Novel ceRNA network construction associated with programmed cell death in acute rejection of heart allograft in mice.

Background: T cell-mediated acute rejection(AR) after heart transplantation(HT) ultimately results in graft failure and is a common indication for secondary transplantation. It's a serious threat to heart transplant recipients. This study aimed to explore the novel lncRNA-miRNA-mRNA networks that contributed to AR in a mouse heart transplantation model. Methods: The donor heart from Babl/C mice was transplanted to C57BL/6 mice with heterotopic implantation to the abdominal cavity. The control group was syngeneic heart transplantation with the same kind of mice donor. The whole-transcriptome sequencing was performed to obtain differentially expressed mRNAs (DEmRNAs), miRNAs (DEmiRNAs) and lncRNAs (DElncRNAs) in mouse heart allograft. The biological functions of ceRNA networks was analyzed by GO and KEGG enrichment. Differentially expressed ceRNA involved in programmed cell death were further verified with qRT-PCR testing. Results: Lots of DEmRNAs, DEmiRNAs and DElncRNAs were identified in acute rejection and control after heart transplantation, including up-regulated 4754 DEmRNAs, 1634 DElncRNAs, 182 DEmiRNAs, and down-regulated 4365 DEmRNAs, 1761 DElncRNAs, 132 DEmiRNAs. Based on the ceRNA theory, lncRNA-miRNA-mRNA regulatory networks were constructed in allograft acute rejection response. The functional enrichment analysis indicate that the down-regulated mRNAs are mainly involved in cardiac muscle cell contraction, potassium channel activity, etc. and the up-regulated mRNAs are mainly involved in T cell differentiation and mononuclear cell migration, etc. The KEGG pathway enrichment analysis showed that the down-regulated DEmRNAs were mainly enriched in adrenergic signaling, axon guidance, calcium signaling pathway, etc. The up-regulated DEmRNAs were enriched in the adhesion function, chemokine signaling pathway, apoptosis, etc. Four lncRNA-mediated ceRNA regulatory pathways, Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox, 1700071M16Rik/miR-145a-3p/Themis2, were finally validated. In addition, increased expression of PVT1, 1700071M16Rik, Tox and Themis2 may be considered as potential diagnostic gene biomarkers in AR. Conclusion: We speculated that Pvt1/miR-30c-5p/Pdgfc, 1700071M16Rik/miR-145a-3p/Pdgfc, 1700071M16Rik/miR-145a-3p/Tox and 1700071M16Rik/miR-145a-3p/Themis2 interaction pairs may serve as potential biomarkers in AR after HT.

Association between nonalcoholic fatty liver disease and increased glucose-to-albumin ratio in adults without diabetes.

Background: Nonalcoholic fatty liver disease (NAFLD) affects approximately 30% of individuals globally. Both serum glucose and albumin were demonstrated to be potential markers for the development of NAFLD. We hypothesized that the risk of NAFLD may be proportional to the glucose-to-albumin ratio (GAR). Methods: Based on information from the National Health and Nutrition Examination Survey (NHANES) 1999-2018, it was determined that GAR was associated with an increased risk of NAFLD and liver fibrosis utilizing weighted multivariable logistic regression. Participants with a fatty liver index (FLI) over 60 were identified with NAFLD, and those with an NAFLD fibrosis score (NFS) >0.676 with evidence of NAFLD were labeled with advanced hepatic fibrosis (AHF). The liver biopsy was utilized to verify the relationship between GAR and FLD in our center cohort. Mendelian randomization analysis investigated the genetic relationship between GAR and NAFLD. Results: Of 15,534 eligible participants, 36.4% of participants were identified as NAFLD without AHF. GAR was positively correlated with the probability of NAFLD following full adjustment for possible variables (OR = 1.53, 95% CI: 1.39-1.67). It was confirmed that patients with NAFLD and AHF had an inferior prognosis. The relationship between GAR and NFS was favorable (R = 0.46, P< 0.0001), and NAFLD patients with a higher GAR tended to develop poor survival. In our center cohort, the association between GAR and NAFLD was verified. Conclusion: Among participants without diabetes, greater GAR was linked to higher risks of NAFLD. In addition, NAFLD patients with higher GAR tended to develop liver fibrosis and adverse outcomes.