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Objectives: We aimed to explore the shared and specific signalling pathways involved in diabetic retinopathy (DR), diabetic peripheral neuropathy (DPN) and diabetic nephropathy (DN). Methods: Differentially expressed mRNAs and lncRNAs were identified by high-throughput sequencing. Subsequently, functional enrichment analysis, protein-protein interaction (PPI) analysis and lncRNAs-mRNAs networks were conducted to determine the pathogenic mechanisms underlying DR, DPN and DN. Results: Twenty-six biological pathways were shared among DR, DPN and DN groups compared to the type 2 diabetes mellitus (T2DM) group without complications, and most of the shared pathways and core proteins were involved in immune and inflammatory responses of microvascular damage. Cytokine‒cytokine receptor interactions and chemokine signalling pathway were the most significant and specific pathways for DR, and the lncRNA‒mRNA regulatory networks affected DR by targeting these pathways. Sphingolipid metabolism and neuroactive ligand-receptor pathways were found to be specific for the pathogenesis of DPN. Moreover, multiple amino acid metabolic pathways were involved in the occurrence and progression of DN. Conclusions: Diabetic retinopathy, DPN and DN exhibited commonality and heterogeneity simultaneously. The shared pathologic mechanisms underlying these diabetic complications are involved in diabetic microvascular damage via immune and inflammatory pathways. Our findings predict several biomarkers and therapeutic targets for these diabetic complications. [ABSTRACT FROM AUTHOR]

Objective: Gestational diabetes mellitus (GDM) is one of the most common complications of pregnancy, and its pathogenesis is still unclear. Studies have shown that circular RNAs (circRNAs) can regulate blood glucose levels by targeting mRNAs, but the role of circRNAs in GDM is still unknown. Therefore, a joint microarray analysis of circRNAs and their target mRNAs in GDM patients and healthy pregnant women was carried out. Methods: In this study, microarray analyses of mRNA and circRNA in 6 GDM patients and 6 healthy controls were conducted to identify the differentially expressed mRNA and circRNA in GDM patients, and some of the discovered mRNAs and circRNAs were further validated in additional 56 samples by quantitative realtime PCR (qRT-PCR) and droplet digital PCR (ddPCR). Results: Gene ontology and pathway analyses showed that the differentially expressed genes were significantly enriched in T cell immune-related pathways. Cross matching of the differentially expressed mRNAs and circRNAs in the top 10 KEGG pathways identified 4 genes (CBLB , ITPR3 , NFKBIA , and ICAM1) and 4 corresponding circRNAs (circ-CBLB, circ-ITPR3, circ-NFKBIA, and circ-ICAM1), and these candidates were subsequently verified in larger samples. These differentially expressed circRNAs and their linear transcript mRNAs were all related to the T cell receptor signaling pathway, and PCR results confirmed the initial microarray results. Moreover, circRNA/miRNA/mRNA interactions and circRNA-binding proteins were predicted, and circ-CBLB, circ-ITPR3, and circ-ICAM1 may serve as GDM-related miRNA sponges and regulate the expression of CBLB, ITPR3, NFKBIA, and ICAM1 in cellular immune pathways. Conclusion: Upregulation of T cell receptor signaling pathway components may represent the major pathological mechanism underlying GDM, thus providing a potential approach for the prevention and treatment of GDM. [ABSTRACT FROM AUTHOR]

Philadelphia chromosome-like (Ph-like) acute lymphoblastic leukaemia (ALL), a high-risk subtype characterised by genomic alterations that activate cytokine receptor and kinase signalling, is associated with inferior outcomes in most childhood ALL clinical trials. Half of the patients with Ph-like ALL have kinase rearrangements or fusions. We examined the frequency and spectrum of these fusions using a retrospective cohort of 212 newly diagnosed patients with childhood B-cell ALL. Samples without known chromosomal alterations were subject to multiplex reverse transcription polymerase chain reaction to identify known Ph-like kinase fusions. Immunoglobulin heavy chain locus (IGH) capture and kinase capture were applied to samples without known kinase fusions. We detected known kinase fusions in five of 212 patients, comprising EBF1-PDGFRB, ETV6-ABL1, ZC3HAV1-ABL2, EPOR-IGH, and CNTRL-ABL1. Two patients with P2RY8-CRLF2 were identified. Patients with non-Ph kinase fusions had inferior 5-year event-free survival and overall survival compared with patients with other common genetic alterations. The prevalence of non-Ph kinase fusions in our Taiwanese cohort was lower than that reported in Caucasian populations. Future clinical trials with tyrosine kinase inhibitors may be indicated in Taiwan because of the inferior outcomes for B-cell ALL with kinase fusions. [ABSTRACT FROM AUTHOR]

• miR-205 exerts hepatoprotective effect against alcohol-associated liver disease (ALD). • miR-205 targets and inhibits importinα5 expression. • Baicalin upregulates miR-205 expression. • Baicalin inhibits importinα5 to repress the activation of NF-κB signaling pathway. • This study provides better understanding of the hepatoprotective effect of baicalin in ALD. Recently, baicalin refers to flavonoid compound extracted from Scutellaria baicalensis Georgi has been indicated to hold promising therapeutic effects in alcohol-associated liver disease (ALD). However, knowledge of the molecular mechanisms for its hepatoprotective effect is still very limited. Evidence exists suggesting potential association between miR-205 and baicalin's function. Bioinformatic analysis and dual luciferase reporter assay were conducted to determine the binding affinity between miR-205 and importinα5. Our findings revealed that baicalin could alleviate ALD by raising the expression of miR-205. Additionally, miR-205 repressed NF-κB signaling pathway activation by binding to importinα5 to relieve ALD. Baicalin inhibited importinα5-mediated NF-κB signaling pathway to protect the liver against alcohol-induced injury, inflammation, oxidative stress and hepatocyte apoptosis. Taken conjointly, baicalin confers hepatoprotective effect against ALD through miR-205-mediated importinα5 inhibition via the NF-κB signaling pathway, highlighting a promising therapeutic target for ALD treatment with the help of traditional Chinese medicine. [ABSTRACT FROM AUTHOR]