Search

Recognition of pathogen-associated molecular patterns can triggerthe inositol- requiring enzyme 1[alpha] (IRE1[alpha]) arm of the endoplasmic reticulum (ER) stress response in innate immune cells. This process maintains ER homeostasis and also coordinates diverse immunomodulatory programs during bacterial and viral infections. However, the role of innate IRE1[alpha] signaling in response to fungal pathogens remains elusive. Here, we report that systemic infection with the human opportunistic fungal pathogen Candida albicans induced proinflammatory IRE1[alpha] hyperactivation in myeloid cells that led to fatal kidney immunopathology. Mechanistically, simultaneous activation of the TLR/IL-1R adaptor protein MyD88 and the C-type lectin receptor dectin-1 by C. albicans induced NADPH oxidase-driven generation of ROS, which caused ER stress and IRE1[alpha]-dependent overexpression of key inflammatory mediators such as IL-1[beta], IL-6, chemokine (C-C motif) ligand 5 (CCL5), prostaglandin E2 ([PCE.sub.2]), and TNF- [alpha]. Selective ablation of IRE1[alpha] in leukocytes, ortreatment with an IRE1[alpha] pharmacological inhibitor, mitigated kidney inflammation and prolonged the survival of mice with systemic C. albicans infection. Therefore, controlling IRE1[alpha] hyperactivation may be useful for impeding the immunopathogenic progression of disseminated candidiasis., Introduction Sensing and responding to pathogens entails massive protein synthesis, folding, modification, and trafficking in immune cells, which are processes governed by the endoplasmic reticulum (ER). The excess demand in [...]

Background: Optical coherence tomography (OCT) is an emerging, radiation-free diagnostic tool in dentistry, providing high-resolution, real-time imaging of both hard and soft tissues, including periodontal areas, for more accurate postoperative evaluations. This study aims to investigate the efficacy of OCT on periodontal tissues in animals by comparing the healing effects of laser therapy with those of conventional surgical instruments. Methods: Six rabbits underwent periodontal surgery using a laser, scalpel, and punch to perform an apically positioned flap on the mandibular anterior incisors and to create a tongue ulcer on the dorsal surface of the tongue. Visual and OCT evaluations were conducted on days 1, 2, 3, 7, and 14. Results: In periodontal surgery, the laser exhibited slightly faster healing compared to other methods. In tongue ulcer formation, the scalpel and punch groups demonstrated slightly faster healing than that of the laser. However, both methods ultimately showed similar healing outcomes. Conclusions: In the dental field, OCT is emerging as a valuable tool for assessing healing, including early stages of healing, in periodontal therapy. [ABSTRACT FROM AUTHOR]

Mechanosensitive ion channels, particularly Piezo channels, are widely expressed in various tissues. However, their role in immune cells remains underexplored. Therefore, this study aimed to investigate the functional role of Piezo1 in the human eosinophil cell line AML14.3D10. We detected Piezo1 mRNA expression, but not Piezo2 expression, in these cells, confirming the presence of the Piezo1 protein. Activation of Piezo1 with Yoda1, its specific agonist, resulted in a significant calcium influx, which was inhibited by the Piezo1-specific inhibitor Dooku1, as well as other nonspecific inhibitors (Ruthenium Red, Gd3+, and GsMTx-4). Further analysis revealed that Piezo1 activation modulated the expression and secretion of both pro-inflammatory and anti-inflammatory cytokines in AML14.3D10 cells. Notably, supernatants from Piezo1-activated AML14.3D10 cells enhanced capsaicin and ATP-induced calcium responses in the dorsal root ganglion neurons of mice. These findings elucidate the physiological role of Piezo1 in AML14.3D10 cells and suggest that factors secreted by these cells can modulate the activity of transient receptor potential 1 (TRPV1) and purinergic receptors, which are associated with pain and itch signaling. The results of this study significantly advance our understanding of the function of Piezo1 channels in the immune and sensory nervous systems. [ABSTRACT FROM AUTHOR]

Objective and Background: This research aimed to examine the role of C‐X‐C motif chemokine ligand 5 (CXCL5) and C‐X‐C motif chemokine ligand 8 (CXCL8; also known as IL‐8) in neutrophilic inflammation triggered by peri‐implantitis and to shed light on the underlying mechanisms that link them to the development of this condition. Materials: This study included 40 patients who visited the Department of Periodontology at Kyungpook University Dental Hospital. They were divided into two groups based on their condition: healthy implant (HI) group (n = 20) and peri‐implantitis (PI) group (n = 20). Biopsy samples of PI tissue were collected from the patients under local anesthesia. HI tissue was obtained using the same method during the second implant surgery. To construct libraries for control and test RNAs, the QuantSeq 3′ mRNA‐Seq Library Prep Kit (Lexogen, Inc., Austria) was used according to the manufacturer's instructions. Samples were pooled based on representative cytokines obtained from RNA sequencing results and subjected to Reverse transcription‐quantitative polymerase chain reaction (RT‐qPCR). Hematoxylin and eosin staining, and immunohistochemistry (IHC) analysis were performed to visually assess expression levels and analyze tissue histology. Student's t‐test was employed to conduct statistical analyses. Results: Initially, heatmaps were used to examine gene expression variations between the HI and PI groups based on the results of RNA sequencing. Notably, among various cytokines, CXCL5 and CXCL8 had the highest expression levels in the PI group compared with the HI group, and they are known to be associated with inflammatory responses. In the gingival tissues, the expression of genes encoding cytokines such as interleukin (IL)‐1β, tumor necrosis factor‐alpha (TNF)‐α, interleukin (IL)‐6, and CXCL5/CXCL8 was assessed via RT‐qPCR. The mRNA expression level of CXCL5/CXCL8 significantly increased in the PI group compared with the HI group (p <.045). Contrarily, the mRNA expression level of interleukin 36 receptor antagonist (IL36RN) significantly decreased (p <.008). IHC enabled examination of the distribution and intensity of CXCL5/CXCL8 protein expression within the tissue samples. Specifically, increased levels of CXCL5/CXCL8 promote inflammatory responses, cellular proliferation, migration, and invasion within the peri‐implant tissues. These effects are mediated through the activation of the PI3K/Akt/NF‐κB signaling pathway. Conclusions: This study found that the PI sites had higher gene expression level of CXCL8/CXCL5 in the soft tissue than HI sites, which could help achieve more accurate diagnosis and treatment planning. [ABSTRACT FROM AUTHOR]