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Understanding the role of iron in ethanol-derived hepatic stress could help elucidate the efficacy of dietary or clinical interventions designed to minimize liver damage from chronic alcohol consumption. We hypothesized that normal levels of iron are involved in ethanol-derived liver damage and reduced dietary iron intake would lower the damage caused by ethanol. We used a pair-fed mouse model utilizing basal Lieber-DeCarli liquid diets for 22 weeks to test this hypothesis. In our mouse model, chronic ethanol exposure led to mild hepatic stress possibly characteristic of early-stage alcoholic liver disease, seen as increases in liver-to-body weight ratios. Dietary iron restriction caused a slight decrease in non-heme iron and ferritin (FeRL) expression while it increased transferrin receptor 1 (TfR1) expression without changing ferroportin 1 (FPN1) expression. It also elevated protein lysine acetylation to a more significant level than in ethanol-fed mice under normal dietary iron conditions. Interestingly, iron restriction led to an additional reduction in nicotinamide adenine dinucleotide (NAD+) and NADH levels. Consistent with this observation, the major mitochondrial NAD+-dependent deacetylase, NAD-dependent deacetylase sirtuin-3 (SIRT3), expression was significantly reduced causing increased protein lysine acetylation in ethanol-fed mice at normal and low-iron conditions. In addition, the detection of superoxide dismutase 1 and 2 levels (SOD1 and SOD2) and oxidative phosphorylation (OXPHOS) complex activities allowed us to evaluate the changes in antioxidant and energy metabolism regulated by ethanol consumption at normal and low-iron conditions. We observed that the ethanol-fed mice had mild liver damage associated with reduced energy and antioxidant metabolism. On the other hand, iron restriction may exacerbate certain activities of ethanol further, such as increased protein lysine acetylation and reduced antioxidant metabolism. This metabolic change may prove a barrier to the effectiveness of dietary reduction of iron intake as a preventative measure in chronic alcohol consumption.
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Antioxidantes , Metabolismo Energético , Etanol , Animais , Camundongos , Acetilação/efeitos dos fármacos , Metabolismo Energético/efeitos dos fármacos , Antioxidantes/metabolismo , Masculino , Ferro/metabolismo , Superóxido Dismutase-1/metabolismo , Superóxido Dismutase-1/genética , Superóxido Dismutase/metabolismo , Lisina/metabolismo , Fígado/metabolismo , Fígado/efeitos dos fármacos , Receptores da Transferrina/metabolismo , Sirtuína 3/metabolismo , Sirtuína 3/genética , NAD/metabolismo , Ferritinas/metabolismo , Proteínas de Transporte de Cátions/metabolismo , Proteínas de Transporte de Cátions/genética , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Hepatopatias Alcoólicas/metabolismo , Hepatopatias Alcoólicas/patologia , Hepatopatias Alcoólicas/etiologiaRESUMO
Introduction: Ovarian cancer is one of the leading causes of death for women with cancer worldwide. Energy requirements for tumor growth in epithelial high-grade serous ovarian cancer (HGSOC) are fulfilled by a combination of aerobic glycolysis and oxidative phosphorylation (OXPHOS). Although reduced OXPHOS activity has emerged as one of the significant contributors to tumor aggressiveness and chemoresistance, up-regulation of mitochondrial antioxidant capacity is required for matrix detachment and colonization into the peritoneal cavity to form malignant ascites in HGSOC patients. However, limited information is available about the mitochondrial biogenesis regulating OXPHOS capacity and generation of mitochondrial reactive oxygen species (mtROS) in HGSOC. Methods: To evaluate the modulation of OXPHOS in HGSOC tumor samples and ovarian cancer cell lines, we performed proteomic analyses of proteins involved in mitochondrial energy metabolism and biogenesis and formation of mtROS by immunoblotting and flow cytometry, respectively. Results and discussion: We determined that the increased steady-state expression levels of mitochondrial- and nuclear-encoded OXPHOS subunits were associated with increased mitochondrial biogenesis in HGSOC tumors and ovarian cancer cell lines. The more prominent increase in MT-COII expression was in agreement with significant increase in mitochondrial translation factors, TUFM and DARS2. On the other hand, the ovarian cancer cell lines with reduced OXPHOS subunit expression and mitochondrial translation generated the highest levels of mtROS and significantly reduced SOD2 expression. Evaluation of mitochondrial biogenesis suggested that therapies directed against mitochondrial targets, such as those involved in transcription and translation machineries, should be considered in addition to the conventional chemotherapies in HGSOC treatment.
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OBJECTIVE: The purpose of this systematic review is to determine the evidence-based information and results about the effectiveness of telehealth programs on the mental health of women with breast cancer. Methods: The research process was carried out using PRISMA guidelines. Randomized controlled trials with available abstract and full text, which were published in English with the keywords "telehealth," "telemedicine," "web-based therapy," "telepsychiatry," "online therapy" and "breast cancer" in Pub Med, PsycINFO, Medline, Science Direct, Scopus, Web of Sciences and Cochrane databases between 2015-2019 were searced. As a result of the evaluations, the research was completed with 16 studies meeting the research criteria. Results: There was strong evidence for reduce the fear of relapse of cancer, depressive symptoms and severity of depression, distress, intrusive thoughts, anxiety, sleep disorder, insomnia, improve quality of life and for improve cognitive functions, improve psychological strength and sleep quality of telehealth programs in women with breast cancer. Furthermore, evidence was found for increase psychological health, functionality, optimism and control over the future, positive mood and life appreciation, and drug compliance of these programs. Conclusion: This review found evidence for the effectiveness of telehealth programs on the mental problems of women with breast cancer. In this sense, it is recommended to expand the use of telehealth programs, which can save time and cost, are accessible and easily applicable by nurses, to improve the mental health of women with breast cancer, and further studies are recommended.
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BACKGROUND: Depression has long been accepted as a serious disability and burden globally, while suicide is a misunderstood and complex cause of death. Psychache is the psychological variable most strongly associated with suicidality. Spirituality is considered an important buffer against stressful events and may help people overcome distress and difficulties. AIMS: This study aims to determine how psychache and suicide risk are related to levels of spiritual well-being in patients with depression. METHODS: Data were collected using the Suicide Probability Scale, the Psychache Scale, and the Spiritual Well-Being Scale. The sample study consisted of 150 Turkish patients diagnosed with depression and receiving psychiatric care. RESULTS: It was found that higher level of spiritual well-being led to decreased risk of suicide and lower level of psychache. Suicide risk increased in parallel to the increasing levels of psychache (p < .001). CONCLUSIONS: It was observed that higher levels of spiritual well-being may promote a significantly lower risk of suicide and lower levels of psychache. Likewise, increasing levels of psychache may lead to an increase in suicide risk.
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Type 2 diabetes has become an epidemic disease largely explained by the dramatic increase in obesity in recent years. Mitochondrial dysfunction is suggested as an underlying factor in obesity and type 2 diabetes. In this study, we evaluated changes in oxidative phosphorylation and mitochondrial biogenesis in a new human obesity and type 2 diabetes model, TALLYHO/Jng mice. We hypothesized that the sequence variants identified in the whole genome analysis of TALLYHO/Jng mice would affect oxidative phosphorylation and contribute to obesity and insulin resistant phenotypes. To test this hypothesis, we investigated differences in the expression and activity of oxidative phosphorylation complexes, including the transcription and translation of nuclear- and mitochondrial-encoded subunits and enzymatic activities, in the liver and kidney of TALLYHO/Jng and C57BL/6â¯J mice. A significant decrease was observed in the expression of nuclear- and mitochondrial-encoded subunits of complex I and IV, respectively, in TALLYHO/Jng mice, which coincided with significant reductions in their enzymatic activities. Furthermore, sequence variants were identified in oxidative phosphorylation complex subunits, a mitochondrial tRNA synthetase, and mitochondrial ribosomal proteins. Our data suggested that the lower expression and activity of oxidative phosphorylation complexes results in the diminished energy metabolism observed in TALLYHO/Jng mice. Sequence variants identified in mitochondrial proteins accentuated a defect in mitochondrial protein synthesis which also contributes to impaired biogenesis and oxidative phosphorylation in TALLYHO/Jng mice. These results demonstrated that the identification of factors contributing to mitochondrial dysfunction will allow us to improve the disease prognosis and treatment of obesity and type 2 diabetes in humans.
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Diabetes Mellitus Tipo 2/metabolismo , Regulação da Expressão Gênica , Mitocôndrias/metabolismo , Obesidade/metabolismo , Fosforilação Oxidativa , Aminoacil-tRNA Sintetases/genética , Aminoacil-tRNA Sintetases/metabolismo , Animais , Diabetes Mellitus Tipo 2/genética , Diabetes Mellitus Tipo 2/patologia , Modelos Animais de Doenças , Complexo I de Transporte de Elétrons/genética , Complexo I de Transporte de Elétrons/metabolismo , Complexo II de Transporte de Elétrons/genética , Complexo II de Transporte de Elétrons/metabolismo , Complexo IV da Cadeia de Transporte de Elétrons/genética , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Insulina/metabolismo , Resistência à Insulina , Rim/metabolismo , Rim/patologia , Fígado/metabolismo , Fígado/patologia , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Transgênicos , Mitocôndrias/genética , Obesidade/genética , Obesidade/patologia , Proteínas Ribossômicas/genética , Proteínas Ribossômicas/metabolismoRESUMO
Of the 200 Clostridium spp. known to exist, approximately 30 have been associated with human disease. Commonly found in soil, marine sediment and mammalian intestinal tracts, these gram-positive bacilli are known to cause infections ranging from cellulitis to septicemia. Isolates that are identified by clinical microbiology laboratories include Clostridium perfrigens species in 20-40% of cases. However, when Clostridium sporogenes is identified, is rarely considered to be pathogenic. We present a case of Clostridium sporogenes bacteremia secondary to lower limb cellulitis and osteomyelitis in an immunocompetent patient.
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BACKGROUND: How genotype affects phenotype in hereditary angioedema with C1 inhibitor deficiency (C1-INH-HAE) has not been totally clarified. In this study, we investigated the relationship between different types of mutations and various phenotypic characteristics. METHODS: Clinical data from 81 patients from 47 families were recorded. Complement proteins were analyzed from 61 untreated patients. The coding exons and the exon-intron boundaries of the SERPING1 gene were sequenced, and deletion/duplication analysis with multiple ligation dependent probe amplification was performed. The relationship of complement protein with the mutation type was analyzed by using generalized estimating equations. RESULTS: Thirty-five different mutations (15 novel and 2/15 homozygous) were identified. There was no causative mutation in 6 patients (7.4%). Patients with deletion and large deletion had the lowest (5.05%, 0-18.7; 5.8%, 0-16.5%, respectively), and the none mutation group had the highest C1 inhibitor function (23.3%, 11-78%, p < 0.001). C1 inhibitor function levels decreased as the age of the disease progressed (r = -0.352, p = 0.005). Lower C1 inhibitor function levels caused severer disease (r = -0.404, p = 0.001) and more frequent annual attacks (r = -0.289, p = 0.024). In the off-attack period, C1q levels were lower than normal in 9.8% of the patients. CONCLUSION: Deletion mutations may represent the most unfavorable effect on C1 inhibitor function. The earlier disease onset age could be a sign for lower C1 inhibitor function levels in adult life. C1q levels could also be low in C1-INH-HAE patients, as in acquired angioedema. Lower C1 inhibitor function can predict disease severity and may have negative impacts on the course of C1-INH-HAE.
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Angioedemas Hereditários/genética , Proteína Inibidora do Complemento C1/genética , Proteína Inibidora do Complemento C1/metabolismo , Estudos de Associação Genética , Deleção de Sequência , Adulto , Alelos , Angioedemas Hereditários/diagnóstico , Angioedemas Hereditários/imunologia , Angioedemas Hereditários/metabolismo , Biomarcadores , Proteínas do Sistema Complemento/imunologia , Proteínas do Sistema Complemento/metabolismo , Feminino , Estudos de Associação Genética/métodos , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Mutação de Sentido Incorreto , Prognóstico , Sítios de Splice de RNARESUMO
Xanthogranulomatous pyelonephritis is a rare form of chronic pyelonephritis that generally afflicts middle-aged women with a history of recurrent urinary tract infections. Its pathogenesis generally involves calculus obstructive uropathy and its histopathology is characterized by replacement of the renal parenchyma with lipid filled macrophages. This often manifests as an enlarged, nonfunctioning kidney that may be complicated by abscess or fistula. This case details the first reported case of xanthogranulomatous pyelonephritis complicated by urinothorax, which resolved on follow-up chest X-ray after robot-assisted nephrectomy.
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BACKGROUND: Immunosuppression at the feto-maternal interface is crucial for a successful pregnancy outcome. Human leukocyte antigen-G (HLA-G) seems to be a major contributor to fetal tolerance. The HLA-G expression is seen in cytotrophoblasts and in maternal blood. Fetal HLA-G acts on decidual antigen-presenting cells (APCs), natural killers (NKs) and T cells. Recent findings revealed that defects in placentation and their consequences are associated with maternal HLA-G variants and their expression levels. OBJECTIVES: The objective of this article is to investigate the relationship between fetal HLA-G alleles and miscarriage, which has not been investigated to date. MATERIAL AND METHODS: The present study includes 204 recurrent miscarriage (RM) cases who were admitted to our clinic between 2012 and 2016. Twenty-eight miscarriage products without maternal cell contamination and any known pathology were analyzed by HLA-G typing. In addition, 3' untranslated region (UTR) 14-base pair (bp) insertion/deletion polymorphism was also investigated by Sanger sequencing. RESULTS: For our population, the most frequent HLA-G type was G*01:01, both in the study group (30.3%) and in the control group (47%). The study revealed that the G*01:04 allele was significantly associated with miscarriage (p = 0.007). The 3' UTR 14bp deletion was more frequent in the miscarriage group, but there was no significant correlation. CONCLUSIONS: HLA-G alleles seem to be related with miscarriage and should be considered in RM cases.
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Aborto Habitual/genética , Aborto Habitual/imunologia , Antígenos HLA/genética , Antígenos HLA-G/fisiologia , Aborto Habitual/fisiopatologia , Alelos , Feminino , Antígenos HLA-G/genética , Humanos , Polimorfismo Genético , Gravidez , Resultado da GravidezRESUMO
BACKGROUND: It has been suggested that latex-specific IgE analysis may lead to false-positive results, especially in patients with pollen allergy. In the present study, the reasons underlying clinically irrelevant latex-specific IgE positivity were investigated. METHODS: Thirty patients with latex allergy (group 1), 89 patients sensitised to aeroallergens (group 2a), and 98 healthy individuals without allergy (group 2b) were enrolled. Participants from all 3 groups were subjected to skin prick tests with aeroallergens including latex, latex-specific IgE analysis (ImmunoCAP), and nasal provocation test with latex. All cases demonstrating positive latex-specific IgE also underwent specific IgE tests (ImmunoCAP) with latex profilin, birch pollen profilin, peach lipid transfer protein, and pineapple bromelain as cross-reactive carbohydrate determinants. RESULTS: Comparison of the atopic and healthy control groups showed that the rate of positive latex-specific IgE was significantly higher in group 2a. Latex profilin-, birch pollen profilin-, and bromelain-specific IgE were remarkably higher in group 2a. CONCLUSION: False positivity to latex-specific IgE in ImmunoCAP analysis may be observed in approximately 19% of patients with pollen allergy. Profilins and bromelain are the main contributors to clinically irrelevant positive latex-specific IgE.
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Alérgenos/imunologia , Antígenos de Plantas/imunologia , Bromelaínas/imunologia , Proteínas de Transporte/imunologia , Hipersensibilidade ao Látex/diagnóstico , Proteínas de Plantas/imunologia , Profilinas/imunologia , Rinite Alérgica Sazonal/diagnóstico , Adulto , Ananas/imunologia , Biomarcadores/sangue , Estudos de Casos e Controles , Reações Cruzadas , Reações Falso-Positivas , Feminino , Humanos , Imunoglobulina E/sangue , Hipersensibilidade ao Látex/sangue , Hipersensibilidade ao Látex/imunologia , Masculino , Pessoa de Meia-Idade , Prunus persica/imunologia , Rinite Alérgica Sazonal/sangue , Rinite Alérgica Sazonal/imunologia , Testes CutâneosRESUMO
Diagnosis and treatment procedures in cancers and resulting anxiety negatively affect the individual and the family. Particularly treatment methods may generate psychological symptoms. The aim of this study was to determine the level of such symptoms in Turkish gynecologic cancer patients receiving chemotherapy. A total of 41 patients who were referred to our gynecologic oncology research clinic between January-March 2012, receiving 3 months or more chemotherapy and who agreed to participate were enrolled in study. All the data were collected using a personal information form, Edmonton Symptom Assesment System and State-Trait Anxiety Inventory. Patients received highest point average from fatigue symptom (6.53±2.67) and lowest point average from dyspnea (1.53±3.03) according to Edmonton Symptom Assesment System. The mean State Anxiety score of patients was 43.1±9.77 and mean Trait Anxiety score was 46.7±7.01. Comparing symptoms of patients and mean State Anxiety score it was found that there was a statistically significant corelation with symptoms like pain (p<0.05), sadness (p<0.001), insomnia (p<0.05), state of well being (p<0.001) and dyspnea (p<0.05). Similarly comparing symptoms of patients and mean Trait Anxiety score demonstrated significant correlations for fatigue (p<0.05), sadness (p<0.01), insomnia (p<0.01) and state of well-being (p<0.01). As a result, patients with gynecological cancers experienced symptoms related to chemotherapy and a moderate level of anxiety. In accordance, appropriate interventions should recommended for the evaluation and improvement of anxiety and symptoms related to treatment in cancer patients.