Construction and validation of a m6A RNA methylation and ferroptosis-related prognostic model for pancreatic cancer by integrated bioinformatics analysis.

Background: Both N6-methyladenosine (m6A) ribonucleic acid (RNA) methylation and ferroptosis regulators are demonstrated to have significant effects on the malignant clinicopathological characteristics of pancreatic adenocarcinoma (PAAD) patients. However, the currently available clinical indexes are not sufficient to predict precise prognostic outcomes pf PAAD patients accurately. This study aims to examine the clinicopathologic features of m6A RNA methylation and ferroptosis regulators in predicting the outcomes of different types of cancer. Methods: As the foundation for this research, the differentially expressed genes (DEGs) between PAAD tissues and adjacent normal tissues were first identified. Next, dimensional reduction analysis (DCA) based on m6A RNA methylation regulators and ferroptosis regulators were performed and DEGs between good/poor prognosis PAAD patient clusters were identified. DEGs were then screened by Cox analysis, and finally a risk signature was established by least absolute shrinkage and selection operator (LASSO) analyses. The prediction model based on risk score was further evaluated by a validation set from Gene Expression Omnibus (GEO) database. Results: In total, 4 m6A RNA methylation regulator genes and 29 ferroptosis regulator genes were found to have close causal relationships with the prognosis of PAAD, and a risk score with 3 m6A methylation regulators (i.e., IGF2BP2, IGF2BP3, and METTL16) and 4 ferroptosis regulators (i.e., ENPP2, ATP6V1G2, ITGB4, and PROM2) was constructed and showed to be highly involved in PAAD progression and could serve as effective markers for prognosis with AUC value equaled 0.753 in training set and 0.803 in validation set. Conclusions: The combined prediction model, composed of seven regulators of m6A methylation and ferroptosis, in this study more effectively reflects the progression and prognosis of PAAD than previous single genome or epigenetic analysis. Our study provides a broader perspective for the subsequent establishment of prognostic models and the patients may benefit from more precision management.

[Research progress of dummy template molecularly imprinted polymers in separation of natural products].

The dummy template molecularly imprinted polymers not only has such characteristics of normal imprinted polymers as rapid identification, easy preparation, stable structure and multiple reuse, but also can imprint the compounds in natural products that are not suitable as direct template. Therefore, it has drawn more and more attention in the field of the study of natural products. This paper summarizes the methods for the selection of dummy template molecules by investigating the relevant literatures in the past ten years, analyzes the advantages and disadvantages of dummy template molecules in the practical application, and based on the types of natural products active ingredients, this paper is the first to review of the latest progress in extraction and separation of dummy template molecularly imprinted polymers. We believed that this paper could provide references for better applications of the dummy template molecularly imprinted polymers to extract and separate natural products.

[Molecular imprinting technology and its application in terpenoids].

Molecular imprinting technology is widely used in the separation and analysis of compounds such as flavonoids, alkaloids and polyphenols, due to its high selectivity and specific recognition and so on. However, no much of attention has been paid to the terpenoids. This paper is aimed to not only review the effects of common synthetic elements such as functional monomers, cross-linking agents and porogens on the polymer properties, but also highlight the application of terpene molecular imprinting in solid phase extraction, sensor, membrane separation and chromatographic separation by means of statistical analysis of literature. Furthermore, the shortcomings and improvement directions are discussed.We believed that this paper could provide references for better applications of molecular imprinting techniques to the analysis of terpenoid compounds.

A Sample and Sensitive HPLC-MS/MS Method for Simultaneous Determination of Ziyuglycoside I and Its Metabolite Ziyuglycoside II in Rat Pharmacokinetics.

Ziyuglycoside I (ZGS1) is a promising drug candidate for the treatment of leucopenia. Currently, information on ZGS1 and its in vivo metabolite ziyuglycoside II (ZGS2) is limited. The objective of this study was to investigate the pharmacokinetics, tissue distribution, and excretion of ziyuglycoside I (ZGS1) and its metabolite ziyuglycoside II (ZGS2) in rats. In our study, a simple and sensitive high-performance liquid chromatography-mass spectrometry (HPLC-MS/MS) method was established for simultaneous determination of ZGS1 and its metabolite for Sprague-Dawley rat pharmacokinetics studies. The method was validated following internationally-approved guidelines. The results presented in this study indicated that subcutaneous administration of ZGS1 prolonged its extension time and increased the area under the curve (AUC0-t) of ZGS2 during 0 to t minutes. In summary, in this study, the pharmacokinetic characteristics of ZGS1 and its metabolite ZGS2 were defined and its tissue distribution, and excretion in rats were described. Our finding may be beneficial for leucopenia drug that focus on ZGS1.

Ginkgetin inhibits proliferation of human leukemia cells via the TNF-α signaling pathway.

Ginkgetin is known to be an anticancer agent in many studies. However, its effectiveness in treating chronic myeloid leukemia [corrected] remains unknown. The present study aimed to evaluate the effects of ginkgetin on the growth of the K562 cell line. The MTT assay was employed to examine the proliferation of K562, and a terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate nick end labeling (TUNEL) staining was conducted to detect the apoptotic rates. Furthermore, changes of tumor necrosis factor-α (TNF-α) were detected by Western blot analysis. Ginkgetin inhibited the proliferation of K562 cells in a dose- and time-dependent manner. Concentrations of ginkgetin required to induce 50% death of K562 at 24, 48 and 72 h were 38.9, 31.3 and 19.2 µM, respectively. Moreover, treatment of ginkgetin increased K562 apoptosis in vitro along with increased levels of TNF-α. Interestingly, anti-TNF-α antibody prevented ginkgetin-induced K562 cell apoptosis and growth inhibition via deactivation of caspase-8, caspase-9 and caspase-3. Concomitantly, downregulation of TNF-α by etanercept in vivo attenuated ginkgetin-induced inhibitory effects on the tumor growth in an xenograft mouse model. Our results indicate that ginkgetin effectively inhibits K562 cell proliferation, and TNF-α plays a key role in ginkgetin-induced cell apoptosis.

Six new furostanol glycosides from Smilax glauco-china and their cytotoxic activity.

Six new steroidal saponins, namely glauco-chinaosides A-F, and one known compound were isolated from the tubers of Smilax glauco-china. Their structures were elucidated by a combination of spectroscopic analysis and hydrolysis followed by spectral and chromatographic analysis. Compounds 1-7 were tested in vitro for their cytotoxic activities against four human tumor cell lines (SH-SY5Y, SGC-7901, HCT-116, and Lovo). Compounds 1, 2, and 5 exhibited cytotoxic activity against SGC-7901, with IC50 values of 2.7, 11.5, and 6.8 µM, respectively.

Long-term effect of exercise on improving fatty liver and cardiovascular risk factors in obese adults: A 1-year follow-up study.

Exercise training can reduce hepatic fat accumulation and cardiovascular risk among patients with non-alcoholic fatty liver disease (NAFLD), but how long these benefits extend beyond the period of active intervention is unclear. Intrahepatic triglyceride (IHTG) content, measured by proton magnetic resonance spectroscopy, and metabolic risk factors among 220 obese people with NAFLD, who were randomly assigned to vigorous/moderate exercise, moderate exercise or no exercise (control), were assessed at 1 year after the 12-month exercise intervention. IHTG content was significantly reduced in the 2 exercise groups compared with the control group over the 12-month active intervention. It was significantly lower (by -2.39%) in the vigorous/moderate exercise group compared with the control group at the 1-year follow-up (95% confidence interval -4.72 to -0.05%; P = .045). Waist circumference and blood pressure remained significantly lower in the vigorous/moderate exercise group and the moderate exercise group compared with the control group at the 1-year follow-up. Visceral adipose fat remained significantly reduced, but with no differences among 3 groups. These findings suggest 12-month exercise intervention induced reductions in hepatic fat accumulation, abdominal obesity and blood pressure for up to 1 year after the active intervention, with some attenuation of the benefits.

Effects of Moderate and Vigorous Exercise on Nonalcoholic Fatty Liver Disease: A Randomized Clinical Trial.

IMPORTANCE: Nonalcoholic fatty liver disease (NAFLD) is a prevalent risk factor for chronic liver disease and cardiovascular disease. OBJECTIVE: To compare the effects of moderate and vigorous exercise on intrahepatic triglyceride content and metabolic risk factors among patients with NAFLD. DESIGN, SETTING, AND PARTICIPANTS: In this randomized clinical trial, participants with central obesity and NAFLD were recruited from community-based screening in Xiamen, China, from December 1, 2011, through December 25, 2013. Data analysis was performed from August 28, 2015, through December 15, 2015. INTERVENTIONS: Participants were randomly assigned to vigorous-moderate exercise (jogging 150 minutes per week at 65%-80% of maximum heart rate for 6 months and brisk walking 150 minutes per week at 45%-55% of maximum heart rate for another 6 months), moderate exercise (brisk walking 150 minutes per week for 12 months), or no exercise. MAIN OUTCOMES AND MEASURES: Primary outcome, change in intrahepatic triglyceride content measured by proton magnetic resonance spectroscopy at 6 and 12 months; secondary outcomes, changes in body weight, waist circumference, body fat, and metabolic risk factors. RESULTS: A total of 220 individuals (mean [SD] age, 53.9 [7.1] years; 149 woman [67.7%]) were randomly assigned to control (n = 74), moderate exercise (n = 73), and vigorous-moderate exercise (n = 73) groups. Of them, 211 (95.9%) completed the 6-month follow-up visit; 208 (94.5%) completed the 12-month follow-up visit. Intrahepatic triglyceride content was reduced by 5.0% (95% CI, -7.2% to 2.8%; P < .001) in the vigorous-moderate exercise group and 4.2% (95% CI, -6.3% to -2.0%; P < .001) in the moderate exercise group compared with the control group at the 6-month assessment. It was reduced by 3.9% (95% CI, -6.0% to -1.7%; P < .001) in the vigorous-moderate exercise group and 3.5% (95% CI, -5.6% to -1.3%; P = .002) in the moderate exercise group compared with the control group at the 12-month assessment. Changes in intrahepatic triglyceride content were not significantly different between vigorous-moderate and moderate exercise at the 6- or 12-month assessment. Body weight, waist circumference, and blood pressure were significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 6-month assessment and in the vigorous-moderate and moderate exercise groups compared with the control group at the 12-month assessment. In addition, body fat was significantly reduced in the vigorous-moderate exercise group compared with the moderate exercise and control groups at the 12-month assessment. After adjusting for weight loss, the net changes in intrahepatic triglyceride content were diminished and became nonsignificant between the exercise and control groups (except for the moderate exercise group at the 6-month assessment). CONCLUSIONS AND RELEVANCE: Vigorous and moderate exercise were equally effective in reducing intrahepatic triglyceride content; the effect appeared to be largely mediated by weight loss. TRIAL REGISTRATION: clinicaltrials.gov Identifier: NCT01418027.

Intrahepatic triglyceride content is independently associated with chronic kidney disease in obese adults: A cross-sectional study.

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD) are associated with some common critical cardio-metabolic risk factors. The aim of this study was to explore the association between intrahepatic triglyceride (IHTG) content and CKD in obese subjects. METHODS: A total of 1068 obese participants received anthropometric, biochemical measurements and hepatic ultrasonography. Of those, 485 participants received magnetic resonance spectroscopy ((1)H-MRS) for the determination of IHTG content. CKD was defined as a urinary albumin:creatinine ratio (UACR)≥30 mg/g and/or estimated glomerular filtration rate (eGFR)<60 mL/min per 1.73 m(2). RESULTS: The prevalence of CKD was significantly higher in NAFLD subjects compared to subjects without NAFLD, while the prevalence of CKD was gradually increased as the IHTG content increased by quartiles (P for trend<0.001). After adjustment for multivariate metabolic factors, the risk of abnormal albuminuria and CKD was increased by 68% [OR (95% CI): 1.68 (1.21-2.33), P<0.01] and 54% [OR (95% CI): 1.54 (1.14-2.07), P<0.01] respectively per one standard deviation (SD) increase in IHTG content. The association between IHTG content and CKD was not changed by conventional risk factors, including age, BMI and hypertension (all P<0.05). CONCLUSION: IHTG content is independently associated with CKD in obese adults.

Serum alanine aminotransferase independently correlates with intrahepatic triglyceride contents in obese subjects.

BACKGROUND AND AIM: Liver enzymes including serum alanine aminotransferase (ALT), aspartate aminotransferase (AST) and gamma-glutamyltransferase (GGT) are well recognized as surrogate makers reflecting non-alcoholic fatty liver disease (NAFLD). However, the associations of serum ALT, AST and GGT with hepatic lipid contents are not well established. The aim of this study was to investigate the relationship between liver enzymes and intrahepatic triglyceride (IHTG) contents, and explore the feasibility in using liver enzymes to reflect accumulation of IHTG in obese subjects. METHODS: A cross-sectional analysis was conducted in 475 obese adults aged 40-65 years. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose and lipid profiles were measured. The liver triglyceride contents of subjects were determined by (1)H-MRS. RESULTS: Serum ALT, AST and GGT were positively correlated with IHTG contents (p < 0.01). Serum ALT, AST and GGT levels at the highest quartile of IHTG contents were significantly elevated as compared with those in the lowest quartile (p < 0.01). Multivariate linear regression analysis demonstrated that serum ALT, but not AST or GGT was independently associated with IHTG contents. By logistic regression analysis, the odds ratio for higher IHTG contents was increased by 1.464 times/1 SD increase in serum ALT level after adjusting for multiple confounding factors [OR (95% CI) 2.464 (1.584-3.834)]. However, these relationships could not be observed between serum AST or GGT with IHTG contents. CONCLUSIONS: Serum ALT level is independently correlated with the hepatic triglyceride contents in obese subjects and more appropriate to be used as a predictor for the degree of NAFLD rather than AST and GGT.

Change of glutamic acid decarboxylase antibody and protein tyrosine phosphatase antibody in Chinese patients with acute-onset type 1 diabetes mellitus.

BACKGROUND: Glutamic acid decarboxylase antibody (GADA) and protein tyrosine phosphatase antibody (IA-2A) are two major autoantibodies, which exert important roles in the process of type 1 diabetes mellitus (T1D). Our study aimed to investigate the changes in positivity and titers of GADA and IA-2A during the course of Chinese acute-onset T1D patients and their relationships with clinical features. METHODS: Two hundreds and forty-seven Chinese newly diagnosed acute-onset T1D patients were consecutively recruited. GADA and IA-2A were detected at the time of diagnosis, one year later, 3-5 years later after diagnosis during the follow-up; all the clinical data were recorded and analyzed as well. RESULTS: During the course of acute-onset T1D, the majority of patients remained stable for GADA or IA-2A, however, a few patients changed from positivity to negativity and fewer patients converted from negativity to positivity. The prevalence of GADA was 56.3% at diagnosis, decreasing to 50.5% one year later, and 43.3% 3-5 years later while the corresponding prevalence of IA-2A were 32.8%, 31.0% and 23.3%, respectively. The median GADA titers were 0.0825 at diagnosis, declining to 0.0585 one year later and 0.0383 3-5 years later (P < 0.001), while the corresponding median titers were 0.0016, 0.0010, 0.0014 for IA-2A, respectively. Fasting C-peptide (FCP) and postprandial C-peptide 2 hours (PCP2h) levels of GADA or IA-2A negativity persistence patients were higher than those of positivity persistence and negativity conversion patients (P < 0.05) which indicated GADA or IA-2A negativity persistence T1D patients had a less loss of ß cell function. CONCLUSION: Our data suggest that repeated detection of GADA and IA-2A are necessary for differential diagnosis of autoimmune diabetes and the indirect prediction of the ß cell function in Chinese patients.

Irisin is inversely associated with intrahepatic triglyceride contents in obese adults.

BACKGROUND & AIMS: Obesity is closely related to non-alcoholic fatty liver disease (NAFLD), which has become an important public health problem because of its high prevalence and association with metabolic syndromes. Irisin was recently identified as a novel peptide to improve obesity and glucose homeostasis, and considered to be therapeutic for human metabolic diseases. The aim of this study was to examine the association of serum irisin concentration and liver triglyceride contents in obese Chinese adults. METHODS: Serum irisin levels were measured and liver fat contents determined by (1)H MRS in 296 obese adults. Anthropometric parameters and blood biochemical indexes including liver enzymes, glucose, and lipid profiles were detected. The liver triglyceride contents of subjects were measured by (1)H MRS. The protein levels of irisin were determined by quantitative ELISA. RESULTS: We found that serum irisin levels were reduced in obese adults with NAFLD. By dividing the distribution of intrahepatic triglyceride (IHTG) contents into quartiles, serum irisin levels were reduced gradually with the increase of IHTG contents (p<0.01). Higher serum irisin levels were associated with preferable TG levels. Serum ALT and AST concentrations were inversely correlated with serum irisin levels. Multivariate linear regression analysis demonstrated that serum irisin levels were independently associated with liver fat (p<0.01). By logistic regression analysis, the odds ratio for higher IHTG contents was reduced by 12.4% per 1 SD increase in serum irisin concentrations after adjustment for multivariate metabolic factors [OR (95% CI); 0.876 (0.777-0.987)]. CONCLUSIONS: These results demonstrated that serum irisin concentrations were inversely associated with the triglyceride contents in the liver and liver enzymes in obese Chinese adults.

CA 125, PET alone, PET-CT, CT and MRI in diagnosing recurrent ovarian carcinoma: a systematic review and meta-analysis.

BACKGROUND AND PURPOSE: Ovarian cancer is the commonest tumor in female patients with a propensity for recurrence even after primary chemotherapy in early stage. The accuracy of CA 125, PET alone, PET-CT, CT and MRI in diagnosing the recurrent ovarian carcinoma has never been systematically assessed, and present systematic review was aimed at this issue. METHODS: We searched for articles published from January 1995 to November 2007, inclusion criteria including: articles were reported in English or Chinese; CA 125, PET whether interpreted with or without the use of CT, CT or MRI was used to detect recurrent ovarian carcinoma; Histopathologic analysis and/or close clinical and imaging follow-up for at least 6 months. We extracted data to calculate sensitivity, specificity, SROC curves and AUC and to test for heterogeneity. RESULT: In 34 included studies, CA 125 had the highest pooled specificity, 0.93 (95% CI: 0.89-0.95); PET-CT had highest pooled sensitivity, 0.91 (95% CI: 0.88-0.94). The AUC of CA 125, PET alone, PET-CT, CT and MRI were 0.9219, 0.9297, 0.9555, 0.8845 and 0.7955, respectively. Results of pairwise comparison between each modality demonstrated AUC of PET, whether interpreted with or without the use of CT, was higher than that of CT or MR, p<0.05. The pooled sensitivity, pooled specificity and AUC showed no statistical significance between PET alone and PET-CT. There was heterogeneity among studies and evidence of publication bias. CONCLUSION: PET-CT might be a useful supplement to current surveillance techniques, particularly for those patients with an increasing CA 125 level and negative CT or MR imaging. However, regarding to diagnostic accuracy, interpreted CT images may have limited additional value on PET in detecting recurrent ovarian cancer.

[NIR spectrometer for non-destruction measurement of oil contents in a corn seed].

NIR spectromneter for non-destruction measurement of oil contents in an integrated kernel of corn was manufactured. Using LED (light emitting diode) as the light source and six filters as the monochromator, the specifications of the instrument are compared with those of the commercial instruments. The regression coefficient, the standard error, and the relative error of measuring oil contents in an integrated kernel of corn are 0.9688, 0.72 and 0.062 respectively. The results meet the demand of high-oil corn breeding.