Long noncoding RNAs (lncRNAs) are emerging as key species-specific regulators of cellular and disease processes. To identify potential lncRNAs relevant to acute and chronic renal epithelial injury, we performed unbiased whole transcriptome profiling of human proximal tubular epithelial cells (PTECs) in hypoxic and inflammatory conditions. RNA sequencing revealed that the protein-coding and noncoding transcriptomic landscape differed between hypoxia-stimulated and cytokine-stimulated human PTECs. Hypoxia- and inflammation-modulated lncRNAs were prioritized for focused followup according to their degree of induction by these stress stimuli, their expression in human kidney tissue, and whether exposure of human PTECs to plasma of critically ill sepsis patients with acute kidney injury modulated their expression. For three lncRNAs (MIR210HG, linc-ATP13A4-8, and linc-KIAA1737-2) that fulfilled our criteria, we validated their expression patterns, examined their loci for conservation and synteny, and defined their associated epigenetic marks. The lncRNA landscape characterized here provides insights into novel transcriptomic variations in the renal epithelial cell response to hypoxic and inflammatory stress.

The fractalkine (CX3CL1-CX3CR1) chemokine system is associated with obesity-related inflammation and type 2 diabetes, but data on effects of Cx3cr1 deficiency on metabolic pathways is contradictory. We examined male C57BL/6 Cx3cr1-/- mice on chow and high-fat diet to determine the metabolic effects of Cx3cr1 deficiency. We found no difference in body weight and fat content or feeding and energy expenditure between Cx3cr1-/- and WT mice. Cx3cr1-/- mice had reduced glucose intolerance assessed by intraperitoneal glucose tolerance tests at chow and high-fat fed states, though there was no difference in glucose-stimulated insulin values. Cx3cr1-/- mice also had improved insulin sensitivity at hyperinsulinemic-euglycemic clamp, with higher glucose infusion rate, rate of disposal, and hepatic glucose production suppression compared to WT mice. Enhanced insulin signaling in response to acute intravenous insulin injection was demonstrated in Cx3cr1-/- by increased liver protein levels of phosphorylated AKT and GSK3β proteins. There were no differences in adipose tissue macrophage populations, circulating inflammatory monocytes, adipokines, lipids, or inflammatory markers. In conclusion, we demonstrate a moderate and reproducible protective effect of Cx3cr1 deficiency on glucose intolerance and insulin resistance.

The retinal pigment epithelium (RPE) supports the outer retina through essential roles in the retinoid cycle, nutrient supply, ion exchange, and waste removal. Each day the RPE removes the oldest ~10% of photoreceptor outer segment (OS) disk membranes through phagocytic uptake, which peaks following light onset. Impaired degradation of phagocytosed OS material by the RPE can lead to toxic accumulation of lipids, oxidative tissue damage, inflammation, and cell death. OSs are rich in very long chain fatty acids, which are preferentially catabolized in peroxisomes. Despite the importance of lipid degradation in RPE function, the regulation of peroxisome number and activity relative to diurnal OS ingestion is relatively unexplored. Using immunohistochemistry, immunoblot analysis, and catalase activity assays, we investigated peroxisome abundance and activity at 6 AM, 7 AM (light onset), 8 AM, and 3 PM, in wild-type (WT) mice and mice lacking microtubule-associated protein 1 light chain 3B ( Lc3b), which have impaired phagosome degradation. We found that catalase activity, but not the amount of catalase protein, is 50% higher in the morning compared with 3 PM, in RPE of WT, but not Lc3b−/−, mice. Surprisingly, we found that peroxisome abundance was stable during the day in RPE of WT mice; however, numbers were elevated overall in Lc3b−/− mice, implicating LC3B in autophagic organelle turnover in RPE. Our data suggest that RPE peroxisome function is regulated in coordination with phagocytosis, possibly through direct enzyme regulation, and may serve to prepare RPE peroxisomes for daily surges in ingested lipid-rich OS.

ObjectiveTo explore the impact of dual targeting of C-C motif chemokine receptor-2 (CCR2) and fractalkine receptor (CX3CR1) on the metabolic and inflammatory consequences of high fat diet (HFD)-induced obesity.MethodsC57BL/6J wild type (WT), Cx3cr1−/−, Ccr2−/− and Cx3cr1−/−Ccr2−/− double knockout male and female mice were fed a 45% HFD for up to 25 weeks starting at 12-weeks of age.ResultsAll groups gained weight at a similar rate and developed similar degree of adiposity, hyperglycemia, glucose intolerance and impairment of insulin sensitivity in response to HFD. As expected, the circulating monocyte count was decreased in Ccr2−/− and Cx3cr1−/−Ccr2−/−, but not in Cx3cr1−/− Mice. Flow cytometric analysis of perigonadal adipose of male, but not female, mice revealed trends to lower CD11c+MGL1− M1- like macrophages and higher CD11c−MGL1+ M2- like macrophages as a percentage of CD45+F4/80+CD11b+ macrophages in Cx3cr1−/−Ccr2−/− mice vs. WT mice, suggesting reduced adipose tissue macrophage activation. In contrast, single knockout of Ccr2 or Cx3cr1 did not differ in their adipose macrophage phenotypes.ConclusionAlthough CCR2 and CX3CR1 may synergistically impact inflammatory phenotypes, their joint deficiency did not influence metabolic effects of 45% HFD-induced obesity in these model conditions.

The incisive branch of the inferior alveolar nerve is a vital anatomical structure within the anterior mandible that has not been thoroughly defined and outlined in reports in the literature until recent years. Advances in radiological imaging, particularly the widespread use of cone-beam computed tomography has allowed for accurate visualization of the mandibular incisive canal (MIC) and its associated incisive branch of the inferior alveolar nerve. Surgical damage to the MIC, which could result in hemorrhage and sensory disturbance, may occur in commonly practiced oral and maxillofacial procedures, such as chin bone harvesting, implant placement, fracture repair and removal of pathologic entities of the anterior mandible. Knowledge of both the presence, dimensions and location of the incisive branch is a vital component to pre and peri-operative planning of oral and maxillofacial surgeries performed within the mandible, particularly within the interforaminal zone. In this article, the terminology, anatomy, imaging, surgical consideration, and pathology of the incisive branch will be discussed.

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