Project description:Diabetic peripheral neuropathy (DPN) is the most common neurological complication of diabetes. More than 500 differentially expressed genes (DEGs) belonging to multiple functional pathways were identified in diabetic spinal cord and of those the most enriched was RAGE-Diaph1 related PI3K-Akt pathway.
Project description:Diabetes mellitus (DM) after transplantation remains a crucial clinical problem in kidney transplantation. To obtain insights into molecular mechanisms underlying the development of post-transplant diabetes mellitus (PTDM) and its early impact on glomerular structures, here we comparatively analyze the proteome of histologically normal appearing glomeruli from patients with PTDM from normoglycemic (NG) transplant recipients, and from recipients with pre-existing type 2 DM (PTDM)
Project description:A study of diabetic neuropathy in dorsal root ganglia from streptozotocin-diabetic male wistar rats over the first 8 weeks of diabetes
Project description:Autologous nonmyeloablative hematopoietic stem cell transplantation (AHST) was the first therapeutic approaches that can improve beta cell function in type 1 diabetic (T1D) patients. This study was designed to investigate the potential mechanisms involved.We applied AHST to nine T1D patients diagnosed within six months and analyzed the acute response in peripheral blood genomic expression profiling at the six-month follow-up. Peripheral blood mononuclear of newly diagnosed type1 diabetes patients at diagnosis and at six months post-transplantation by autologous peripheral stem cell were purified by LymphoprepTm gradient purification according to the manufacturer's instructions (Axis-Shield PoC AS, Oslo, Norway) for futher microarray analysis.
Project description:Chemotherapy-induced peripheral neuropathy (CIPN) is a serious adverse reaction of chemotherapy with limited treatment. Previous research indicates neutrophil extracellular traps (NETs) is a critical pathogenesis of CIPN. LPS/HMGB1 serve as important inducers of NETs. Here, we aim to target inhibiting NETs formation (NETosis) to alleviate CIPN. Clinically we found the content of LPS, HMGB1 and NETs in the plasma of CIPN patients was significantly increased and positively correlated with VAS scores. Fucoidan decreased LPS/HMGB1/NETs content and relieved CIPN in mice. Mechanistically, fucoidan upregulated the scavenger receptor A1 (SR-A1) expression and promoted bone marrow derived macrophage (BMDM) to phagocytize LPS/HMGB1. Fucoidan also facilitated BMDM to engulf NETs via the recognition and localization of SR-A1 and HMGB1. The therapeutic effects of fucoidan were abolished by SR-A1 knockout. RNA-seq analysis showed that fucoidan significantly increased sqstm1 (p62) gene expression. Fucoidan promoted the competitive binding of sqstm1 and Nrf2 to Keap1, increasing Nrf2 nuclear translocation and SR-A1 transcription. Additionally, microbial diversity sequencing analysis (16S) showed that fucoidan increased gut microbiota diversity and abundance, and upregulated the Bacteroides/Firmicutes ratio. In conclusion, fucoidan promotes SR-A1-mediated phagocytosis of LPS/HMGB1/NETs and maintains gut microbial homeostasis, providing a potential therapeutic strategy for CIPN.
Project description:Diabetic peripheral neuropathy (DPN) is a common complication of diabetes mellitus (DM). It is not diagnosed or managed properly in the majority of patients, because its pathogenesis remains controversial. In this study, using microarray-based genome-wide expression analyses, we sought to identify both common and distinct mechanisms underlying the pathogenesis of DM and DPN. The results demonstrated that down-regulation of the neurotrophin-MAPK signaling pathway may be the major mechanism of DPN pathogenesis, thus providing a potential approach for DPN treatment.
Project description:Peripheral neuropathy (PN) is the most common microvascular complication of type 2 diabetes mellitus (T2D). However, a thorough understanding of the mechanisms underlying PN pathogenesis is currently lacking. Thus, the goal of the current study was to use system biology approaches to investigate the development and progression of PN in a high-fat diet (HFD)-induced mouse model of T2D. Transcriptomic data sets from sciatic nerve (SCN) and dorsal root ganglia (DRG) tissue were collected from 12- and 36-week-old HFD-fed mice and analyzed using self-organizing map and differentially expressed gene analysis with functional enrichment. Consistent with prior literature, pathways related to immune function and inflammation, mTOR signaling, and lipid metabolism were dysregulated in the SCN and DRG of HFD-fed mice. Additionally, cell-type abundance analysis revealed changes in cell composition in the SCN and DRG of HFD-fed T2D mice over time, particularly in the SCN. Comparison of differentially expressed genes from the SCN of HFD-fed mice to transcriptomic data from human sural nerve further supported the role of inflammation, mTOR signaling, and lipid metabolism in PN. Results from this study provide the basis for mechanistic studies investigating nerve damage in T2D and support the development of mechanism-based treatment options for PN.