SFI, a sex hormone binding globulin based nomogram for predicting non-alcoholic fatty liver disease in the Chinese population.

Background: The purpose of this study is to establish a novel nomogram model for accurate detection of non-alcoholic fatty liver disease (NAFLD) in the Chinese population based on sex hormone binding globulin (SHBG) and other routine laboratory tests. Methods: A total of 1417 participants (1003 testing and 414 validations) were enrolled into the study. Risk factors independently associated with NAFLD were identified and incorporated in the new nomogram, SFI. The performance of nomogram was assessed by analysis of receiver operating characteristic (ROC) curve, calibration curve, and decision curve. Results: We formulated a new nomogram incorporating four independent factors: SHBG, body mass index (BMI), ALT/AST, and triglycerides (TG). The nomogram achieved good indexes of area under ROC 0.898 (95% confidence interval 0.865-0.926) in predicting NAFLD, which was significantly superior to previously reported models of FLI, HSI, LFS, and LAP. The calibration curve and decision curve demonstrated high performance and clinical utility of the nomogram in predicting NAFLD. Conclusion: The nomogram SFI has high performance in predicting NAFLD in Chinese population and may be used as a cost-effective screening model to assess NAFLD in the general population.

Protective Effect of MFG-E8 on Necroptosis-Induced Intestinal Inflammation and Enteroendocrine Cell Function in Diabetes.

Low-grade inflammation is one of the characteristics of metabolic disorders induced by diabetes mellitus. The present study explores the underlying mechanism of milk fat globule epidermal growth factor 8 (MFG-E8) on necroptosis-induced intestinal inflammation and intestinal epithelial endocrine cell dysfunction in diabetes. Compared with the normal control group, pathological changes such as blunt and shortened villus and denuded villus tips were observed in ileum tissue of streptozotocin (STZ) induced senescence-resistant 1 (SAMR1) and senescence-accelerated prone 8 (SAMP8) diabetic mice under light microscope. Western blotting and immunohistochemistry (IHC) displayed significantly decreased protein expression of MFG-E8 in SAMR1 and SAMP8 diabetic mice, accompanied by an increased expression of phosphorylated mixed lineage kinase domain-like (p-MLKL) and HMGB1. In addition, advanced glycation end products (AGEs) significantly increased the pro-inflammatory mediators (TNF-α, IL-1ß, IL-6) and HMGB1 by activating the receptor-interacting protein kinase 3 (RIPK3)/MLKL signaling pathway in enteroendocrine STC-1 cells. D-pinitol pretreatment markedly attenuated the release of pro-inflammatory mediators and increased the expression of MFG-E8. MFG-E8 small interfering RNA (siRNA) promoted, while MFG-E8 overexpression inhibited, the activation of receptor-interacting proteins (RIPs) pathway and pro-inflammatory factors. Our study demonstrated that downregulation of MFG-E8 is an important phenomenon in the pathogenesis of diabetes-related intestinal inflammatory damage. MFG-E8 overexpression and D-pinitol intervention could protect against necroptosis-induced intestinal inflammation and maintain the function of enteroendocrine STC-1 cells in diabetes.

Intensity Switchable and Wide-Angle Mid-Infrared Perfect Absorber with Lithography-Free Phase-Change Film of Ge2Sb2Te5.

The range of fundamental phenomena and applications achievable by metamaterials (MMs) can be significantly extended by dynamic control over the optical response. A mid-infrared tunable absorber which consists of lithography-free planar multilayered dielectric stacks and germanium antimony tellurium alloy (Ge2Sb2Te5, GST) thin film was presented and studied. The absorption spectra under amorphous and crystalline phase conditions was evaluated by the transfer matrix method (TMM). It was shown that significant tuning of absorption can be achieved by switching the phase of thin layer of GST between amorphous and crystalline states. The near unity (>90%) absorption can be significant maintained by incidence angles up to 75 under crystalline state for both transverse electric (TE) and transverse magnetic (TM) polarizations. The proposed method enhances the functionality of MMs-based absorbers and has great potential for application to filters, emitters, and sensors.

Analyzing EGFR mutations and their association with clinicopathological characteristics and prognosis of patients with lung adenocarcinoma.

Epidermal growth factor receptor (EGFR) is an important gene in the development of lung adenocarcinoma. However, there is controversy regarding the association between EGFR mutations and survival time of patients with lung adenocarcinoma. In the present study, tissue specimens and clinical data were collected from 219 patients with lung adenocarcinoma who had not undergone prior radiotherapy or chemotherapy. EGFR mutations were detected using a fluorescence polymerase chain reaction method, and the association between EGFR mutations and clinicopathological characteristics was analyzed. Overall survival (OS) curves were constructed using the Kaplan-Meier method and the influence of clinicopathological characteristics on OS was analyzed using the Cox regression model. The EGFR mutation rate was 50.7%, and the most common mutations were the L858R substitution mutation in exon 21 (L858R; 54.9%) and the deletion mutation in exon 19 (19-Del; 36%). The presence of EGFR mutations varied significantly with sex, smoking history, T stage, vascular invasion and adenocarcinoma subtypes (P<0.05). The survival time was significantly longer for female, young (<60 years-old), non-smokers or patients exhibiting EGFR mutations (G719X, 19-Del, L858R and L861Q). The survival time was also significantly longer for patients with a 19-Del mutation, early stage tumors, tyrosine kinase inhibitors targeted therapy-treated patients, for those not exhibiting nerve or vascular invasion, and for those without disease recurrence (P<0.05). Multivariate analysis revealed that tumor pathological Tumor-Node-Metastasis (pTNM) stage, nerve invasion, vascular invasion, EGFR mutation and the 19-Del mutation were independent predictors (P<0.05). Therefore, tumor pTNM stage, nerve invasion, vascular invasion and EGFR mutation status, particularly that of 19-Del, were independent prognostic factors for patients with lung adenocarcinoma.

Non-alcoholic fatty liver disease is an influencing factor for the association of SHBG with metabolic syndrome in diabetes patients.

Metabolic syndrome (MS) and non-alcoholic fatty liver disease (NAFLD) have been identified as risk factors affecting serum sex hormone binding globulin (SHBG) levels. We conducted this cross-sectional study to delineate whether MS or NAFLD has more impact on circulating SHBG levels in type 2 diabetes (T2D) patients. Anthropometric and biochemical parameters including serums SHBG, testosterone (TT), liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Regardless of the MS status, SHBG level was significantly lower in NAFLD patients than in non-NAFLD patients (P < 0.001). In the multiple linear regression analysis, lower serum SHBG level was strongly correlated with a higher incidence of NAFLD, but not MS components. In logistic regression analyses, after adjusted for age, sex, duration of diabetes, smoking status, and alcohol use, the ORs and 95%CI for presence of MS was 2.26 (95%CI 1.91-2.68) and for presence of NAFLD was 6.36 (95%CI 4.87-8.31) with per one SD decrease in serum SHBG (both P < 0.001). In conclusion, lower serum SHBG is associated with a higher prevalence of NAFLD, compared with MS and other metabolic disorders, in T2D patients. NAFLD might be an important influencing factor for the association of circulating SHBG with MS in T2D patients.

The anti-inflammatory effects of asiatic acid in lipopolysaccharide-stimulated human corneal epithelial cells.

AIM: To investigate the anti-inflammatory effects of asiatic acid (AA) on lipopolysaccharide (LPS)-induced inflammatory response in human corneal epithelial cells (HCECs). METHODS: Cell viability was measured using a cell counting kit-8 (CCK-8) assay. Quantitative real-time polymerase chain reaction (qRT-PCR) was used to determine the mRNA expression of interleukin-8 (IL-8), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), tumor necrosis factor-alpha (TNF-α), and transforming growth factor-ß (TGF-ß) in HCECs. Intracellular reactive oxygen species (ROS) was measured using the ROS assay kit. Glutathione (GSH) concentration was measured using the total GSH assay kit. Akt1 and Akt phosphorylation (p-Akt1) levels were measured by Western blotting and immunofluorescence. RESULTS: AA induced toxicity at high concentrations and significantly stimulated the proliferation of HCECs at concentrations of 20 µmol/L for 1h. LPS at concentrations of 300 ng/mL for 1h significantly stimulated the mRNA expression of IL-8, IL-6, IL-1ß, TNF-α, and TGF-ß in HCECs, while the stimulation effects were significantly inhibited by AA (20 µmol/L). In addition, AA was found to decrease the content of ROS, increase GSH generation, and also inhibit LPS-induced p-Akt in HCECs. CONCLUSION: AA decreases the generation of inflammatory factors IL-8, IL-6, IL-1ß, TNF-α, and TGF-ß in LPS-stimulated HCECs. AA significantly inhibites the intracellular concentrations of ROS and increases GSH generation. AA also inhibites LPS-induced p-Akt in HCECs. These findings reveal that AA has anti-inflammation effects in LPS-stimulated HCECs.

Papillary tumor of the pineal region: A case report and review of the literature.

Papillary tumor of the pineal region (PTPR) was first described as a distinct tumor entity in 2003 and was introduced into the World Health Organization classification of central nervous system tumors in 2007. This tumor is rare and, to the best of our knowledge, only 7 cases have been reported in children <16 years of age, while the youngest documented patient was a 15-month-old boy. The present study reported a case of PTPR in a 10-year-old girl who underwent magnetic resonance imaging and surgical resection of tumors. Histological and immunohistochemical staining results were presented. Patients with PTPR require long-term follow-up, and the patient of the present study has continued to do well, with no recurrence of the tumor at the 15-month follow-up examination. In addition, a review of the literature on this unusual neoplasm was performed, along with discussion of their differential diagnosis.

DNA methylation level of promoter region of activating transcription factor 5 in glioma.

Transcription factors, which represent an important class of proteins that play key roles in controlling cellular proliferation and cell cycle modulation, are attractive targets for cancer therapy. Previous researches have shown that the expression level of activating transcription factor 5 (ATF5) was frequently increased in glioma and its acetylation level was related to glioma. The purposes of this study were to explore the methylation level of ATF5 in clinical glioma tissues and to explore the effect of ATF5 methylation on the expression of ATF5 in glioma. Methylation of the promoter region of ATF5 was assayed by bisulfite-specific polymerase chain reaction (PCR) sequencing analysis in 35 cases of glioma and 5 normal tissues. Quantitative real-time PCR (qRT-PCR) was also performed to detect ATF5 mRNA expression in 35 cases of glioma and 5 normal tissues. Clinical data were collected from the patients and analyzed. The percentages of methylation of the ATF5 gene in the promoter region in healthy control, patients with well-differentiated glioma, and those with poorly differentiated glioma were 87.78%, 73.89%, and 47.70%, respectively. Analysis of the methylation status of the promoter region of the ATF5 gene showed a gradually decreased methylation level in poorly differentiated glioma, well-differentiated glioma, and normal tissues (P<0.05). There was also a significant difference between well-differentiated glioma and poorly differentiated glioma (P<0.05). ATF5 mRNA expression in glioma was significantly higher than that in the normal tissues (P<0.05). This study provides the first evidence that the methylation level of ATF5 decreased, and its mRNA expression was evidently up-regulated in glioma.

High-level expression, purification and study of bioactivity of fusion protein M-IL-2((88)Arg, (125)Ala) in Pichia pastoris.

M-IL-2((88)Arg, (125)Ala) is a fusion protein comprising melittin genetically linked to a mutant human interleukin 2((88)Arg, (125)Ala). In this study, we constructed an expression system of M-IL-2((88)Arg, (125)Ala) in Pichia pastoris: GS115/pPICZα A/M-IL-2((88)Arg, (125)Ala), and achieved the high-level expression of the fusion protein. The maximum yield of the fusion protein M-IL-2((88)Arg, (125)Ala) reached up to 814.5mg/L, higher than the system in Escherichiacoli. The fusion protein was purified by means of ammonium sulfate fractionation, dialysis and nickel ion affinity chromatography. The molecular weight of the fusion protein is about 26kDa, conforming the theoretical value. And M-IL-2((88)Arg, (125)Ala) possesses strong antigen-specificity by Western blot detection. Bioassay results indicated that the fusion protein could directly inhibit the growth of human ovarian cancer SKOV3 cells and Hela cells in vitro. This study provides an alternative strategy for large-scale production of bioactive M-IL-2((88)Arg, (125)Ala) using P. pastoris as an expression host and paves the way to clinical practice.

Low serum sex hormone-binding globulin is associated with nonalcoholic fatty liver disease in type 2 diabetic patients.

INTRODUCTION: Studies have indicated that low serum sex hormone-binding globulin (SHBG) and testosterone levels are associated with nonalcoholic fatty liver disease (NAFLD). However, it remains unclear whether an association exists between SHBG and NAFLD independent of testosterone. OBJECTIVE: This study was aimed to investigate the relationship between SHBG and both total and free testosterone levels with NAFLD. SUBJECTS AND MEASURES: One hundred and twenty patients with NAFLD and 120 age-, sex- and BMI-matched patients with non-NAFLD were enrolled into a case-control study. Serums SHBG, total testosterone (TT), liver enzymes, lipids, insulin, C-peptide and plasma glucose were measured. Free testosterone (FT) and fatty liver index were calculated. RESULTS: Serum SHBG levels were significantly lower in NAFLD group than in non-NAFLD group (24·5 ± 11·0 vs 37·6 ± 14·4 nm, P < 0·001). After adjustment for age, smoking status, alcohol use, duration of diabetes, BMI and fasting C-peptide, serum SHBG levels in men and women were inversely associated with NAFLD, with odds ratio (OR) and 95% confidence interval (CI) in the forth quartile as 0·05 (0·01-0·30) and 0·25 (0·08-0·77) compared with the first quartile (OR = 1·00). Additional adjustment for TT in men and FT in women did not materially alter the association. The relationship between serum TT (for men) and FT (for women) with NAFLD was attenuated and even diminished after multivariable adjustment for known risk factors and SHBG. CONCLUSION: Low serum SHBG levels, but not TT or FT, are associated with NAFLD in type 2 diabetic patients.

Intensive insulin therapy increases sex hormone-binding globulin in newly diagnosed type 2 diabetic patients.

OBJECTIVE: Many studies have shown that low sex hormone-binding globulin (SHBG) is associated with insulin resistance, but only few studies have examined how serum SHBG is regulated by insulin in humans. This interventional study aimed to investigate the effect of insulin therapy (IT) on serum SHBG levels in newly diagnosed type 2 diabetic patients. METHODS: A total of 80 newly diagnosed type 2 diabetic subjects were enrolled and randomly grouped into a 2-week intensive IT with/without metformin. Serum SHBG, total testosterone, glucose, liver enzymes, lipids, insulin, and C-peptide levels were measured before and after IT. RESULTS: Before IT, serum SHBG levels were negatively correlated with BMI, waist circumference (WC), alanine aminotransferase (ALT), gamma-glutamyl transpeptidase (γ-GT), triglyceride (TG), fasting insulin, and C-peptide, and homeostatic model assessment of insulin resistance (HOMA-IR), and positively with HDL-C (all P for trend <0.05), after adjustment for age and sex. IT increased serum SHBG levels from 26.5±14.5 to 33.2±15.0 nmol/l (P<0.001), increased by 25.2% (95% CI, 20.3 to 30.9%, P<0.001). In a multiple linear regression model adjusting for age, sex, BMI, and WC, the decreases in ΔALT (standardized regression coefficient ß=-0.374, P=0.012) and ΔTG (ß=-0.380, P=0.020) were independent contributors to the increase in ΔSHBG. CONCLUSIONS: IT increases serum SHBG likely through improving insulin resistance and liver function.