Ovarian cancer G protein-coupled receptor 1 deficiency exacerbates crystal deposition and kidney injury in oxalate nephropathy in female mice

Ovarian cancer G protein-coupled receptor 1 (OGR1) (Gpr68) and G protein-coupled receptor 4 (GPR4) (Gpr4) are proton-activated G protein-coupled receptors that are stimulated upon increased extracellular acidity. These receptors have various physiological and pathophysiological roles in renal acid–base physiology, tissue inflammation, and fibrosis among others. Their function in injured renal tissue, however, remains mostly unclear. To address this, we investigated their role in crystalline nephropathy by increasing the oxalate intake of GPR4 KO and OGR1 KO mice. After 10 days of high-oxalate intake and 4 days of recovery, renal crystal content, histopathology, filtration function, and inflammation were assessed. While GPR4 deficiency did not show major alterations in disease progression, OGR1 KO mice had higher urinary calcium levels and exacerbated crystal accumulation accompanied by decreased creatinine clearance and urea excretion and a decreased presence of regulatory T (Treg) cells in kidney tissue. When lowering the severity of the kidney injury, OGR1 KO mice were more prone to develop crystalline nephropathy. In this setting, OGR1 KO mice displayed an increased activation of the immune system and a higher production of proinflammatory cytokines by T cells and macrophages. Taken together, in the acute setting of oxalate-induced nephropathy, the lack of the proton-activated G protein-coupled receptor (GPCR) GPR4 does not influence disease. OGR1 deficiency, however, increases crystal deposition leading to impaired kidney function. Thus, OGR1 may be important to limit kidney crystal deposition, which might subsequently be relevant for the pathophysiology of oxalate kidney stones or other crystallopathies

Laboratory Assessment of Fracture Resistance of Endodontically Treated Teeth Restored With Three Different Post and Core Systems

Background and Aim : Prefabricated posts are advantageous in restoring endodontically treated teeth because of their lower cost and operation time. Since selecting a suitable restoration is important in the survival of these teeth, in this study fracture resistance and the mode of failure of endodontically treated teeth restored with three different post and core systems were evaluated .   Materials and Methods : In this in vitro study, 36 human premolars were divided into three groups namely, group 1, non precious cast post and core group 2, prefabricated metal post with amalgam core group 3, FRC post and composite core. All groups received crowning. Specimens were thermocycled and loaded until definite failure. The fracture resistance and failure modes were analyzed with one way ANOVA and Fisher Exact tests .   Results: The mean failure load for the three groups was 794, 647 and 724 N, respectively. Statistical analysis did not show any significant differences between the fracture resistance of the three experimental groups (P=0.0579). All failures in group 1, eight in group 2 and three in group 3, were unrestorable. Fisher’s Exact test showed significant difference between group 3 and the two other groups (P<0.05 ).   Conclusion : If there is a 2-mm ferrule, the type of post and core does not have a significant effect on the fracture resistance, but it has a significant effect on the failure mode

Alkali therapy protects renal function, suppresses inflammation, and improves cellular metabolism in kidney disease

Chronic kidney disease (CKD) affects approximately 10–13% of the population worldwide and halting its progression is a major clinical challenge. Metabolic acidosis is both a consequence and a possible driver of CKD progression. Alkali therapy counteracts these effects in CKD patients, but underlying mechanisms remain incompletely understood. Here we show that bicarbonate supplementation protected renal function in a murine CKD model induced by an oxalate-rich diet. Alkali therapy had no effect on the aldosterone–endothelin axis but promoted levels of the anti-aging protein klotho; moreover, it suppressed adhesion molecules required for immune cell invasion along with reducing T-helper cell and inflammatory monocyte invasion. Comparing transcriptomes from the murine crystallopathy model and from human biopsies of kidney transplant recipients (KTRs) suffering from acidosis with or without alkali therapy unveils parallel transcriptome responses mainly associated with lipid metabolism and oxidoreductase activity. Our data reveal novel pathways associated with acidosis in kidney disease and sensitive to alkali therapy and identifies potential targets through which alkali therapy may act on CKD and that may be amenable for more targeted therapies