bioinformatics-identification-candidate-biomarkers-associated-with

Bioinformatics Identification of Candidate Biomarkers Associated with Periodontitis in Cytokine-Treated Periodontal Ligament Stem Cells

The primary objective of the current study was to investigate the potential molecular mechanism underlying cytokine-induced periodontal ligament stem ...

GGsTOP is a novel and selective inhibitor of gamma-glutamyl transferase (GGT), a cell-surface enzyme that has a key role in glutathione homeostasis and the maintenance of cellular reactive oxygen species (ROS). ROS are essential for wound healing. However, little is known about the molecular mechanisms underlying the inhibition of GGT by GGsTOP in human periodontal ligament cells (hPLCs). The present study assessed GGT expression in mouse periodontal ligament tissues, GGT activity in hPLCs, and the potential physiological effect of GGsTOP on hPLC migration. Immunohistochemical analysis confirmed that GGT was widely expressed in mouse periodontal ligament tissue. Treatment with GGsTOP was associated with greater proliferation and migration of hPLCs, and higher levels of cellular ROS compared with untreated hPLCs. However, the increase in intracellular ROS was attenuated in hPLCs co‑cultured with the anti‑oxidant N‑acetylcysteine (NAC), a precursor of glutathione. The higher ROS levels associated with GGsTOP treatment were in parallel with increases in the levels of type I collagen and alpha smooth muscle actin, which was inhibited in hPLCs co‑cultured with NAC. Thus, GGsTOP may promote hPLC migration and participate in the maintenance of the periodontal ligament apparatus via the ROS pathway. 

GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway.

Exacerbations of oral lichen planus (OLP) have been linked to the periods of psychological stress, anxiety and depression. The specific mechanism of the interaction is unclear. The aim of this study was to explore the candidate genes or molecules that play important roles in the interaction between OLP and depression. The BITOLA system was used to search all intermediate concepts relevant to the "Gene or Gene Product" for OLP and depression, and the gene expression data and tissue-specific gene data along with manual checking were then employed to filter the intermediate concepts. Finally, two genes (NCAM1, neural cell adhesion molecule 1; CD4, CD4 molecule) passed the follow-up inspection. By using the text mining can formulate a new hypothesis: NCAM1 and CD4 were identified as involved or potentially involved in the interaction between OLP and depression. These results offer a new clue for the experimenters and hold promise for developing innovative therapeutic strategies for these two diseases.

Using the BITOLA system to identify candidate molecules in the interaction between oral lichen planus and depression.

Hypoxia regulates a number of cell biological processes, including cell survival, development and differentiation. Deferoxamine (DFO), an oral chelator for blood transfusion patients, has been demonstrated to induce hypoxia and is frequently used as a hypoxia‑mimicking agent. The purpose of the present study was to investigate the influence of DFO on the proliferation, migration and osteogenic differentiation of human periodontal ligament cells (hPDLCs). The effects of DFO on hPDLC viability and migration were measured using an MTT and wound healing assay. To characterize the hypoxia microenvironment, the expression of hypoxia‑inducible factor‑1α (HIF‑1α) in hPDLCs treated with DFO was quantified using the reverse transcription‑quantitative polymerase chain reaction (RT‑qPCR). Subsequently, the osteogenic differentiation potential of DFO was determined by RT‑qPCR of the mRNA of osteogenic markers (runt‑related transcription factor 2 [Runx‑2], osteopontin [OPN] and collagen type I [Col‑1]). The alkaline phosphatase activity and mineral deposition were analyzed using alizarin red S staining. The MTT and wound healing assays demonstrated that low‑concentrations of DFO had little impact on hPDLC viability and migration 48 h into the treatment. DFO upregulated the expression of hPDLC genes specific for osteogenic differentiation: HIF‑1α, Runx‑2, OPN and Col‑1. Furthermore, formation of mineralized nodules was enhanced by DFO. The present study suggests that DFO provided favorable culture conditions to promote the osteogenic differentiation and mineralization of hPDLCs. The mechanism underlying these alterations remains to be elucidated.

Effects of deferoxamine on the osteogenic differentiation of human periodontal ligament cells.

Aspirin has positive effects on bone marrow mesenchymal stem cells (BMSCs) osteogenic differentiation. However, researchers did not give much thought to its effect on BMSCs adipogenic differentiation. Here, we analyzed the effect of aspirin on the BMSCs adipogenic differentiation. To detect whether the effect of aspirin on the adipogenic differentiation of BMSCs is associated with the disturbed epigenetic modification, the expression of histone deacetylases (HDACs), activity of HDACs and HAT, global histone H3 acetylation and H3k9 acetylation alterations were investigated. Moreover, to further explore and understand the binding mode between aspirin and HDACs, an attempt was made to identify the interaction between aspirin and the HDACs with the aid of in silico docking study. The results showed that aspirin could induce inhibition of BMSCs adipogenesis. The level of HDAC activity, global histone H3 acetylation, and H3k9 acetylation were all down regulated during adipogenic differentiation, and aspirin can reverse these decreases. Furthermore, the HDAC isoforms have different expression patterns in those progresses. The expression of HDAC9 was increased in a does-dependent manner when aspirin was introduced during BMSCs adipogenic differentiation. Docking study showed that high affinity of HDAC9 to aspirin was existed, suggesting that HDAC9 may has an important role in the process of aspirin-induced suppression of adipogenesis. Further studies are needed to define the intricate mechanisms of the HDAC isoforms, and all of these enable us to understand aspirin and its efficacy of inhibition of adipogenic differentiation and pave the way to aspirin clinical using for the tissue regenerating.

Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification.

Family with sequence similarity 20‑member C (FAM20C), a recently characterized Golgi kinase, performs numerous biological functions by phosphorylating more than 100 secreted proteins. However, the role of FAM20C in the salivary glands remains undefined. The present study demonstrated that FAM20C is mainly located in the cytoplasm of duct epithelial cells in the salivary glands. Fam20cf/f; Mmtv‑Cre mice were created in which Fam20c was inactivated in the salivary gland cells and observed that the number of ducts and the ductal cross‑sectional area increased significantly, while the number of acinar cells was reduced. The granular convoluted tubules (GCTs) exhibited an accumulation of aberrant secretory granules, along with a reduced expression and altered distribution patterns of β nerve growth factor, α‑amylase and bone morphogenetic protein (BMP) 4. This abnormality suggested that the GCT cells were immature and exhibited defects in developmental and secretory functions. In accordance with the morphological alterations and the reduced number of acinar cells, FAM20C deficiency in the salivary glands significantly decreased the salivary flow rate. The Na+, Cl- and K+ concentrations in the saliva were all significantly increased due to dysfunction of the ducts. Furthermore, Fam20c deficiency significantly increased BMP2 and BMP7 expression, decreased BMP4 expression, and attenuated the canonical and noncanonical BMP signaling pathways in the salivary glands. Collectively, the results of the present study demonstrate that FAM20C is a key regulator of acinar and duct structure and duct maturation and provide a novel avenue for investigating novel therapeutic targets for oral diseases including xerostomia.

Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice.

Behcet's syndrome, as a vasculitic disease involving multiple systems, often induces oral mucosal ulcers. However, levels of inflammatory cytokines and metabolites are unknown for the probability of developing the disease. This study aims to reveal the causal relationship between the cytokines and metabolites and Behcet's syndrome through Mendelian randomization analysis.

Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization.

Effective treatment of apical periodontitis remains challenging due to the persistent bacterial biofilms within the complex root canal anatomy. To address the limitations of conventional disinfectants regarding penetration depth and tissue irritation, this study developed a self-propelled hollow "urchin-like" MnO micromotor  a facile one-step hydrothermal method. The micromotors are propelled by oxygen bubbles generated through catalytic decomposition of HO, demonstrating remarkable autonomous motion at 33.8 ± 2.5 μm s in 2% HO, enabling deep penetration into the complex root canal architecture. Their unique spiny architecture not only enhanced HO catalytic efficiency for reactive oxygen species generation but also physically disrupted biofilms (67% disruption rate) through mechanical friction. This synergistic mechano-chemical action achieved 93.6% antibacterial efficacy against  while oxygenating the anaerobic microenvironment in deep root canal regions, with superior biocompatibility to sodium hypochlorite. This work presents an innovative disinfection strategy combining superior penetration, synergistic antibacterial activity, and clinical safety, offering a promising alternative to current disinfection methods in endodontics.

Biomimetic MnO micromotors with asymmetric sea urchin architecture for synergistic mechano-chemical eradication of endodontic biofilms.

Oral lichen planus (OLP) is a chronic immune-mediated inflammatory disease affecting the oral mucosa, with tongue lesions being clinically significant due to their association with oral cancer risk and taste dysfunction. However, the layer-specific molecular heterogeneity of the basal layer (BL), spinous layer (SL), and lamina propria (LP) in tongue OLP remains poorly characterized, limiting mechanistic understanding and therapeutic development.

Article	Year
GGsTOP increases migration of human periodontal ligament cells in vitro via reactive oxygen species pathway. Molecular medicine reports\| PubMed ID: 27035100	2016
Using the BITOLA system to identify candidate molecules in the interaction between oral lichen planus and depression. Behavioural brain research\| PubMed ID: 27913255	2017
Effects of deferoxamine on the osteogenic differentiation of human periodontal ligament cells. Molecular medicine reports\| PubMed ID: 29039615	2017
Aspirin-induced attenuation of adipogenic differentiation of bone marrow mesenchymal stem cells is accompanied by the disturbed epigenetic modification. The international journal of biochemistry & cell biology\| PubMed ID: 29471042	2018
Loss of Fam20c causes defects in the acinar and duct structure of salivary glands in mice. International journal of molecular medicine\| PubMed ID: 30864688	2019
Exploring the causal relationship between inflammatory cytokines, metabolites, and Behcet's syndrome: Mendelian randomization. Cytokine\| PubMed ID: 39756125	2025
Biomimetic MnO micromotors with asymmetric sea urchin architecture for synergistic mechano-chemical eradication of endodontic biofilms. Journal of materials chemistry. B\| PubMed ID: 41017585	2025
Spatial Proteomics Reveals Layer-Specific Molecular Landscapes and KRT17-Mediated Inflammatory Crosstalk in Tongue Oral Lichen Planus. The British journal of dermatology\| PubMed ID: 41640051	2026

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