scholarly journals Expression Profiling and Clinical Significance of Plasma MicroRNAs in Diabetic Nephropathy

2019 ◽  
Vol 2019 ◽  
pp. 1-12 ◽  
Author(s):  
Jianqin Wang ◽  
Gouqin Wang ◽  
Yaojun Liang ◽  
Xiaochun Zhou
Keyword(s):  
Diabetic Nephropathy ◽  
Clinical Significance ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Clinicopathological Parameters ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Expression Levels ◽  
Plasma Mirnas

Aims. MicroRNAs (miRNAs) stably and abundantly exist in body fluids and have been considered as novel and noninvasive biomarkers for several diseases. The present study is aimed at investigating the expression profiling and clinical significance of plasma miRNAs in the pathogenesis and progression of diabetic nephropathy (DN). Methods. Plasma samples were obtained from 66 DN patients (36 had microalbuminuria and 30 had macroalbuminuria), 36 diabetic patients with normoalbuminuria, and 40 healthy controls. The plasma miRNA profiles were obtained by miRNA low-density array chip and validated by quantitative real-time polymerase chain reaction. The correlations between the differential expression of plasma miRNAs and clinicopathological parameters were explored. Results. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 were found to be differentially expressed in plasma samples among these three groups: diabetic patients with microalbuminuria, diabetic patients with normoalbuminuria, and healthy controls (P<0.05). The expression levels of miR-150-5p and miR-155-5p in patients with macroalbuminuria were 2.3-fold (P=0.001) and 1.5-fold (P=0.033) higher than patients with microalbuminuria, respectively. However, the expression levels of miR-30e, miR-3196, miR-320, and let-7a-5p were not significantly different between these two groups (P>0.05). Furthermore, plasma miR-150-5p (P=0.016, r = -0.460) and miR-155-5p (P=0.014, r = -0.467) were negatively correlated with the albuminuria excretion rate, while plasma miR-150-5p (P=0.01, r = 0.318) and miR-155-5p (P=0.030, r=0.271) were positively correlated with the estimated glomerular filtration rate. Conclusion. miR-150-5p, miR-155-5p, miR-30e, miR-320e, and miR-3196 are potentially new diagnostic biomarkers for early DN. miR-150-5p and miR-155-5p may be involved in the pathogenesis and progression of DN. Further research is required to verify these findings and clarify the specific molecular mechanisms.

Elevated Concentrations of Soluble Adhesion Molecules and Large Platelets in Diabetic Patients: Are They Markers of Vascular Disease and Diabetic Nephropathy?

2007 ◽  
Vol 13 (4) ◽  
pp. 391-397 ◽  
Author(s):  
N. Bavbek ◽  
A. Kargili ◽  
O. Kaftan ◽  
F. Karakurt ◽  
A. Kosar ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Nephropathy ◽  
Mean Platelet Volume ◽  
Plasma Levels ◽  
Platelet Reactivity ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Platelet Volume ◽  
Soluble Adhesion Molecules ◽  
Protein Excretion

P-selectin, E-selectin, and mean platelet volume are markers associated with platelet reactivity that have been demonstrated to be increased in diabetes. We were particularly interested to see if there was a difference in mean platelet volume and selectins between diabetics and nondiabetics, and in diabetics with and without nephropathy, and whether there was a correlation between mean platelet volume and selectins. One hundred and fourteen diabetic patients and 31 healthy controls were investigated. Plasma levels of P-selectin and E-selectin were higher in the diabetic group than in controls ( P = .001 and P = .007, respectively) and in diabetic patients with proteinuria than in patients without proteinuria ( P = .002 and P = .004, respectively). Protein excretion was lower in patients with low mean platelet volume values ( P = .004). In conclusion, elevated platelet volume and high selectin values may play a role in the development of vasculopathies and complications in diabetes mellitus. Further studies are needed to prove these results.

scholarly journals Circulating miR-99a-5p Expression in Plasma: A Potential Biomarker for Early Diagnosis of Breast Cancer

2020 ◽  
Vol 21 (19) ◽  
pp. 7427
Author(s):  
Iris Garrido-Cano ◽  
Vera Constâncio ◽  
Anna Adam-Artigues ◽  
Ana Lameirinhas ◽  
Soraya Simón ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Healthy Controls ◽  
Plasma Samples ◽  
Breast Cancer Patients ◽  
Expression Levels ◽  
Healthy Donors ◽  
Potential Biomarker ◽  
Cancer Tissues ◽  
Breast Tissues

MicroRNAs have emerged as new diagnostic and therapeutic biomarkers for breast cancer. Herein, we analysed miR-99a-5p expression levels in primary tumours and plasma of breast cancer patients to evaluate its usefulness as a minimally invasive diagnostic biomarker. MiR-99a-5p expression levels were determined by quantitative real-time PCR in three independent cohorts of patients: (I) Discovery cohort: breast cancer tissues (n = 103) and healthy breast tissues (n = 26); (II) Testing cohort: plasma samples from 105 patients and 98 healthy donors; (III) Validation cohort: plasma samples from 89 patients and 85 healthy donors. Our results demonstrated that miR-99a-5p was significantly downregulated in breast cancer tissues compared to healthy breast tissues. Conversely, miR-99a-5p levels were significantly higher in breast cancer patients than in healthy controls in plasma samples from both testing and validation cohorts, and ROC curve analysis revealed that miR-99a-5p has good diagnostic potential even to detect early breast cancer. In conclusion, miR-99a-5p’s deregulated expression distinguished healthy patients from breast cancer patients in two different types of samples (tissues and plasma). Interestingly, expression levels in plasma were significantly lower in healthy controls than in early-stage breast cancer patients. Our findings suggest circulating miR-99a-5p as a novel promising non-invasive biomarker for breast cancer detection.

scholarly journals Elevated Squamous Cell Carcinoma Antigen, Cytokeratin 19 Fragment, and Carcinoembryonic Antigen Levels in Diabetic Nephropathy

2017 ◽  
Vol 2017 ◽  
pp. 1-6 ◽  
Author(s):  
Jianzhong Chen ◽  
Feng Tao ◽  
Bin Zhang ◽  
Qingguang Chen ◽  
Yan Qiu ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Diabetic Nephropathy ◽  
Cell Carcinoma ◽  
Urinary Albumin Excretion ◽  
Urinary Albumin ◽  
Cytokeratin 19 ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Squamous Cell Carcinoma Antigen ◽  
Cytokeratin 19 Fragment

Objective. We aimed to explore whether squamous cell carcinoma antigen (SCC), cytokeratin 19 fragment (Cyfra21-1), neuron-specific enolase (NSE), and carcinoembryonic antigen (CEA) are elevated in diabetic nephropathy (DN) and the association between urinary albumin-to-creatinine ratio (UACR) and tumor markers in diabetic patients. Methods. Nondialysis patients with diabetes (n=261) and 90 healthy controls were enrolled. DN was defined as an UACR ≥ 30 mg/g in the absence of a urinary tract infection or other renal abnormalities. Results. Patients with DN had significantly higher serum SCC, Cyfra21-1, and CEA levels than those with normoalbuminuria and healthy controls. The rates of positive SCC, Cyfra21-1, and CEA significantly increased with increasing urinary albumin excretion (all P for trend < 0.001). In contrast, NSE was not affected by DN. SCC, Cyfra21-1, and CEA were significantly and positively correlated with UACR. In logistic regression, after multivariable adjustment, increased UACR was associated with increased odds ratio of elevated tumor marker levels (all P for trend < 0.05). Conclusions. Serum levels of SCC, Cyfra21-1, and CEA are markedly increased with increasing urinary albumin excretion, which affects the specificity for diagnosis for lung cancer. Appropriate interpretation of tumor markers in diabetic patients is mandatory to avoid unnecessary and even hazardous biopsies.

scholarly journals Expression and Clinical Significance of ILF2 in Gastric Cancer

2017 ◽  
Vol 2017 ◽  
pp. 1-9 ◽  
Author(s):  
Zi-huan Yin ◽  
Xing-wang Jiang ◽  
Wu-bing Shi ◽  
Qian-le Gui ◽  
Dong-feng Yu
Keyword(s):  
Gastric Cancer ◽  
Protein Expression ◽  
Clinical Significance ◽  
Disease Free Survival ◽  
High Expression ◽  
Clinicopathological Parameters ◽  
Rank Test ◽  
Depth Of Invasion ◽  
Clinical Prognosis ◽  
Expression Levels

The aim of this study is to investigate the expression levels and clinical significance of ILF2 in gastric cancer. The mRNA and protein expression levels of ILF2 were, respectively, examined by quantitative real-time PCR (qRT-PCR) and Western blot from 21 paired fresh frozen GC tissues and corresponding normal gastric tissues. In order to analyze the expression pattern of ILF2 in GC, 60 paired paraffin-embedded GC slides and corresponding normal gastric slides were detected by immunohistochemistry (IHC) assay. The correlation between ILF2 protein expression levels and clinicopathological parameters, overall survival (OS), disease-free survival (DFS), and clinical prognosis were analyzed by statistical methods. Significantly higher levels of ILF2 were detected in GC tissues compared with normal controls at both mRNA and protein level. High expression of ILF2 was tightly correlated with depth of invasion, lymph node metastasis, pathological stage, and histological differentiation. Log-rank test showed that high expression of ILF2 was positively associated with poor clinical prognosis. Multivariate analysis identified that ILF2 was an independent prognostic factor for OS and DFS. Our findings suggest that ILF2 may be a valuable biomarker and a novel potential prognosis predictor for GC patients.

scholarly journals PO-046 Gene expression profiling of peripheral blood mononuclear cells in young male trampoline athletes

2018 ◽  
Vol 1 (3) ◽  
Author(s):  
Li Gao ◽  
Yong Jie Yang ◽  
En Qi Li ◽  
Jia Ning Mao
Keyword(s):  
Gene Expression ◽  
Differentially Expressed Genes ◽  
Bone Health ◽  
Expression Profiling ◽  
Molecular Mechanisms ◽  
Interaction Network ◽  
Differentially Expressed ◽  
Signal Pathways ◽  
Healthy Controls ◽  
Mineral Density

Objective Evidence indicates that physical activity influence bone health. However, the molecular mechanisms mediating the beneficial adaptations to exercise are not well understood. The purpose of this study was to examine the differentially expressed genes in PBMC between athletes and healthy controls, and to analyze the important functional genes and signal pathways that cause increased bone mineral density in athletes, in order to further reveal the molecular mechanisms of exercise promoting bone health. Methods Five professional trampoline athletes and five age-matched untrained college students participated in this study. Used the human expression Microarray V4.0 expression profiling chip to detect differentially expressed genes in the two groups, and performed KEGG Pathway analysis and application of STRING database to construct protein interaction Network; Real-Time PCR technology was used to verify the expression of some differential genes.  Results Compared with healthy controls, there were significant improvement in lumbar spine bone mineral density, and 236 up-regulated as well as 265 down-regulated in serum samples of athletes. The differentially expressed genes involved 28 signal pathways, such as cell adhesion molecules. Protein interaction network showed that MYC was at the core node position. Real-time PCR results showed that the expression levels of CD40 and ITGα6 genes in the athletes were up-regulated compared with the healthy controls, the detection results were consistent with that of the gene chip. Conclusions The findings highlight that long-term high-intensity trampoline training could induce transcriptional changes in PBMC of the athletes. These data suggest that gene expression fingerprints can serve as a powerful research tool to design novel strategies for monitoring exercise. The findings of the study also provide support for the notion that PBMC could be used as a substitute to study exercise training that affects bone health.

scholarly journals Targeting POLE2 Creates a Novel Vulnerability in Renal Cell Carcinoma via Modulating Stanniocalcin 1

2021 ◽  
Vol 9 ◽  
Author(s):  
Chuanjie Zhang ◽  
Yan Shen ◽  
Lili Gao ◽  
Xiaojing Wang ◽  
Da Huang ◽  
...  
Keyword(s):  
Renal Cell Carcinoma ◽  
Western Blot ◽  
Cell Carcinoma ◽  
Renal Cell ◽  
Molecular Mechanisms ◽  
Cancer Genome ◽  
Clinicopathological Parameters ◽  
Expression Levels

ObjectiveThe aim of this study is to investigate the biological functions and the underlying mechanisms of DNA polymerase epsilon subunit 2 (POLE2) in renal cell carcinoma (RCC).MethodsThe datasets of POLE2 expression in The Cancer Genome Atlas Kidney Clear Cell Carcinoma (TCGA-KIRC) and International Cancer Genome Consortium (ICGC) databases was selected and the correlation between POLE2 and various clinicopathological parameters was analyzed. The POLE2 expression in RCC tissues was examined by immunohistochemistry. The POLE2 knockdown cell lines were constructed. In vitro and in vivo experiments were carried out to investigate the function of POLE2 on cellular biology of RCC, including cell viability assay, clone formation assay, flow cytometry, wound-healing assay, Transwell assay, qRT-PCR, Western blot, etc. Besides, microarray, co-immunoprecipitation, rescue experiment, and Western blot were used to investigate the molecular mechanisms underlying the functions of POLE2.ResultsPOLE2 was overexpressed in RCC tissues, and high expression of POLE2 was correlated with poor prognosis of RCC. Furthermore, knockdown of POLE2 significantly inhibited cell proliferation, migration, and facilitated apoptosis in vitro. In vivo experiments revealed that POLE2 attenuated RCC tumorigenesis and tumor growth. we also illuminated that stanniocalcin 1 (STC1) was a downstream gene of POLE2, which promoted the occurrence and development of RCC. Besides, knockdown of POLE2 significantly upregulated the expression levels of Bad and p21 while the expression levels of HSP70, IGF-I, IGF-II, survivin, and sTNF-R1 were significantly downregulated. Western blot analysis also showed that knockdown of POLE2 inhibited the expression levels of Cancer-related pathway proteins including p-Akt, CCND1, MAPK9, and PIK3CA.ConclusionKnockdown of POLE2 attenuates RCC cells proliferation and migration by regulating STC1, suggesting that POLE2-STC1 may become a potential target for RCC therapy.

scholarly journals The Clinical Value of Serum Adropin Level in Early Detection of Diabetic Nephropathy

2021 ◽  
pp. 1-7
Author(s):  
Ali Es-haghi ◽  
Tuqa Al-Abyadh ◽  
Hassan Mehrad-Majd
Keyword(s):  
Type 2 Diabetes ◽  
Logistic Regression ◽  
Diabetic Nephropathy ◽  
Early Detection ◽  
Assay Method ◽  
Enzyme Linked Immunosorbent Assay ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Peripheral Tissues

<b><i>Background/Aims:</i></b> Adropin is a metabolic hormone secreted by the liver, brain, and many peripheral tissues and is involved in energy homeostasis and insulin sensitivity. Some reports have indicated a significant decrease in serum adropin levels in type 2 diabetic patients. However, the significance of a decline in adropin level in early detection of diabetic nephropathy (DN) remains to be clarified. The purpose of this study was to evaluate the serum levels of adropin in patients with type 2 diabetes with and without nephropathy. <b><i>Methods:</i></b> A total of 135 unrelated subjects (including 45 diabetic patients with nephropathy, 45 without nephropathy, and 45 healthy controls) were enrolled in this study. Fasting venous blood samples were collected from all patients. Serum adropin levels of all cases were analyzed by an enzyme-linked immunosorbent assay method. The correlations of serum adropin levels with anthropometric and biochemistry variables were determined. Logistic regression was performed to assess the association of adropin with odds of nephropathy. A receiver operating characteristic (ROC) curve was obtained to explore the optimum serum adropin concentration in distinguishing diabetic patients with and without nephropathy. <b><i>Results:</i></b> Diabetic patients with nephropathy showed lower serum adropin levels than those in patients without nephropathy and healthy controls (<i>p</i> &#x3c; 0.001). Pearson correlation analysis indicated that serum adropin was negatively correlated with BMI, FBS, HbA1c, blood urea, creatinine, LDL, and ACR and positively correlated with HDL and albumin. Logistic regression analysis showed that serum adropin was correlated with decreased risk of developing diabetic nephropathy. Moreover, in ROC analysis, at cutoff value 3.20 (mg/dL) with an AUC = 0.830, adropin had 80% sensitivity and 60% specificity for distinguishing the diabetic nephropathy. <b><i>Conclusions:</i></b> This study demonstrates that decreased level of adropin is associated with renal dysfunction in patients with type 2 diabetes mellitus. Serum adropin concentrations may be used as a biomarker for early detection of diabetic nephropathy.

scholarly journals Identification of Key Genes and MicroRNAs in Gastric Cancer via miRNA-mRNA Regulatory Network

2020 ◽  
Author(s):  
Chao Huang ◽  
Xiaojian Zhu ◽  
Jiefeng Zhao ◽  
Fanqin Bu ◽  
Jun Huang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Gastric Cancer ◽  
Molecular Markers ◽  
Expression Profiling ◽  
Regulatory Network ◽  
Molecular Mechanisms ◽  
Critical Role ◽  
Differentially Expressed ◽  
Expression Levels ◽  
Receptor Interactions

Abstract Background Gastric cancer (GC) is a malignant tumor with high mortality. MicroRNAs (miRNAs) participate in various biological processes and disease pathogenesis by targeting messenger RNA (mRNA). The purpose of this study was to identify potential prognostic molecular markers of GC and to characterize the molecular mechanisms of GC. Methods A gene expression profiling dataset (GSE54129) and miRNA expression profiling dataset (GSE113486) were downloaded from the Gene Expression Omnibus (GEO) database. A miRNA-mRNA interaction network was established. Functional and pathway enrichment analyses were performed for differentially expressed genes (DEGs) and differentially expressed miRNAs (DEMs) using FunRich, the clusterProfiler package, and DIANA-mirPath. Survival analysis of key molecular markers was performed using the online tool Kaplan-Meier Plotter and the database OncomiR. Finally, experiments were carried out to verify the expression levels and biological functions of a key gene. Results A total of 390 DEMs and 341 DEGs were identified. Ultimately, 45 genes and 31 miRNAs were selected to establish a miRNA-mRNA regulatory network. Four hub genes (ZFPM2, FUT9, NEUROD1 and LIPH) and six miRNAs (hsa-let-7d-5p, hsa-miR-23b-3p, hsa-miR-23a-3p, hsa-miR-133b, hsa-miR-130a-3p and hsa-miR-124-3p) were identified in the network. DEGs and DEMs were associated with ECM-receptor interactions and metabolic pathways. Two genes (ZFPM2 and LIPH) and two miRNAs (hsa-miR-23a-3p and hsa-miR-130a-3p) were observed to be related to the prognosis of GC. ZFPM2 was highly expressed in GC tissues and various GC cell lines and could promote the proliferation, invasion and migration of GC cells. Conclusion The expression levels of ZFPM2, LIPH, hsa-miR-23a-3p and hsa-miR-130a-3p were closely related to the prognosis of GC. ZFPM2 may serve as a potential molecular marker and therapeutic target for GC. ECM receptor interactions and metabolic abnormalities play a critical role in the GC progression.

scholarly journals The Interaction of miR-378i-Skp2 Regulates Cell Senescence in Diabetic Nephropathy

2018 ◽  
Vol 7 (12) ◽  
pp. 468 ◽  
Author(s):  
Yi-Chun Tsai ◽  
Po-Lin Kuo ◽  
Mei-Chuan Kuo ◽  
Wei-Wen Hung ◽  
Ling-Yu Wu ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Human Study ◽  
Cell Senescence ◽  
Diabetic Patients ◽  
Type 2 Diabetic Patients ◽  
Bioinformatics Analyses ◽  
Type 2 Diabetic

Diabetic nephropathy (DN) is the major cause of end stage renal disease. Proximal tubular epithelial cell (PTEC) injury occurs early in diabetic kidney, and it is correlated with consequent renal failure. Cellular senescence participates in the pathophysiology of DN, but its role remains unclear. We conducted a cross-disciplinary study, including human, in vivo, and in vitro studies, to explore the novel molecular mechanisms of PTEC senescence in DN. We found that HG induced cell senescence in PTECs, supported by enhanced β-galactosidase staining, p53 and p27 expression, and reduced cyclin E levels. Transcriptome analysis of PTECs from a type 2 diabetic patient and a normal individual using next generation sequencing (NGS) and systematic bioinformatics analyses indicated that miR-378i and its downstream target S-phase kinase protein 2 (Skp2) contribute to HG-induced senescence in PTECs. High glucose (HG) elevated miR-378i expression in PTECs, and miR-378i transfection reduced Skp2 expression. Urinary miR-378i levels were elevated in both db/db mice and type 2 diabetic patients, whereas decreased Skp2 levels were shown in proximal tubule of db/db mice and human DN. Moreover, urinary miR-378i levels were positively correlated with urinary senescence-associated secretory phenotype cytokines and renal function in in vivo and human study. This study demonstrates that the interaction between miR-378i and Skp2 regulates PTEC senescence of DN. miR-378i has the potential to predict renal injury in DN. These findings suggest future applications in both therapy and in predicting renal dysfunction of DN.

scholarly journals Alteration of autophagy-related protein 5 (ATG5) levels and Atg5 gene expression in diabetes mellitus with and without complications

2021 ◽  
Vol 18 (6) ◽  
pp. 147916412110620
Author(s):  
Remah Yassin* ◽  
Hagar Tadmor* ◽  
Evgeny Farber ◽  
Anas Igbariye ◽  
Aida Armaly-Nakhoul ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Diabetic Retinopathy ◽  
Diabetic Nephropathy ◽  
Western Blot ◽  
Mononuclear Cells ◽  
Immunohistochemical Analysis ◽  
Diabetic Patients ◽  
Healthy Controls ◽  
Peripheral Blood Mononuclear ◽  
Blood Mononuclear Cells

Background Autophagy is a catabolic mechanism that involves lysosomal-dependent degradation of unnecessary intracellular components and responsible for normal cellular homeostasis. Autophagy pathway and its key participant ATG5/LC3 are associated with several pathologies such as diabetes mellitus and its complications. Methods Levels and expression of autophagy key components ATG5 and LC3B were analyzed in both human model and murine tissues. One hundred and twenty human subjects were divided into four groups: Healthy (control), diabetes mellitus without complications, diabetic nephropathy, and diabetic retinopathy. Additionally, we used kidneys from WT healthy and diabetic nephropathy mice. Lysate derived from human peripheral blood mononuclear cells and murine renal cortex lysates were subjected to western blot and immunohistochemical analysis. Results Western blot and immunohistochemical analysis demonstrate that ATG5 protein levels were significantly decreased in diabetes mellitus, diabetic nephropathy (DN), and diabetic retinopathy patients versus healthy controls and in DN mice compared to healthy mice (0.65 ± 0.04; 1.15 ± 0.13 A.U. units, respectively). Quantification of staining area (%) of ATG5 mice tissue expression also decreased in DN versus healthy mice (4.42 ± 1.08%; 10.87 ± 1.01%, respectively). LC3B levels and expression Significant reduction in peripheral blood mononuclear cells in diabetic patients (with or without complications) vs. healthy controls. Renal LC3B levels were lower in DN versus healthy mice (0.36 ± 0.03; 0.68 ± 0.07 A.U. units). Renal LC3B staining quantification revealed significant reduction in DN versus healthy mice (1.7 ± 0.23%; 8.56 ± 1.7%). Conclusion We conclude that ATG5, as well as LC3B, are down regulated in diabetic patients with or without complications. This diminution contributes to deficiencies in the autophagy process.

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