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1.
Curr Gene Ther ; 24(5): 410-421, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-39005063

RESUMO

BACKGROUND: Injury systemically disrupts the homeostatic balance and can cause organ failure. LF mediates both iron-dependent and iron-independent mechanisms, and the role of LF in regulating iron homeostasis is vital in terms of metabolism. OBJECTIVES: In this study, we evaluated the organ-level effect and gene expression change of bLf in the cutaneous repair process. MATERIALS AND METHODS: An excisional full-thickness skin defect (FTSD) wound model was created in male Sprague Dawley rats (180-250 g) (n = 48) fed a high-fat diet (HFD) and the PHGPx, SLC7A11 and SLC40A1 genes and iron metabolism were evaluated. The animals were randomly divided into 6 groups: 1- Control, 2- bLf (200 mg/kg/day, oral), 3- FTSD (12 mm in diameter, dorsal), 4- HFD + bLf, 5- HFD + FTSD, 6- HFD + FTSD + bLf. Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Gene expression analysis was performed with qPCR. RESULTS: Histologically, iron accumulation was demonstrated by Prussian blue staining in the liver, kidney, and intestinal tissues. Prussian blue reactions were detected in the kidney. PHPGx and SLC7A11 genes in kidney and liver tissue were statistically significant (P < 0.05) except for the SLC40A1 gene (P > 0.05). Expression changes of the three genes were not statistically significant in analyses of rat intestinal tissue (P = 0.057). CONCLUSION: In the organ-level ferroptotic damage mechanism triggered by wound formation. BLf controls the expression of three genes and manages iron deposition in these three tissues. In addition, it suppressed the increase in iron that would drive the cell to ferroptosis and anemia caused by inflammation, thereby eliminating iron deposition in the tissues.


Assuntos
Homeostase , Ferro , Lactoferrina , Ratos Sprague-Dawley , Cicatrização , Animais , Ferro/metabolismo , Ratos , Masculino , Homeostase/efeitos dos fármacos , Lactoferrina/farmacologia , Lactoferrina/genética , Cicatrização/efeitos dos fármacos , Cicatrização/genética , Bovinos , Insuficiência de Múltiplos Órgãos/genética , Insuficiência de Múltiplos Órgãos/metabolismo , Insuficiência de Múltiplos Órgãos/tratamento farmacológico , Proteínas de Transporte de Cátions/genética , Proteínas de Transporte de Cátions/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Fígado/metabolismo , Fígado/efeitos dos fármacos
2.
Chest ; 166(2): 405-412, 2024 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-38554817

RESUMO

BACKGROUND: Image-guided or assisted needle biopsies and the increasing use of medical thoracoscopy (MT) have increased the diagnostic accuracy of pleural diseases significantly. However, no consensus exists regarding which patients with pleural effusion should undergo MT and which patients should undergo image-guided or assisted needle biopsy as the first procedure to ensure greater diagnostic accuracy. RESEARCH QUESTION: Which biopsy method is more appropriate for which patient to provide the highest diagnostic accuracy in the diagnosis of pleural effusion? STUDY DESIGN AND METHODS: This prospective, randomized, parallel study included 228 patients with undiagnosed exudative pleural effusion. Patients were divided into two groups based on CT scan findings. Group 1 included patients with pleural effusion only. Group 2 included patients with pleural thickening or lesion in addition to pleural effusion. Patients in each group were assigned randomly to an image-assisted Abrams needle pleural biopsy (IA-ANPB) or MT arm. The diagnostic sensitivity, reliability, and safety were determined for both groups. RESULTS: The false-negative rate was 30.3% for the IA-ANPB arm and 3.1% for the MT arm in group 1. The same rates were 11.9% for IA-ANPB and 4.7% for MT in group 2. In group 1, the sensitivity for the IA-ANPB arm was 69.7%, and the negative likelihood ratio was 0.30. The same rates for the MT arm were 96.9% and 0.03 (P = .009). In group 2, these values were 88.1% and 0.12 for the IA-ANPB arm and 95.4% and 0.05 for the MT arm (P = .207). The rate of complications between the two biopsy methods was not different (8.5% and 15.8%, respectively; P = .107). INTERPRETATION: MT showed a high diagnostic success in all patients with pleural fluid. However, IA-ANPB showed similar diagnostic success as MT in patients with pleural effusion and associated pleural thickening or lesions. Therefore, in the latter case, IA-ANPB could be preferable to MT. TRIAL REGISTRY: ClinicalTrials.gov; No.: NCT05428891; URL: www. CLINICALTRIALS: gov.


Assuntos
Biópsia Guiada por Imagem , Derrame Pleural , Toracoscopia , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Toracoscopia/métodos , Biópsia Guiada por Imagem/métodos , Estudos Prospectivos , Derrame Pleural/diagnóstico , Derrame Pleural/patologia , Biópsia por Agulha/métodos , Biópsia por Agulha/efeitos adversos , Idoso , Tomografia Computadorizada por Raios X/métodos , Pleura/patologia , Pleura/diagnóstico por imagem , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Adulto
3.
Mol Biol Rep ; 51(1): 279, 2024 Feb 07.
Artigo em Inglês | MEDLINE | ID: mdl-38324049

RESUMO

BACKGROUND: Epilepsy is a neurological disease characterized by recurrent seizures, hyperexcitable neurons and various behavioral comorbidities. The electrical charge during seizures depletes the antioxidant defense mechanism in the epileptic brain and increases the oxidative burden. Natural antioxidant compounds are potential therapeutics in the treatment of two major pathologies of epilepsy with their anticonvulsant and anxiolytic effects and can modulate these targets. Gum Arabic is one of the natural plant polysaccharides that is non-toxic and biodegradable. METHODS AND RESULTS: A total of 30 Wistar albino male rats (8-12 weeks, 350-500 g), were randomly divided into 5 groups with 6 animals in each group: 1-Control, 2-Sham (Phosphate buffer saline (PBS)), 3-PTZ, 4-Gum Arabic, 5-PTZ + Gum Arabic. PTZ was administered i.p at 35 mg/kg/day for 11 days. After 48 h, the injection was completed with 75 mg/kg PTZ. Locomotor activity, immobilization, rearing, grooming, eating, and drinking behaviors were recorded with the LABORAS behavior system for 30 min after kindling. Animals were treated with Gum Arabic (2 mg/kg/day, oral gavage) for 10 days. At the end of the period, animal behavior was recorded again. Then the hippocampus tissues were removed. Oxidative parameters (TAS and TOS), early growth response 1 (EGR1) and nuclear receptor subfamily 1 group D member 1 (Rev-erbα) gene expressions and behaviors were analyzed. CONCLUSION: Gum Arabic increased TAS levels (P = 0.000), decreased TOS levels (P = 0.000), and thus exhibited antioxidant properties by reducing oxidative stress burden. EGR1, which was upregulated in the seizure group, was downregulated after treatment (P = 0.000), and Rev-erbα was downregulated in seizure and upregulated after treatment (P = 0.000). Gum arabic may be an antiepileptic and anxiolytic therapeutic in improving epileptic seizures by reducing oxidative stress burden through EGR1 and Rev-erbα.0.


Assuntos
Ansiolíticos , Proteína 1 de Resposta de Crescimento Precoce , Epilepsia , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares , Animais , Ratos , Anticonvulsivantes , Antioxidantes , Goma Arábica , Ratos Wistar , Convulsões , Proteína 1 de Resposta de Crescimento Precoce/genética , Membro 1 do Grupo D da Subfamília 1 de Receptores Nucleares/genética
4.
OMICS ; 27(1): 34-44, 2023 01.
Artigo em Inglês | MEDLINE | ID: mdl-36594931

RESUMO

Alzheimer's disease (AD) is a neurodegenerative disease characterized by progressive memory loss and cognitive decline, with hallmark pathologies related to amyloid beta (Aß) and TAU. Natural phytochemicals show promise for drug discovery to fill the current therapeutic innovation gap in AD. This study investigated the effect of cucurbitacin E (CuE), one of the bioactive components of Ecballium elaterium, on TAU fibril formation in okadaic acid-induced AD in rats. In a randomized design, we assigned 30 female Sprague Dawley rats to one of five experimental groups: (1) control, (2) stereotaxic surgery, (3) stereotaxic surgery + artificial cerebrospinal fluid, (4) stereotaxic surgery + okadaic acid (AD model), and (5) stereotaxic surgery + okadaic acid + CuE treatment. For experimental groups 4 and 5, rats were administered OKA-ICV (200 ng/kg) followed by CuE (4 mg/[kg·day], intraperitoneally) for 20 days. Expression of the MAPK1/3 and MAPK14 genes associated with TAU metabolism, hippocampal protein levels of these genes, cognitive functions of the rats, and histological accumulation of TAU in the brain were evaluated. Our findings in this preclinical model collectively suggest that phytochemical CuE contributes to memory gain by reducing TAU protein accumulation, which warrants further evaluation in future in vitro and in vivo studies.


Assuntos
Doença de Alzheimer , Doenças Neurodegenerativas , Ratos , Feminino , Animais , Proteínas tau/metabolismo , Ácido Okadáico/farmacologia , Doença de Alzheimer/induzido quimicamente , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Ratos Sprague-Dawley , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/farmacologia , Doenças Neurodegenerativas/metabolismo , Encéfalo/metabolismo , Modelos Animais de Doenças
5.
Mol Biol Rep ; 49(12): 11997-12006, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-36271980

RESUMO

BACKGROUND: Epileptogenesis is a process that results in neurons firing abnormally, causing seizures. Increasing evidence has shown that miRNAs expressed in the epileptic hippocampus are involved in epileptogenesis. We demonstrated the expression changes of miRNAs that may be effective in epileptogenesis in silico analysis in the kindling model created with Pentylenetetrazole (PTZ). Thus, we aimed to identify the target genes responsible for epileptogenesis. METHODS AND RESULTS: Fifteen male Wistar-albino rats (200-230 g) were randomly divided into two groups control (n = 6) and PTZ (n = 9). The control group received 0.5 ml saline, and the PTZ group (35 mg/kg i.p.) intraperitoneally (i.p.) (11 times, every other day) to induce tonic-clonic seizures. Seizures were observed and scored 30 min after PTZ injection. After the last dose of PTZ (75 mg/kg) administration, the hippocampus tissues of the rats were removed by anesthesia. Analysis of miRNAs was performed with the Affymetrix gene chip miRNA sequence (728 miRNA) and confirmed by the Real-Time Polymerase Chain Reaction (Real-Time PCR) method (29 miRNAs). We evaluated the expression change of the target gene of miRNA, whose expression change was detected using in silico analysis, by q-RT PCR. Eight miRNAs with changes in expression were detected. Of these miRNAs, miR-342-p was downregulated in the PTZ group and was statistically significant (p < 0.005). Ultimately, we determined that the target gene of miR-342-p is a metabotropic glutamate receptor 2 (GRM2) and that GRM2 expression is upregulated. CONCLUSIONS: Downregulation of miR-342-3p in the PTZ kindling model may result in the upregulation of GRM2.


Assuntos
MicroRNAs , Pentilenotetrazol , Animais , Masculino , Ratos , Regulação para Baixo/genética , Hipocampo/metabolismo , MicroRNAs/metabolismo , Pentilenotetrazol/metabolismo , Pentilenotetrazol/farmacologia , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/genética , Convulsões/metabolismo
6.
Lung ; 200(6): 807-815, 2022 12.
Artigo em Inglês | MEDLINE | ID: mdl-36173482

RESUMO

PURPOSE: The aim of this study is to determine the diagnostic performances of pleural procedures in undiagnosed exudative pleural effusions and to evaluate factors suggestive of benign or malignant pleural effusions in tertiary care centers. METHODS: This was a multicenter prospective observational study conducted between January 1 and December 31, 2018. A total of 777 patients with undiagnosed exudative pleural effusion after the initial work-up were evaluated. The results of diagnostic procedures and the patients' diagnoses were prospectively recorded. Sensitivity, specificity, and accuracy estimates with 95% confidence intervals were used to examine the performance of pleural procedures to detect malignancy. RESULTS: The mean age ± SD of the 777 patients was 62.0 ± 16.0 years, and 68.3% of them were male. The most common cause was malignancy (38.3%). Lung cancer was the leading cause of malignant pleural effusions (20.2%). The diagnostic sensitivity and accuracy of cytology were 59.5% and 84.3%, respectively. The diagnostic sensitivity of image-guided pleural biopsy was 86.4%. The addition of image-guided pleural biopsy to cytology increased diagnostic sensitivity to more than 90%. Thoracoscopic biopsy provided the highest diagnostic sensitivity (94.3%). The highest diagnostic sensitivity of cytology was determined in metastatic pleural effusion from breast cancer (86.7%). CONCLUSION: The diagnostic performance increases considerably when cytology is combined with image-guided pleural biopsy in malignant pleural effusions. However, to avoid unnecessary interventions and complications, the development of criteria to distinguish patients with benign pleural effusions is as important as the identification of patients with malignant pleural effusions.


Assuntos
Derrame Pleural Maligno , Derrame Pleural , Humanos , Masculino , Feminino , Derrame Pleural Maligno/diagnóstico , Derrame Pleural Maligno/etiologia , Derrame Pleural Maligno/patologia , Estudos Prospectivos , Derrame Pleural/diagnóstico , Derrame Pleural/etiologia , Derrame Pleural/patologia , Exsudatos e Transudatos , Pleura/patologia
7.
Neurol Res ; 44(8): 726-737, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35282795

RESUMO

OBJECTIVES: Epilepsy is a neurological disease that pathologically affects brain functions. The epileptic hippocampus has modified microRNA(miRNA) levels. Therefore, we aimed to evaluate the neuroprotective effect of thymoquinone (TQ) in PTZ-induced epilepsy and to demonstrate the overlap between miRNA and mRNA expression profiles. METHODS: Male adult Wistar albino rats (200-230 g, n = 20) were divided into three groups as control (n = 6), PTZ (n = 7), and TQ + PTZ (n = 7). The PTZ kindling model was created by injecting PTZ in sub convulsive doses to rats on days 1, 3, 5, 8, 10, 12, 15, 17, 19, 22, and 24 of the study into animals. Clonic and tonic seizures were induced by injecting a convulsive dose of PTZ on day 26 of the study. Rats in the TQ+PTZ group were treated by oral gavage with a 20 mg/kg TQ 2 h before each PTZ injection. The rats in the control group were treated with 0.5 ml saline. Seizure severity was evaluated with the Racine scale. The genes and signaling pathways targeted by miRNAs were determined by bioinformatics analysis. RESULTS: In the rat hippocampus, mature 728 miRNAs were analyzed by microarray and the nine miRNA were verified by quantitative Real-Time PCR. rno-miR-182 and rno-miR-27b-3p were up-regulated in the PTZ group and down-regulated in the TQ + PTZ group. DISCUSSION: In the PTZ kindling epilepsy model, the expression of these two miRNAs was regulated by TQ and exerted a neuroprotective effect by controlling the activities of target genes.


Assuntos
Epilepsia , Excitação Neurológica , MicroRNAs , Fármacos Neuroprotetores , Animais , Benzoquinonas , Epilepsia/induzido quimicamente , Epilepsia/tratamento farmacológico , Epilepsia/metabolismo , Hipocampo , Masculino , MicroRNAs/metabolismo , Fármacos Neuroprotetores/uso terapêutico , Pentilenotetrazol/toxicidade , Ratos , Ratos Wistar , Convulsões/induzido quimicamente , Convulsões/tratamento farmacológico , Convulsões/metabolismo
8.
Turk J Med Sci ; 52(1): 113-123, 2022 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-34590799

RESUMO

BACKGROUND: Fine-needle non-aspiration cytology (FNNAC) is an easy-to-apply, minimally invasive diagnostic method that contributes to the diagnosis and staging of lung cancer. FNNAC can be performed from peripheral lymph nodes as well as in peripheral lung lesions. This study aimed to evaluate the contribution of FNNAC performed from peripheral lesions or lymph nodes to diagnosis in patients with pulmonary malignant lesions. METHODS: FNNAC was applied from a peripherally located mass in the lung, chest wall lesion, or peripheral lymph node using a needle without an injector or active suction. The collected material was evaluated using the cytoblock method. The FNNAC accuracy was obtained by dividing the true positivity value by a number of needle biopsies performed. The 95% confidence interval of the obtained rate was also calculated. RESULTS: The mean age of 56 patients, two female (3.6%) and 54 male (96.4%), was 63.9 ± 9.1 (38-80) years. FNNAC was performed from the peripheral lymph node in 48 patients, the peripheral pulmonary lesion in four, and the accompanying chest wall lesion in four. While true positivity was present in 42 patients, two patients had true negativity, and 12 had false negativity. In five of the 12 cases reported as false negative, the collected material was evaluated as insufficient, while the malignant diagnoses of the remaining seven cases were confirmed by other diagnostic methods. The diagnostic success of FNNAC was determined as 78.57% (95% CI: 65.56-88.41). FNNAC was more successful in diagnosis when performed from the peripheral lymph node compared to the peripheral pulmonary lesion (p=0.033).


Assuntos
Citodiagnóstico , Neoplasias Pulmonares , Humanos , Masculino , Feminino , Pessoa de Meia-Idade , Biópsia por Agulha Fina/métodos , Pulmão/patologia , Linfonodos/patologia , Neoplasias Pulmonares/diagnóstico , Neoplasias Pulmonares/patologia , Sensibilidade e Especificidade
9.
Mol Biol Rep ; 48(6): 5319-5326, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-34247340

RESUMO

BACKGROUND: Nicotine dependence (ND) is characterized by regular smoking, anxiety, irritation, difficulty concentrating, impatience, restlessness, tremor, dizziness, hunger, nicotine demand, and the individual's reluctance to quit despite knowing the health risks of smoking. Recently, it has been reported that the Neuregulin 3 (NRG3)/Erb-B2 receptor tyrosine kinase 4 (ERBB4) signaling pathway plays a role in ND. NRG3, which is activated after nicotine intake, binds to ERBB4 and causes GABA release. GABA reduces anxiety and tension, which are one of the nicotine withdrawal symptoms. Therefore we aimed to investigate the relationship between NRG3 and ERBB4 gene polymorphisms and ND. MATERIALS AND METHODS: The study population was comprised of patients with ND (n = 200) and healthy non-smoker control subjects (n = 200) who were matched for age, sex, and compared for comorbidity factors such as alcohol, smoking, duration, and education (age range 18-60). Genotypes were detected by Real-Time PCR using TaqMan technology. The Fagerström Nicotine Dependence Test (FTND) score was 5 and above for the patient group and 0 for the control group. DNA was obtained from whole peripheral blood and six polymorphisms of Neuregulin 3 (NRG3) (rs1836724, rs7562566, and rs10048757) and Erb-B2 Receptor Tyrosine Kinase 4 (ERBB4) (rs1764072, rs6584400, and rs10883934) genes were analyzed by real-time PCR method. RESULTS: Our findings show that the six selected SNPs are not significantly associated with ND in the Turkish population and no correlation with dependence levels (p > 0.05). CONCLUSION: Although our findings do not show a relationship between ND and these polymorphisms, it is the first study to investigate these single nucleotide polymorphisms (SNPs) for the first time in ND and to find some genotypes in the Turkish population when compared to other populations. Also, our findings are important in terms of their contribution to the literature and forensic genetics.


Assuntos
Neurregulinas/genética , Receptor ErbB-4/genética , Tabagismo/genética , Adulto , DNA/genética , Feminino , Predisposição Genética para Doença/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Neurregulinas/metabolismo , Nicotina/efeitos adversos , Nicotina/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor ErbB-4/metabolismo , Fumar/genética , Tabagismo/metabolismo , Turquia/epidemiologia
10.
J Occup Environ Med ; 63(3): 238-243, 2021 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-33399308

RESUMO

OBJECTIVE: The aim of this study is to investigate the effect of asbestos exposure on cancer-driver mutations. METHODS: Between January 2014 and September 2018, epidermal growth factor receptor (EGFR), anaplastic lymphoma receptor tyrosine kinase (ALK), and c-ros oncogene 1 receptor tyrosine kinase gene (ROS1) alterations, demographic characteristics, asbestos exposure, and asbestos-related radiological findings of 1904 patients with lung adenocarcinoma were recorded. RESULTS: The frequencies of EGFR mutations, ALK, and ROS1 rearrangements were 14.5%, 3.7%, and 0.9%, respectively. The rates of EGFR mutations and ALK rearrangements were more frequent in asbestos exposed non-smokers (48.7% and 9%, respectively). EGFR mutation rate was correlated to female gender and not-smoking, ALK rearrangement rate was correlated to younger age, not-smoking, and a history of asbestos exposure. CONCLUSIONS: The higher rate of ALK rearrangements in asbestos-exposed lung adenocarcinoma cases shows that asbestos exposure may most likely cause genetic alterations that drive pulmonary adenocarcinogenesis.


Assuntos
Adenocarcinoma de Pulmão , Amianto , Neoplasias Pulmonares , Adenocarcinoma de Pulmão/genética , Quinase do Linfoma Anaplásico/genética , Receptores ErbB/genética , Feminino , Humanos , Neoplasias Pulmonares/genética , Mutação , Oncogenes , Proteínas Tirosina Quinases/genética , Proteínas Proto-Oncogênicas/genética
11.
Support Care Cancer ; 29(6): 3357-3365, 2021 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-33128137

RESUMO

PURPOSE: The study aimed to determine the poor nutritional status, related factors, and its effect on the prognosis of patients with locally advanced and advanced stage lung cancer. METHODS: The study consisted of 539 patients, 412 (76.4%) of whom were non-small cell lung cancer (NSCLC), and 127 (23.6%) were small cell lung cancer (SCLC). The nutritional status of the patients was evaluated by the Controlling Nutritional Status (CONUT) and Prognostic Nutritional Index (PNI). Poor nutritional status was diagnosed with the CONUT score of ≥ 2 and PNI of ≥the median value. The factors related to nutritional status were determined using a multivariate logistic regression model. The effect of poor nutritional status on survival was calculated by Cox regression analysis. RESULTS: The median age was 64 years (29-87). Poor nutritional status was found in 56.4% (57.8% for NSCLC and 52.0% for SCLC) and 49.2% (51.5% for NSCLC and 41.7% for SCLC) of patients according to CONUT and PNI, respectively. The factors associated with poor nutritional status according to CONUT were age, gender, KPS < 80, and BMI < 18.5 for NSCLC and KPS for SCLC. According to PNI, only KPS < 80 was associated with poor nutritional status by the multivariate logistic regression model. The median overall survival significantly decreased with poor nutritional status according to CONUT and PNI in NSCLC (p < 0.001 and p < 0.001, respectively) and in SCLC (p = 0.05 and p = 0.007, respectively). CONCLUSION: Poor nutritional status is a common factor associated with poor prognosis in patients with locally advanced and advanced stage lung cancer. Patients should be screened for nutritional status and supported.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/dietoterapia , Neoplasias Pulmonares/dietoterapia , Estado Nutricional/fisiologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Carcinoma Pulmonar de Células não Pequenas/mortalidade , Feminino , Humanos , Neoplasias Pulmonares/mortalidade , Masculino , Pessoa de Meia-Idade , Estadiamento de Neoplasias , Prognóstico , Estudos Retrospectivos , Análise de Sobrevida
12.
P R Health Sci J ; 39(3): 264-269, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-33031695

RESUMO

OBJECTIVE: The proto-oncogene Bax (Bcl-2-associated X protein) and related protein Bcl-2 (B-cell chronic lymphocytic leukemia/lymphoma-2) genes are triggers of apoptosis in Alzheimer's disease (AD). The balance of these proteins has an important role in the death or life of a neuronal cell, and the functional polymorphisms in genes expressing these proteins have been found to promote apoptosis. To investigate the role of Bax and Bcl-2 genes in AD, we examined the presence of the 2 polymorphisms in peripheral blood. To our knowledge, this is the first clinical association study of these 2 functional SNPs using the peripheral blood of patients with AD. METHODS: Bax (rs4645878) and Bcl-2 (rs2279115) in Alzheimer's patients (N = 132) and healthy controls (N = 109), aged 65 to 85 years, were analyzed by qPCR (Quantitative Polymerase Chain Reaction) using TaqMan probe technology. Statistical analyses were done using SPSS, 11.5. The differences between groups were analyzed using an independent-samples t test. The relationships between genotypes and alleles were analyzed using chi-square or likelihood ratio test. The Hardy-Weinberg balance was checked for the patient and control groups. A p-value of less than 0.05 was taken as significant. RESULTS: Sporadic AD patients and non-demented age matched control subjects were genotyped in this case-control study. No statistically significant relationship was found between the patients and controls for allele or genotype frequencies (p>0.05). CONCLUSION: Our data suggest that these two polymorphisms do not contribute to AD in the population from the Mersin region of the Eastern Mediterranean. Further studies with larger sample sizes must be conducted to ascertain the association between the 2 polymorphisms.


Assuntos
Doença de Alzheimer/genética , Genes bcl-2 , Polimorfismo de Nucleotídeo Único , Proteínas Proto-Oncogênicas c-bcl-2/genética , Proteína X Associada a bcl-2/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Apoptose/genética , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Feminino , Genótipo , Humanos , Funções Verossimilhança , Masculino , Resultados Negativos , Proto-Oncogene Mas , Turquia
13.
Pathol Oncol Res ; 26(4): 2703-2708, 2020 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-32661837

RESUMO

If a patient's cancer progresses while undergoing targeted therapy, a re-biopsy is not mandatory. But when evaluating the benefits and risks on a case-by-case basis (transformation to small cell, assessing for a clinical trial), physicians should inform patients about the possible need for a re-biopsy (5). This was a retrospective and multicentre study. A total of 644 patients with lung adenocarcinoma were reviewed, 625 of whom were ruled eligible. From them, 399 were found to show disease progression, and 126 re-biopsies were performed. Progression status, re-biopsy sites, success of obtaining adequate tissue, molecular patterns after re-biopsy and subsequent treatments were analysed. Survival differences among patients with disease progression were then examined according to re-biopsy status. Overall, 625 patients with adenocarcinoma and a median age of 61.4 were evaluated. Initial tyrosine kinase inhibitor (TKI) usage numbered 37 patients (5.9%). Progression was diagnosed in 399 (63.8%) patients, out of which 26 (31.6%) underwent re-biopsies. The successful number of re-biopsies was 103 (81.7%). No complications were observed after any of the biopsy procedures. Subsequent treatments were changed in 15 patients (11.9%), who began new TKI treatments. Poor performance status was the most common reason for not performing a biopsy (n = 65; 23.8%), followed by the physician's decision (n = 40; 14.6%). Re-biopsies can demonstrate the new characteristics of a tumour and can detect the activation of pre-existing clones, making possible new treatment opportunities for patients. According to the performance status of the patient and the availability of the progressive lesion, we should increase the rate of re-biopsies before the decision to follow up with the best supportive care.


Assuntos
Adenocarcinoma de Pulmão/patologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Resistencia a Medicamentos Antineoplásicos , Neoplasias Pulmonares/patologia , Mutação , Inibidores de Proteínas Quinases/uso terapêutico , Adenocarcinoma de Pulmão/tratamento farmacológico , Adenocarcinoma de Pulmão/genética , Adenocarcinoma de Pulmão/cirurgia , Biópsia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Carcinoma Pulmonar de Células não Pequenas/cirurgia , Progressão da Doença , Receptores ErbB/genética , Feminino , Seguimentos , Humanos , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/cirurgia , Masculino , Pessoa de Meia-Idade , Prognóstico , Estudos Retrospectivos
14.
OMICS ; 21(3): 177-182, 2017 03.
Artigo em Inglês | MEDLINE | ID: mdl-28253085

RESUMO

Public policies to stop or reduce cigarette smoking and exposure to secondhand smoke and associated diseases have yielded successful results over the past decade. Yet, the growing worldwide popularity of another form of tobacco consumption, water pipe smoking, has received relatively less attention. To the best of our knowledge, no study to date has evaluated the effects of water pipe smoking on cytochrome P450 (CYP450) activities and drug interaction potential in humans, whereas only limited information is available on the impact of secondhand smoke on drug metabolism. In a sample of 99 healthy volunteers (28 water pipe smokers, 30 secondhand tobacco smoke exposed persons, and 41 controls), we systematically compared CYP1A2 and CYP2A6 enzyme activities in vivo using caffeine urine test. The median self-reported duration of water pipe smoking was 7.5 h/week and 3 years of exposure in total. The secondhand smoke group had a median of 14 h of self-reported weekly exposure to tobacco smoke indoor where a minimum of five cigarettes were smoked/hour for a total of 3.5 years (median). Analysis of variance did not find a significant difference in CYP1A2 and CYP2A6 activities among the three study groups (p > 0.05). Nor was there a significant association between the extent of water pipe or secondhand smoke exposure and the CYP1A2 and CYP2A6 activities (p > 0.05). Further analysis in a subsample with smoke exposure more than the median values also did not reveal a significant difference from the controls. Although we do not rule out an appreciable possible impact of water pipe smoke and secondhand smoke on in vivo activities of these two drug metabolism pathways, variability in smoke constituents from different tobacco consumption methods (e.g., water pipe) might affect drug metabolism in ways that might differ from that of cigarette smoke. Further studies in larger prospective samples are recommended to evaluate water pipe and secondhand tobacco smoke effects on CYP450 function, particularly at higher smoke exposure conditions.


Assuntos
Cafeína/urina , Citocromo P-450 CYP1A2/metabolismo , Citocromo P-450 CYP2A6/metabolismo , Nicotiana/efeitos adversos , Fumar/efeitos adversos , Adulto , Humanos , Masculino , Medicina de Precisão , Estudos Prospectivos
15.
Int J Occup Environ Health ; 23(3): 243-249, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-29737238

RESUMO

Background Asbestos-contaminated soil has been used by people for many years in the rural part of Anatolia. However, there is no program to control usage of asbestos in this region. Objective To determine the knowledge and awareness level about asbestos in a region where asbestos-related diseases are endemic due to environmental exposure to asbestos in the rural setting. Methods This study included 760 participants, recruited using non-probability sampling, who were classified into four groups according to residence and asbestos exposure type (urban, rural; asbestos-exposed, asbestos-unexposed). Asbestos knowledge and awareness was measured via the Asbestos Knowledge and Awareness Questionnaire (AKAQ). The cut-off value of questionnaire was determined by the K-means cluster analysis for sufficient and insufficient knowledge and awareness level. A multiple logistic regression analysis was performed to determine independent factors affecting sufficient knowledge and awareness of participants about asbestos. Results The median and mean score of the AKAQ in study group were 30 and 33.9, respectively. The urban asbestos-exposed group had a higher score than the urban asbestos-unexposed and both rural groups (p < 0.001). Factors affecting asbestos knowledge and awareness were education status (p = 0.035), asbestos exposure (p = 0.003) and living in the rural area (p = 0.005). Sufficient knowledge and awareness (score > 45) was higher among participants who had graduated from university and had asbestos exposure. Insufficient knowledge and awareness level was higher among participants living in rural areas. Conclusion In this region of Anatolia, knowledge and awareness level of asbestos was low among people at risk for environmental asbestos exposure. People should be aware of asbestos and its hazards by a well-designed training program and be monitored for asbestos-related diseases.


Assuntos
Amianto , Exposição Ambiental , Conhecimentos, Atitudes e Prática em Saúde , População Rural , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , População Rural/estatística & dados numéricos , Turquia , Adulto Jovem
16.
Ital J Pediatr ; 41: 100, 2015 Dec 29.
Artigo em Inglês | MEDLINE | ID: mdl-26714766

RESUMO

BACKGROUND: Acute appendicitis (AA) (OMIM: 107700) is an inflammatory disease which is characterized by appendiceal inflammation. Genetic and environmental factors contribute to the development of AA. Especially, multiple genetic factors appear to be promising in the explanation of etiopathogenesis of AA. IL-6 (Interleukin-6) is an inflammatory cytokine and IL-6 receptor (IL-6R) plays an important role in the immune response. IL-6 (-572G/C rs1800796) and IL-6R (1:G.154448302 T > C rs7529229) gene polymorphisms may have an impact on cytokine production, immune response and these gene polymorphisms may be used as inflammatory markers in the diagnosis of appendicitis. METHOD: A total of 75 children with appendicitis, and 75 healthy children were included in the study. DNA extracts were obtained from peripheral lymphocytes. Single-nucleotide polymorphisms (SNPs) were analysed using an automated SYBR® Green RT-PCR system in pediatric patients with appendicitis (n = 75) and healthy controls (n = 75). RESULTS: The allele and genotype frequencies for IL-6 rs1800796 and IL-6R rs7529229 polymorphisms were not different between the study groups (p > 0.05). Any statistically significant differences as for age, sex and other laboratory factors were not detected between the patients with appendicitis for genotype-allele frequencies (p > 0.05). Still in analyses performed to determine correlations among age, and gender of the patients, routine laboratory parameters and allele-genotype frequencies, a statistically significant intergroup difference was not detected. Genotype and allele frequencies were consistent with Hardy-Weinberg equilibrium (HWE) in all groups. DISCUSSION: This is the first study to investigate the effects of functional two polymorphisms on IL-6 and IL-6R genes in a pediatric patient group with AA risk. With this study we investigated the contribution of IL-6 (-572G/C rs1800796) and IL-6R (1:G.154448302 T > C rs7529229) polymorphisms on pathogenesis, and severity of AA in pediatric patients with AA: These results will guide further genetic researches to be performed on the role of IL-6 and IL-6R in AA. CONCLUSIONS: Given the putative biological importance of this SNPs, these emerging data can provide a new foundation to stimulate future debate and genetic investigations of AA, focusing on new molecular mechanisms such as other IL gene polymorphisms, particularly in accessible peripheral tissues for novel molecular diagnostics for appendicitis.


Assuntos
Apendicite/diagnóstico , DNA/genética , Predisposição Genética para Doença , Interleucina-6/genética , Polimorfismo Genético , Receptores de Interleucina-6/genética , Doença Aguda , Adolescente , Alelos , Apendicite/genética , Apendicite/metabolismo , Biomarcadores/metabolismo , Criança , Feminino , Seguimentos , Frequência do Gene , Genótipo , Humanos , Interleucina-6/metabolismo , Masculino , Reação em Cadeia da Polimerase em Tempo Real , Receptores de Interleucina-6/metabolismo , Estudos Retrospectivos
17.
Mol Med Rep ; 12(2): 3039-46, 2015 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-25936369

RESUMO

Latent infection with adenovirus and respiratory syncytial virus (RSV) is associated with chronic obstructive pulmonary disease (COPD). The role of respiratory viral infections are emerging in COPD exacerbations. The present study aimed to investigate the prevalence of adenovirus and RSV serotypes A and B in individuals with acute exacerbations of COPD (COPD-AE) and stable COPD. Twenty seven patients with COPD-AE were evaluated using a prospective longitudinal study design. Induced sputum, sera and nasal smears were sampled from patients experiencing COPD-AE and those in a stable condition. Adenoplex® multiplex polymerase chain reaction (PCR) kits and Invitek RTP® DNA/RNA Virus Mini kits were used for PCR assays of adenovirus and RSV, respectively. Eighteen patients who experienced a COPD-AE were also evaluated while in a stable condition. The results showed that three sputum samples were positive for adenovirus in patients experiencing an exacerbation, while one was positive among the patients in a stable condition. RSV serotype A was detected in 17/27 (63%) patients with COPD-AE and 10/18 (55.6%) patients in a stable condition. RSV serotype B was not detected. Patients with COPD-AE, who were positive for RSV serotype A exhibited higher serum fibrinogen levels than those who were negative (438.60 ± 126.08 mg/dl compared with 287.60 ± 85.91 mg/dl; P=0.004). Eight/ten patients who were positive for RSV serotype A while in a stable condition, were also positive during COPD-AE. The results of the present study suggested that RSV infection may be prevalent in patients with COPD-AE and in those in a stable condition. Therefore, chronic RSV infection may occur in COPD. The detection and prevention of RSV may be useful in the management of COPD.


Assuntos
Infecções por Adenoviridae/diagnóstico , Adenoviridae/genética , Doença Pulmonar Obstrutiva Crônica/diagnóstico , Infecções por Vírus Respiratório Sincicial/diagnóstico , Vírus Sinciciais Respiratórios/genética , Adenoviridae/isolamento & purificação , Infecções por Adenoviridae/patologia , Infecções por Adenoviridae/virologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase Multiplex , Estudos Prospectivos , Doença Pulmonar Obstrutiva Crônica/patologia , Doença Pulmonar Obstrutiva Crônica/virologia , Infecções por Vírus Respiratório Sincicial/patologia , Infecções por Vírus Respiratório Sincicial/virologia , Vírus Sinciciais Respiratórios/isolamento & purificação , Sorotipagem , Índice de Gravidade de Doença , Escarro/virologia
18.
Int J Radiat Biol ; 91(7): 555-61, 2015 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-25775055

RESUMO

PURPOSE: MicroRNAs (miRNA) play a paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. However, their interaction with radiofrequencies is still unknown. The aim of this study was to investigate the long-term effects of radiofrequency radiation emitted from a Wireless Fidelity (Wi-Fi) system on some of the miRNA in brain tissue. MATERIALS AND METHODS: The study was carried out on 16 Wistar Albino adult male rats by dividing them into two groups such as sham (n = 8) and exposure (n = 8). Rats in the exposure group were exposed to 2.4 GHz radiofrequency (RF) radiation for 24 hours a day for 12 months (one year). The same procedure was applied to the rats in the sham group except the Wi-Fi system was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. miR-9-5p, miR-29a-3p, miR-106b-5p, miR-107, miR-125a-3p in brain were investigated in detail. RESULTS: The results revealed that long-term exposure of 2.4 GHz Wi-Fi radiation can alter expression of some of the miRNAs such as miR-106b-5p (adj p* = 0.010) and miR-107 (adj p* = 0.005). We observed that mir 107 expression is 3.3 times and miR- 106b-5p expression is 3.65 times lower in the exposure group than in the control group. However, miR-9-5p, miR-29a-3p and miR-125a-3p levels in brain were not altered. CONCLUSION: Long-term exposure of 2.4 GHz RF may lead to adverse effects such as neurodegenerative diseases originated from the alteration of some miRNA expression and more studies should be devoted to the effects of RF radiation on miRNA expression levels.


Assuntos
Encéfalo/metabolismo , Encéfalo/efeitos da radiação , MicroRNAs/genética , Ondas de Rádio/efeitos adversos , Transcriptoma/efeitos da radiação , Tecnologia sem Fio/instrumentação , Animais , Masculino , Ratos , Ratos Wistar , Fatores de Tempo
19.
Int J Radiat Biol ; 91(4): 306-11, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25529971

RESUMO

PURPOSE: We still do not have any information on the interaction between radiofrequency radiation (RF) and miRNA, which play paramount role in growth, differentiation, proliferation and cell death by suppressing one or more target genes. The purpose of this study was to bridge this gap by investigating effects of long-term 900 MHz mobile phone exposure on some of the miRNA in brain tissue. MATERIALS AND METHODS: The study was carried out on 14 Wistar Albino adult male rats by dividing them into two groups: Sham (n = 7) and exposure (n = 7). Rats in the exposure group were exposed to 900 MHz RF radiation for 3 h per day (7 days a week) for 12 months (one year). The same procedure was applied to the rats in the sham group except the generator was turned off. Immediately after the last exposure, rats were sacrificed and their brains were removed. rno-miR-9-5p, rno-miR-29a-3p, rno-miR-106b-5p, rno-miR-107 and rno-miR-125a-3p in brain were investigated in detail. RESULTS: Results revealed that long-term exposure of 900 MHz RF radiation only decreased rno-miR107 (adjP* = 0.045) value where the whole body (rms) SAR value was 0.0369 W/kg. However, our results indicated that other microRNA evaluated in this study was not altered by 900 MHz RF radiation. CONCLUSION: 900 MHz RF radiation can alter some of the miRNA, which, in turn, may lead to adverse effects. Therefore, further studies should be performed.


Assuntos
Encéfalo/efeitos da radiação , Telefone Celular , MicroRNAs/análise , Ondas de Rádio/efeitos adversos , Doença de Alzheimer/genética , Animais , Encéfalo/metabolismo , Masculino , Ratos , Ratos Wistar
20.
Cont Lens Anterior Eye ; 32(1): 16-21, 2009 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-18799346

RESUMO

PURPOSE: To assess retrospectively the course, the rate of bilateralness, prognosis, visual acuity with contact lenses, and corneal changes of a cohort with keratoconus. METHODS: Patients applying to Istanbul Faculty of Medicine, Department of Ophthalmology, Contact Lens Division during the period 1975-2005 with the diagnosis of keratoconus were recruited. The follow-up time ranged from 1.5 years to 25 years. This cohort consisted of 273 male, 245 female patients. The patients' ages ranged from 12 years to 54 years (mean age 34.8+/-10.1 years). 518 cases' 1004 eyes were divided into four groups according to their mean keratometry values. The changes in visual acuity, keratometry values and the measurements of the used contact lenses were compared with each other, and statistical significance was sought. RESULTS: By self-report, the mean starting age of keratoconus was found to be 22.5+/-7.6 years (range 7-35 years). 59 (11.4%) of 518 patients had unilateral keratoconus occurrence. The acute hydrops rate was found to be 0.3% (5 patients). In patients with advanced keratoconus, new contact lenses were applied with steeper radius of curvature. Penetrating keratoplasty was applied to 15 eyes (1.5%). Visual acuity examination on the patients' last visit, when compared to previous examinations, was found to have decreased by 2-3 Snellen lines due to advancing keratoconus. CONCLUSION: Keratoconus has shown to be a self-limited disease and in our study, with the use of contact lenses, successful outcomes which delayed the need for surgery were achieved in 98.9% of eyes (989/1004 eyes).


Assuntos
Lentes de Contato/estatística & dados numéricos , Ceratocone/terapia , Prescrições/estatística & dados numéricos , Adolescente , Adulto , Criança , Feminino , Seguimentos , Humanos , Incidência , Ceratocone/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Tempo , Resultado do Tratamento , Turquia/epidemiologia , Adulto Jovem
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