Erratum: Polymorphism -433 C>T of the Osteopontin Gene is Associated with the Susceptibility to Develop Gliomas and their Prognosis in a Chinese Cohort

<b><i>Aim: </i></b>To investigate role of the Osteopontin (OPN) genetic polymorphisms in the susceptibility to gliomas and their prognosis. <b><i>Methods: </i></b>A total of 248 Chinese glioma patients and 281 age and sex matched healthy controls were recruited. The genetic polymorphisms at three loci, namely, -156 GG>G, -443 C>T and -66T>G, were determined. The log-rank test and Kaplan- Meier analysis were introduced to assess the effect of OPN gene polymorphisms on patient survival. <b><i>Results: </i></b>We found that the genotype frequencies of OPN -443 C>T polymorphism were significantly different between glioma patients and controls. Multivariable analyses showed a higher risk for gliomas in -443 CC genotype carriers compared to -443TT carriers (P<0.001). In addition, we also found the OPN -443 C>T polymorphism was closely related to the gliomas' tumor grade. The -443 C>T polymorphism also affected the tumor OPN expression level, but not the serum OPN level. More importantly, the -443 C>T polymorphism was significantly associated with the prognosis of these patients regardless of their treatment status. The patients with -443CC genotype had a poorer prognosis than those with -443TT and -443CT genotypes. In contrast, the -156 G>GG and -66T>G polymorphisms were not associated with risk, clinical characteristics, or prognosis of gliomas. <b><i>Conclusion: </i></b>This study suggests that the -443C>T gene polymorphisms may be used as a molecular marker for glioma occurrence and clinical outcome in glioma patients. © 2014 S. Karger AG, Base

Supplementary Material for: Endoplasmic Reticulum Stress Is Involved in Cochlear Cell Apoptosis in a Cisplatin-Induced Ototoxicity Rat Model

<p>Endoplasmic reticulum (ER) stress arises when excessive improperly folded proteins accumulate in the ER lumen. When ER stress occurs, the unfolded protein response (UPR) is subsequently activated to restore ER proteostasis. However, severe ER stress leads to apoptosis. Recent studies have suggested that cisplatin cytotoxicity may be related to ER stress. The purpose of this study was to determine whether ER stress participates in cochlear cell apoptosis in a cisplatin-induced ototoxicity rat model and to also determine the possible relationship between ER stress and hearing loss. Our results revealed that treatment with cisplatin upregulated the expression of active caspase-12 in cochlear cells, which is indicative of cisplatin-induced activation of ER-specific apoptosis. Increased expression of C/EBP homologous protein (CHOP) and cleaved caspase-9 suggested a close relationship between severe ER stress and mitochondria-dependent apoptosis in the cochlear cells of cisplatin-treated rats. In addition, we found that tauroursodeoxycholic acid (TUDCA), a promoter of ER proteostasis, had a protective effect on cisplatin-induced hearing loss. These results demonstrate that ER stress is involved in the cisplatin-induced apoptosis of cochlear cells in vivo.</p

Supplementary Material for: Fasting Plasma Glucose Levels Predict Steroid-Induced Abnormal Glucose Metabolism in Patients with Non-Diabetic Chronic Kidney Disease: A Prospective Cohort Study

<b><i>Background/Aims:</i></b> Glucocorticoids-induced abnormal glucose metabolism (AGM) is a common medical problem in patients with non-diabetic chronic kidney disease (CKD). However, little information is available regarding the prediction of steroid-induced AGM in this patient population. <b><i>Methods:</i></b> In this prospective cohort study, we consecutively enrolled 303 non-diabetic CKD patients with fasting plasma glucose (FPG) levels <5.6 mmol/l and normal oral glucose tolerance test (OGTT). OGTT was performed every 3 months during glucocorticoid treatment to identify new-onset AGM, and patients were followed for 12 months post steroid withdrawal. <b><i>Results:</i></b> During 593 person-years, there were 107 incident cases of steroid-induced AGM (18/100 person-year), including 55 (51.4%) diabetes and 52 (48.6%) pre-diabetes. In a multivariate model, each millimole increase per liter in FPG enhanced the risk of AGM by 4.6-fold (hazard ratio 4.58, 95% confidence interval, 2.67-7.83). After adjusting other risk factors, a progressively increased risk of AGM or DM was observed in patients with FPG levels ≥4.8 mmol/l, as compared with those whose levels were ≤4.3 mmol/l (p for trend <0.001). Furthermore, a greater increase in FPG level (≥0.3 mmol/l) during the first 3 months of glucocorticoid treatment was associated with an increased risk for future diabetes. For predicting steroid-induced diabetes, the area under the receiver-operating characteristic curve was 0.90 for the combination of FPG and changes in FPG levels at month 3. <b><i>Conclusion:</i></b> Higher-normal FPG and a greater increase in FPG levels during glucocorticoid treatment may help to identify non-diabetic CKD patients at increased risk of steroid-induced AGM or diabetes

Supplementary Material for: Gene Expression Profiling of Cecropin B-Resistant Haemophilus parasuis

Synthetically designed antimicrobial peptides (AMPs) present the potential of replacing antibiotics in the treatment of bacterial infections. However, microbial resistance to AMPs has been reported and little is known regarding the underlying mechanism of such resistance. The naturally occurring AMP cecropin B (CB) disrupts the anionic cell membranes of Gram-negative bacteria. In this study, CB resistance (CBR) was induced in <i>Haemophilus</i><i>parasuis</i> SH0165 by exposing it to a series of CB concentrations. The CB-resistant <i>H.</i><i>parasuis</i> strains CBR30 and CBR30-50 were obtained. The growth curves of SH0165 and CBR30 showed that CBR30 displayed lower growth rates than SH0165. The result of transmission electron microscopy showed cell membranes of the CB-resistant CBR30 and CBR30-50 were smoother than SH0165. Microarrays detected 257 upregulated and 254 downregulated genes covering 20 clusters of orthologous groups (COGs) of the CB-resistant CBR30 compared with SH0165 (>1.5-fold change, p < 0.05). Sixty genes were affected in CBR30-50 covering 18 COGs, with 28 upregulated and 32 downregulated genes. Under the COG function classification, the majority of affected genes in the CB-resistant CBR30 and CBR30-50 belong to the category of inorganic ion transport, amino acid transport, and metabolism. The microarray results were validated by real-time quantitative reverse transcription PCR. This study may provide useful guidance for understanding the molecular mechanism underlying <i>H.</i><i>parasuis</i> resistance to CB

Supplementary Material for: Hippocampal dynamic functional connectivity, HPA axis activity, and personality trait in bipolar disorder with suicidal attempt

Introduction Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associate with suicide-related personality traits. The objective of our study was to clarify this. Methods Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA) and 40 without SA, and 35 healthy controls. The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits

Supplementary Material for: Hippocampal dynamic functional connectivity, HPA axis activity, and personality trait in bipolar disorder with suicidal attempt

Introduction Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associate with suicide-related personality traits. The objective of our study was to clarify this. Methods Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA) and 40 without SA, and 35 healthy controls. The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits

Supplementary Material for: Hippocampal dynamic functional connectivity, HPA axis activity, and personality trait in bipolar disorder with suicidal attempt

Introduction Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associate with suicide-related personality traits. The objective of our study was to clarify this. Methods Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA) and 40 without SA, and 35 healthy controls. The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits

Supplementary Material for: Hippocampal dynamic functional connectivity, HPA axis activity, and personality trait in bipolar disorder with suicidal attempt

Introduction Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associate with suicide-related personality traits. The objective of our study was to clarify this. Methods Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA) and 40 without SA, and 35 healthy controls. The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits

Supplementary Material for: Hippocampal dynamic functional connectivity, HPA axis activity, and personality trait in bipolar disorder with suicidal attempt

Introduction Suicide in bipolar disorder (BD) is a multifaceted behavior, involving specific neuroendocrine and psychological mechanisms. According to previous studies, we hypothesized that suicidal BD patients may exhibit impaired dynamic functional connectivity (dFC) variability of hippocampal subregions and hypothalamic-pituitary-adrenal (HPA) axis activity, which may be associate with suicide-related personality traits. The objective of our study was to clarify this. Methods Resting-state functional magnetic resonance imaging data were obtained from 79 patients with BD, 39 with suicidal attempt (SA) and 40 without SA, and 35 healthy controls. The activity of the HPA axis was assessed by measuring morning plasma adrenocorticotropic hormone (ACTH) and cortisol (CORT) levels. All participants underwent personality assessment using Minnesota Multiphasic Personality Inventory-2 (MMPI-2). Results BD patients with SA exhibited increased dFC variability between the right caudal hippocampus and the left superior temporal gyrus (STG) when compared with non-SA BD patients and HCs. BD with SA also showed significantly lower ACTH levels in comparison with HCs, which was positively correlated with increased dFC variability between the right caudal hippocampus and the left STG. BD with SA had significantly higher scores of Hypochondriasis, Depression and Schizophrenia than non-SA BD. Additionally, multivariable regression analysis revealed the interaction of ACTH × dFC variability between the right caudal hippocampus and the left STG independently predicted MMPI-2 score (depression evaluation) in suicidal BD patients. Conclusion These results suggested that suicidal BD exhibited increased dFC variability of hippocampal-temporal cortex and less HPA axis hyperactivity, which may affect their personality traits

Supplementary Material for: The Fatty Liver Index, the Strongest Risk Factor for Low Testosterone Level

Introduction: The study aimed to determine if hepatic steatosis assessed by Fatty Liver Index (FLI) was an independent risk factor for male testosterone insufficiencylow testosterone level and whether the FLI was the strongest risk factor for testosterone insufficiencylow testosterone level in two different age groups. Methods: Two cross-sectional studies were performed. A total of 3443 male participants (aged 46-75) were recruited into study A (part of lONgitudinal study (REACTION)). Then a total of 267 male participants (aged 25-45) were recruited into study B. Serum TT and sex hormone-binding globulin (SHBG) levels, indicators for assessing hepatic steatosis were measured. The Pearson correlation and regression analysis were performed to investigate the risk factors for testosterone insufficiencylow testosterone level. Results: The FLI had the strongest negative correlation with serum testosterone in the study A (r=-0.436) and B (r=-0.542). Compared with patients with a FLI lower than 30, the risk for testosterone insufficiencylow testosterone level increased by 3.48–fold in subjects with a FLI higher than 60 adjusted for potential risk factors in study A. In study B, the OR of testosterone insufficiencylow testosterone level in patients with potential hepatic steatosis was 4.26 (1.57-11.60) after adjusted for age and HOMA-IR, and 0.59 (0.14-2.60) after adjusted for age, HOMA-IR, waist circumference, body mass index, and SHBG. Conclusions: FLI, was the strongest risk factor for male testosterone insufficiencylow testosterone level independent of insulin resistance in a male populations of different ages, however the association can be modulated by SHBG levels in the young