Serum retinol-binding protein 4 levels are elevated but do not contribute to insulin resistance in newly diagnosed Chinese hypertensive patients

BACKGROUND: Insulin resistance (IR) is closely correlated with cardiovascular disease (CVD). Retinol-binding protein 4 (RBP4) is a novel adipokine that modulates the action of insulin in various diseases. This study addressed the relationship between RBP4 and IR in newly diagnosed essential hypertension. METHODS: Serum RBP4, anthropometric and metabolic parameters were determined in 267 newly diagnosed essential hypertensive patients not taking antihypertensive medications. The patients along with 64 control (NC) normotensive and lean subjects paired by age and sex were divided into two groups depending on body mass index (BMI), hypertension with obesity (HPO) and hypertension without obesity (HP). RESULTS: A striking difference was observed in RBP4 levels between the HP and NC groups. Significantly higher levels were noted in the HP group compared with the NC group; slightly, but not significantly, lower levels were observed in the HPO group compared with the HP group. After adjusting for BMI, WC and WHR, a modestly linear relationship was observed between RBP4 levels and SBP (r = 0.377; p = 0.00), DBP (r = 0.288; p = 0.00) and HOMA-β(r = 0.121; p = 0.028). Multiple stepwise regression analysis showed that SBP, WHR and drinking were independently related with serum RBP4 levels. CONCLUSIONS: The results of this study indicated that RBP4 levels were increased in naive hypertensive patients; however, no differences were observed in obese or non-obese hypertensive subjects. Our data suggest for the first time that RBP4 levels are significantly increased but do not contribute to the development of IR in newly diagnosed hypertensive Chinese patients

Mycobacterium tuberculosis -Induced Upregulation of the COX-2/mPGES-1 Pathway in Human Macrophages Is Abrogated by Sulfasalazine

Macrophages are the primary human host cells of intracellular Mycobacterium tuberculosis ( M.tb ) infection, where the magnitude of inflammatory reactions is crucial for determining the outcome of infection. Previously, we showed that the anti-inflammatory drug sulfasalazine (SASP) significantly reduced the M.tb bactericidal burden and histopathological inflammation in mice. Here, we asked which genes in human inflammatory macrophages are affected upon infection with M.tb and how would potential changes impact the functional state of macrophages. We used a flow cytometry sorting system which can distinguish the dead and alive states of M.tb harbored in human monocyte-derived macrophages (MDM). We found that the expression of cyclooxygenase-2 and microsomal prostaglandin E 2 synthase (mPGES)-1 increased significantly in tagRFP + MDM which were infected with alive M.tb . After exposure of polarized M1-MDM to M.tb (H37Rv strain)-conditioned medium (MTB-CM) or to the M.tb -derived 19-kD antigen, the production of PGE 2 and pro-inflammatory cytokines increased 3- to 4-fold. Upon treatment of M1-MDM with SASP, the MTB-CM-induced expression of COX-2 and the release of COX products and cytokines decreased. Elevation of PGE 2 in M1-MDM upon MTB-CM stimulation and modulation by SASP correlated with the activation of the NF-κB pathway. Together, infection of human macrophages by M.tb strongly induces COX-2 and mPGES-1 expression along with massive PGE 2 formation which is abrogated by the anti-inflammatory drug SASP

Association between Serum Cystatin C and Diabetic Foot Ulceration in Patients with Type 2 Diabetes: A Cross-Sectional Study

Serum cystatin C (CysC) has been identified as a possible potential biomarker in a variety of diabetic complications, including diabetic peripheral neuropathy and peripheral artery disease. We aimed to examine the association between CysC and diabetic foot ulceration (DFU) in patients with type 2 diabetes (T2D). 411 patients with T2D were enrolled in this cross-sectional study at a university hospital. Clinical manifestations and biochemical parameters were compared between DFU group and non-DFU group. The association between serum CysC and DFU was explored by binary logistic regression analysis. The cut point of CysC for DFU was also evaluated by receiver operating characteristic (ROC) curve. The prevalence of coronary artery disease, diabetic nephropathy (DN), and DFU dramatically increased with CysC (P<0.01) in CysC quartiles. Multivariate logistic regression analysis indicated that the significant risk factors for DFU were serum CysC, coronary artery disease, hypertension, insulin use, the differences between supine and sitting TcPO2, and hypertension. ROC curve analysis revealed that the cut point of CysC for DFU was 0.735 mg/L. Serum CysC levels correlated with DFU and severity of tissue loss. Our study results indicated that serum CysC was associated with a high prevalence of DFU in Chinese T2D subjects

Comparison of Population-Based Association Study Methods Correcting for Population Stratification

Population stratification can cause spurious associations in population–based association studies. Several statistical methods have been proposed to reduce the impact of population stratification on population–based association studies. We simulated a set of stratified populations based on the real haplotype data from the HapMap ENCODE project, and compared the relative power, type I error rates, accuracy and positive prediction value of four prevailing population–based association study methods: traditional case-control tests, structured association (SA), genomic control (GC) and principal components analysis (PCA) under various population stratification levels. Additionally, we evaluated the effects of sample sizes and frequencies of disease susceptible allele on the performance of the four analytical methods in the presence of population stratification. We found that the performance of PCA was very stable under various scenarios. Our comparison results suggest that SA and PCA have comparable performance, if sufficient ancestral informative markers are used in SA analysis. GC appeared to be strongly conservative in significantly stratified populations. It may be better to apply GC in the stratified populations with low stratification level. Our study intends to provide a practical guideline for researchers to select proper study methods and make appropriate inference of the results in population-based association studies

Microarray and bioinformatic analysis reveal the parental genes of m6A modified circRNAs as novel prognostic signatures in colorectal cancer

BackgroundAccumulating evidences have revealed that the abnormal N6-methyladenosine (m6A) modification is closely associated with the occurrence, development, progression and prognosis of cancer. It is noteworthy that m6A modification is widely existed in circRNAs and found its key biological functions in regulating circRNAs metabolism. However, the role of m6A modified circRNAs in colorectal cancer (CRC) remains unknown. To better understand the role of circRNAs in the pathogenesis of CRC, we focus on the relationship between m6A-modified circRNAs and their parental genes.MethodsArraystar m6A-circRNA epitranscriptomic microarray was used to identify differentially m6A modified circRNAs between CRC and the control group. In addition, TCGA-COAD and GSE106582 cohort were used to identify differentially expressed mRNAs. In this study, we screened the parental genes for which both circRNAs and mRNAs were down-regulated further to analyze, including gene expression, survival prognosis, enrichment analysis. Additionally, Western Blotting was used to further validate the role of the parental gene in CRC.ResultsWe found that 1405 significantly downregulated circRNAs in CRC by our microarray data. Moreover, we obtained 113 parental genes for which both circRNAs and mRNAs were down-regulated to analyze the relationship with the prognosis of CRC based on TCGA-COAD cohort. And we identified nine potential prognostic genes, including ABCD3, ABHD6, GAB1, MIER1, MYOCD, PDE8A, RPS6KA5, TPM1 and WDR78. And low expression of these genes was associated with poor survival prognosis of the patients with CRC. In addition, we found that TPM1 is downregulated in CRC by western blotting experiment. And the calcium-signaling pathway may involve the process of the CRC progression.ConclusionsWe identified nine potential prognostic genes, after analyzed the relationship between the parental genes of m6A modified circRNAs and the progression of CRC. Above all, our study further validated TPM1 can serve as a potentail signature for CRC patients

A nanobody-based molecular toolkit for ubiquitin–proteasome system explores the main role of survivin subcellular localization

Targeted protein degradation is a powerful tool for determining the function of specific proteins nowadays. Survivin is the smallest member of the inhibitor of the apoptosis protein (IAP) family. It exists in the cytoplasm and nucleus of cells, but the exact function of survivin in different subcellular locations retained unclear updates due to the lack of effective and simple technical means. In this study, we created a novel nanoantibody-based molecular toolkit, namely, the ubiquitin–proteasome system (Nb4A-Fc-T2A-TRIM21), that can target to degrade survivin localized in cytoplasmic and cell nuclear by ubiquitinating, and by which to verify the potential roles of survivin subcellular localization. Also, the results showed that the cytoplasmic survivin mainly plays an anti-apoptotic function by directly or indirectly inhibiting the caspase pathway, and the nuclear survivin mainly promotes cell proliferation and participates in the regulation of the cell cycle. In addition, the Nb4A-Fc-T2A-TRIM21 system can degrade the endogenous survivin protein in a large amount by the ubiquitin–proteasome pathway, and the system can provide theoretical support for ubiquitination degradation targeting other endogenous proteins

Enhancement of Low-field Magnetoresistance in Self-Assembled Epitaxial La0.67Ca0.33MnO3:NiO and La0.67Ca0.33MnO3:Co3O4 Composite Films via Polymer-Assisted Deposition

Polymer-assisted deposition method has been used to fabricate self-assembled epitaxial La(0.67)Ca(0.33)MnO(3):NiO and La(0.67)Ca(0.33)MnO(3):Co(3)O(4) films on LaAlO(3) substrates. Compared to pulsed-laser deposition method, polymer-assisted deposition provides a simpler and lower-cost approach to self-assembled composite films with enhanced low-field magnetoresistance effect. After the addition of NiO or Co(3)O(4), triangular NiO and tetrahedral Co(3)O(4) nanoparticles remain on the surface of La(0.67)Ca(0.33)MnO(3) films. This results in a dramatic increase in resistivity of the films from 0.0061 Ω•cm to 0.59 Ω•cm and 1.07 Ω•cm, and a decrease in metal-insulator transition temperature from 270 K to 180 K and 172 K by the addition of 10%-NiO and 10%-Co(3)O(4), respectively. Accordingly, the maximum absolute magnetoresistance value is improved from −44.6% to −59.1% and −52.7% by the addition of 10%-NiO and 10%-Co(3)O(4), respectively. The enhanced low-field magnetoresistance property is ascribed to the introduced insulating phase at the grain boundaries. The magnetism is found to be more suppressed for the La(0.67)Ca(0.33)MnO(3):Co(3)O(4) composite films than the La(0.67)Ca(0.33)MnO(3):NiO films, which can be attributed to the antiferromagnetic properties of the Co(3)O(4) phase. The solution-processed composite films show enhanced low-field magnetoresistance effect which are crucial in practical applications. We expect our polymer-assisted deposited films paving the pathway in the field of hole-doped perovskites with their intrinsic colossal magnetoresistance

Abnormal Degree Centrality Associated With Cognitive Dysfunctions in Early Bipolar Disorder

Delayed diagnosis of bipolar disorder (BD) is common. However, diagnostic validity may be enhanced using reliable neurobiological markers for BD. Degree centrality (DC) is one such potential marker that enables researchers to visualize neuronal network abnormalities in the early stages of some neuropsychiatric disorders. In the present study, we measured resting-state DC abnormalities and cognitive deficits in order to identify early neurobiological markers for BD. We recruited 23 patients with BD who had recently experienced manic episodes (duration of illness &lt;2 years) and 46 matched healthy controls. Our findings indicated that patients with BD exhibited DC abnormalities in frontal areas, temporal areas, the right postcentral gyrus, and the posterior lobe of the cerebellum. Moreover, correlation analysis revealed that psychomotor speed indicators were associated with DC in the superior temporal and inferior temporal gyri, while attention indicators were associated with DC in the inferior temporal gyrus, in patients with early BD. Our findings suggest that DC abnormalities in neural emotion regulation circuits are present in patients with early BD, and that correlations between attention/psychomotor speed deficits and temporal DC abnormalities may represent early markers of BD