scholarly journals Prediction of the molecular mechanisms and potential therapeutic targets for diabetic nephropathy by bioinformatics methods

2016 ◽  
Vol 37 (5) ◽  
pp. 1181-1188 ◽  
Author(s):  
WAN-NING WANG ◽  
WEN-LONG ZHANG ◽  
GUANG-YU ZHOU ◽  
FU-ZHE MA ◽  
TAO SUN ◽  
...  
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Therapeutic Targets

MicroRNAs in diabetic nephropathy: From molecular mechanisms to new therapeutic targets of treatment

2020 ◽  
pp. 114301
Author(s):  
Amir Yarahmadi ◽  
Seyedeh Zahra Shahrokhi ◽  
Zohreh Mostafavi-Pour ◽  
Negar Azarpira
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
New Therapeutic Targets

scholarly journals Diabetic Nephropathy: Novel Molecular Mechanisms and Therapeutic Targets

2020 ◽  
Vol 11 ◽  
Author(s):  
Carlamaria Zoja ◽  
Christodoulos Xinaris ◽  
Daniela Macconi
Keyword(s):  
Diabetic Nephropathy ◽  
Molecular Mechanisms ◽  
Microvascular Complications ◽  
Therapeutic Targets ◽  
Renin Angiotensin System ◽  
Pressure Control ◽  
Experimental Models ◽  
Lipid Lowering ◽  
Diabetic Patients ◽  
Functional Changes

Diabetic nephropathy (DN) is one of the major microvascular complications of diabetes mellitus and the leading cause of end-stage kidney disease. The standard treatments for diabetic patients are glucose and blood pressure control, lipid lowering, and renin-angiotensin system blockade; however, these therapeutic approaches can provide only partial renoprotection if started late in the course of the disease. One major limitation in developing efficient therapies for DN is the complex pathobiology of the diabetic kidney, which undergoes a set of profound structural, metabolic and functional changes. Despite these difficulties, experimental models of diabetes have revealed promising therapeutic targets by identifying pathways that modulate key functions of podocytes and glomerular endothelial cells. In this review we will describe recent advances in the field, analyze key molecular pathways that contribute to the pathogenesis of the disease, and discuss how they could be modulated to prevent or reverse DN.

MO262THE SINGLE-CELL TRANSCRIPTOMICS OF HUMAN IGA NEPHROPATHY

2021 ◽  
Vol 36 (Supplement_1) ◽  
Author(s):  
Yong Zhong ◽  
Xiangcheng Xiao
Keyword(s):  
Gene Expression ◽  
Single Cell ◽  
Signaling Pathways ◽  
Iga Nephropathy ◽  
Molecular Mechanisms ◽  
Mesangial Cells ◽  
Therapeutic Targets ◽  
Cell Types ◽  
Receptor Crosstalk ◽  
Overt Proteinuria

Abstract Background and Aims The exact molecular mechanisms underlying IgA nephropathy (IgAN) remains incompletely defined. Therefore, it is necessary to further elucidate the mechanism of IgA nephropathy and find novel therapeutic targets. Method Single-cell RNA sequencing (scRNA-seq) was applied to kidney biopsies from 4 IgAN and 1 control subjects to define the transcriptomic landscape at the single-cell resolution. Unsupervised clustering analysis of kidney specimens was used to identify distinct cell clusters. Differentially expressed genes and potential signaling pathways involved in IgAN were also identified. Results Our analysis identified 14 cell subsets in kidney biopsies from IgAN patients, and analyzed changing gene expression in distinct renal cell types. We found increased mesangial expression of several novel genes including MALAT1, GADD45B, SOX4 and EDIL3, which were related to proliferation and matrix accumulation and have not been reported in IgAN previously. The overexpressed genes in tubule cells of IgAN were mainly enriched in inflammatory pathways including TNF signaling, IL-17 signaling and NOD-like receptor signaling. Moreover, the receptor-ligand crosstalk analysis revealed potential interactions between mesangial cells and other cells in IgAN. Specifically, IgAN with overt proteinuria displayed elevated genes participating in several signaling pathways which may be involved in pathogenesis of progression of IgAN. Conclusion The comprehensive analysis of kidney biopsy specimen demonstrated different gene expression profile, potential pathologic ligand-receptor crosstalk, signaling pathways in human IgAN. These results offer new insight into pathogenesis and identify new therapeutic targets for patients with IgA nephropathy.

scholarly journals Investigation of the Mechanism of Complement System in Diabetic Nephropathy via Bioinformatics Analysis

2021 ◽  
Vol 2021 ◽  
pp. 1-14
Author(s):  
Bojun Xu ◽  
Lei Wang ◽  
Huakui Zhan ◽  
Liangbin Zhao ◽  
Yuehan Wang ◽  
...  
Keyword(s):  
Gene Expression ◽  
Diabetic Nephropathy ◽  
Protein Interactions ◽  
Molecular Mechanisms ◽  
Bioinformatics Analysis ◽  
Topological Analysis ◽  
Gene Expression Omnibus ◽  
Complement Cascade ◽  
Hub Genes ◽  
Novel Biomarkers

Objectives. Diabetic nephropathy (DN) is a major cause of end-stage renal disease (ESRD) throughout the world, and the identification of novel biomarkers via bioinformatics analysis could provide research foundation for future experimental verification and large-group cohort in DN models and patients. Methods. GSE30528, GSE47183, and GSE104948 were downloaded from Gene Expression Omnibus (GEO) database to find differentially expressed genes (DEGs). The difference of gene expression between normal renal tissues and DN renal tissues was firstly screened by GEO2R. Then, the protein-protein interactions (PPIs) of DEGs were performed by STRING database, the result was integrated and visualized via applying Cytoscape software, and the hub genes in this PPI network were selected by MCODE and topological analysis. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses were carried out to determine the molecular mechanisms of DEGs involved in the progression of DN. Finally, the Nephroseq v5 online platform was used to explore the correlation between hub genes and clinical features of DN. Results. There were 64 DEGs, and 32 hub genes were identified, enriched pathways of hub genes involved in several functions and expression pathways, such as complement binding, extracellular matrix structural constituent, complement cascade related pathways, and ECM proteoglycans. The correlation analysis and subgroup analysis of 7 complement cascade-related hub genes and the clinical characteristics of DN showed that C1QA, C1QB, C3, CFB, ITGB2, VSIG4, and CLU may participate in the development of DN. Conclusions. We confirmed that the complement cascade-related hub genes may be the novel biomarkers for DN early diagnosis and targeted treatment.

scholarly journals Mechanisms of Action And Clinical Implications of MicroRNAs in the Drug Resistance of Gastric Cancer

2021 ◽  
Vol 11 ◽  
Author(s):  
Ying Liu ◽  
Xiang Ao ◽  
Guoqiang Ji ◽  
Yuan Zhang ◽  
Wanpeng Yu ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Drug Resistance ◽  
Molecular Mechanisms ◽  
Malignant Tumors ◽  
Life Quality ◽  
Therapeutic Targets ◽  
Chemotherapeutic Agents ◽  
Response To Chemotherapy ◽  
Novel Biomarkers ◽  
Related Proteins

Gastric cancer (GC) is one of the most common malignant tumors of digestive systems worldwide, with high recurrence and mortality. Chemotherapy is still the standard treatment option for GC and can effectively improve the survival and life quality of GC patients. However, with the emergence of drug resistance, the clinical application of chemotherapeutic agents has been seriously restricted in GC patients. Although the mechanisms of drug resistance have been broadly investigated, they are still largely unknown. MicroRNAs (miRNAs) are a large group of small non-coding RNAs (ncRNAs) widely involved in the occurrence and progression of many cancer types, including GC. An increasing amount of evidence suggests that miRNAs may play crucial roles in the development of drug resistance by regulating some drug resistance-related proteins as well as gene expression. Some also exhibit great potential as novel biomarkers for predicting drug response to chemotherapy and therapeutic targets for GC patients. In this review, we systematically summarize recent advances in miRNAs and focus on their molecular mechanisms in the development of drug resistance in GC progression. We also highlight the potential of drug resistance-related miRNAs as biomarkers and therapeutic targets for GC patients.

scholarly journals Long noncoding RNA FAM225A promotes the malignant progression of gastric cancer through the miR-326/PADI2 axis

2022 ◽  
Vol 8 (1) ◽  
Author(s):  
Xiang Ma ◽  
Gang Wang ◽  
Hao Fan ◽  
Zengliang Li ◽  
Wangwang Chen ◽  
...  
Keyword(s):  
Gastric Cancer ◽  
Noncoding Rna ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
In Vitro Assays ◽  
Advanced Tumor Stage ◽  
Advanced Tumor ◽  
Mechanistic Investigation

AbstractGastric cancer (GC) is a global health problem and further studies of its molecular mechanisms are needed to identify effective therapeutic targets. Although some long noncoding RNAs (lncRNAs) have been found to be involved in the progression of GC, the molecular mechanisms of many GC-related lncRNAs remain unclear. In this study, a series of in vivo and in vitro assays were performed to study the relationship between FAM225A and GC, which showed that FAM225A levels were correlated with poor prognosis in GC. Higher FAM225A expression tended to be correlated with a more profound lymphatic metastasis rate, larger tumor size, and more advanced tumor stage. FAM225A also promoted gastric cell proliferation, invasion, and migration. Further mechanistic investigation showed that FAM225A acted as a miR-326 sponge to upregulate its direct target PADI2 in GC. Overall, our findings indicated that FAM225A promoted GC development and progression via a competitive endogenous RNA network of FAM225A/miR-326/PADI2 in GC, providing insight into possible therapeutic targets and prognosis of GC.

scholarly journals Bioinformatic analysis identifies potential biomarkers and therapeutic targets of septic-shock-associated acute kidney injury

Hereditas ◽  
2021 ◽  
Vol 158 (1) ◽  
Author(s):  
Yun Tang ◽  
Xiaobo Yang ◽  
Huaqing Shu ◽  
Yuan Yu ◽  
Shangwen Pan ◽  
...  
Keyword(s):  
Gene Expression ◽  
Septic Shock ◽  
Acute Kidney Injury ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Kidney Injury ◽  
Enrichment Analysis ◽  
Pathway Enrichment Analysis ◽  
Blood Samples ◽  
Potential Biomarkers

Abstract Background Sepsis and septic shock are life-threatening diseases with high mortality rate in intensive care unit (ICU). Acute kidney injury (AKI) is a common complication of sepsis, and its occurrence is a poor prognostic sign to septic patients. We analyzed co-differentially expressed genes (co-DEGs) to explore relationships between septic shock and AKI and reveal potential biomarkers and therapeutic targets of septic-shock-associated AKI (SSAKI). Methods Two gene expression datasets (GSE30718 and GSE57065) were downloaded from the Gene Expression Omnibus (GEO). The GSE57065 dataset included 28 septic shock patients and 25 healthy volunteers and blood samples were collected within 0.5, 24 and 48 h after shock. Specimens of GSE30718 were collected from 26 patients with AKI and 11 control patents. AKI-DEGs and septic-shock-DEGs were identified using the two datasets. Subsequently, Gene Ontology (GO) functional analysis, Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis, and protein-protein interaction (PPI) network analysis were performed to elucidate molecular mechanisms of DEGs. We also evaluated co-DEGs and corresponding predicted miRNAs involved in septic shock and AKI. Results We identified 62 DEGs in AKI specimens and 888, 870, and 717 DEGs in septic shock blood samples within 0.5, 24 and 48 h, respectively. The hub genes of EGF and OLFM4 may be involved in AKI and QPCT, CKAP4, PRKCQ, PLAC8, PRC1, BCL9L, ATP11B, KLHL2, LDLRAP1, NDUFAF1, IFIT2, CSF1R, HGF, NRN1, GZMB, and STAT4 may be associated with septic shock. Besides, co-DEGs of VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 coupled with corresponding predicted miRNAs, especially miR-29b-3p, miR-152-3p, and miR-223-3p may be regarded as promising targets for the diagnosis and treatment of SSAKI in the future. Conclusions Septic shock and AKI are related and VMP1, SLPI, PTX3, TIMP1, OLFM4, LCN2, and S100A9 genes are significantly associated with novel biomarkers involved in the occurrence and development of SSAKI.

scholarly journals The Expression and Function of Circadian Rhythm Genes in Hepatocellular Carcinoma

2021 ◽  
Vol 2021 ◽  
pp. 1-13
Author(s):  
Yanan Jiang ◽  
Xiuyun Shen ◽  
Moyondafoluwa Blessing Fasae ◽  
Fengnan Zhi ◽  
Lu Chai ◽  
...  
Keyword(s):  
Hepatocellular Carcinoma ◽  
Circadian Rhythm ◽  
Circadian Rhythms ◽  
Molecular Mechanisms ◽  
Therapeutic Targets ◽  
Pathogenic Mechanism ◽  
Research Progress ◽  
Biological Processes ◽  
And Function ◽  
Novel Therapeutic

Hepatocellular carcinoma (HCC) is among the most common and lethal form of cancer worldwide. However, its diagnosis and treatment are still dissatisfactory, due to limitations in the understanding of its pathogenic mechanism. Therefore, it is important to elucidate the molecular mechanisms and identify novel therapeutic targets for HCC. Circadian rhythm-related genes control a variety of biological processes. These genes play pivotal roles in the initiation and progression of HCC and are potential diagnostic markers and therapeutic targets. This review gives an update on the research progress of circadian rhythms, their effects on the initiation, progression, and prognosis of HCC, in a bid to provide new insights for the research and treatment of HCC.

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