EGFR/MAPK signaling pathway acts as a potential therapeutic target for sulforaphane-rescued heart tube malformation induced by various concentrations of PhIP exposure.

BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo [4,5-b] pyrimidine (PhIP) is a known carcinogen generated mainly from cooking meat and environmental pollutants. It is worth exploring the potential of natural small-molecule drugs to protect against adverse effects on embryonic development. PURPOSE: In this study, we investigated the potential toxicological effects of PhIP on embryonic heart tube formation and the effect of Sulforaphane (SFN) administration on the anti-toxicological effects of PhIP on embryonic cardiogenesis. STUDY DESIGN AND METHODS: First, the chicken embryo model was used to investigate the different phenotypes of embryonic heart tubes induced by various concentrations of PhIP exposure. We also proved that SFN rescues PhIP-induced embryonic heart tube malformation. Second, immunofluorescence, western blot, Polymerase Chain Reaction (PCR) and flow cytometry experiments were employed to explore the mechanisms by which SFN protects cardiac cells from oxidative damage in the presence of PhIP. We used RNA-seq analysis, molecular docking, in situ hybridization, cellular thermal shift assay and solution nuclear magnetic resonance spectroscopy to explore whether SFN protects cardiogenesis through the EGFR/MAPK signaling pathway. RESULTS: The study showed that PhIP might dose-dependently interfere with the C-looping heart tube (mild) or the fusion of a pair of bilateral endocardial tubes (severe) in chick embryos, while SFN administration prevented cardiac cells from oxidative damage in the presence of high-level PhIP. Furthermore, we found that excessive reactive oxygen species (ROS) production and subsequent apoptosis were not the principal mechanisms by which low-level PhIP induced malformation of heart tubes. This is due to PhIP-disturbed Mitogen-activated protein kinase (MAPK) signaling pathway could be corrected by SFN administration. CONCLUSIONS: This study provided novel insight that PhIP exposure could increase the risk of abnormalities in early cardiogenesis and that SFN could partially rescue various concentrations of PhIP-induced abnormal heart tube formation by targeting EGFR and mediating EGFR/MAPK signaling pathways.

Regional Homogeneity of the Left Posterior Cingulate Gyrus May Be a Potential Imaging Biomarker of Manic Episodes in First-Episode, Drug-Naive Bipolar Disorder.

Introduction: Abnormal brain networks with emotional response in bipolar disorder (BD). However, there have been few studies on the local consistency between manic episodes in drug-naive first-episode BD patients and healthy controls (HCs). The purpose of this study is to evaluate the utility of neural activity values analyzed by Regional Homogeneity (ReHo). Methods: Thirty-seven manic episodes in first-episode, drug-naive BD patients and 37 HCs participated in resting-state functional magnetic resonance rescanning and scale estimation. Reho and receiver operating characteristic (ROC) curve methods were used to analyze the imaging data. Support vector machine (SVM) method was used to analyze ReHo in different brain regions. Results: Compared to HCs, ReHo increased in the left middle temporal gyrus (MTG.L), posterior cingulate gyrus (PCG), inferior parietal gyrus, and bilateral angular gyrus, and decreased in the left dorsolateral superior frontal gyrus in target group. The ROC results showed that the ReHo value of the left PCG could discriminate the target group from the HCs, and the AUC was 0.8766. In addition, the results of the support vector machine show that the increase in ReHo value in the left PCG can effectively discriminate the patients from the controls, with accuracy, sensitivity, and specificity of 86.02%, 86.49%, and 81.08%, respectively. Conclusion: The increased activity of the left PCG may contribute new evidence of participation in the pathophysiology of manic episodes in first-episode, drug-naive BD patients. The Reho value of the left posterior cingulate gyrus may be a potential neuroimaging biomarker to discriminate target group from HCs.

Incidence and Factors Associated with Hyperglycemia in Patients with First Hospitalization for Major Depression Disorder: A Large Cross-Sectional Sample.

Purpose: Major depressive disorder (MDD) is a mood disorder characterized by persistent spontaneous depression and has a high rate of disability and mortality. There is a complex relationship between MDD and disorders of glucose metabolism, and our study aimed to investigate the prevalence and risk factors for hyperglycemia in patients with MDD who were hospitalized for the first times. Patients and Methods: A total of 981 first-time inpatients with MDD were recruited, socio-demographic information, anthropometric data, and biochemical parameters were collected for each participant. The 17-item Hamilton Assessment Scale for Depression (HAMD-17), the 14-item Hamilton Anxiety Scale (HAMA-14), the Positive Syndrome Scale (PSS), and Clinical General Impressions Inventory-Severity of Illness (CGI-SI) scores were used to assess patients' clinical symptoms. Results: The prevalence of hyperglycemia was 9.28% among patients with MDD who were hospitalized for the first time. Compared to the non-hyperglycemic subgroup, patients in the hyperglycemic subgroup were found to have more extensive and significant demographic and clinical characteristics, higher levels of metabolism-related parameters, and more severe psychological and psycho-pathological symptoms. Age, thyroid stimulating hormone (TSH), triglycerides (TG) were risk factors for hyperglycemia in MDD patients, while course of disease was a protective factor. Conclusion: The study findings suggest that the prevalence of hyperglycemia is not high in patients with MDD who are hospitalized for the first time. The risk variables for predicting hyperglycemia include age, TSH and TG. The above three factors and course of disease have good combined diagnostic ability for hyperglycemia.

Effect of percutaneous transhepatic cholangial drainag + radiofrequency ablation combined with biliary stent implantation on the liver function of patients with cholangiocarcinoma complicated with malignant obstructive jaundice.

OBJECTIVE: To investigate the effect of percutaneous transhepatic cholangial drainage (PTCD) + radiofrequency ablation (RFA) combined with biliary stent implantation on the liver function of patients with cholangiocarcinoma complicated with malignant obstructive jaundice. METHODS: Retrospective analysis of 120 patients with cholangiocarcinoma complicated with malignant obstructive jaundice were divided into the research group (n=60) and the control group (n=60) according to different treatments. The research group received PTCD + RFA combined with biliary stent implantation, while the control group received only PTCD combined with biliary stent implantation. The changes of liver function indexes before and after treatment, the condition of postoperative jaundice in different periods after operation, toxicity and survival time were observed. RESULTS: There was no statistically significant difference between the two groups in general data (P>0.05). Before treatment, there was no statistically significant difference between the two groups in albumin (ALB), alkaline phosphatase (ALP), glutamyltranspeptidase (GGT), total bilirubin (TBil) and direct bilirubin (DBil) (all P>0.05). After treatment, the above indicators were all decreased (all P<0.05), and the patient's condition improved, but there was no significant difference between the research group and the control group (P>0.05). There were patients with postoperative jaundice in the two groups at 1 month, 3 months, and 6 months after surgery. The total incidence of postoperative jaundice in the research group and the control group within 6 months was 11.67% and 30.00%, respectively (P<0.05). After treatment, the aftereffects were observed in the research group (15.00%) and the control group (25.00%), including infection, cholangitis, and biliary bleeding, without statistical significance (P>0.05). There was no statistical significant difference in progression-free survival between the two groups (P>0.05), while patients in the research group had higher median survival and 1-year survival rates than those of the control group (both P<0.05). CONCLUSION: After PTCD + RFA combined with biliary stent implantation was performed on the patients with cholangiocarcinoma complicated with malignant obstructive jaundice, the number of patients with postoperative jaundice at different time points was reduced; 1-year survival rate and median survival were increased; patents' liver function and condition were improved. Thus, this method is worthy of promotion and application.

Effect of enhanced recovery after surgery on patients with malignant obstructive jaundice complicated with diabetes mellitus.

OBJECTIVE: To explore the effect of enhanced recovery after surgery on patients with malignant obstructive jaundice complicated with diabetes mellitus. METHODS: Patients with malignant obstructive jaundice complicated with diabetes mellitus received surgery in Hengshui People's Hospital were divided into two groups: patients in one group received routine care (routine care group, RC group), and patients in another group received enhanced recovery after surgery on the basis of routine care (accelerated care group, AC group). The differences in patients' satisfaction with care and nursing effects between the two groups were compared. RESULTS: The scores of nursing effects such as nursing records and surgical safety in the RC group were significantly lower than those in the AC group (P<0.001). The psychological state of patients in the AC group was better than that in the RC group after care (P<0.001). The nursing-sensitive quality indicators, the quality of life scores and the patients' nursing satisfaction in the AC group were all higher than those in the RC group (P<0.001). The incidence of adverse events in the AC group was significantly lower than that in the RC group (P=0.01). CONCLUSION: Compared with routine care, the effect of enhanced recovery after surgery is better on patients with malignant obstructive jaundice complicated with diabetes mellitus.

Nano-sulforaphane attenuates PhIP-induced early abnormal embryonic neuro-development.

BACKGROUND: 2-Amino-1-methyl-6-phenylimidazo[4,5-b]pyrimidine (PhIP), one of the most abundant heterocyclic aromatic amines (HAA) formed by cooking meat at high temperatures, may modify humans and rodents through the metabolic process prior to affecting nervous system development. In humans and rodents may be modified by metabolic processes and then affecting nervous system development. METHODS: In this paper, PhIP was used to prepare a chicken embryo model with abnormal embryonic nervous system defects. Sulforaphane (SFN) is a derivative of a glucosinolate, which is abundant in cruciferous vegetables, and can pass through the placental barrier. Moreover, SFN has antioxidant and anti-apoptotic functions and is considered as a bioactive antioxidant with significant neuroprotective effects. Nano-sulforaphane (Nano-SFN, sulforaphane nanoparticles) was prepared by self-assembly using biocompatible, biodegradable methoxy polyethylene glycol 5000-b-polyglutamic acid 10,000 (mPEG5K-PGA10K) as the substrate, to explore the new application of Nano-SFN and its modified compounds as leading compounds in protecting against the abnormal development of the embryonic nervous system. RESULTS: The results show that Nano-SFN could protect against PhIP-induced central nervous system (CNS, derived from neural tube) and peripheral nervous system (PNS, derived from neural crest cells, NCCs) defects and neural tube defects (NTDs), and increase the embryo survival rate. CONCLUSIONS: This study indicates that Nano-SFN can effectively alleviate the developmental defects of embryonic nervous system induced by PhIP in the microenvironment and has a protective effect on embryonic development. It not only helps with expanding the application of SFN and improving its medicinal value, but also provides a possibility of SFN being developed as a novel drug for neuroprotection.

Long Noncoding RNA PRR34-AS1 Aggravates the Progression of Hepatocellular Carcinoma by Adsorbing microRNA-498 and Thereby Upregulating FOXO3.

PURPOSE: Long noncoding RNAs are differentially expressed in hepatocellular carcinoma (HCC) and have been validated as essential regulators in HCC. However, there is limited knowledge regarding the detailed roles and mechanisms of most lncRNAs in HCC cells. In this study, the expression profiles of PRR34 antisense RNA 1 (PRR34-AS1) in HCC tissues and cell lines were determined. In addition, the detailed roles and underlying mechanisms of PRR34-AS1 in HCC cells were comprehensively elucidated. METHODS: Reverse transcription-quantitative polymerase chain reaction (PCR) was performed to measure PRR34-AS1 expression in HCC cells. Cell proliferation, apoptosis, and migration and invasion were evaluated in vitro using the cell counting kit-8 (CCK-8) assay, flow cytometric analysis, and transwell cell migration and invasion assays, respectively. In vivo tumor growth was determined using tumor xenograft experiments. The potential miRNA targets of PRR34-AS1 were predicted via bioinformatic analysis and further confirmed using the luciferase reporter assay, RNA immunoprecipitation assay, and reverse transcription-quantitative PCR. RESULTS: PRR34-AS1 was highly expressed in HCC tissues and cell lines, and its interference suppressed HCC cell proliferation, migration, and invasion but promoted cell apoptosis in vitro. In addition, loss of PRR34-AS1 decreased tumor growth in HCC cells in vivo. Mechanistically, PRR34-AS1 functions as a miR-498 sponge and subsequently increases forkhead box O3 (FOXO3) expression in HCC cells. Rescue experiments revealed that the suppressive effects triggered by PRR34-AS1 knockdown on the malignant characteristics of HCC cells could be abrogated by inhibiting miR-498 or restoring FOXO3 expression. CONCLUSION: The depletion of PRR34-AS1 suppresses the oncogenicity of HCC cells by targeting the miR-498/FOXO3 axis. Therefore, the PRR34-AS1/miR-498/FOXO3 pathway may offer a basis for HCC treatment.