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The A disintegrin and metalloprotease (ADAM) family is involved in many vital cellular events, from proliferation to migration, and accumulated evidence suggests its increased expression in malignant tumors. In this study, we investigated ADAM17 expression in non-small cell lung cancer (NSCLC) and its relationship with clinicopathological factors and survival. Immunohistochemical staining of ADAM expression was performed in 108 patients with NSCLC and in 54 control cases with no known malignant diagnosis. Association between ADAM17 expression, clinicopathological factors, and survival were analyzed. The Kaplan-Meier method was used for survival analysis. ADAM17 was lowly expressed in 89 (82.4%) and highly expressed in 19 (17.6%) of the patients with NSCLC. In univariate analysis, high ADAM17 expression, lymphovascular invasion, stage, and treatment response significantly affected progression-free survival (PFS) and overall survival (OS) (p < 0.05). Multivariate analysis also showed that high ADAM17 expression, lymphovascular invasion, stage, and treatment response were important prognostic factors for PFS and OS (p < 0.05). Our study revealed that high ADAM17 expression significantly associated with OS and PFS in patients with NSCLC. ADAM17 may potentially be the area of a new targeted treatment strategy in NSCLC. Thus, routine evaluation of ADAM17 expression in patients with NSCLC may be a future consideration.
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Objective: Task-oriented therapy (TOT) is used to increase the effectiveness of upper extremity (UE) in activity daily living (ADL). This study aimed to investigate the effect of TOT on the participation and ADLs of stroke patients. Methods: Between October 2018 and February 2019, 28 chronic stroke patients were included in the study treated in Kocaeli University Hospital, Department of Physical Medicine and Rehabilitation, Turkey. The performance areas and participation status of the patients in which they experienced limitations were evaluated with the Canadian Occupational Performance Scale (COPM), and their level of independence in ADLs was evaluated with the Modified Frenchay Activity Index (mFAI) and Barthel Index (BI). All patients were included in the occupational therapy (OT) program five days a week for three weeks at Kocaeli University Hospital. Three ADLs in which they had difficulties were studied with 28 patients. Each of the activities was designed specifically for the patient. All assessments were repeated after three weeks of treatment. Results: A total of 28 patients, 12 females and 16 males, diagnosed with stroke, were included in the study. A statistically significant increase was found in the COPM performance and satisfaction value compared to the pre-treatment value (p<0.001). A statistically significant difference was found between pre- and post-treatment mFAI and BI values (p<0.001). Conclusions: Adding task-oriented therapy to the rehabilitation programs of stroke patients will contribute to the improvement of ADL.
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OBJECTIVES: This study aimed to investigate the prevalence of sexual disorders in stage 2 - 5 chronic kidney disease (CKD) during predialysis and its relationship with laboratory parameters. METHODS AND RESULTS: This cross-sectional study included 110 predialysis patients and 110 healthy controls admitted to clinics. The International Index of Erectile Function (IIEF) and Female Sexual Function Index (FSFI) were used. Sexual dysfunction was detected in 76% of female patients and 31.4% of the control group, and the FSFI total and subscale scores of the patients were significantly lower than those of the control group. The frequency of erectile dysfunction in male patients and controls was 56.7% and 33.3%, respectively. The erectile function, sexual satisfaction, and overall satisfaction scores on the IIEF scale were significantly lower than those in the control group. Low glomerular filtration rate, high calcium levels, increased C-reactive protein, anemia, and metabolic acidosis in male and female patients, and testosterone deficiency in male patients were associated with sexual dysfunction. In multiple regression analysis, eGFR was the only independent variable associated with sexual dysfunction. Luteinizing hormone (LH) and prolactin levels increased as the disease progressed in men and women with sexual dysfunction, while testosterone levels decreased in male patients. Low testosterone levels were related to erectile dysfunction. The increase in parathormone and prolactin levels was related to loss of libido in the male and female patient groups. CONCLUSION: Metabolic acidosis and low eGFR appear to be the most important risk factors contributing to sexual disorders in patients with CKD.
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Acidose , Disfunção Erétil , Taxa de Filtração Glomerular , Insuficiência Renal Crônica , Disfunções Sexuais Fisiológicas , Humanos , Masculino , Feminino , Estudos Transversais , Pessoa de Meia-Idade , Acidose/epidemiologia , Acidose/sangue , Acidose/etiologia , Acidose/diagnóstico , Insuficiência Renal Crônica/complicações , Insuficiência Renal Crônica/epidemiologia , Insuficiência Renal Crônica/fisiopatologia , Insuficiência Renal Crônica/sangue , Adulto , Disfunções Sexuais Fisiológicas/epidemiologia , Disfunções Sexuais Fisiológicas/etiologia , Disfunções Sexuais Fisiológicas/sangue , Disfunção Erétil/epidemiologia , Disfunção Erétil/sangue , Disfunção Erétil/etiologia , Diálise Renal , Prevalência , Testosterona/sangue , Fatores de Risco , Idoso , Estudos de Casos e Controles , Prolactina/sangue , Hormônio Luteinizante/sangueRESUMO
Introduction Multiple sclerosis (MS) is a chronic and autoimmune disease that has a significant influence on the central nervous system, such as the brain and spinal cord, affecting millions of individuals globally. Understanding the connection between subcortical brain regions and MS is crucial for effective diagnostic and therapeutic approaches for treating this disabling disease. This study explores the relationship between volume and contours of asymmetry index of subcortical brain regions in individuals with MS using volBrain software (https://www.volbrain.net; developed by José V. Manjón (Valencia Polytechnic University, Valencia, Spain) and Pierrick Coupé (University of Bordeaux, Bordeaux, France)). Methods In our retrospective investigation, we admitted 100 Turkish individuals, comprising 50 patients diagnosed with relapsing-remitting MS (RRMS) (24 (48%) males and 26 (52%) females) and 50 healthy controls (23 (46%) males and 27 (54%) females), registered between October 2017 and February 2022 for five years and underwent assessment in the radiology department at the Teaching and Research Hospital of Kocaeli University; 1,150 Turkish patients were excluded from our study based on our exclusion criteria. We used magnetic resonance imaging with a 3-Tesla (3T) scanner and volBrain software to assess volumes (cm3) and asymmetry indexes due to asymmetry for different levels of atrophy of total intracranial, total brain, gray matter, white matter, and subcortical regions, the most affected regions in MS patients for both patient and control cohorts. Results Statistical analysis revealed a significant difference between patient and control groups (p < 0.001), with patient group mean age at 38.32 years and control group mean age at 32.88 years. Patient group exhibited lower values for total intracranial, total brain, gray matter, white matter, and cerebrospinal fluid volume compared to control group (p < 0.05). The results indicated a statistically significant decrease (p < 0.05) in the values for total intracranial and total brain volume, whereas all other values remained unchanged. We compared volumes of subcortical structures on the right and left sides and found that the putamen, thalamus, and globus pallidus had statistically lower values in the patient group than in the control group (p < 0.001), apart from the lateral ventricle. Furthermore, our retrospective investigation demonstrated a statistically significant difference in the globus pallidus asymmetry index, indicating a preference for the patient group (p < 0.05). A lower asymmetry index value signifies a larger volume for the right side of the subcortical regions of the brain when compared to the left side. Conclusion Brain atrophy, although characterized by irreversible tissue damage, is targeted by therapeutic interventions to prevent progression. It is, therefore, imperative to develop a universally accepted measurement standard for subcortical structures that also considers the inherent variability present within each structure. Our findings serve as an important basis and indicator for the determination of subcortical atrophy and asymmetry in MS, the prognosis of the disease, and the etiology of clinical symptoms. Subsequent research may benefit by adopting the novel approach of considering brain atrophy as an outcome rather than a predictor, thereby facilitating the elucidation of the intricate biological mechanisms that give rise to volume loss.
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OBJECTIVE: Craniopharyngiomas are locally invasive neoplasms, and they cause potential lifelong morbidity because of their tendency for local recurrence. Despite advancements in endoscopic techniques, gross-total resection (GTR) of tumors with invasion or adhesion to important surrounding anatomical structures is extremely difficult. The authors present a single-center study that evaluated the impact of the endoscopic endonasal approach (EEA) on the surgical outcomes of pediatric craniopharyngiomas, the factors affecting the resection rate, and recurrence. METHODS: A total of 44 pediatric patients (age ≤ 18 years) who were treated via the EEA for craniopharyngioma from August 1997 to June 2022, as well as their 53 operations, were included in this study. The preoperative radiological configuration and surgical data of these cases were assessed. Also, preoperative and postoperative clinical (endocrinologic, neurological, and ophthalmological), hypothalamic, physical and social development, and neurocognitive assessment data were described. RESULTS: In total, 37 cases (69.8%) had no history of operation beforehand. The most common symptoms at presentation were endocrine disturbances (98.1%), headache without vomiting (84.3%), and visual disturbance (51%). Cases were classified as infrasellar (1.9%), sellar (32.1%), sellar-suprasellar (52.8%), and suprasellar (13.2%) localization. GTR was achieved in 34/53 cases (64.1%). The rate of GTR was higher in infrasellar and sellar tumors compared with sellar-suprasellar and suprasellar tumors (p = 0.003), and preoperative hypothalamic involvement was associated with lower likelihood of GTR (p = 0.024). Moreover, with experience, the rate of GTR increased (p = 0.037). Postoperative complications, other than endocrine impairment, occurred in 10/53 cases (18.9%). The mean duration of follow-up was 53.57 months. At follow-up, 21/53 (39.6%) cases presented with tumor recurrence. The 5-year progression-free survival (PFS) rate was 48.5%. There was a statistically significant difference between the GTR and other-than-GTR groups in terms of PFS (p < 0.001). According to univariate analysis, smaller tumor (p = 0.017), infrasellar and sellar localization (p = 0.031), and GTR (p < 0.001) were significantly associated with decreased rate of recurrence. Also, there was a statistically significant association between the recurrence rate and adhesion strength of the tumor (p < 0.001). CONCLUSIONS: This retrospective cohort study revealed surgical indications for EEA, as well as factors affecting the resection rate, recurrence, and quality of life during the follow-up period of the included cases. The authors believe that GTR should be the goal for craniopharyngioma treatment, but the authors' treatment approach was to provide a balance between radical surgery with maximum safety and adjuvant treatment for long-term disease control.
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Craniofaringioma , Neoplasias Hipofisárias , Humanos , Criança , Adolescente , Craniofaringioma/diagnóstico por imagem , Craniofaringioma/cirurgia , Craniofaringioma/patologia , Seguimentos , Estudos Retrospectivos , Neoplasias Hipofisárias/diagnóstico por imagem , Neoplasias Hipofisárias/cirurgia , Neoplasias Hipofisárias/patologia , Qualidade de Vida , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Intervalo Livre de ProgressãoRESUMO
Lung cancer, known for its high mortality rates and poor prognosis, remains one of the most prevalent cancer types. Early detection and effective treatment methods are crucial for improving survival rates. Non-small cell lung cancer (NSCLC) accounts for approximately 85 % of all lung cancer cases. Long non-coding RNAs (lncRNAs), which play vital roles in various biological processes, have been implicated in the development of cancer and can impact key therapeutic targets in different cancer types. In NSCLC, the dysregulation of specific lncRNAs, such as MALAT1 and NORAD, has been associated with neoplastic initiation, progression, metastasis, tumor angiogenesis, chemoresistance, and genomic instability. Both MALAT1 and NORAD directly regulate the expression of the transcription factor E2F1, thereby influencing cell cycle progression. Additionally, MALAT1 has been reported to affect the expression of p53 target genes, leading to cell cycle progression through the repression of p53 promoter activity. NORAD, on the other hand, is indirectly regulated by p53. The AT-rich interaction domain (ARID) family of DNA-binding proteins, particularly ARID3A and ARID3B, are involved in various biological processes such as cell proliferation, differentiation, and development. They also play significant roles in E2F-dependent transcription and are transcriptional targets of p53. The intricate balance between promoting cellular proliferation through the pRB-E2F pathway and inducing growth arrest through the p53 pathway underscores the crucial regulatory role of ARID3A, ARID3B, and their interaction with lncRNAs MALAT1 and NORAD. In this study, we aimed to investigate the potential interactive and functional connections among ARID3A, ARID3B, MALAT1, and NORAD in NSCLC, considering their involvement in the pRB-E2F and p53 pathways. Our findings strongly suggest that ARID3A and ARID3B play a regulatory role in controlling MALAT1 and NORAD in NSCLC. Specifically, our study demonstrates that the activities of MALAT1 and NORAD were markedly increased upon the overexpression of ARID3A and ARID3B. Therefore, we can conclude that ARID3A and ARID3B likely contribute significantly to the oncogenic functions of MALAT1 and NORAD in NSCLC. Consequently, targeting ARID3A and ARID3B could hold promise as a therapeutic approach in NSCLC, given their direct control over the expression of MALAT1 and NORAD.
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Carcinoma Pulmonar de Células não Pequenas , Neoplasias Pulmonares , MicroRNAs , RNA Longo não Codificante , Humanos , Carcinoma Pulmonar de Células não Pequenas/genética , Linhagem Celular Tumoral , Proliferação de Células , Proteínas de Ligação a DNA/genética , Proteínas de Ligação a DNA/metabolismo , Regulação Neoplásica da Expressão Gênica/genética , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , MicroRNAs/genética , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Fatores de Transcrição/metabolismo , Proteína Supressora de Tumor p53/metabolismoRESUMO
PURPOSE: This study aims to analyze the clinicopathological features, diagnostic steps, and therapeutic results of TSHomas and to reveal the effective factors on remission. METHODS: The clinical, radiological, and pathological features and surgical and endocrinological results of 41 TSHoma cases followed between 2005 and 2022 were retrospectively analyzed. The factors affecting the surgical cure were investigated by comparing the groups with and without remission. RESULTS: A total of 41 patients (23 male,18 female) were included in the study and the mean age was 42 (31.5-49). Palpitation and headache were the most common complaints. The time from the onset of symptoms to diagnosis was 8 (3-20) months. There were 8 patients with a preoperative clinical and biochemical diagnosis of TSH + GH co-secretion. In the TRH stimulation test, a blunted TSH response was obtained in 18 patients (90.0%). Complete suppression could not be obtained in any of the patients who underwent the T3 suppression test. The median maximum tumor diameter was 19.0 mm (6.8-41). There was microadenoma in 4 (9.8%) patients and macroadenoma in 37 patients (92.8%). Remission was achieved in 31 (75.6%) of 40 patients who underwent endoscopic transsphenoidal surgery (eTSS). The Ki-67 labeling index was 2% (1.00-4.00) in the entire patient group. Preoperative use of antithyroid drugs appears to be significantly associated with surgical cure. CONCLUSION: Diagnosis of TSHoma is still full of challenges and dynamic tests remain important. Recognition and good management of inappropriate TSH secretion states affect subsequent surgical outcomes.
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Adenoma , Neoplasias Hipofisárias , Humanos , Masculino , Feminino , Adulto , Neoplasias Hipofisárias/cirurgia , Tireotropina , Seguimentos , Estudos Retrospectivos , Adenoma/patologiaRESUMO
[This corrects the article DOI: 10.1007/s12288-022-01574-6.].
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INTRODUCTION: With increased fluid intake and tolvaptan treatment, the growth rate of cysts can be theoretically decelerated in autosomal polycystic kidney disease. In this prospective study, it was planned to evaluate thirst sensation in these patients and the parameters affecting its intensity. METHODS: Forty-one ADPKD patients on tolvaptan and 40 ADPKD patients not on tolvaptan as the control group were evaluated for thirst distress sensation and intensity. The feeling of thirst and the discomfort caused by excessive fluid intake was assessed with Thirst Distress Scale-HF 12 questions (60/12). Thirst intensity was evaluated with a 100 mm visual scale. RESULTS: Of the whole group, 35.8% (29) were males, and 64.2% (52) were females. The mean age of the tolvaptan group was 39.17 ± 9.35 years and for the control group, it was 41.95 ± 12.29 years. There was a negative correlation between the thirst distress score of the patients and an increase in creatinine level after a year of tolvaptan treatment (r = - 0.335, p = 0.035). The patients not taking thiazide had higher thirst intensity scores (p = 0.004). There was no impact of tolvaptan dosage, total kidney volume, serum sodium, urinary osmolarity or eGFR on thirst distress and thirst intensity scores. DISCUSSION/CONCLUSION: Only thiazide co-treatment had a positive impact on thirst distress and intensity when given tolvaptan. Thirst Distress Scale for ADPKD patients can be used to classify patients before and during tolvaptan treatment.
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Rim Policístico Autossômico Dominante , Masculino , Feminino , Humanos , Adulto , Pessoa de Meia-Idade , Tolvaptan/uso terapêutico , Rim Policístico Autossômico Dominante/tratamento farmacológico , Antagonistas dos Receptores de Hormônios Antidiuréticos , Estudos Prospectivos , SedeRESUMO
Objective: In the present study, we investigated the expression of CD56, ADAM17 and FGF21 antibodies (Ab), which we think have an effect on the pathophysiology of preeclampsia (PE), in pregnant patients with healthy placentas and placentas with PE. The expression of these antibodies has been investigated in a limited amount of former research, but their role in PE has not yet been clarified. With this study, we aimed to contribute to the elucidation of the pathophysiology of PE and the detection of new target molecules for treatment. Materials and Methods: Parturients with singleton pregnancy at 32 weeks or above without any maternal or fetal pathology who were admitted to the Department of Obstetrics and Gynecology, Zonguldak Bülent Ecevit University Practice and Research Hospital between 11 January 2020 and 7 January 2022 were included in the present study. Pregnant women with coexisting disease or a pathology related to the placenta (ablation placenta, vasa previa, hemangioma, etc.) were excluded. CD56, ADAM17 and FGF21 antibodies were histopathologically and immunohistochemically detected in 60 placentas with PE (study group) and 43 healthy placentas (control group). Results: CD56, ADAM17 and FGF21 proteins were all more intensely expressed in preeclamptic placentas and a statistically significant difference was found between the two groups for all three antibodies (p < 0.001). Deciduitis, perivillous fibrin deposition, intervillous fibrin, intervillous hemorrhage, infarct, calcification, laminar necrosis and syncytial node were found to be significantly more common in the study group (p < 0.001). Conclusions: We observed that CD56, ADAM17 and FGF21 expressions increased in preeclamptic placentas. These Ab may be responsible for the pathogenesis of PE, which can be illuminated with further studies.
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Proteína ADAM17 , Antígeno CD56 , Fatores de Crescimento de Fibroblastos , Pré-Eclâmpsia , Feminino , Humanos , Gravidez , Proteína ADAM17/metabolismo , Anticorpos , Fatores de Crescimento de Fibroblastos/metabolismo , Placenta , Pré-Eclâmpsia/metabolismo , Antígeno CD56/metabolismoRESUMO
Purpose: The receptor for advanced glycation end products (RAGE) upregulated during the onset and progression of cancer and bone-related pathologies. In this study, we aimed to investigate the role of serum advanced glycation end products (AGEs), soluble RAGE (sRAGE) and high mobility group box 1 (HMGB1), in multiple myeloma (MM). Methods: AGEs, sRAGE and HMGB1 concentrations of 54 newly diagnosed MM patients and 30 healthy volunteers were measured by ELISA. The estimations were done only once at diagnosis. The medical records of the patients were evaluated. Results: There was no significant difference between the AGEs and sRAGE levels between the patient and control groups (p = 0.273, p = 0.313). In ROC analysis, a HMGB1 cutoff value of > 9170 pg/ml accurately discriminated MM patients (AUC = 0.672, 95% CI 0.561-0.77, p = 0.0034). AGEs level was found to be significantly higher in early-stage disease and HMGB1 in advanced disease (p = 0.022, p = 0.026). High HMGB1 levels were detected in patients whose with better first-line treatment response (p = 0.019). At 36 months, 54% of patients with low AGE were alive, compared to 79% of patients with high AGE (p = 0.055). Patients with high HMGB1 levels tended to have a longer PFS (median 43 mo [95% CI; 20.68-65.31] ) compared to patients with low HMGB1 levels (median 25 mo [95% CI; 12.39-37.6], p = 0.054). Conclusion: In this study, a significant elevation of serum HMGB1 level was found in MM patients. In addition, the positive effects of RAGE ligands on treatment response and prognosis were determined.
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Multicentric carpotarsal osteolysis (MCTO) syndrome, is typically characterized by progressive bone resorption in especially carpal and tarsal bones, in addition to abnormal facial appearance and proteinuria. This disorder is caused by monoallelic pathogenic MAFB mutations, which result in excessive osteoclastogenesis via aberrant receptor activator of nuclear factor kappa-B ligand activation. Most cases are sporadic with de-novo mutations, and it is still unclear why carpal and tarsal bones are predominantly affected. The early phases of MCTO resemble juvenile idiopathic arthritis (JIA) with ankle and wrist swelling and pain, even with inflammatory changes in magnetic resonance imaging. Herein we report a pediatric patient, previously treated with antirheumatic drugs, and eventually diagnosed with MCTO. This case was a descriptive case with exophthalmos, significant proteinuria, and total loss of carpal and tarsal bones at the time of genetic diagnosis. Similar to the literature, our case had typical radiological findings despite methotrexate and anti-tumor necrosis factor-alpha treatment. However, while arthritis affecting joints other than wrists and ankles has not been reported so far in the literature, our case had bilateral sacroiliitis which completely resolved after adalimumab treatment. We cannot be sure if sacroiliitis was incidental or occurred as a component of the disease, nonetheless, we think that sharing our experience may lead to easy and early recognition of MCTO, with more knowledge on rare manifestations of MCTO, and thus we may be able to clarify the benefits of denosumab, which is the most promising agent in early phases of the disease.
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Osteólise , Sacroileíte , Humanos , Criança , Osteólise/diagnóstico por imagem , Osteólise/tratamento farmacológico , Mutação , Proteinúria , Fator de Transcrição MafB/genéticaRESUMO
OBJECTIVE: Eating Disorder-15 (ED-15) is a self-report scale recommended for use to evaluate weekly progress and treatment results in eating disorders. This research aims to examine the factor structure, psychometric properties, validity, and reliability of the Turkish version of ED-15 (ED-15-TR) for clinical and non-clinical samples. METHOD: Translation-back translation method was used for language equivalence of ED-15-TR. The research was conducted with a total of 1049 volunteers, with two sample groups as non-clinical (n=978) and clinical (n=71). The participants completed an information form, ED-15-TR, Eating Disorder Examination Scale (EDE-Q), and Beck Depression Inventory (BDI). Three hundred fifty-two participants from the non-clinical group and 18 from the clinical group completed ED-15-TR again within a week. RESULTS: Factor analysis confirmed the two-factor structure of ED-15- TR. Cronbach's alpha value was 0.911 (0.773, and 0.904 for the two subscales respectively), the intraclass correlation coefficient for testretest reliability was 0.943 in the clinical group (0.906, and 0.942 for the two subscales respectively); 0.777 (0.699, and 0.776 for the two subscales respectively) in the non-clinical group (for all p<0.001). The high level of a positive correlation between ED-15-TR and EDE-Q supported concurrent validity. CONCLUSION: This research indicates that ED-15-TR is an acceptable, valid, and reliable self-report scale for Turkish society.
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Transtornos da Alimentação e da Ingestão de Alimentos , Humanos , Psicometria/métodos , Reprodutibilidade dos Testes , Inquéritos e Questionários , Transtornos da Alimentação e da Ingestão de Alimentos/diagnóstico , IdiomaRESUMO
OBJECTIVE: Pathological destruction of insulin signaling molecules such as insulin receptor substrate, especially due to the increase in suppressors of cytokine signaling molecules, has been demonstrated in experimental diabetes. The contribution of suppressors of cytokine signaling proteins to the development of insulin resistance and the effects of antidiabetic drugs and exercise on suppressors of cytokine signaling proteins are not clearly known. METHODS: A total of 48 Wistar albino adult male rats were divided into six groups: control group, obese group with diabetes, obese diabetic rats treated with metformin, obese diabetic rats treated with pioglitazone, obese diabetic rats treated with exenatide, and obese diabetic rats with applied exercise program. Immunohistochemical staining was performed in both the liver and adipose tissue. RESULTS: There was a statistically significant decrease in suppressors of cytokine signaling-1, a decrease in suppressors of cytokine signaling-3, an increase in insulin receptor substrate-1, and a decrease in immunohistochemical staining in the obese group treated with metformin and exenatide compared to the obese group without treatment in the liver tissue (p<0.05). A statistically significant decrease in immunohistochemical staining of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 was found in the obese group receiving exercise therapy compared to the obese group without treatment in visceral adipose tissue (p<0.05). Likewise, no significant immunohistochemistry staining was seen in diabetic obese groups. CONCLUSION: Metformin or exenatide treatment could prevent the degradation of insulin receptor substrate-1 protein by reducing the effect of suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins, especially in the liver tissue. In addition, exercise can play a role as a complementary therapy by reducing suppressors of cytokine signaling-1 and suppressors of cytokine signaling-3 proteins in visceral adipose tissue.
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Diabetes Mellitus Experimental , Resistência à Insulina , Metformina , Animais , Humanos , Masculino , Ratos , Citocinas/metabolismo , Exenatida/metabolismo , Terapia por Exercício , Hipoglicemiantes , Insulina/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Obesidade/metabolismo , Ratos Wistar , Proteínas Supressoras da Sinalização de Citocina/metabolismoRESUMO
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.
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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 DoençasRESUMO
Migraine is a neurological disease characterized by severe headache attacks. Combinations of different genetic variations such as copy number variation (CNV) in a gene and microRNA (miRNA) expression can provide a holistic approach to the disease as a pathophysiological, diagnostic, and therapeutic target. CNVs, the Cholinergic Receptor Nicotinic Alpha 7 Subunit (CHRNA7) gene, and expression of gene-targeting miRNAs (hsa-miR-548e-5p and hsa-miR-3158-5p) in migraineurs (n = 102; with aura, n = 43; without aura, n = 59) and non-migraines (n = 120) aged 15-60 years, comparative, case-control study was conducted. Genetic markers were compared with biochemical parameters (BMI, WBC, Urea, GFR, ESR, CRP, HBG). All analyzes were performed by quantitative Real-Time PCR (q-PCR) and fold change was calculated with the 2-ΔΔCT method. The diagnostic power of the CHRNA7 gene, CNV, and miRNAs were analyzed with the receiver operating curve (ROC). CHRNA7 gene and hsa-miR-3158-5p are down-regulated in migraineurs and the gene is controlled by this miRNA via CNVs (p < .05). Both deletion and duplication were detected in patients with migraine for CVN numbers (p = .05). The number of CNV deletions was higher than duplications. When CHRNA7-CNV-hsa-miR-3158-5p was modeled together in the ROC analysis, the area under the curve (AUC) was 0.805, and the diagnostic power was "good". In migraineurs, the CHRNA7 gene can be controlled by hsa-miR-3158-5p via CNVs to modulate the mechanism of pain. These three genetic markers have diagnostic potential and may be used in antimigraine treatments.
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Variações do Número de Cópias de DNA , MicroRNAs , Transtornos de Enxaqueca , Receptor Nicotínico de Acetilcolina alfa7 , Humanos , Receptor Nicotínico de Acetilcolina alfa7/genética , Estudos de Casos e Controles , Marcadores Genéticos , MicroRNAs/genética , Transtornos de Enxaqueca/genéticaRESUMO
Objective: Due to the high increase in rate of autism, it has gained great importance to determine the etiology of autism spectrum disorder. The purpose of our study was to assess the role of Candida albicans as a risk factor to cause autism behavior. Methods: We searched Scopus, PubMed, Web of Science and PsycINFO for articles up to December, 2021. The studies involving children diagnosed with autism spectrum disorder were included. Children' outcomes were selected as Candida albicans (positive) and Candida albicans (negative). Odds ratios were reported using fixed-effect and random-effect meta-analysis. The heterogeneity was assessed by the Chi-square test and Higgins' I2 test. The publication bias was examined via funnel plot and Hegger's test. Results: Our meta-analysis was conducted based on 254 diagnosed with Autism Spectrum Disease cases and 161 healthy cases from 4 studies. Compared to the healthy cases, the odds of presence of Candida albicans (OR=7.21; 95% CI: 3.75-13.85; p<0.001) were higher in those diagnosed with autism spectrum disorder. Conclusion: This study as a whole showed that children diagnosed with autism spectrum disorder have higher frequency of the presence of the fungus Candida albicans. Therefore, Candida albicans may be an etiological factor for the autistic behavior in children.
Assuntos
Transtorno do Espectro Autista , Candida albicans , Humanos , Candida albicans/isolamento & purificação , Fatores de Risco , Transtorno do Espectro Autista/microbiologia , Transtorno do Espectro Autista/epidemiologia , Criança , Candidíase/epidemiologia , Candidíase/microbiologia , Transtorno Autístico/microbiologia , Transtorno Autístico/epidemiologia , Pré-EscolarRESUMO
OBJECTIVE: Genome-length association studies have shown that Gasdermin B (GSDMB) and Orosomucoid-like 3 (ORMDL3) genes located on the long arm of chromosome 17 are associated with asthma. In this study, it was aimed to determine the possible relationship between asthma control test (ACT), exercise provocation test (ECT), and fractional nitric oxide (FENO) levels and GSDMB and ORMDL3 gene expressions. METHODS: 59 asthmatic and 38 non-asthmatic children were included in the study. We divided the patient group into two subgroups as mild persistent asthma (29 patients) and moderate persistent asthma (30 patients). ORMDL3, GSDMB gene expression levels, ECT, total IgE levels, and eosinophil counts were measured in all cases. In addition, ACT and FeNO levels were measured in children with asthma. Afterward, the relationship of ORMDL3 and GSDMB gene expression coefficient changes with ECT, ACT, and FeNO was examined. RESULTS: When patients with ACT ≤15 were compared with patients with ACT ≥20, ORMDL3 and GSDMB gene expressions were increased 6.74 and 11.74 times, respectively. Comparing patients with ACT ≥20 and ACT ≤15 in terms of coefficient changes (ΔCq), higher change values were observed for ΔCq ORMDL3 in patients with ACT ≤15 (p=0.015). Similarly, when patients with FENO ≤25 ppb were compared with patients with FENO >25 ppb, ORMDL3 and GSDMB gene expressions were increased by 2.93 and 3.56 times, respectively. When the coefficient changes were compared, no significant difference was found between FENO≤25 and FENO >25 patients. There was a slight negative correlation between ΔCq values and ACT score (p=0.003, r=-0.418 for ORMDL3, and p=0.016, r=-0.345 for GSDMB). In addition, we observed a statistically significant positive correlation between ORMDL3 and GSDMB gene expressions (r=0.80, p<0.001). CONCLUSION: We showed that increased ORMDL3 and GSDMB gene expression levels may be associated with ACT scores, FeNO and ECT in asthma. These findings may encourage future studies with larger numbers of subjects that can use gene expression levels in various asthma phenotypes for prognostic prediction.