Oxidative Stress and Thiol/Disulfide Homeostasis in Human Papillomavirus Infections.

Introduction: Viral warts are a group of dermatological diseases caused by human papillomavirus (HPV). Several studies have demonstrated an association between HPV infections and oxidative stress. Thiols are important components of cellular redox homeostasis as antioxidant molecules in the organism. Aim: This study aimed to investigate the role of oxidative stress in patients with HPV infection by analyzing native thiol/disulfide homeostasis. Material and Methods: Forty-two patients with HPV infection and 40 healthy subjects were analyzed for the levels of native thiols, total thiols, and disulfide. Disulfide/native thiol, disulfide/total thiol, and native thiol/total thiol ratios were also calculated. Results: Disulfide and total thiol levels were higher in the patients compared to the healthy controls. The disulfide/native thiol ratio was also higher in the patient group. Native and total thiol levels decreased with the increasing duration of the disease. Conclusion: The native thiol/disulfide homeostasis was shifted toward disulfide in the patients' group, indicating the existence of oxidative stress in HPV infection.

Is Thiol/Disulphide homeostasis important in prostate cancer diagnosis? / Es importante la homeostasis del Tiol/Disulfito en el diagnóstico del cáncer de próstata?

OBJECTIVES: To assess the relationship between prostate cancer and thiol/disulphide homeostasisas an important indicator of oxidative stress. METHODS: After ethics committee approval (546/2015); 388 patients aged between 46-75 years who underwent transrectal ultrasound guided prostatebiopsy in three different centers between July 2015-2016 owing to serum prostate specific antigen (PSA) levels ≥2.5 ng/ml and/or abnormal digital rectal examination were involved in this study. The plasma levels of thiol/disulphide homeostasis parameters were compared in patients with and without prostate cancer. RESULTS: The mean age of the patients was 62.9±7 years. In patients with prostate cancer (n=130, 33.5% ) the mean plasma levels of native thiol and total thiol were lower (332.9 vs 362.1 µmol/L and 363 vs 392.6 µmol/L, p=0.001). Plasma disulphide levels were not statistically different between the groups (15 vs 15.3 µmol/L, p=0.936). In prostate cancer group; patients with Gleason score ≥7 had lower plasma native thiol levels than patients with Gleason score<7 (321.3  vs 342.6 µmol/L, p=0.029) while there were no significant differences in total thiol and disulphide levels (352.3 vs 371.9 µmol/L, ptotal Thiol =0.064 and 15.5 vs 14.6 µmol/L, pdisulphide =0.933). CONCLUSIONS: Lower plasma levels of thiol in patients with prostate cancer and high Gleason score is an oteworthy result. We believe that our results should be supported by further studies.

OBJETIVOS: Establecer la relación entre cáncer de próstata y la homeostasis del tiol/disulfito como un importante indicador de estrés oxidativo.MÉTODOS: Con la aprobacion del comité ético (546/2015), 388 pacientes entre 46 y 75 años que recibieron una biopsia transrectal prostática ecoguiada en diferentes centros entre julio 2015 y 2016 por un PSA superior a 2,5 ng/ml o tacto rectal anómalo, fueron incluidos en este estudio. Los niveles plasmáticos de la homeostasis de tiol/disulfito se compararon en pacientes con y sin cáncer de próstata. RESULTADOS: La edad media de los pacientes fue de 62,9 =/- 7 años. En pacientes con cáncer de próstata (n=130, 33,5%) el nivel plasmático de tiol nativo y tiol total fue menor (332,9 vs 362,1 µmol/L y 363 vs 392,6 µmol/L, p=0,001). Los niveles de disulfito en plasma no fueron estadísticamente diferentes entre los grupos (15 vs 15,3 µmol/L, p=0,936). En el grupo con cáncer de próstata; pacientes con Gleason 7 o más tuvieron niveles menores de tiol nativo en relación a los pacientes con Gleason menor de 7 (321,3 vs 342,6 µmol/L, p=0,029), mientras no hubo diferencias en eltiol total y los disulfitos (352,3 vs 371,9 µmol/L, ptotaltiol =0,064 y 15,5 vs 14,6 µmol/L, pdisulfito =0,933). CONCLUSIONES: Niveles bajos de tiol en pacientes con cáncer de próstata y Gleason alto es un resultado notable. Creemos que nuestros resultados deberian tenerse en cuenta para otros estudios.

Clinical and laboratory features of COVID-19: Predictors of severe prognosis.

BACKGROUND: Coronavirus disease 2019 (COVID-19) emerged first in December 2019 in Wuhan, China and quickly spread throughout the world. Clinical and laboratory data are of importance to increase the success in the management of COVID-19 patients. METHODS: Data were obtained retrospectively from medical records of 191 hospitalized patients diagnosed with COVID-19 from a tertiary single-center hospital between March and April 2020. Prognostic effects of variables on admission among patients who received intensive care unit (ICU) support and those who didn't require ICU care were compared. RESULTS: Patients required ICU care (n = 46) were older (median, 71 vs. 43 years), with more underlying comorbidities (76.1% vs. 33.1%). ICU patients had lower lymphocytes, percentage of large unstained cell (%LUC), hemoglobin, total protein, and albumin, but higher leucocytes, neutrophils, neutrophil-lymphocyte ratio (NLR), monocyte-lymphocyte ratio (MLR), platelet-lymphocytes ratio (PLR), urea, creatinine, aspartate amino transferase (AST), lactate dehydrogenase (LDH), and D-dimer when compared with non-critically ill patients (p < 0.001). A logistic regression model was created to include ferritin, %LUC, NLR, and D-dimer. %LUC decrease and D-dimer increase had the highest odds ratios (0.093 vs 5.597, respectively) to predict severe prognosis. D-dimer, CRP, and NLR had the highest AUC in the ROC analysis (0.896, 0.874, 0.861, respectively). CONCLUSIONS: The comprehensive analysis of clinical and admission laboratory parameters to identify patients with severe prognosis is important not only for the follow-up of the patients but also to identify the pathophysiology of the disease. %LUC decrease and D-dimer, NLR, and CRP increases seem to be the most powerful laboratory predictors of severe prognosis.

Thiol-disulfide homeostasis: an integrated approach with biochemical and clinical aspects

Dynamic thiol-disulfide homeostasis (TDH) is a new area has begun to attract more scrutiny. Dynamic TDH is reversal of thiol oxidation in proteins and represents the status of thiols (-SH) and disulfides (-S-S-). Organic compounds containing the sulfhydryl group is called thiol, composed of sulfur and hydrogen atoms. Disulfides are the most important class of dynamic, redox responsive covalent bonds build in between two thiol groups. For many years, thiol levels were analyzed by several methods. During last years, measurements of disulfide levels have been analyzed by a novel automated method, developed by Erel and Neselioglu. In this method, addition to thiol (termed as native thiol) levels, disulfide levels were also measured and sum of native thiol and disulfide levels were termed as total thiol. Therefore, TDH was begun to be understood in organism. In healthy humans, TDH is maintained within a certain range. Dysregulated dynamic TDH has been implicated several disorders with unknown etiology. A growing body of evidence has demonstrated that the thiol-disulfide homeostasis is involved in variety diseases, such as diabetes mellitus, hypertension, nonsmall cell lung cancer, familial Mediterranean fever (FMF), inflammatory bowel diseases, occupational diseases, gestational diabetes mellitus and preeclampsia. These results may elucidate some pathogenic mechanism or may be a predictor indicating diagnostic clue, prognostic marker or therapeutic sign. In conclusion, protection of the thiol-disulfide homeostasis is of great importance for the human being. Evidence achieved so far has proposed that thiol-disulfide homeostasis is an important issue needs to elucidate wholly.

Dynamic Thiol/Disulfide Balance in Patients with Seborrheic Dermatitis: A Case-Control Study.

BACKGROUND: Seborrheic dermatitis is a chronic, inflammatory skin disease, in which many endogenous and exogenous factors play a role. Recent studies have shown that oxidative stress increases in these patients. The role of the dynamic thiol/disulfide homeostasis, an important component of the oxidative stress, in the pathogenesis of seborrheic dermatitis has not yet been investigated. OBJECTIVES: The objective was to investigate the relationship between the dynamic thiol/disulfide balance in the plasma of seborrheic dermatitis patients and disease severity. METHODS: In this case-control study, 70 seborrheic dermatitis patients and 61 age- and sex-matched healthy controls were included. Thiol/disulfide homeostasis was calculated from venous blood samples, and tests were performed by automated spectrophotometric method. The thiol/disulfide balance between the patient and control groups was compared. In addition, disease severity and other demographic characteristics and thiol/disulfide balance parameters were compared. RESULTS: Native and total thiols were significantly higher in the patient group than that in the control group (P < 0.001). Disulfide levels were nonsignificantly lower in the patient group than controls (P = 0.821). Patients' age and age at the onset of disease were found to have a negative correlation with native and total thiol levels. CONCLUSION: Higher levels of thiols in the serum may be responsible for the increased proliferation of seborrheic dermatitis lesions. To the best of the authors' knowledge, this is the first report on the correlation between thiol/disulfide homeostasis in patients with seborrheic dermatitis.

A new potential biomarker in early diagnosis of firefighter lung function impairment: dynamic thiol/disulphide homeostasis.

OBJECTIVES: The aim of this study was to investigate the associations between urinary arsenic, oxidative stress, assessed by thiol/disulphide homeostasis, and lung diseases in firefighters. METHODS: The study conducted among the municipality-based male firefighters (n = 100) who were admitted to occupational diseases clinic for periodic medical examination. The control group consisted of non-exposed male office workers (n = 50). Urinary arsenic levels, thiol/disulphide homeostasis parameters of participants were determined. Also, lung diseases were assessed by chest X-ray and pulmonary function tests. RESULTS: The mean age and work year did not differ in the study and control group. The median urinary arsenic concentration of firefighters was significantly higher than in the control group: 15.65 (2.5-246) µg/L and 3 (0.10-6) µg/L, respectively (p < 0.001). The parameters of pulmonary function tests (PFT) FVC (%), FEV1 (%), FEV1/FVC ratio and FEF 25-75 (%) were all significantly lower in firefighters compared to controls. A significant increase in mean serum disulphide concentration (17.10 ± 8.31 µmol/L vs. 7.48 ± 5.91) (Fig. 1) and disulphide/native thiol % ratio: 3.63 (0.53-11.43) vs. 1.51 (0.03-7.65) (p < 0.001) were found between exposed group and controls. The Spearman's correlation analysis revealed a positive correlation between urinary arsenic and disulphide (r = 0.422, p < 0.001), disulphide/native thiol % ratio (r = 0.409, p < 0.001). Nevertheless, urinary arsenic correlated negatively with all PFT parameters including FVC (%), FEV1 (%), FEV1/FVC and FEF 25-75 (%) (p < 0.001). CONCLUSION: We showed the arsenic-induced oxidative stress in firefighters with impairments of several lung functions determined by thiol/disulphide homeostasis using a novel method.

Thiol Disulfide Homeostasis in Schizophrenic Patients Using Atypical Antipsychotic Drugs.

OBJECTIVE: Schizophrenia is a severe, debilitating mental disorder characterized by behavioral abnormalities. Although several studies have investigated the role of oxidative stress and the effects of antipsychotic drugs on oxidative markers in schizophrenia, adequate information is not available on these issues. The aim of this study is to determine the changes in oxidative status and thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs. METHODS: Thirteen schizophrenic patients using atypical antipsychotic drugs and 30 healthy controls were included this study. The concentrations of total oxidant status (TOS), total antioxidant status (TAS), native thiol, total thiol, and disulfide levels were determined in the study population. RESULTS: The TAS (p=0.001), total thiol, and native thiol levels (p＜0.001) were higher in the patients compared to the controls, whereas the TOS and disulfide levels were lower in the patients than in the controls (p＜0.001). CONCLUSION: These results may suggest that atypical antipsychotic drugs have a useful therapeutic effect by reducing oxidative stress via the inhibition of the formation of disulfide bonds. The study population number was one of the limitations of this study. Therefore, further studies are needed to establish the association between thiol disulfide homeostasis in schizophrenic patients using atypical antipsychotic drugs.

The effects of transport by car on coagulation tests.

BACKGROUND: This research investigated the effects of the transport of blood samples between centers/laboratories by car on coagulation tests. METHODS: Five tubes of blood samples were taken from 20 healthy volunteers. The samples consisted of a baseline (control) group, centrifuged and noncentrifuged transported samples; centrifuged and noncentrifuged untransported samples. The groups of centrifuged and noncentrifuged samples were transported by car for 2 h. The centrifuged and noncentrifuged untransported samples were incubated in the laboratory until the transported samples arrived. Prothrombin time (PT) and activated partial thromboplastin time (APTT) tests were conducted for all samples. RESULTS: Significant differences between the baseline group and the centrifuged and noncentrifuged transported samples and the noncentrifuged untransported samples were found for APTT levels (p<0.05, for all). In addition, significant mean percentage differences in PT values were found between the baseline group and the noncentrifuged transported samples (p<0.001) and the noncentrifuged untransported samples (p=0.005). The mean level of PT in the noncentrifuged transported samples was outside the upper limit of the clinical decision level. CONCLUSIONS: Noncentrifuged transported samples showed clinically significant differences in PT test results that may have stemmed from mechanical agitation during transportation. Therefore, we recommend not transporting noncentrifuged specimens for PT testing by car.

An evaluation of thiol/disulphide homeostasis in patients with psoriasis.

INTRODUCTION: The role of oxidative stress in the pathogenesis of psoriasis has been investigated in previous studies with conflicting results. On the other hand, well-established treatments currently used in psoriasis exert their effects via a boost of oxidative stress. Recently, a strong positive association between psoriasis, metabolic syndrome and dyslipidemia has also been described showing the complex nature of the disease. AIM: To examine thiol/disulphide homeostasis, a newly developed homeostasis assay in psoriasis and evaluate the possible association between thiol/disulphide homeostasis and dyslipidemia in psoriasis. MATERIAL AND METHODS: The study population included 92 psoriasis patients and 71 healthy subjects. Serum native thiol, total thiol and disulphide levels were investigated in patients with psoriasis and in healthy subjects. In addition, lipid profile (serum total cholesterol, triglyceride, high-density lipoprotein cholesterol and low-density lipoprotein cholesterol) levels were investigated in both groups. The association between thiol-disulphide parameters and dyslipidemia was also evaluated. RESULTS: Serum total cholesterol and triglyceride levels were found to be higher in patients with psoriasis than in the healthy group. Lower plasma disulphide and higher native thiol levels were found in patients with psoriasis indicating an antioxidant status. CONCLUSIONS: To our knowledge, this is the first study showing the shift of dynamic thiol/disulphide homeostasis towards the thiol form in psoriasis which indicate higher antioxidant status.

Thiol/disulfide parameters as a novel oxidative marker in medical labor induction with oxytocin.

BACKGROUND: The aim of this study was to analyze the alterations in thiol levels among mothers and neonates who were prone to medical oxytocin induction. MATERIALS AND METHODS: A total of 40 pregnant women who underwent medical labor induction with oxytocin (Group A) were compared with 53 women whose labor progressed spontaneously without any kind of induction (Group B). We measured the thiol/disulfide homeostasis parameters (native thiol, total thiol, disulfide, disulfide/total thiol, disulfide/native thiol) of maternal and cord blood. RESULTS: There were no statistically significant differences with respect to the maternal and cord blood thiol/disulfide homeostasis between the two groups. CONCLUSION: Being an artificial intervention during labor, oxytocin induction has been found to be safe in terms of oxidative stress (OS) according to the results of this study. Both the maternal and the fetal sides were safe in this molecular manner against oxytocin infusion.

Serum vaspin and adiponectin levels in patients with prolactinoma.

BACKGROUND: Studies investigating serum vaspin and adiponectin levels in patients with prolactinoma are inconclusive. The aim of this study was to evaluate serum vaspin and adiponectin levels in patients with prolactinoma and healthy controls. METHODS: A total of 42 prolactinoma patients (Group 1, 21 patients; Group 2, 21 patients) and 30 healthy controls were enrolled in the study. Group 1 consisted of newly diagnosed patients who were never treated or had not received a dopamine agonist (DA) within 6 months prior to screening. Group 2 consisted of prolactinoma patients who were on DA treatment for at least 6 months at the time of screening. The control group (group 3) consisted of healthy controls. RESULTS: Patients with prolactinoma had higher homeostasis model assessment of insulin resistance and lower quantitative insulin sensitivity check index values in comparison to healthy controls (p < 0.001 for both). Serum levels of adiponectin and vaspin were also significantly lower in prolactinoma patients when compared to the control group (p < 0.01 and p < 0.001, respectively). Following adjustment for confounding factors, the respective odds ratios for prolactinoma in patients in the lower subgroup compared with those in the higher subgroup for adiponectin and vaspin were 2.733 (0.621-12.035; p > 0.05) and 5.041 (1.191-21.339; p < 0.05). CONCLUSION: This is the first study to demonstrate the presence of low vaspin levels in patients with prolactinomas. Further studies are needed to help establish the roles of vaspin and adiponectin in prolactinoma patients.

Inflammation and chemerin in colorectal cancer.

Chemerin is expressed mainly in the adipose tissue. It is an agonist of chemokine-like receptor-1, which is expressed by the immune system cells. Chemerin stimulates the chemotaxis of the immune system cells, and this indicates the function of chemerin and chemokine-like receptor-1 in the immune response. The tumor microenvironment is very important for determining cancer cell growth and spreading. Therefore, we aimed to investigate the association between colorectal cancer, inflammation, and adipokines including chemerin, adiponectin, and vaspin. The study group consisted of patients with colon cancer, whereas the control subjects consisted of patients with benign conditions, diagnosed with colonoscopy. The two groups were compared in terms of the C-reactive protein (CRP), erythrocyte sedimentation rate (ESR), fibrinogen, adiponectin, chemerin, and vaspin. A total of 41 (28 men, 13 women) patients with confirmed colon cancer, and 27 (15 men, 12 women) controls without, confirmed by colonoscopy, were enrolled. The median chemerin levels were found significantly higher in the study group than the controls (390 vs. 340 ng/mL, p = 0.032), whereas the mean vaspin and adiponectin levels were not significantly different. The median values for the CRP, fibrinogen, and ESR were significantly higher in the patients with colon cancer, when compared to the control group (6.08 vs. 1.4 mg/L, p < 0.0001; 408 vs. 359 mg/dL, p = 0.002; and 30 vs. 8 mm/h, p < 0.0001, respectively). Our results show that higher levels of circulating chemerin, CRP, fibrinogen, and ESR are associated with an increased risk of developing colorectal cancer.

Thiol/disulfide homeostasis: A prognostic biomarker for patients with advanced non-small cell lung cancer?

BACKGROUND: The aim of this study was to investigate oxidative stress and thiol/disulfide status with a novel automated homeostasis assay in advanced non-small cell lung cancer (NSCLC). METHODS: Thirty-five patients with advanced NSCLC, who had been newly diagnosed and previously untreated, and 35 healthy subjects were chosen for the study. We measured plasma total thiol (-SH+-S-S-), native thiol (thiol) (-SH), and disulfide (-S-S-) levels in the patients with NSCLC and the healthy subjects. The thiol/disulfide (-SH/-S-S-) ratio was also calculated. RESULTS: Statistically significant differences between the patient group and the control group were detected for the thiol/disulfide parameters. The mean native thiol, total thiol, and disulfide levels were significantly lower in the group with advanced stage NSCLC. The cut-off value was 313 and 13.8 for native thiol and disulfide, respectively. Median overall survival (OS) was significantly shorter in patients with low native thiol and disulfide levels according to the cut-off value (respectively, P = 0.001; P = 0.006). Native thiol, total thiol, and disulfide levels were correlated with Karnofsky performance status (KPS), OS, and age. Additionally, hierarchical regression analyses showed gender, KPS, lung metastases, and plasma native thiol levels were the determinants of OS in the final model. CONCLUSION: These results suggest that in advanced stage NSCLC, the native thiol, total thiol, and disulfide levels decrease, while the native thiol/disulfide ratio does not change. Low levels of thiol/disulfide parameters are related to tumor aggressiveness and may predict a poor outcome for patients with NSCLC.

The role of reactive oxygen species and oxidative stress in carbon monoxide toxicity: an in-depth analysis.

The underlying mechanism of the central nervous system (CNS) injury after acute carbon monoxide (CO) poisoning is interlaced with multiple factors including apoptosis, abnormal inflammatory responses, hypoxia, and ischemia/reperfusion-like problems. One of the current hypotheses with regard to the molecular mechanism of CO poisoning is the oxidative injury induced by reactive oxygen species, free radicals, and neuronal nitric oxide. Up to now, the relevant mechanism of this injury remains poorly understood. The weakening of antioxidant systems and the increase of lipid peroxidation in the CNS have been implicated, however. Accordingly, in this review, we will highlight the relationship between oxidative stress and CO poisoning from the perspective of forensic toxicology and molecular toxicology.

Serum amyloid A, fetuin-A, and pentraxin-3 levels in patients with ischemic stroke: novel prognostic biomarkers?

AIM: Inflammation plays an important role in acute ischemic stroke. In this study we aimed to investigate the relationship between acute ischemic stroke and serum amyloid A, fetuin-A, and pentraxin-3 which are inflammation markers. MATERIALS AND METHODS: We enrolled 52 patients with acute ischemic stroke and 30 sex-matched control subjects in the study. The patients were followed for 3 months. We evaluated the common risk factors, laboratory variables, and neurological examination of stroke patients according to prognosis scales. RESULTS: The median serum amyloid A, fetuin-A, and pentraxin-3 levels in the stroke patients were higher than in control subjects (respectively, P = 0.000, P = 0.002, and P = 0.037). National Institutes of Health Stroke Scale scores, glucose, C-reactive protein, fibrinogen, and white blood cell count showed differences within the group in terms of the serum amyloid A tertiles statistically. CONCLUSION: Pentraxin-3, fetuin-A, and serum amyloid A all arise together as novel prognostic factors in a group of patients with ischemic stroke. Relationships between higher levels of inflammation markers, especially serum amyloid A, and the severity of acute ischemic stroke were shown.

Liver enzymes, mean platelet volume, and red cell distribution width in gestational diabetes.

AIM: To investigate the value of measuring liver enzymes, red cell distribution width (RDW), and mean platelet volume (MPV) in predicting the development of gestational diabetes mellitus (GDM). MATERIALS AND METHODS: The medical records of all pregnant women followed by the obstetrics clinic between January 2010 and November 2012 were systematically evaluated, and patients with a diagnosis of GDM were identified. A total of 68 patients with GDM and 61 healthy controls were included in the study. Results of relevant laboratory parameters were recorded. RESULTS: Out of all the parameters evaluated, mean values for platelet distribution width (PDW) and mean activities of alanine transaminase (ALT) and gamma-glutamyl transferase (GGT) were significantly higher in the GDM group compared to healthy controls (P = 0.003, P = 0.015, and P = 0.021, respectively), whereas mean plateletcrit (PCT) levels were significantly lower in the GDM group (P = 0.002). No significant difference was observed between groups in terms of MPV, RDW, platelet count, and aspartate transaminase levels. CONCLUSION: Our study results suggest that ALT, GGT, PCT, and PDW may be useful as predictors of impending GDM.

Markers in nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD), the most common liver disorder worldwide, encompasses a spectrum of abnormal liver histology ranging from simple steatosis to nonalcoholic steatohepatitis (NASH) and cirrhosis. Population studies show that NAFLD is strongly associated with insulin resistance, obesity, type 2 diabetes mellitus, and lipid abnormalities. In the context of hepatic steatosis, factors that promote cell injury, inflammation, and fibrosis include oxidative stress, early mitochondrial dysfunction, endoplasmic reticulum stress, iron accumulation, apoptosis, adipocytokines, and stellate cell activation. The exact NASH prevalence is unknown because of the absence of simple noninvasive diagnostic tests. Although liver biopsy is the "gold standard" for the diagnosis of NASH, other tests are needed to facilitate the diagnosis and greatly reduce the requirement for invasive liver biopsy. In addition, the development of new fibrosis markers in NASH is needed to facilitate the assessment of its progression and the effectiveness of new therapies. The aim of this chapter, which is overview of biomarkers in NASH, is to establish a systematic approach to laboratory findings of the disease.

Evaluating vaspin and adiponectin in postmenopausal women with endometrial cancer.

Insulin resistance is a well-documented risk factor for the development of endometrial cancer. Adiponectin and vaspin are insulin-sensitizing proteins that are secreted from adipose tissue. A clear association between serum levels of adipokines and endometrial cancer has yet to be established. The study group consisted of postmenopausal women with confirmed endometrial cancer, whereas patients with benign endometrial conditions constituted the control group. The two groups were compared in terms of insulin resistance and serum levels of adiponectin and vaspin. A total of 60 patients with confirmed endometrial cancer and 70 controls with benign endometrial conditions (polyps and atrophy) were enrolled. Median homeostasis model assessment of insulin resistance value was significantly higher in the study group compared with the control group (2.93 vs 1.27, P<0.0001), whereas mean quantitative insulin sensitivity check index value was significantly lower (0.33 ± 0.02 vs 0.37 ± 0.37, P<0.0001). Median values for both adiponectin and vaspin were significantly lower in patients with endometrial cancer compared with the control group (4.09 vs 17.13 µg/ml, P<0.0001 and 0.21 vs 0.39 ng/ml, P<0.0001 respectively). Low levels of both adiponectin and vaspin were found to be significantly associated with an increased risk for endometrial cancer. Following adjustment for confounding factors, the respective odds ratios for endometrial cancer in patients in the first tertile compared with those in the third tertile were 10.80 (2.76-42.24; P=0.001) and 13.23 (2.94-59.64; P=0.001). Our results show that lower levels of circulating adiponectin and vaspin levels are associated with an increased risk of developing endometrial cancer.

The relationship between oxidative stress and nonalcoholic fatty liver disease: Its effects on the development of nonalcoholic steatohepatitis.

Nonalcoholic fatty liver disease (NAFLD) and nonalcoholic steatohepatitis (NASH) are the most common underlying causes of chronic liver injury. They are associated with a wide spectrum of hepatic disorders including basic steatosis, steatohepatitis, and cirrhosis. The molecular and cellular mechanisms underlying hepatic injury in NAFLD and NASH are still unknown. This review describes the roles of oxidative stress and inflammatory responses in the pathogenesis of NAFLD and its progression to NASH.

ADAMTS1, ADAMTS5, ADAMTS9 and aggrecanase-generated proteoglycan fragments are induced following spinal cord injury in mouse.

ADAMTS (a disintegrin and metalloproteinase with thrombospondin motifs) proteinases are involved in a variety of biological processes such as angiogenesis, cancer and arthritis. ADAMTSs appears to be responsible for the cleavage of proteoglycans in several tissues including brain and cartilage. Chondroitin sulfate proteoglycans (CSPGs) maintains the integrity of the brain extracellular matrix and major inhibitory contributors for glial scar and neural plasticity. The activity of aggrecanases in the central nervous system (CNS) has been reported. ADAMTSs are an enzyme degrading CSPGs in the brain. However, there is a little knowledge regarding ADAMTSs in the CNS. We investigated the expression levels of ADAMTSs mRNAs by RT-PCR after spinal cord injury in mouse. Transcripts encoding 4 of the 19 known ADAMTSs were evaluated in the mouse spinal cord following injury. ADAMTS1, -5 and -9 expression levels were found to be upregulated. No change was observed in ADAMTS4 expression. By means of immunohistochemistry, ADAMTSs were detected in the astrocytes implying its cellular source in SCI. Western blot analyses indicated that aggrecanase-generated proteoglycan fragments are produced after SCI.