Objective Inflammatory bowel diseases (IBDs) feature multiple cellular stress responses, including endoplasmic reticulum (ER) unfolded protein responses (UPRs). UPRs represent autoregulatory pathways that adjust organelle capacity to cellular demand. A similar mechanism, mitochondrial UPR (mtUPR), has been described for mitochondria. ER UPR in intestinal epithelial cells (IECs) contributes to the development of intestinal inflammation, and since mitochondrial alterations and dysfunction are implicated in the pathogenesis of IBDs, the authors characterised mtUPR in the context of intestinal inflammation. Methods Truncated ornithine transcarbamylase was used to selectively induce mtUPR in a murine IEC line. Dextran sodium sulphate (DSS) was administered to PKR (double-stranded-RNA-activated protein kinase) knockout mice to induce IEC stress in vivo and to test for their susceptibility to DSS-induced colitis. Expression levels of the mitochondrial chaperone chaperonin 60 (CPN60) and PKR were quantified in IECs from patients with IBDs and from murine models of colitis using immunohistochemistry and Western blot analysis. Results Selective mtUPR induction by truncated ornithine transcarbamylase transfection triggered the phosphorylation of eukaryotic translation initiation factor (eIF) 2α and cJun through the recruitment of PKR. Using pharmacological inhibitors and small inhibitory RNA, the authors identified mtUPR-induced eIF2α phosphorylation and transcription factor activation (cJun/AP1) as being dependent on the activities of the mitochondrial protease ClpP and the cytoplasmic kinase PKR. Pkr−/− mice failed to induce CPN60 in IECs upon DSS treatment at early time points and subsequently showed an almost complete resistance to DSS-induced colitis. Under inflammatory conditions, primary IECs from patients with IBDs and two murine models of colitis exhibited a strong induction of the mtUPR marker protein CPN60 associated with enhanced expression of PKR. Conclusion PKR integrates mtUPR into the disease-relevant ER UPR via eIF2α phosphorylation and AP1 activation. Induction of mtUPR and PKR was observed in IECs from murine models and patients with IBDs. The authors’ results indicate that PKR might link mitochondrial stress to intestinal inflammation.

Cell death mechanisms have been associated with the development of inflammatory bowel diseases in humans and mice. Recent studies suggested that a complex crosstalk between autophagy/apoptosis, microbe sensing, and enhanced endoplasmic reticulum stress in the epithelium could play a critical role in these diseases. In addition, necroptosis, a relatively novel programmed necrosis-like pathway associated with TNF receptor activation, seems to be also present in the pathogenesis of Crohn's disease and in specific animal models for intestinal inflammation. This review attempts to cover new data related to cell death mechanisms and inflammatory bowel diseases.

Objectives To compare the treatments used to treat dentin hypersensitivity (DH), based on its efficacy and effect duration. Methods Medline/PubMed, Cochrane Library, EMBASE and ClinicalTrials were searched for articles published between 1 January 2008 and 14 November 2018, in English, Portuguese or Spanish, reporting clinical trials, completed and with results. This systematic review protocol was registered in PROSPERO, number CRD42019121986. Results Seventy‐four randomised clinical trials were included in the systematic review, reporting patients from 16 to 65 years old, with a clinical diagnosis of DH, that evaluate the efficacy of a desensitising product, compared to pre‐treatment, used the evaporative method stimulation and the visual analogue scale. These studies evaluated 5366 patients and at least 9167 teeth. Seven follow‐up periods were considered corresponding to an immediate, medium or long‐time effect. Sixty‐six studies were included in the quantitative synthesis. Glutaraldehyde with HEMA, glass ionomer cements and Laser present significant immediate (until 7 days) DH reduction. Medium‐term (until 1 month) reduction was observed in stannous fluoride, glutaraldehyde with HEMA, hydroxyapatite, glass ionomer cements and Laser groups. Finally, long‐term significant reduction was seen at potassium nitrate, arginine, glutaraldehyde with HEMA, hydroxyapatite, adhesive systems, glass ionomer cements and LASER. Conclusions All active ingredients show efficacy in DH reduction in different follow‐up times. Only in‐office treatments are effective in immediate DH reduction, maintaining its efficacy over time. For long‐time effects, at‐home treatments can also be used. More standardised evaluation protocols should be implemented to increase the robustly of the results.