Objectives: The aim of this systematic review was to assess the oral health‐related quality of life (OHRQoL) of patients with osteoarthritis (OA) of the temporomandibular joint (TMJ).Methods: This systematic literature search applied the search terms "oral health‐related quality of life AND osteoarthritis of jaw OR arthritis of temporomandibular joint AND oral health‐related quality of life" in PubMed, Medline, Web of Science and Scopus. Eligibility criteria were publication until 31 August 2021, examination of children or adults with OA of TMJ, reporting of any OHRQoL measurement and a full text in English language. Two different, independent and experienced reviewers performed this systematic literature search. The analysis of respective data was qualitative. For quality appraisal, the available checklist from the Agency for Healthcare Research and Quality (AHRQ) was applied.Results: Out of 102 findings, eight studies were included in qualitative analysis. Seven clinical investigations were performed in adults aged between 34 and 43 years. The other included study was performed on children. The quality of two studies was moderate, and six studies were evaluated as of high quality. Most studies applied the 14‐item short form of the oral health impact profile (OHIP 14) for assessment of OHRQoL. OHIP 14 ranged between 9.24 and 38.86 points in means of sum score. Comparison with healthy individuals revealed worse OHRQoL of OA patients in two studies. Associations between OHRQoL with either oral health, general quality of life or disease‐related parameters were rarely reported and heterogeneous. Five of the included studies reported subscales of OHIP 14, showing an impairment in all subscales.Conclusions: There are hints that patients with OA of the TMJ show a reduced OHRQoL. More studies are needed, especially regarding oral health, disease‐related parameters and pain intensity and its potential influence on OHRQoL.

Aim. To identify the critical genetic and epigenetic biomarkers by constructing the long noncoding RNA- (lncRNA-) related competing endogenous RNA (ceRNA) network involved in irreversible pulp neural inflammation (pulpitis). Materials and Methods. The public datasets regarding irreversible pulpitis were downloaded from the gene expression omnibus (GEO) database. The differential expression analysis was performed to identify the differentially expressed genes (DEGs) and DElncRNAs. Functional enrichment analysis was performed to explore the biological processes and signaling pathways enriched by DEGs. By performing a weighted gene coexpression network analysis (WGCNA), the significant gene modules in each dataset were identified. Most importantly, DElncRNA-DEmRNA regulatory network and DElncRNA-associated ceRNA network were constructed. A transcription factor- (TF-) DEmRNA network was built to identify the critical TFs involved in pulpitis. Result. Two datasets (GSE92681 and GSE77459) were selected for analysis. DEGs involved in pulpitis were significantly enriched in seven signaling pathways (i.e., NOD-like receptor (NLR), Toll-like receptor (TLR), NF-kappa B, tumor necrosis factor (TNF), cell adhesion molecules (CAMs), chemokine, and cytokine-cytokine receptor interaction pathways). The ceRNA regulatory relationships were established consisting of three genes (i.e., LCP1, EZH2, and NR4A1), five miRNAs (i.e., miR-340-5p, miR-4731-5p, miR-27a-3p, miR-34a-5p, and miR-766-5p), and three lncRNAs (i.e., XIST, MIR155HG, and LINC00630). Six transcription factors (i.e., GATA2, ETS1, FOXP3, STAT1, FOS, and JUN) were identified to play pivotal roles in pulpitis. Conclusion. This paper demonstrates the genetic and epigenetic mechanisms of irreversible pulpitis by revealing the ceRNA network. The biomarkers identified could provide research direction for the application of genetically modified stem cells in endodontic regeneration.

Background. Oxidative stress is implicated in the progression of many neurological diseases, which could be induced by various chemicals, such as hydrogen peroxide (H₂O₂) and acrylamide. Triphala is a well‐recognized Ayurvedic medicine that possesses different therapeutic properties (e.g., antihistamine, antioxidant, anticancer, anti‐inflammatory, antibacterial, and anticariogenic effects). However, little information is available regarding the neuroprotective effect of Triphala on oxidative stress. Materials and Methods. An in vitro H₂O₂‐induced SH‐SY5Y cell model and an in vivo acrylamide‐induced zebrafish model were established. Cell viability, apoptosis, and proliferation were examined by MTT assay, ELISA, and flow cytometric analysis, respectively. The molecular mechanism underlying the antioxidant activity of Triphala against H₂O₂ was investigated dose dependently by Western blotting. The in vivo neuroprotective effect of Triphala on acrylamide‐induced oxidative injury in Danio rerio was determined using immunofluorescence staining. Results. The results indicated that Triphala plays a neuroprotective role against H₂O₂ toxicity in inhibiting cell apoptosis and promoting cell proliferation. Furthermore, Triphala pretreatment suppressed the phosphorylation of the mitogen‐activated protein kinase (MARK) signal pathway (p‐Erk1/2, p‐JNK1/2, and p‐p38), whereas it restored the activities of antioxidant enzymes (superoxide dismutase 1 (SOD1) and catalase) in the H₂O₂‐treated SH‐SY5Y cells. Consistently, similar protective effects of Triphala were observed in declining neuroapoptosis and scavenging free radicals in the zebrafish central neural system, possessing a critical neuroprotective property against acrylamide‐induced oxidative stress. Conclusion. In summary, Triphala is a promising neuroprotective agent against oxidative stress in SH‐SY5Y cells and zebrafishes with significant antiapoptosis and antioxidant activities.

Background. The human antimicrobial peptide defensin beta 1 (DEFB1) has been found to play antimicrobial and anti-inflammatory roles in oral diseases; however, its tumor-regulating role in oral squamous cell carcinoma (OSCC) has not yet been researched by using an integrative bioinformatics approach. Objective. To investigate the regulating mechanisms of the DEFB1 gene in OSCC in terms of its expression patterns, prognostic values, biological functions, and implication for tumor immunity. Methods. The DEFB1 gene expression pattern and regulatory involvement in OSCC were investigated using publically accessible data from TCGA database. R software tools and public web servers were utilized to conduct statistical analysis of data from cancer and noncancerous samples. Results. DEFB1 was found to be significantly downregulated in OSCC tumor samples compared with healthy control oral samples. The DEFB1 gene was found associated with the prognostic outcomes of OSCC, and its upregulation represented better survival outcome. Gene set enrichment analysis (GSEA) results showed that DEFB1-significantly correlated genes were mainly enriched in four signaling pathways mediating the antitumor role of DEFB1 in OSCC, including extracellular matrix-related pathway, RTK/PI3K/AKT/mTOR pathway, keratinization, and cytokine-related pathway. The gene-gene interaction network showed that DEFB1 was closely correlated with several genes, for example, CCR6 (C-C motif chemokine receptor 6), CXCL1 (C-X-C motif chemokine ligand 1), MAP4K2 (mitogen-activated protein kinase kinase kinase kinase 2), PTGER3 (prostaglandin E receptor 3), and MMP7 (matrix metallopeptidase 7). Moreover, DEFB1 was found to be involved in the tumor immunity of OSCC by regulating the function of tumor macrophage cells, mast cells, T cells, and NK cells. Conclusions. Given the dysregulation, prognostic value, and tumor progression-related biological pathway alteration, indicating the tumor immune-modulatory role of DEFB1 in OSCC, the DEFB1 gene should be regarded as a potential therapeutic target for treating oral cancer.

Objective. This study investigated the nature of shared transcriptomic alterations in PBMs from periodontitis and atherosclerosis to unravel molecular mechanisms underpinning their association. Methods. Gene expression data from PBMs from patients with periodontitis and those with atherosclerosis were each downloaded from the GEO database. Differentially expressed genes (DEGs) in periodontitis and atherosclerosis were identified through differential gene expression analysis. The disease-related known genes related to periodontitis and atherosclerosis each were downloaded from the DisGeNET database. A Venn diagram was constructed to identify crosstalk genes from four categories: DEGs expressed in periodontitis, periodontitis-related known genes, DEGs expressed in atherosclerosis, and atherosclerosis-related known genes. A weighted gene coexpression network analysis (WGCNA) was performed to identify significant coexpression modules, and then, coexpressed gene interaction networks belonging to each significant module were constructed to identify the core crosstalk genes. Results. Functional enrichment analysis of significant modules obtained by WGCNA analysis showed that several pathways might play the critical crosstalk role in linking both diseases, including bacterial invasion of epithelial cells, platelet activation, and Mitogen-Activated Protein Kinases (MAPK) signaling. By constructing the gene interaction network of significant modules, the core crosstalk genes in each module were identified and included: for GSE23746 dataset, RASGRP2 in the blue module and VAMP7 and SNX3 in the green module, as well as HMGB1 and SUMO1 in the turquoise module were identified; for GSE61490 dataset, SEC61G, PSMB2, SELPLG, and FIBP in the turquoise module were identified. Conclusion. Exploration of available transcriptomic datasets revealed core crosstalk genes (RASGRP2, VAMP7, SNX3, HMGB1, SUMO1, SEC61G, PSMB2, SELPLG, and FIBP) and significant pathways (bacterial invasion of epithelial cells, platelet activation, and MAPK signaling) as top candidate molecular linkage mechanisms between atherosclerosis and periodontitis.

Head and neck squamous cell carcinoma (HNSCC) develops within a chronically inflamed tumor microenvironment (TME) where metabolic reprogramming and immune suppression tightly co-evolve. A prominent example is the tryptophan–kynurenine (Trp–Kyn) pathway, initiated by indoleamine 2,3-dioxygenase 1/2 (IDO1/IDO2) and tryptophan 2,3-dioxygenase (TDO2), which converts tryptophan into kynurenine and downstream metabolites that engage stress-response programs and aryl hydrocarbon receptor (AhR) signaling. In HNSCC, Trp–Kyn enzymes are inducible by interferons and oncogenic cues and are distributed across malignant cells as well as cancer-associated fibroblasts, endothelial cells and tumor-associated myeloid populations, generating spatially restricted “Trp-low/Kyn-high” immunometabolic niches. Within these niches, tryptophan starvation and kynurenine-driven signaling converge to suppress effector T-cell expansion, promote regulatory T-cell programs, undermine dendritic-cell priming and reinforce tolerogenic myeloid states, collectively fostering T-cell exhaustion and reduced sensitivity to PD-1/PD-L1 blockade. Emerging bulk, single-cell and spatial multi-omics studies support the idea that pathway activity is compartmentalized rather than uniform, providing a mechanistic rationale for the limited performance of first-generation IDO1 inhibitor strategies in unselected clinical settings. This mini-review synthesizes current evidence on Trp–Kyn microdomains in the HNSCC TME and discusses therapeutic opportunities that move beyond single-enzyme inhibition, including dual IDO1/TDO2 targeting, AhR antagonism and biomarker-guided combination regimens to restore antitumor immunity.