Effects of repetitive insertion/removal and occlusal load on the retentive force of rest plate-I bar clasps made by selective laser melting.

The objective of this study was to investigate the effects of repetitive removal/insertion and a load equivalent to the occlusal force on the retentive force of rest plate-I bar (RPI) clasps fabricated by selective laser melting (SLM) on powder bed fusion. RPI clasp fabricated by SLM and casting were evaluated to the retentive force by repetitive removal/insertion (SLM-RI and Cast-RI), and the retentive force of RPI clasp by SLM was also evaluated by repetitive removal/insertion under load (SLM-L). SLM-RI group was kept superior retentive force during repetitive removal/insertion than Cast-RI group.

Lowering an ER stress-regulated long noncoding RNA protects mice from diabetes and isolated pancreatic islets from cell death.

We investigated the role of the endoplasmic reticulum (ER) stress-regulated long noncoding RNA (lncRNA) lncMGC in pancreatic islets and the pathology of type 1 diabetes (T1D), as well as the potential of lncMGC-based therapeutics. , blood glucose levels (BGLs) and HbA1c were significantly lower in lncMGC-knockout (KO)-streptozotocin (STZ)-treated diabetic mice compared to wild-type STZ. Antisense oligonucleotides (GapmeR) targeting lncMGC significantly attenuated insulitis and BGLs in T1D NOD mice compared to GapmeR-negative control (NC).

Long non-coding RNA lncMGC mediates the expression of TGF-β-induced genes in renal cells via nucleosome remodelers.

MicroRNAs (miRNAs) and long non-coding RNAs (lncRNAs) play key roles in diabetic kidney disease (DKD). The miR-379 megacluster of miRNAs and its host transcript lnc-megacluster (lncMGC) are regulated by transforming growth factor-β (TGF-β), increased in the glomeruli of diabetic mice, and promote features of early DKD. However, biochemical functions of lncMGC are unknown.

Identify MicroRNA Targets Using AGO2-CLASH (Cross-linking, Ligation, and Sequencing of Hybrids) and AGO2-CLIP (Cross-Linking and Immuno-Precipitation) in Cells with or Without the MicroRNA of Interest Depleted.

MicroRNAs (miRNAs) are short noncoding RNAs and important players in the regulation of gene expression through post-transcriptional mechanisms. MicroRNAs regulate many cellular processes and are involved in disease progression. Identification of novel miRNA-to-target RNA connections can fill the gaps in the signaling pathways and suggest new therapeutic targets.

miR-379 mediates insulin resistance and obesity through impaired angiogenesis and adipogenesis regulated by ER stress.

We investigated the role of microRNA (miR-379) in the pathogenesis of obesity, adipose tissue dysfunction, and insulin resistance (IR). We used miR-379 knockout (miR-379KO) mice to test whether loss of miR-379 affects high-fat diet (HFD)-induced obesity and IR via dysregulation of key miR-379 targets in adipose tissue. Increases in body weight, hyperinsulinemia, and IR in wild-type (WT)-HFD mice were significantly attenuated in miR-379KO-HFD mice with some sex differences.

Role of miR-379 in high-fat diet-induced kidney injury and dysfunction.

Obesity is associated with increased risk for diabetes and damage to the kidneys. Evidence suggests that miR-379 plays a role in the pathogenesis of diabetic kidney disease. However, its involvement in obesity-induced kidney injury is not known and was therefore investigated in this study by comparing renal phenotypes of high-fat diet (HFD)-fed wild-type (WT) and miR-379 knockout (KO) mice.

Effects of repetitive insertion/removal cycles and simulated occlusal loads on retention of denture retainers.

The purpose of this study was to investigate the effects of repetitive insertion/removal cycle tests on denture retainers with simulated occlusal loads on the retentive force and deformation of clasp. Abutment teeth in the form of mandibular secondary premolars and clasp in the form of Akers clasps were prepared. The retentive force of the clasp on the abutment teeth were evaluated before and after undergoing repetitive insertion/removal cycle tests with or without cyclic loading.

miR-379 deletion ameliorates features of diabetic kidney disease by enhancing adaptive mitophagy via FIS1.

Diabetic kidney disease (DKD) is a major complication of diabetes. Expression of members of the microRNA (miRNA) miR-379 cluster is increased in DKD. miR-379, the most upstream 5'-miRNA in the cluster, functions in endoplasmic reticulum (ER) stress by targeting EDEM3.

Epigenetics and epigenomics in diabetic kidney disease and metabolic memory.

The development and progression of diabetic kidney disease (DKD), a highly prevalent complication of diabetes mellitus, are influenced by both genetic and environmental factors. DKD is an important contributor to the morbidity of patients with diabetes mellitus, indicating a clear need for an improved understanding of disease aetiology to inform the development of more efficacious treatments. DKD is characterized by an accumulation of extracellular matrix, hypertrophy and fibrosis in kidney glomerular and tubular cells.

A Novel Angiotensin II-Induced Long Noncoding RNA Giver Regulates Oxidative Stress, Inflammation, and Proliferation in Vascular Smooth Muscle Cells.

Rationale: AngII (angiotensin II)-mediated vascular smooth muscle cell (VSMC) dysfunction plays a major role in hypertension. Long noncoding RNAs have elicited much interest, but their molecular roles in AngII actions and hypertension are unclear.

Objective: To investigate the regulation and functions of a novel long noncoding RNA growth factor- and proinflammatory cytokine-induced vascular cell-expressed RNA ( Giver), in AngII-mediated VSMC dysfunction.

Noncoding RNAs as therapeutic targets in early stage diabetic kidney disease.

Diabetic kidney disease (DKD) is a major renal complication of diabetes that leads to renal dysfunction and end-stage renal disease (ESRD). Major features of DKD include accumulation of extracellular matrix proteins and glomerular hypertrophy, especially in early stage. Transforming growth factor-β plays key roles in regulation of profibrotic genes and signal transducers such as Akt kinase and MAPK as well as endoplasmic reticulum stress, oxidant stress, and autophagy related to hypertrophy in diabetes.

Reduced Autophagy by a microRNA-mediated Signaling Cascade in Diabetes-induced Renal Glomerular Hypertrophy.

Autophagy plays a key role in the pathogenesis of kidney diseases, however its role in diabetic nephropathy (DN), and particularly in kidney glomerular mesangial cells (MCs) is not very clear. Transforming Growth Factor- β1 (TGF-β), a key player in the pathogenesis of DN, regulates expression of various microRNAs (miRNAs), some of which are known to regulate the expression of autophagy genes. Here we demonstrate that miR-192, induced by TGF-β signaling, plays an important role in regulating autophagy in DN.

Inhibition of the processing of miR-25 by HIPK2-Phosphorylated-MeCP2 induces NOX4 in early diabetic nephropathy.

Phosphorylated methyl-CpG binding protein2 (p-MeCP2) suppresses the processing of several microRNAs (miRNAs). Homeo-domain interacting protein kinase2 (HIPK2) phosphorylates MeCP2, a known transcriptional repressor. However, it is not known if MeCP2 and HIPK2 are involved in processing of miRNAs implicated in diabetic nephropathy.

An endoplasmic reticulum stress-regulated lncRNA hosting a microRNA megacluster induces early features of diabetic nephropathy.

It is important to find better treatments for diabetic nephropathy (DN), a debilitating renal complication. Targeting early features of DN, including renal extracellular matrix accumulation (ECM) and glomerular hypertrophy, can prevent disease progression. Here we show that a megacluster of nearly 40 microRNAs and their host long non-coding RNA transcript (lnc-MGC) are coordinately increased in the glomeruli of mouse models of DN, and mesangial cells treated with transforming growth factor-β1 (TGF- β1) or high glucose.

Epigenetic Histone Modifications Involved in Profibrotic Gene Regulation by 12/15-Lipoxygenase and Its Oxidized Lipid Products in Diabetic Nephropathy.

Aims: Epigenetic mechanisms, including histone post-translational modifications and DNA methylation, are implicated in the pathogenesis of diabetic nephropathy (DN), but the mediators are not well known. Moreover, although dyslipidemia contributes to DN, epigenetic changes triggered by lipids are unclear. In diabetes, increased expression of 12/15-lipoxygenase (12/15-LO) enhances oxidized lipids such as 12(S)-hydroxyeicosatetraenoic acid [12(S)-HETE], which promote oxidant stress, glomerular and mesangial cell (MC) dysfunction, and fibrosis, and mediate the actions of profibrotic growth factors.

MicroRNAs in diabetic nephropathy: functions, biomarkers, and therapeutic targets.

MicroRNAs (miRNAs) are short noncoding RNAs that regulate gene expression by posttranscriptional and epigenetic mechanisms and thereby affect many cellular processes and disease states. Over 2,000 human mature miRNAs have been identified, and at least 60% of all human protein-coding genes are known to be regulated by miRNAs. MicroRNA biogenesis involves classical transcription regulation and processing by key ribonucleases, as well as other protein factors and epigenetic mechanisms.

Repression of let-7 by transforming growth factor-β1-induced Lin28 upregulates collagen expression in glomerular mesangial cells under diabetic conditions.

Accumulation of mesangial extracellular matrix (ECM) proteins such as collagen type 1-α2 (Col1a2) and collagen type 4-α1 (Col4a1) is a key feature of diabetic nephropathy (DN). Transforming growth factor (TGF)-β1 plays important roles in ECM accumulation in DN, and evidence shows a mediatory role for microRNAs. In the present study, we found that microRNA let-7 family members (let-7b/c/d/g/i) were downregulated in TGF-β-treated mouse mesangial cells (MMCs) along with upregulation of Col1a2 and Col4a1.

Transforming growth factor β1 (TGF-β1) enhances expression of profibrotic genes through a novel signaling cascade and microRNAs in renal mesangial cells.

Increased expression of transforming growth factor-β1 (TGF-β1) in glomerular mesangial cells (MC) augments extracellular matrix accumulation and hypertrophy during the progression of diabetic nephropathy (DN), a debilitating renal complication of diabetes. MicroRNAs (miRNAs) play key roles in the pathogenesis of DN by modulating the actions of TGF-β1 to enhance the expression of profibrotic genes like collagen. In this study, we found a significant decrease in the expression of miR-130b in mouse MC treated with TGF-β1.

Diabetic nephropathy--emerging epigenetic mechanisms.

Diabetic nephropathy (DN), a severe microvascular complication frequently associated with both type 1 and type 2 diabetes mellitus, is a leading cause of renal failure. The condition can also lead to accelerated cardiovascular disease and macrovascular complications. Currently available therapies have not been fully efficacious in the treatment of DN, suggesting that further understanding of the molecular mechanisms underlying the pathogenesis of DN is necessary for the improved management of this disease.

TGF-β-induced signaling circuit loops mediated by microRNAs as new therapeutic targets for renal fibrosis?

MicroRNAs (miRNAs) are emerging molecules in the pathogenesis of human diseases. Identification of miRNAs related to renal fibrosis provides clues to find new signaling pathways to fill the gaps between signaling molecules. Li et al.