-beta 1 (TGF-ß1) concentrations. A statistically significant decrease of AA-to-EPA ratio was observed in group VII when compared with the groups receiving HFDs. This group also showed the lowest serum IL-6 level and highest TGF-ß1 level. In conclusion, ω3-enriched diet along with drugs (e.g. celecoxib) and herbal medications (e.g. safranal) may have an anti-inflammatory effect in lipotoxicity. GC-MS with single-ion monitoring is valid for the analysis of FAs.


Assuntos
Anti-Inflamatórios/farmacologia , Dieta Hiperlipídica , Ácidos Graxos Insaturados , Inflamação/metabolismo , Obesidade/metabolismo , Animais , Celecoxib/farmacologia , Citocinas/sangue , Citocinas/metabolismo , Modelos Animais de Doenças , Ácidos Graxos Insaturados/sangue , Ácidos Graxos Insaturados/farmacologia , Cromatografia Gasosa-Espectrometria de Massas/métodos , Masculino , Ratos
16.
Asian Pac J Cancer Prev ; 20(7): 2145-2152, 2019 07 01.
Artigo em Inglês | MEDLINE | ID: mdl-31350978

RESUMO

Abdominal imaging leads to the detection of a large number of renal tumors without the ability to distinguish the type of tumor detected. It is necessary to find a precise way to know the type of tumor to determine the appropriate treatment. The use of urine samples for detecting new biomarkers especially proteins has a great potential. In this work we assessed the proteomic profiling difference in a cohort of Egyptian population with renal neoplasms. Methods: This cohort study was conducted on 85 subjects. They were classified as 40 RCC, 15 benign kidney patients, and 30 healthy controls. Morning urine samples were used for peptidome separation using magnetic beads. Matrix assisted laser desorption ionization time of flight mass spectrometry (MALDI-TOF MS) was applied Using FlexControlTM software. Results: Benign tumors were differentiated from controls by 5 integrated peaks, 12 significant and 2 integrated significant peaks, 17:3,418.8 and 25:4,173.41. While RCC were differentiated from benign by 5 integrated, 28 significant and one integrated significant peak. The RCC group was discriminated from the controls by 5 peaks which were integrated from which 1 was integrated and significant (with mass to charge ratio of 12:3,408.97). The three groups showed protein profiles ranging from 1 to 10 kDa. The external validation was performed for the RCC group versus the control reveled sensitivity of 88.7% and specificity of 73.2% by genetic algorithm. Conclusion: Proteomic approach can be used as a sensitive urinary marker differentiating renal masses in an early diagnostic approach.


Assuntos
Biomarcadores Tumorais/metabolismo , Carcinoma de Células Renais/diagnóstico , Neoplasias Renais/classificação , Neoplasias Renais/diagnóstico , Proteoma/análise , Adulto , Idoso , Carcinoma de Células Renais/metabolismo , Estudos de Casos e Controles , Estudos de Coortes , Diagnóstico Diferencial , Feminino , Seguimentos , Humanos , Neoplasias Renais/metabolismo , Masculino , Pessoa de Meia-Idade , Prognóstico
17.
Trop Med Int Health ; 24(3): 371-378, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30549391

RESUMO

OBJECTIVE: To evaluate three non-invasive assays for the diagnosis of schistosomiasis mansoni in an Egyptian village. METHODS: Urine was collected for the detection of circulating cathodic antigen (CCA) and cell-free parasite DNA (cfpd) by Point-of-contact (POC)-cassette assay and PCR, respectively. These tests were compared to Kato-Katz (KK) faecal thick smear for detection of Schistosoma mansoni eggs. RESULTS: Disease prevalence by POC-CCA assay was 86%; by PCR it was 39% vs. 27% by KK. Compared to KK, the sensitivity of POC-CCA reached 100%, but its specificity was only 19.2% with 41% accuracy. Sensitivity of the PCR assay for cfpd was 55.56%, and specificity was 67.12% with 64% accuracy. A new end point was calculated for combined analysis of KK, POC-CCA assay and PCR. Sensitivity for the three tests was 52.94%, 90.2% and 76.47%; specificity was 100% for KK and PCR and 18.37% for POC-CCA. The accuracy calculated for the three tests at the end point was 76% for KK, 55% for POC-CCA assay and 88% for PCR. CONCLUSION: Conventional PCR assay for detection of cfpd provides a potential screening tool for intestinal schistosomiasis with reliable specificity, reasonable accuracy and affordable financial and technical cost.


OBJECTIF: Evaluer trois tests non invasifs pour le diagnostic de la schistosomiase mansoni dans un village égyptien. MÉTHODES: L'urine a été collectée pour la détection de l'antigène cathodique circulant (ACC) et de l'ADN du parasite libéré des cellules (cfpd) par le test en cassette POC (point-of-contact) et par PCR, respectivement. Ces tests ont été comparés au test de Kato Katz (KK) sur frottis fécal épais pour la détection des œufs de Schistosoma mansoni. RÉSULTATS: La prévalence de la maladie par dosage POC-ACC était de 86%; elle était de 39% par PCR contre 27% par KK. Par rapport à KK, la sensibilité du POC-ACC atteignait 100%, mais sa spécificité n'était que de 19,2% avec une précision de 41%. La sensibilité du PCR pour la cfpd était de 55,56% et sa spécificité de 67,12% avec une précision de 64%. Un nouveau seuil a été calculé pour l'analyse combinée des tests KK, POC-ACC et PCR. La sensibilité pour les trois tests était de 52,94%, 90,2% et 76,47%; la spécificité était de 100% pour KK et PCR et de 18,37% pour POC-ACC. La précision calculée pour les trois tests au point seuil était de 76% pour KK, 55% pour le POC-ACC et 88% pour la PCR. CONCLUSION: Le test PCR conventionnel pour la détection de la cfpd constitue un outil de dépistage potentiel de la schistosomiase intestinale avec une spécificité fiable, une précision raisonnable et un coût financier et technique abordable.


Assuntos
Antígenos de Helmintos/urina , Bioensaio/métodos , Schistosoma mansoni/isolamento & purificação , Esquistossomose mansoni/urina , Adolescente , Adulto , Animais , Ácidos Nucleicos Livres , Criança , Feminino , Humanos , Masculino , Prevalência , Sensibilidade e Especificidade , Adulto Jovem
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