Retinol binding protein 4 correlates with and is an early predictor of carotid atherosclerosis in type 2 diabetes mellitus patients

The association of retinol binding protein 4 （RBP4） with atherosclerosis of the carotid artery in type 2 diabetes mellitus （T2DM） remains undefined. We aimed to investigate the correlation of RBP4 expression with atherosclerosis of the carotid artery in T2DM. A total of 1,076 subjects were investigated for intima-media thickness of the bilateral common carotid arteries, and they were divided into three groups： in group Ⅰ, patients had normal neck vascular ultra- sound, in group Ⅱ, intimal carotid artery media thickness was equal to or more than 1 mm, and in group Ⅲ, carotid artery plaque was present. Height, weight, blood pressure （BP）, fasting plasma glucose （FPG）, hemoglobin Alc （HbA1c）, total cholesterol （TC）, triglyceride （TG）, low-density lipoprotein cholesterol （LDL-C）, high-density lipopro- tein cholesterol （HDL-C）, apolipoprotein A-1 （apoA-1）, apolipoprotein B （apoB） and lipoprotein （a） [Lp（a）] were determined by routine laboratory methods. RBP4 and high sensitivity C reactive protein （HsCRP） were measured by an enzyme-linked immuno-sorbent assay, and insulin concentration was measured by an electrochemiluminescence sandwich immunoassay. Duration of diabetes, waist and BP, FPG, HbAlc, TG, TC, LDL-C, APOB, Lp（a）, HsCRP, RBP4 and homeostasis model assessment insulin resistance index （HOMA-IR） were significantly lower in group I than in the other two groups （P〈0.01, P〈0.01）. Plasma levels of HbAlc, RBP4, LDL-C, TC, HOMA-IR, HsCRP and Lp（a）, waist and BP were significantly increased in group III than in group II （P〈0.01）. Multivariate logistic regression analysis showed that there were seven factors associated with the occurrence of carotid artery atherosclero- sis and its risks in descending order were： high LDL-C, high waist, high HsCRP, duration of diabetes, high HOMA-IR, HbAlc and high RBP4. Our finding supported that RBP4 was positively correlated with carotid atherosclerosis in patients with T2DM and could be used as an early predictor of cardiovascular disease.

Identification of immune feature genes and intercellular profiles in diabetic cardiomyopathy

BACKGROUND Diabetic cardiomyopathy(DCM)is a multifaceted cardiovascular disorder in which immune dysregulation plays a pivotal role.The immunological molecular mechanisms underlying DCM are poorly understood.AIM To examine the immunological molecular mechanisms of DCM and construct diagnostic and prognostic models of DCM based on immune feature genes(IFGs).METHODS Weighted gene co-expression network analysis along with machine learning methods were employed to pinpoint IFGs within bulk RNA sequencing(RNA-seq)datasets.Single-sample gene set enrichment analysis(ssGSEA)facilitated the analysis of immune cell infiltration.Diagnostic and prognostic models for these IFGs were developed and assessed in a validation cohort.Gene expression in the DCM cell model was confirmed through real time-quantitative polymerase chain reaction and western blotting techniques.Additionally,single-cell RNA-seq data provided deeper insights into cellular profiles and interactions.RESULTS The overlap between 69 differentially expressed genes in the DCM-associated module and 2483 immune genes yielded 7 differentially expressed immune-related genes.Four IFGs showed good diagnostic and prognostic values in the validation cohort:Proenkephalin(Penk)and retinol binding protein 7(Rbp7),which were highly expressed,and glucagon receptor and inhibin subunit alpha,which were expressed at low levels in DCM patients(all area under the curves>0.9).SsGSEA revealed that IFG-related immune cell infiltration primarily involved type 2 T helper cells.High expression of Penk(P<0.0001)and Rbp7(P=0.001)was detected in cardiomyocytes and interstitial cells and further confirmed in a DCM cell model in vitro.Intercellular events and communication analysis revealed abnormal cellular phenotype transformation and signaling communication in DCM,especially between mesenchymal cells and macrophages.CONCLUSION The present study identified Penk and Rbp7 as potential DCM biomarkers,and aberrant mesenchymal-immune cell phenotype communication may be an important aspect of DCM pathogenesis.

Anti-diabetic effects of cinnamaldehyde and berberine and their impacts on retinol-binding protein 4 expression in rats with type 2 diabetes mellitus

Background Retinol binding protein 4 （RBP4）, as an adipocyte secreted cytokine, was recently found to be inversely correlated with expression of glucose transporter 4 （GLUT4） in insulin resistance （IR） state and to have an intimate relationship with IR and type 2 diabetes mellitus （T2DM）. The present study aimed to evaluate the anti-diabetic efficacy of cinnamaldehyde （Cin）, berberine （Ber）, and metformin （Met） as well as their impacts on the RBP4-GLUT4 system. Methods Rat models of T2DM were established by combination of intraperitoneal injection of low-dose streptozotocin and high fat diet induction. Rats were divided into five groups： the control group, the diabetes group, the diabetes＋Ber group, the diabetes＋Cin group, and the diabetes＋Met group. Western blotting was used to detect the serum or tissue RBP4 and GLUT4 protein levels. Results After treatment for four weeks, both Cin and Ber displayed significant hypolipidemic, hypoglycemic, and insulin sensitizing functions （P 〈0.01） compared with the control group. Their effects on lowering fasting plasma glucose （FPG）, low density lipoprotein-cholesterol （LDL-C） and homeostasis model assessment of insulin resistance （HOMA-IR） seem even better than that of Met. Cin and Ber markedly lowered serum RBP4 levels and up-regulated the expression of tissue GLUT4 protein, and Cin seemed more notable in affecting these two proteins. Conclusions Both Cin and Ber display an exciting anti-diabetic efficacy in this study and may be of great value for the treatment of type 2 diabetes. Their mechanisms involve the RBP4-GLUT4 system, during which the serum RBP4 levels are lowered and the expression of tissue GLUT4 protein is up-regulated.

Research progress on markers of urine tubular damage in idiopathic membranous nephropathy

Idiopathic membranous nephropathy is a common primary glomerular disease.Recently,it has been found that the progression and prognosis of glomerular diseases are not only related to the glomeruli itself,but also to the severity of renal tubular injury.Although blood creatinine and urinary protein are recognized biomarkers,they appear late,are insensitive,lack specificity,and are difficult to respond to IMN conditions in a timely and accurate manner.Markers such as N-acetyl-β-D-glucosaminidase,kidney injury molecule 1,neutrophil gelatinase-associated lipoprotein in urine can dynamically reflect the progress of kidney injury in the early stage,and are detected as noninvasive,so It has been applied in IMN,but such research is lacking,and the scope needs to be further expanded and discussed in depth.

Research on the changes and significance of serum RBP4 level in patients with senior coronary heart disease accompanying diabetes mellitus

Objective:To explore the significance of serum Retinol binding protein 4(RBP4)and its relationship with coronary artery lesion in patients with senior coronary heart disease accompanying T2DM by determining the level of serum RBP4 and Gensini score.Methods:30 cases of patients who were 60 years old above with coronary heart disease accompanying T2DM were selected and included in the experimental group,and 30 cases of patients of 60 years old above with coronary heart disease alone were included in the control group.Both groups of patients were given CAG examinations.In addition,Gensini score was calculated according to different degrees and parts of coronary artery lesion.It was required to record each patient’s age,gender,fasting blood glucose(FPG),triglycerides(TG),total cholesterol(TC),high density lipoprotein cholesterol(HDL-C),low density lipoprotein cholesterol(LDL-C),glycated hemoglobin(HbA1c)and other laboratory examination indexes.ELISA was used to detect the level of serum RBP4 in each group,and statistical analysis was performed to the data in each group.Results:(1)RBP4 level,GS score,FPG and LDL-C in the experimental group were all higher than those in the control group,and the difference was of statistical significance(p<.05).There was no statistically significant difference in age,gender,TC,TG and HDL-C between two groups.(2)RBP4 was positively correlated to FPG and HbA1c.(3)In patients with senior coronary heart disease accompanying diabetes mellitus,HbA1c was positively correlated to GS score,RBP4 and FPG.(4)RBP4 was a risk factor for coronary artery stenosis in patients with senior coronary heart disease accompanying diabetes mellitus.Conclusions:The level of serum RBP4 in patients with senior coronary heart disease accompanying diabetes mellitus is higher than that in patients with coronary heart disease alone,with a deeper degree of coronary artery lesion.The level of serum RBP4 is increased with the degree of lesion deepened in patients with senior coronary heart disease,suggesting that the level of serum RBP4 is expected to be an early predictor of coronary artery lesion for patients with senior coronary heart disease.

Serum Levels of RBP4 Might Not Be Determined by Diabetes Mellitus but by Kidney Function and Renal Replacement Therapy

It has been reported that retinol-binding protein 4(RBP4) is associated to adiposity,insulin resistance,and type 2 diabetes.Meanwhile,circulating RBP4 levels are also affected by renal function.The aim of the present study is to investigate whether serum levels of RBP4 are primarily associated with different stages of chronic kidney disease(CKD) or type 2 diabetes,if there is more potential relevance between RBP4 and renal replacement therapy.The serum levels of RBP4 were assessed by commercial competitive enzyme-linked immunosorbent assay(ELISA)kit in 212 patients with the CKD stages 1—5 and in 24 healthy controls,while its correlation with clinical and metabolic parameters was analyzed.The serum level of RBP4 had a strong correlation with estimated glomerular filtration rate(e GFR)(P < 0.001).Stratified by e GFR and treatment,no more differences in RBP4 serum concentration were detected between type 2 diabetic and non-diabetic subjects [CKD stages 1—5,non-dialysis(ND),hemodialysis(HD) and peritoneal dialysis(PD);P > 0.05 for all].The elevation of RBP4 become higher in HD than in PD and ND in CKD5 patients(P = 0.008 and P = 0.04,respectively),while there was no significant difference between PD and ND groups.Multivariate linear regression analysis demonstrated three independent predictors of e GFR(β =-0.676,P < 0.001),C-reactive protein(CRP)(β =-0.573,P < 0.001) and creatine(β = 0.509,P = 0.024) in the study population.The study results demonstrated that the serum level of RBP4 was negatively related to the e GFR,whether diabetes mellitus(DM) affected the blood concentration of RBP4 or not.And the serum level of RBP4 exhibited significant difference in different renal replacement therapies.

Study on Effect of Baoyuan Qiangshen (保元强肾) Capsule No. Ⅱ on Tubular Interstitial Injury in Chronic Renal Failure Patients

Objective: To explore the protective effect of Baoyuan Qiangshen Capsule No. Ⅱ (BYQS) and its mechanism in treating chronic renal failure (CRF). Methods: Sixty CRF patients were divided into 2 groups randomly, the treated group used BYQS combined with Lotensin and the control group administered with essential amino acid combined with Lotensin. Changes of renal functions and tubular labelled proteins were observed. Results: The markedly effective rate and total effective rate of the treated group were 63.3% and 93.3% respectively, and those of the control group were 30.0% and 56.7% respectively, the effect of the treated group was obviously better than that of the control group ( P <0.01). In the treated group after medication, blood urea nitrogen, serum creatinine and clearance rate of creatinine were improved significantly ( P <0.01), while Tamm Horfau protein increased significantly ( P <0.01). Conclusion: BYQS could alleviate tubular interstitial injury significantly so as to improve the renal function and enhance the effective rate in treating CRF.