Efficacy and Safety of Topical Traditional Chinese Medicine Monotherapy in Persistent HPV Infection Among Males.

Objective: We studied the efficacy and safety of traditional Chinese medicine paiteling treatment of persistent human papillomavirus (HPV) infection in males. Methods: The study included 159 male patients with persistent HPV infection between January 2018 and July 2022, and categorized into the treatment group (n = 96) and control group (n = 63) based on the treatment. The treatment group was externally treated with paiteling diluent for 4 consecutive days and then stopped for 3 days. The total course of treatment was one month. The treatment group underwent a second test six months after treatment. The control group did not receive any therapy and underwent a second test in the seventh month. Results: 19 of the 159 patients were lost during the 6-month follow-up period, leaving 140 patients. The male HPV infection peaks between the ages of 26-35 years 73(52.14%), and its prevalence decrease with age. 84 (60.0%) were single type infections, and 22 (15.71%) had at least 3 types infections. There were 76 (54.29%) patients with the high-risk types, 34 (24.29%) with the low-risk types, and 30 (21.43%) with the mixed types. After 6 months, complete negative conversion rates and negative conversion rates were 74.7% and 90.8% in the treatment group respectively, compared to the control group (P < .01). A comparison of negative conversion rates among different types reveals that 16 type (89.5%) and 6 type (92.3%) had statistical differences, (P < .01) and (P < .05) respectively. Multivariate analysis revealed that the vaccine status of sexual partners was a protective factor (OR = 0.050-0.848) and multi-type infection was a risk factor (OR = 1.807-22.527) for the curative effect. Conclusion: Paiteling is convenient, safe, and effective for the treatment of persistent HPV infection in males.

Silver nanocluster-based ratiometric fluorescence sensors for X-ray dose detection.

In this paper, we synthesized silver nanoclusters using bovine serum albumin (BSA) as a template (BSA@AgNCs). Then, we anchored hydroxyphenyl fluorescein (HPF) to yield HPF-BSA@AgNCs. When exposed to X-rays, hydroxyl (∙OH) radicals generated by radiolysis of water react with HPF to produce fluorescein, which emits enhanced fluorescence at 515 nm (λex = 480 nm). The fluorescence intensity of BSA@AgNCs at 685 nm (λex = 480 nm) remains stable when exposed to X-rays. This HPF-BSA@AgNCs ratiometric fluorescence sensor can rapidly detect 0.1-20 Gy (the energy deposited per unit mass, J/kg) of X-rays. In addition, HPF-BSA@AgNCs exhibit good durability and temperature stability. Finally, HPF-BSA@AgNCs were used to measure the absorbed doses of A549 cells and evaluate the cell irradiation damage.

Discovery of plant phenolic compounds that act as type III secretion system inhibitors or inducers of the fire blight pathogen, Erwinia amylovora.

Erwinia amylovora causes a devastating disease called fire blight in rosaceous plants. The type III secretion system (T3SS) is one of the important virulence factors utilized by E. amylovora in order to successfully infect its hosts. By using a green fluorescent protein (GFP) reporter construct combined with a high-throughput flow cytometry assay, a library of phenolic compounds and their derivatives was studied for their ability to alter the expression of the T3SS. Based on the effectiveness of the compounds on the expression of the T3SS pilus, the T3SS inhibitors 4-methoxy-cinnamic acid (TMCA) and benzoic acid (BA) and one T3SS inducer, trans-2-(4-hydroxyphenyl)-ethenylsulfonate (EHPES), were chosen for further study. Both the T3SS inhibitors (TMCA and BA) and the T3SS inducer (EHPES) were found to alter the expression of T3SS through the HrpS-HrpL pathway. Additionally, TMCA altered T3SS expression through the rsmBEa-RsmAEa system. Finally, we found that TMCA and BA weakened the hypersensitive response (HR) in tobacco by suppressing the T3SS of E. amylovora. In our study, we identified phenolic compounds that specifically targeted the T3SS. The T3SS inhibitor may offer an alternative approach to antimicrobial therapy by targeting virulence factors of bacterial pathogens.

Profiles and diagnostic value of intestinal microbiota in schizophrenia patients with metabolic syndrome.

Aims/hypothesis: It is widely thought that the intestinal microbiota plays a significant role in the pathogenesis of metabolic disorders. However, the gut microbiota composition and characteristics of schizophrenia patients with metabolic syndrome (MetS) have been largely understudied. Herein, we investigated the association between the metabolic status of mainland Chinese schizophrenia patients with MetS and the intestinal microbiome. Methods: Fecal microbiota communities from 115 male schizophrenia patients (57 with MetS and 58 without MetS) were assessed by 16S ribosomal RNA gene sequencing. We assessed the variations of gut microbiome between both groups and explored potential associations between intestinal microbiota and parameters of MetS. In addition, the Phylogenetic Investigation of Communities by Reconstruction of Unobserved States (PICRUSt) based on the KEGG database was used to predict the function of intestinal microbiota. We also conducted Decision Tree Analysis to develop a diagnostic model for the MetS in patients with schizophrenia based on the composition of intestinal microbiota. Results: The fecal microbial diversity significantly differed between groups with or without MetS (α-diversity (Shannon index and Simpson index): p=0.0155, p=0.0089; ß-diversity: p=0.001). Moreover, the microbial composition was significantly different between the two groups, involving five phyla and 38 genera (p<0.05). In addition, a significant correlation was observed between the metabolic-related parameters and abundance of altered microbiota including HDL-c (r2 = 0.203, p=0.0005), GLU (r2 = 0.286, p=0.0005) and WC (r2 = 0.061, p=0.037). Furthermore, KEGG pathway analysis showed that 16 signaling pathways were significantly enriched between the two groups (p<0.05). Importantly, our diagnostic model based on five microorganisms established by decision tree analysis could effectively distinguish between patients with and without MetS (AUC = 0.94). Conclusions/interpretation: Our study established the compositional and functional characteristics of intestinal microbiota in schizophrenia patients with MetS. These new findings provide novel insights into a better understanding of this disease and provide the theoretical basis for implementing new interventional therapies in clinical practice.

CPLX2 Regulates Ferroptosis and Apoptosis Through NRF2 Pathway in Human Hepatocellular Carcinoma Cells.

Understanding the principle of regulated cell death (RCD) such as ferroptosis and apoptosis provides opportunities to overcome sorafenib resistance of HCC. Complexin II (CPLX2) is involved in calcium-dependent fusion of vesicles and plasma membrane, and recent studies showed CPLX2 is involved in cancer progression. However, the expression and function of CPLX2 are unclear in hepatocellular carcinoma (HCC). qPCR and western blotting assays were used to detect the levels of CPLX2. MTT and colony formation assays were used to detect cell viability. The contents of iron, ROS, MDA, and GSH were used to evaluate the function of CPLX2 on ferroptosis, while the flow cytometry and TUNEL assays were used to evaluate the role of CPLX2 on apoptosis. Our analysis showed CPLX2 is significantly upregulated in HCC, which predicts poor overall survival (OS), progression-free survival (PFS), relapse-free survival (RFS), and disease-specific survival (DSS) for patients with HCC. Further function enrichment analysis of genes related to CPLX2 showed CPLX2 is involved in the NRF2 pathway. Downregulation of CPLX2 can inhibit NRF2 expression and the transcription of its downstream genes, which confirms that CPLX2 is involved in NRF2 pathway. Cell viability assay showed that ferroptosis and apoptosis inhibitors can reverse the inhibition effect of CPLX2-knockdown on cell survival, respectively. And downregulation of CPLX2 significantly promotes the contents of iron, ROS, and MDA, while inhibiting the GSH level of HCC cell lysate, suggesting CPLX2 involved in ferroptosis. Moreover, downregulation of CPLX2 promotes the apoptosis of HCC cells by flow cytometry and TUNEL assay. And upregulation of NRF2 can partly reverse the inhibitory effect of CPLX2-downregulation on ferroptosis and apoptosis. Finally, we found downregulation of CPLX2 aggravates cell death induced by sorafenib. CPXL2 regulates ferroptosis and apoptosis through NRF2 pathway, and CPLX2 knockdown promotes cell death induced by sorafenib. CPLX2 might be an effective target for therapy patients with HCC.

5:2 intermittent fasting tapers food intake in the refeeding state and ameliorates metabolic disturbances in mice exposed to olanzapine.

A considerable number of patients suffer from adverse metabolic reactions caused by atypical antipsychotics (AAPs), however, current management strategies are disappointing to clinicians. Preclinical studies have consistently demonstrated that intermittent fasting (IF) has robust disease-modifying efficacy in animal models in a wide range of pathological conditions, especially obesity and diabetes. However, it is unclear what role IF can play in addressing AAPs-induced metabolic disturbances. In our study, we found that a 5:2 IF regimen significantly ameliorated the metabolic disturbances induced by olanzapine (a drug representative of AAPs) in animal models. Meanwhile, our research suggests that IF altering food intake during the refeeding phase may account for the metabolic benefit. This study provides supporting evidence regarding a potentially cost-effective intervention strategy for AAPs-induced metabolic disturbances.

A new chromone functionalized isoqunoline derived chemosensor with fluorogenic switching effect for selective detection of Zn2+ in real water samples and living cells.

In this work, a selective chemosensor, (E)-N'-((4-oxo-4H-chromen-3-yl)methylene)isoquinoline-1-carbohydrazide (ENO), was rationally developed for colorimetric and fluorogenic detection of Zn2+ ions. It was readily synthesized from 4-oxo-4H-chromene-3-carbaldehyde and isoquinoline-1-carbohydrazide via one-step Schiff reaction. ENO exhibited excellent fluorescent response performances toward Zn2+ over a wide pH range in EtOH/H2O media, including a distinguished color change from colorless to gold, a low limit of detection (LOD) value (34 nM), strong complexation ability (1.36 × 105 M-1) and rapid identification (2 min). The sensing mechanism of ENO toward Zn2+ was proposed on the basis of the chelation-enhanced fluorescence (CHEF) process, which was further supported by IR studies and the density functional theory (DFT) calculation. Moreover, ENO presented here demonstrated outstanding capability in monitoring trace level of Zn2+ ions in real water samples, living cells as well as the on-site assay kit.

IL-1 receptor-associated kinase 1 participates in the modulation of the NLRP3 inflammasome by tumor-associated macrophages in hepatocellular carcinoma.

Background: Hepatocellular carcinomas (HCCs) occur frequently in the digestive system and are associated with high mortality. This current study examined the regulatory relationship between interleukin (IL)-1 receptor-associated kinase 1 (IRAK1), NLR family pyrin domain-containing 3 (NLRP3) inflammasomes, and tumor-associated macrophages (TAMs) in the growth and metastasis of HCC. Methods: The expression of IRAK1 and NLRP3 was assessed in tissues and cells via quantitative real-time polymerase chain reaction (qRT-PCR) and Western blot analysis. Immunohistology was performed to detect the macrophage markers CD68, CD163, and CD168 in tumor tissues. Small interfering (si)RNA targeting IRAK1 (si-IRAK1) was designed to silence IRAK1 expression. Following si-IRAK1 transfection and/or co-culture with TAMs, HCC cell viability, proliferation, migration, and invasion, as well as the expression of NLRP3 and pro-inflammatory cytokines IL-1 ß, IL-18, and monocyte chemotactic protein 1 (MCP-1) were assessed. Results: HCC tissues showed elevated expression of IRAK1 and NLRP3, as well as increased expression of the macrophage markers CD68, CD163, and CD168, compared to adjacent healthy tissues. Silencing of IRAK1 expression in HepG2 and Huh7 cells resulted in suppression of cell proliferation, migration, and invasion, and also reduced expression of NLRP3 and the pro-inflammatory cytokines IL-1ß, IL-18, and MCP-1. Moreover, TAMs promoted HepG2 and Huh7 cell proliferation, migration, and invasion, and elevated the expression of NLRP3, IL-1ß, IL-18, and MCP-1. Furthermore, IRAK1 silencing reversed the effects of TAMs on HepG2 and Huh7 cells. Conclusions: The expression of IRAK1 was associated with HCC growth and metastasis, as well as NLRP3 inflammasome activation. The ability of TAMs to promote HCC growth and metastasis may be activated by NLRP3 inflammasomes and regulated by IRAK1.

Enhanced nitrobenzene removal in soil by biochar supported sulfidated nano zerovalent iron: Solubilization effect and mechanism.

Sulfidated nano zerovalent iron (S-nZVI) is reported to be effective in removal of aqueous organic contaminants. However, little is known about its potential use in reductive degradation of soil-sorbed contaminants. In this study, biochar (BC) supported S-nZVI (S-nZVI@BC) was successfully synthesized through sulfidation and carbon loading modification, which effectively combined the solubilization characteristics of BC and high reduction characteristics of S-nZVI. Transmission electron microscopy (TEM) with an energy-dispersive X-ray spectroscopy (EDS) analysis suggested that sulfur and iron were evenly distributed throughout BC matrix. The degradation of nitrobenzene (NB) in soil was achieved more efficiently with the as-synthesized S-nZVI@BC composites. Results indicated that S-nZVI@BC with S-nZVI/BC mass ratio of 3:1, dosage of 10 mg/g exhibited superior NB removal (98%) and aniline (AN) formation (90%) efficiency within 24 h without formation of other intermediates, higher than those of S-nZVI. Meanwhile, the surface FeSX layer enhanced the antioxidant capacity of S-nZVI@BC and participated in the reduction of NB. The soil-sorbed NB decreased from 14% to 1.4%, indicating that the addition of BC played an important role in solubilization of NB from soil. Solubilization-reduction was the dominant mechanism for NB removal. This research indicated that S-nZVI@BC held the potential to enhance in-situ remediation of NB-contaminated soil.

Differing Prevalence and Correlates of Metabolic Syndromes Between Chlorpromazine and Clozapine: A 10-year Retrospective Study of a Male Chinese Cohort.

BACKGROUND: Antipsychotics are known to be associated with metabolic syndromes (MetS). Chlorpromazine (CPZ) and Clozapine (CLZ) are currently the most commonly used antipsychotics in low-income districts of China. However, potential differences in the long-term effects of CPZ and CLZ on MetS in schizophrenia inpatients are not well understood. Here, we aimed to identify any MetS profile differences between long-term schizophrenia patients who were prescribed either CPZ or CLZ at a primary psychiatric hospital. METHODS: We recruited a total of 204 male schizophrenia patients who received either CPZ or CLZ. We measured their weight, height, body mass index (BMI), waist circumference (WC), diastolic blood pressure (DBP), and systolic blood pressure (SBP), as well as their biochemical indicators, including fasting blood glucose (FBS), triglycerides (TG), cholesterol (TC), high-density lipoprotein cholesterol (HDL-c) and low-density lipoprotein cholesterol (LDL-c). RESULTS: The MetS prevalence in the CPZ and CLZ groups was 31% and 37.5%, respectively. The CLZ group had significantly higher DBP levels and a higher incidence of dyslipidemia (HDL-c) but lower HDL-c and TC levels than the CPZ group. We also determined that smoking history, BMI, and duration of hospitalisation were risk factors for the development of MetS. Moreover, we found that CPZ and CLZ were correlated with the same risk for developing MetS and that BMI was a vital risk factor of MetS for both the CPZ and CLZ groups. CONCLUSION: Long-term CPZ and CLZ prescriptions were associated with similar profiles for developing MetS of schizophrenia patients.

Relationship Between Polymorphism of Thrombin-Activatable Fibrinolysis Inhibitor Gene +1040C/T and a Cohort of Chinese Women With Recurrent Spontaneous Abortion.

The balance between coagulation and fibrinolysis is essential for a successful pregnancy. This study aimed to explore the genetic variant of +1040C/T in the coding region of thrombin-activatable fibrinolysis inhibitor (TAFI) gene in women with recurrent spontaneous abortion (RSA) and in unrelated healthy controls and to investigate the possible association between TAFI +1040C/T polymorphism and RSA. Peripheral blood samples were collected from 137 Chinese patients with RSA and 103 unrelated healthy Chinese controls. The TAFI +1040C/T polymorphism was analyzed using SNaPshot SNP typing after DNA extraction. The frequency of the C allele was lower in RSA patients compared with the controls (0.78 vs 0.84). A subanalysis of the TAFI +1040C/T polymorphism in the 2 populations of RSA women (groups 2RSA and >2RSA) showed that the +1040CT genotype was significantly higher and the +1040CC genotype was significantly lower than from that found in controls. The allele +1040C was associated with a reduced risk of RSA in both group 2RSA (OR = 0.418, 95%CI, 0.255-0.685) and group >2RSA (OR = 0.473, 95%CI, 0.274-0.819) compared with controls. Our data indicate a protective role for TAFI +1040C allele against RSA, and may be associated with the genetic susceptibility of RSA.

Screening of a novel autophagy-related prognostic signature and therapeutic targets in hepatocellular carcinoma.

BACKGROUND: Many studies have indicated that autophagy plays an important role in multiple cancers, including hepatocellular carcinoma (HCC). This study aimed to establish a prognostic signature for HCC based on autophagy-related genes (ARGs) to predict the prognosis of patients. METHODS: The list of ARGs was derived from screening National Center for Biotechnology Information (NCBI)-Gene and Molecular Signatures Database (MSigDB) datasets. Differential analysis was conducted via the R limma package in HCC patients based on The Cancer Genome Atlas (TCGA) database. Univariate and multivariate Cox regression analysis were conducted to identify key prognostic ARGs via the survival package. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were performed by clusterProfiler package. The Estimation of Stromal and Immune cells in MAlignant Tumor tissues using Expression data (ESTIMATE) algorithm was used to conduct immune analysis. Finally, the correlation between the prognostic model and clinical characteristics was also assessed, including age, tumor-node-metastasis (TNM) stages, and tumor grades. RESULTS: Firstly, 106 differential ARGs were identified and 10 candidates were further confirmed via Cox regression analysis, including BAMBI, HIF1A, SERPINE1, EZH2, SLC9A3R1, IGFBP3, HSPB8, DAB2, CXCL1 and PRNP. The receiver operating characteristic (ROC) curve analysis revealed that the ARGs risk model had a well diagnostic positive rate with 1-year area under the curve (AUC) =0.688 and 3-year AUC =0.674. Correlation analysis indicated that only advanced tumor stages were positively associated with high ARGs scores with P=0.0227. There were also significant differences in tumor purity (P=6.71e-05), infiltrating cell analysis (P=7.77e-05), immune analysis (P=7.9e-05), and stromal cells analysis (P=0.0015) in high- and low-risk ARGs samples. The genes HIF1A, IGFBP3, and DAB2 were found to have high frequent missense mutations in samples with high-risk ARGs scores. Lastly, we also established a nomogram to predict overall survival (OS) of HCC by integrating ARGs scores and other clinical parameters. CONCLUSIONS: Our study established an autophagy-related signature for predicting the prognosis of HCC patients, providing a thorough understanding of the underlying mechanisms of autophagy in HCC.

The effect of prohibiting outside food during COVID-19 pandemic on the body weight of schizophrenic patients taking olanzapine or clozapine: a retrospective self-controlled study.

BACKGROUND: Olanzapine and clozapine are atypical antipsychotics (AAPs) with the greatest risk of weight gain, and changes in feeding behavior are among the most important underlying mechanisms. However, few studies have investigated the role of diet-alone interventions in improving individuals' weight gain by taking AAPs. In closed management mental hospitals of China, family members are allowed to bring food to patients regularly, causing patients to have caloric intake added to their 3 daily meals. However, during the global pandemic of coronavirus disease 2019 (COVID-19), bringing food to the hospital was temporarily prohibited in mental health institutions in China to prevent the spread of the virus. This study sought to compare the body weight and body mass index (BMI) changes of patients taking olanzapine or clozapine undergoing diet-alone interventions caused by this prohibition. METHODS: A retrospective self-controlled study was conducted on 90 patients with schizophrenia from a single-center treated with olanzapine or clozapine monotherapy, or combined with aripiprazole or ziprasidone which has a small metabolic impact. A paired-samples t-test was used to compare the changes in body weight and BMI before and after the 3-month prohibition, and general linear regression was used to analyze the effects of gender, age, disease course, duration of drug exposure, and equivalent dose on the BMI improvement. Also, the percentage of people who lost weight and that of individuals who lost 5% of their pre-prohibition body weight were calculated. RESULTS: Paired-samples t-test showed that after 3-month prohibition, the patients' body weight (71.68±6.83 vs. 66.91±7.03, P<0.001) and BMI (26.43±2.11 vs. 24.63±1.81, P<0.001) decreased significantly. Weight loss rate accounted for 99.1%, and weight loss of 5% from the pre-prohibition body weight accounted for 71.8%. General linear regression showed that the duration of drug exposure (ß =-0.678, P<0.001) was significantly and negatively correlated with the BMI changes. No significant correlation of gender, age, disease course, or equivalent dose with BMI changes was found. CONCLUSIONS: Diet-alone interventions facilitate weight loss in chronically hospitalized schizophrenia patients taking AAPs. Conduction of dietary intervention in the early stages of medication may yield greater benefits.

The prevalence and related factors of metabolic syndrome in outpatients with first-episode drug-naive major depression comorbid with anxiety.

Metabolic syndrome (MetS) is associated with depression, but its role in major depressive disorder comorbid with anxiety (AMD) is unclear. This study aimed to investigate the prevalence and clinical correlates of MetS in first-episode drug-naive (FEDN) patients with AMD in a Chinese Han population. In total, 1380 FEDN outpatients with AMD were recruited in this cross-sectional study. The sociodemographic features, clinical characteristics, history of suicide attempts, thyroid-stimulating hormone (TSH) levels, and MetS parameters of each subject were evaluated. All subjects were rated on the Hamilton Depression Rating Scale (HAM-D), Hamilton Anxiety Rating Scale (HAM-A), and the Positive and Negative Syndrome Scale positive symptom subscale. The prevalence of MetS among AMD patients was 8.04%. Compared to the non-MetS group, age, age of onset, TSH level, HAM-A and HAM-D scores, history of attempted suicide, and comorbid psychiatric symptoms were higher in the MetS group. Those in this group were also more likely to be married, and they had a lower educational level. Furthermore, age, psychiatric symptoms, suicide attempts, and higher TSH levels were independently associated with MetS in AMD patients. This study suggests a lower prevalence of MetS in FEDN patients with AMD in a Chinese Han population. Older age, comorbid psychiatric symptoms, history of attempted suicide, and higher TSH levels are related factors for MetS in AMD patients.

Antipsychotics-associated obsessive-compulsive symptoms: individualized treatments and clinical benefits of memantine: a case report.

Antipsychotics with a prominent anti-serotoninergic profile have risks of obsessive-compulsive symptoms (OCS). These types of OCS are remain mostly intractable to existing treatments because of the dilemma between the antipsychotic effects and the OCS adverse effects, both of which brought by serotoninergic-blocking profile. This state forced us to seek non-serotonergic system pharmaceuticals. Memantine, as a glutamatergic drug, is the adjunctive agent most consistently showing an effective impact in primary OCD, however its benefit in antipsychotics-associated OCS has not been reported. Herein, we presented a case of a 34-year-old male schizophrenia patient who experienced antipsychotics-associated OCS which could not be relieved by routine managements. He had fallen into dilemma of either aggravated OCS or poorly controlled schizophrenia. Eventually his condition got significant relief by individualized utilization of antipsychotics to control psychosis and by memantine to deal with his OCS. This is the first case to report the benefit of memantine in SGAs-associated OCS. It suggests that memantine is a worth considering approach, especially when the OCS are resistant to routine managements. Moreover, this case would be helpful for clinicians to know the etiology of SGAs-associated OCS, as indicated by the interesting changes after every adjustment of antipsychotics in the whole therapeutic course.

Human blood gene signature as a marker for smoking exposure: computational approaches of the top ranked teams in the sbv IMPROVER Systems Toxicology challenge.

Crowdsourcing has emerged as a framework to address methodological challenges in omics data analysis and assess the extent to which omics data are predictive of phenotypes of interest. The sbv IMPROVER Systems Toxicology Challenge was designed to leverage crowdsourcing to determine whether human blood gene expression levels are informative of current and past smoking. Participating teams were invited to use a training gene expression dataset to derive parsimonious models (up to 40 genes) that can accurately classify subjects into exposure groups: smokers, former smokers that quit for at least one year, and never-smokers. Teams were ranked based on two classification performance metrics evaluated on a blinded test dataset. The analytical approaches of the first- and third-ranked teams, that are presented in detail in this article, involved feature selection by moderated t-test or LASSO regression and linear discriminant analysis (LDA) and logistic regression classifiers, respectively. While the 12-gene signature of the top team allowed the classification of current smokers with 100% sensitivity at 93% specificity, discriminating former smokers from never-smokers was much more challenging (65% sensitivity at 57% specificity). Gene ontology molecular functions and KEGG pathways associated with current smoking included G protein-coupled receptor activity, signaling receptor activity, calcium ion binding, and the Neuroactive ligand-receptor interaction pathway. Selection of marker genes by either moderated t-test or multivariate LASSO regression followed by LDA or logistic regression, are robust approaches to classification with omics data, confirming in part findings of previous sbv IMPROVER challenges. While current smoking is accurately identified based on blood mRNA levels, smoking cessation for more than one year is accompanied by a "normalization" of the expression of certain mRNAs, making it difficult to distinguish former smokers from never-smokers.

Identification of DNA methylation prognostic signature of acute myelocytic leukemia.

BACKGROUND: The aim of this study is to find the potential survival related DNA methylation signature capable of predicting survival time for acute myelocytic leukemia (AML) patients. METHODS: DNA methylation data were downloaded. DNA methylation signature was identified in the training group, and subsequently validated in an independent validation group. The overall survival of DNA methylation signature was performed. Functional analysis was used to explore the function of corresponding genes of DNA methylation signature. Differentially methylated sites and CpG islands were also identified in poor-risk group. RESULTS: A DNA methylation signature involving 8 DNA methylation sites and 6 genes were identified. Functional analysis showed that protein binding and cytoplasm were the only two enriched Gene Ontology terms. A total of 70 differentially methylated sites and 6 differentially methylated CpG islands were identified in poor-risk group. CONCLUSIONS: The identified survival related DNA methylation signature adds to the prognostic value of AML.

Macrophage migration inhibitory factor mediates metabolic dysfunction induced by atypical antipsychotic therapy.

Atypical antipsychotics are highly effective antischizophrenic medications but their clinical utility is limited by adverse metabolic sequelae. We investigated whether upregulation of macrophage migration inhibitory factor (MIF) underlies the insulin resistance that develops during treatment with the most commonly prescribed atypical antipsychotic, olanzapine. Olanzapine monotherapy increased BMI and circulating insulin, triglyceride, and MIF concentrations in drug-naive schizophrenic patients with normal MIF expression, but not in genotypic low MIF expressers. Olanzapine administration to mice increased their food intake and hypothalamic MIF expression, which led to activation of the appetite-related AMP-activated protein kinase and Agouti-related protein pathway. Olanzapine also upregulated MIF expression in adipose tissue, which reduced lipolysis and increased lipogenic pathways. Increased plasma lipid concentrations were associated with abnormal fat deposition in liver and skeletal muscle, which are important determinants of insulin resistance. Global MIF-gene deletion protected mice from olanzapine-induced insulin resistance, as did intracerebroventricular injection of neutralizing anti-MIF antibody, supporting the role of increased hypothalamic MIF expression in metabolic dysfunction. These findings uphold the potential pharmacogenomic value of MIF genotype determination and suggest that MIF may be a tractable target for reducing the metabolic side effects of atypical antipsychotic therapy.

Investigating the microRNA-mRNA regulatory network in acute myeloid leukemia.

Acute myeloid leukemia (AML) is a common myelogenous malignancy in adults that is often characterized by disease relapse. The pathophysiological mechanism of AML has not yet been elucidated. The present study aimed to identify the crucial microRNAs (miRNAs/miRs) and target genes in AML, and to uncover the potential oncogenic mechanism of AML. miRNA and mRNA expression-profiling microarray datasets were downloaded from the Gene Expression Omnibus database. Differential expression analysis was performed and a regulatory network between miRNAs and target genes was constructed. Gene Ontology and Kyoto Encyclopedia of Genes and Genomes pathway enrichment analyses were used to predict the biological functions of the differentially expressed genes. Reverse transcription-quantitative polymerase chain reaction analysis was employed to verify the expression levels of miRNAs and target genes in AML patient samples. A total of 86 differentially expressed miRNAs and 468 differentially expressed mRNAs between AML and healthy blood samples were identified. In total, 47 miRNAs and 401 mRNAs were found to be upregulated, and 39 miRNAs and 67 mRNAs were found to be downregulated in AML. A total of 223 miRNA-target genes pairs were subjected to the construction of a regulatory network. Differentially expressed target genes were significantly enriched in the Wnt signaling pathway (hsa04310), melanogenesis (hsa04916) and pathways in cancer (hsa05200). Significantly differentially expressed miRNAs and genes, including hsa-miR-155, hsa-miR-192, annexin A2 (ANXA2), frizzled class receptor 3 (FZD3), and pleomorphic adenoma gene 1 (PLAG1), may serve essential roles in AML oncogenesis. Overall, hsa-miR-155, hsa-miR-192, ANXA2, FZD3 and PLAG1 may be associated with the development of AML via the involvement of the Wnt signaling pathway, melanogenesis and other cancer-associated signaling pathways.