The predictive value of miR-377 and phospholipase A2 in the early diagnosis of diabetic kidney disease and their relationship with inflammatory factors.

OBJECTIVE: The value of novel biomarkers for DKD has received increasing attention, and there is an urgent need for novel biomarkers with sensitivity, specificity and ability to detect kidney damage.miR-377 regulates many basic biological processes, plays a key role in tumor cell proliferation, migration and inflammation, and can also increase the expression of matrix proteins and fibronectin, leading to renal tubulointerstitial inflammation and renal fibrosis. Lipoprotein-associated phospholipase A2, as an inflammatory marker, is involved in the pathological process of microalbuminuria production and renal function decline, and is a predictive factor of microalbuminuria production and renal function decline, and can be used as an indicator to evaluate the progression of DKD.The aim of this study was to investigate the effects of miR-377 and phospholipase A2 on the development of diabetic kidney disease through regulation of inflammatory factors and the mechanism of action. METHODS: 80 diabetic patients were divided into two groups according to urinary albumin-to-creatinine ratio (UACR): diabetic normal proteinuria group (n = 42) and diabetic proteinuria group (n = 38). Forty-three healthy people were selected as the normal control group. The serum levels of TGF-ß, IL-6, and IL-18 were measured by ELISA, miR-377 was detected by qPCR, and the serum levels of phospholipase A2 were detected by electrochemiluminescence. Analyze the correlation of study group indicators, ROC curve was used to evaluate the diagnostic efficacy of miR-377 and phospholipase A2 in diabetic kidney disease. RESULTS: The average levels of serum TGF-ß, IL-6, IL-18, miR-377 and phospholipase A2 in diabetic proteinuria group were significantly higher than those in normal control group and diabetic proteinuria normal group(P < 0.05). miR-377, phospholipase A2 were significantly correlated with inflammatory factors such as glomerular filtration rate and TGF-ß. miR-377 and phospholipase A2 are independent predictors of diabetic kidney disease. The area under the curve of miR-377 and phospholipase A2 in the normal diabetic proteinuria group and the diabetic proteinuria group were 0.731 and 0.744, respectively. CONCLUSION: miR-377 and phospholipase A2 have good diagnostic efficiency for the early diagnosis of diabetic kidney disease. They can be used as early biomarkers.miR-377 and phospholipase A2 were positively correlated with inflammatory factors and involved in the occurrence and development of diabetic kidney disease.

Detection of serum HE4 levels contributes to the diagnosis of lung cancer.

Lung cancer (LC) is the most frequently diagnosed cancer and is the leading cause of cancer-associated death. Serum markers that exhibit high sensitivity and specificity for LC may assist in the diagnosis and prognosis of LC. The banked serum samples from 599 individuals, including 201 healthy controls, 124 patients with benign lung diseases, and 274 LC cases, were used. The serum concentrations of biomarkers were determined by electrochemiluminescence immunoassay and chemiluminescence immunoassay. The results showed that the serum human epididymis secretory protein 4 (HE4) levels in the LC group were significantly higher than in the healthy and benign lung disease groups. The serum levels of HE4, NSE, and CYFRA21-1 were significantly higher in patients with LC compared to those in the benign lung disease group. The area under the area under the curve (AUC) of HE4 for discriminating LC from healthy controls was 0.851 (95% CI, 0.818-0.884) and 0.739 (95% CI, 0.695-0.783), 0.747 (95% CI, 0.704-0.790), 0.626 (95% CI, 0.577-0.676), and 0.700 (95% CI, 0.653-0.747) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 combined with NSE, CYFRA21-1, SCC, and proGRP for cancer diagnosis was 0.896 (95% CI, 0.868-0.923). In early LC, the AUC value of HE4 for discriminating early LC from healthy controls was 0.802 (95% CI, 0.758-0.845), 0.728 (95% CI, 0.679-0.778), 0.699 (95% CI, 0.646-0.752), 0.605 (95% CI, 0.548-0.662), and 0.685 (95% CI, 0.630-0.739) for NSE, CYFRA21-1, SCC, and ProGRP, respectively. The AUC value of the combination of serum HE4 with NSE, CYFRA21-1, SCC, and proGRP for early LC was 0.867 (95% CI, 0.831-0.903). Serum HE4 is a promising LC biomarker, particularly for early-stage LC. Measuring serum HE4 levels may improve the diagnostic efficiency of LC.

Serum 25-Hydroxyvitamin D Levels in Type 2 Diabetes Patients in North China: Seasonality and the Association between Vitamin D Status and Glycosylated Hemoglobin Levels.

Background and Aims: Previous studies have reported a correlation between vitamin D levels and seasonality in healthy populations. However, there are few studies on the seasonal variation in vitamin D levels and its relationship with glycosylated hemoglobin (HbA1c) in patients with type 2 diabetes mellitus (T2DM). The objective of this study was to investigate seasonal changes in serum 25-hydroxyvitamin D [25(OH)D] levels and the associations between these vitamin D concentrations and HbA1c levels in T2DM patients in Hebei, China. Methods: A cross-sectional study of 1,074 individuals with T2DM was conducted from May 2018 to September 2021. Levels of 25(OH)D in these patients were assessed based on both sex and season, and relevant clinical or laboratory variables that could impact vitamin D status were also considered. Results: In the T2DM patient cohort, the mean blood 25(OH)D levels were 17.05 ng/mL. A total of 698 patients (65.0%) had insufficient serum 25(OH)D levels. The vitamin D deficiency rates were significantly higher in the winter and spring compared to the autumn (P < 0.05), indicating that seasonal fluctuations can have a significant impact on 25(OH)D levels. The levels of vitamin D inadequacy were highest in the winter (74%), and females were more likely than males to be deficient (73.4% vs. 59.5%, P < 0.001). In comparison to the winter and spring, both males and females showed higher 25(OH)D levels in the summer (P < 0.001). HbA1c levels were 8.9% higher in those with vitamin D deficiencies than in nondeficient patients (P < 0.001). HbA1c and vitamin D levels were negatively correlated (r = -0.119, P < 0.001). Conclusion: Vitamin D deficiencies are particularly prevalent among T2DM patients in Hebei, China, with exceptionally high rates in the winter and spring. Female T2DM patients were at an elevated risk of vitamin D deficiency, and vitamin D levels were negatively correlated with HbA1c.

Relationship Between Estimated Glucose Disposal Rate and Type 2 Diabetic Retinopathy.

Purpose: To investigate the association between diabetic retinopathy (DR), DR intensity, and estimated glucose disposal rate (eGDR) in individuals with type 2 diabetes mellitus (T2DM). Patients and Methods: This study comprised 1762 T2DM patients who were admitted between January and December, 2021. Overall, the DR was identified in 430 patients. Based on the eGDR, the participants were divided into four study groups. One-way analysis of variance was used to compare the groups. The correlations between eGDR and DR risk, eGDR, and DR severity were analyzed using regression analysis. Furthermore, these relationships were analyzed in different sex groups. Results: Patients with T2DM had a 19.75% (348/1762) DR detection rate, whereas those with DR had a 22.41% (78/348) proliferative DR detection rate. The DR group had substantially reduced levels of eGDR compared with the non-DR group. Multivariate logistic regression analysis demonstrated that reduced eGDR was an independent risk factor for DR, after adjusting for confounding variables. eGDR correlated significantly with proliferative DR in women but not in men. Conclusion: In Chinese individuals with T2DM, lower eGDR was independently associated with a higher risk of DR.

Serum Cortistatin Level in Type 2 Diabetes Mellitus and Its Relationship with Nonalcoholic Fatty Liver Disease.

Purpose: To evaluate serum cortistatin (CST) levels in type 2 diabetes mellitus (T2DM) patients with or without non-alcoholic fatty liver disease (NAFLD) and to examine the relationship between CST and NAFLD. Methods: A total of 90 T2DM patients, which included 56 NAFLD patients (referred to as DM+NAFLD group) and 34 patients without NAFLD (DM-only group), and 83 non-diabetes individuals that included 39 NAFLD patients (NAFLD-only group) and 44 without NAFLD that acted as the normal-control group (NC group). The differences in the serum CST levels between the groups were compared, and the correlations between CST and other variables were calculated by applying both correlational analysis and multiple linear regression analysis. Results: The mean serum CST levels were significantly lower in the DM+NAFLD and DM groups than in the NC group (P < 0.05). In addition, the CST levels were lower in the DM group relative to that in the NAFLD group (P < 0.05). However, no statistical difference was noted in the serum CST between diabetic patients with and without NAFLD (P > 0.05). Similarly, in the non-diabetic group, the serum CST level was not significantly different between individuals with and without NAFLD (P > 0.05). Furthermore, the serum CST levels were negatively associated with the levels of total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), fasting plasma glucose (FPG), homeostasis model assessment-insulin resistance (HOMA-IR), and insulin cell function index (HOMA-ß). Conversely, the serum CST levels were positively associated with high-density lipoprotein cholesterol (HDL-C). The data obtained through multiple linear regression implied that LDL-C and HOMA-ß, but not HOMA-IR, were closely related to serum CST levels. Conclusion: T2DM was related to decreased serum CST. However, serum CST was correlated with HOMA-ß in T2DM patients, while HOMA-IR was not. There was no correlation between CST and NAFLD.

Association between hemoglobin glycation index and non-alcoholic fatty liver disease.

Objective: The hemoglobin glycation index (HGI) reflects biological variability in hemoglobin A1c. Even so, studies on the relationship between HGI and non-alcoholic fatty liver disease (NAFLD) are limited. Therefore, this study aimed to explore the relationship between HGI and NAFLD. In addition, the study also aimed to provide new methods to identify patients with a high risk for the development of NAFLD. Methods: This was a retrospective study based on physical examination data from Japan. Patients were divided into quartiles (Q1-Q4) according to their HGI level; the lowest quartile (Q1) was used as the reference group. Patents were also classified into two subgroups based on the presence or absence of NAFLD. Baseline characteristics between the groups were compared. Multivariate logistic regression analysis was used to investigate the association between the HGI and NAFLD. A mediation analysis examined the mediation relationship between HGI and NAFLD. Subgroup analyses were performed to the reliability of the results. Results: A total of 14280 patients were eligible for inclusion in this study; 2515 had NAFLD. Patients in the NAFLD group had higher levels of HGI than patients in the non-NAFLD group. Increases in HGI correlated with an increased risk of NAFLD. After adjusting for confounding factors, the multivariate logistic regression analysis revealed that HGI was positively related to the prevalence of NAFLD. In addition, mediation analysis showed that body mass index (BMI) partly mediated the indirect impact of HGI on NAFLD preference. Subgroup analyses were performed according to age, sex, smoking status, and waist circumference. Our results indicated that HGI significantly correlated with NAFLD in patients with one of the following factors: age ≤60 years, BMI >28 kg/m2, female sex, a history of smoking, and abdominal obesity. Conclusions: HGI was an independent risk factor for NAFLD, and BMI partly mediated the association between HGI and NAFLD.

Circulating Bone Morphogenetic Protein-9 is Decreased in Patients with Type 2 Diabetes and Non-Alcoholic Fatty Liver Disease.

Objective: We aimed to examine the association between bone morphogenetic protein-9 (BMP-9) and type 2 diabetes mellitus (T2DM) in conjunction with non-alcoholic fatty liver disease (NAFLD) and insulin resistance (IR) and to identify evidence supporting the potential role of BMP-9 in the clinical prevention and treatment of T2DM in conjunction with NAFLD. Methods: One hundred and twenty subjects were included in this study. We sorted all of the subjects into four groups of equal size (n=30 each). A trained expert assessed the height, weight, systolic blood pressure (SBP), and diastolic blood pressure (DBP) of the subjects and computed the body mass index (BMI). All subjects had their fasting blood glucose (FBG), fasting insulin (FINS), serum BMP-9, and biochemical indices assessed. Results: Significant variations were observed in BMI, SBP, DBP, ALT, TC, TG, HDL-C, LDL-C, ApoB, FBG, FINS, HOMA-IR, and serum BMP-9 among the four groups (P<0.05). The level of serum BMP-9 was positively correlated with HDL-C, while the level of serum BMP-9 was negatively correlated with BMI, SBP, DBP, ALT, TC, TG, LDL-C, FBG, FINS, and HOMA-IR. Multiple stepwise regression analyses revealed that FINS, LDL-C, HDL-C, and BMI were independent factors impacting serum BMP-9 levels (P<0.05). Logistic regression analyses revealed that BMP-9 was a protective factor for T2DM paired with NAFLD, while HOMA-IR was a risk factor. Conclusion: Serum BMP-9 levels are significantly lower in the T2DM+NAFLD group when compared to other groups, and BMP-9 is an independent risk factor for T2DM paired with NAFLD.

Comprehensive analysis on expression and biological role of miR-224 in hepatocellular carcinoma / 中国肿瘤生物治疗杂志

@#[Abstract] Objective: To analyze the expression level of miR-224 in cancer tissues and plasma of hepatocellular carcinoma (HCC) patients, and its correlation with clinicopathological characteristics, diagnosis and prognosis of HCC patients, and to further analyze its mechanism of action in the occurrence and development of liver cancer through bioinformatics analysis and in vitro experiments. Methods: The expression level of miR-224 in HCC tissues and normal tissues was analyzed using large sample data from Gene Expression Omnibus (GEO). qPCR method was used to verify the expression level of miR-224 in the tumor tissues and corresponding adjacent tissues that surgically resected from 80 HCC patients in Hebei Provincial People ’s Hospital from January 2017 to January 2020; in addition, the miR-224 level was also examined in plasma samples from 30 HCC patients. The Kaplan-Meier plotter database was used to analyze the correlation between the miR-224 expression and the overall survival time of HCC patients. The biological processes and signal pathways involving miR-224 were analyzed using bioinformatics tools. Hepatocellular carcinoma HepG2 cells were transfected with miR-224 inhibitor, and then Clone formation experiment, Transwell chamber experiment, qPCR and WB methods were used to detect the effect of miR-224 knockdown on the proliferation and invasion of HepG2 cells and the expression level of EMT-related molecules. Results: The results of GEO database analysis showed that the expression level of miR-224 in HCC tissues was significantly higher than that in normal tissues. The results of clinical specimen verification showed that the expression level of miR-224 in the tumor tissues and plasma of HCC patients was significantly higher than that in the corresponding adjacent tissues and plasma from healthy controls (all P<0.01). The expression level of miR-224 was significantly correlated with the TNM stage, lymph node metastasis status and tumor size of HCC patients (P<0.05 or P<0.01). ROC analysis indicated that miR-224 showed a prominent diagnostic value in liver cancer, and the increased expression level of miR-224 was significantly related to the poor prognosis of HCC patients (P<0.05). Functional enrichment analysis revealed that miR-224 was mainly involved in the mTOR signaling pathway, AGE-RAGE signaling pathway, Rap1 signaling pathway, Ras signaling pathway, ErbB signaling pathway, HIF-1 signaling pathway and p53 signaling pathway and other signaling pathways related to tumor occurrence and development. Knockdown of miR-224 could significantly inhibit the colony formation and invasion of HepG2 cells and affect the expression of EMT-related markers (P<0.05 or P<0.01). Conclusion: miR-224 is highly expressed in HCC tissues and plasma and is significantly related to the poor prognosis of HCC patients. Knockdown of miR-224 expression can inhibit the colony formation, invasion and EMT process of liver cancer HepG2 cells.

Potential injurious effects of the fine particulate PM2.5 on the progression of atherosclerosis in apoE-deficient mice by activating platelets and leukocytes.

INTRODUCTION: Exposure to the fine particulate matter PM2.5 is strongly associated with atherosclerotic diseases, creating considerable public concern. Nevertheless, the mechanisms have not been fully elucidated. We exposed atherosclerosis-prone apoE-deficient mice to PM2.5 to begin investigating these mechanisms. MATERIAL AND METHODS: Thirty-two 8-week-old male apoE-/- mice were divided to two groups fed with high-fat diet: a control group instilled with 0.9% saline, and an experimental group instilled with PM2.5 (30 mg/kg/day) for 8 weeks. We measured PM2.5 in whole blood by the ICP-MS method, and lipids and inflammatory factors by standard methods. The whole descending arteries were stained with oil red O; Aortic roots were stained with Movat, Sirius Red and immunohistochemical stains for pathological analysis; Brachiocephalic arteries for scanning electron microscopy, the descending arteries for Q-PCR. Echocardiography was used to evaluate cardiac function. RESULTS: In PM2.5 group, we observed elevated heavy metal components, consistent with higher amounts of platelets in total blood. The PM2.5 group also had elevated serum inflammatory factor levels. Finally, the PM2.5 group showed larger atherosclerotic plaques (p = 0.0231), higher numbers of lesion macrophages (p = 0.0183), greater injury to endothelial layers with greater adherence of platelets and leukocytes, elevated inflammatory factor levels, the NAD(P)H oxidase subunits p22phox and p47phox (p = 0.0079 and p = 0.0294), the M1/M2 associated markers IL-6, TNF-α (p = 0.0291, p = 0.0286), iNOS, IL-12 (p = 0.0122 and p = 0.0280) and arginase-1, and CD206 (p = 0.0216 and p = 0.0317). CONCLUSIONS: PM2.5 exposure activated circulating leukocytes, platelets and associated inflammatory factors, contributing to the progression of atherosclerosis in apoE-/- mice.

Polycystic Ovary Syndrome is Associated with Elevated Periostin Levels.

PURPOSE: Periostin is a secreted extracellular matrix protein that is strongly associated with triglyceride metabolism, chronic inflammation, and insulin resistance. Growing evidence suggests that there is a link between periostin and ovarian function. Our aim was to ascertain whether circulating periostin levels are altered in women with polycystic ovary syndrome (PCOS) and to further explore the relationship between periostin and glucose metabolism disorder in PCOS patients. METHODS: In total, 50 women with PCOS and 30 age-matched controls without PCOS were recruited for this cross-sectional study. Periostin levels were measured using ELISA as well. RESULTS: Circulating periostin levels were significantly elevated in PCOS women compared with controls [4206.75(222.00, 4815.25) vs. 430.75(142. 13, 730.86) ng/ml, P=0. 005]. Spearman's correlation analysis showed that serum periostin levels had a positive correlation with body mass index (BMI), uric acid, homeostasis model assessment of insulin resistance (HOMA-IR), high-sensitive C reactive protein (hs-CRP), and a negative correlation with insulin sensitivity index (ISI). Logistic regression models revealed that PCOS was correlated with waist to hip ratio (WHR), fasting blood glucose (FBG), and periostin levels. In addition, multivariate linear regression analyses showed that FBG, HOMA-IR, and the lipid accumulation index (LAP) were independent factors influencing serum periostin levels. CONCLUSION: PCOS is associated with elevated levels of periostin.

Clinical significance of fucosylated GP73 in the differential diagnosis of hepatocellular carcinoma.

OBJECTIVE:: To investigate the clinical value of fucosylated GP73 (Fuc-GP73) levels for differential diagnosis of hepatocellular carcinoma from other liver diseases. METHODS:: Serum specimens were collected from 50 patients with hepatocellular carcinoma, 60 patients with other digestive system diseases (ODSD), and 40 normal controls. Lectin affinity chromatography column combining with the enzyme-linked immunosorbent assay (ELISA) using the ELISA index was utilized to measure the level of Fuc-GP73. By receiver operating characteristic (ROC) curve analysis its sensitivity and specificity were used to evaluate the diagnostic significance of Fuc-GP73 in hepatocellular carcinoma. RESULTS:: The median serum Fuc-GP73 level of hepatocellular carcinoma (20.4 µg/L) was much higher than that of ODSD patients (1.8 µg/L) and the normal controls group (0.3 µg/L), significantly ( P <0.01). There was no significant correlation between serum Fuc-GP73 level and sex, age, and tumor size in the hepatocellular carcinoma group ( P > 0.05); however, it was related to tumor, node, metastasis stage and lymph node metastasis ( P <0.05). The area under the ROC curve (AUC) of Fuc-GP73 to detect hepatocellular carcinoma alone was 0.885; with the prespecified specificity of 95%, the sensitivity and the cutoff value were 82% and 3.1 µg/L. In addition, the combined test of Fuc-GP73 with other biomarkers can improve the clinical diagnostic efficiency; the AUC can reach to 0.983; and with the prespecified specificity of 95% its sensitivity increased to 94%. CONCLUSION:: Fuc-GP73 can act as a superior glycobiomarker for the differential diagnosis of hepatocellular carcinoma; its combined detection with other biomarkers can improve diagnostic accuracy.