Modulating the phenotype and function of bone marrow-derived macrophages via mandible and femur osteoblasts.

Various studies have been investigated the phenotypic and functional distinctions of craniofacial and long bone cells involved in bone regeneration. However, the process of bone tissue regeneration after bone grafting involves complicated interactions between different cell types at the donor-recipient site. Additionally, differences in alterations of the immune microenvironment at the recipient site remained to be explored. Osteoblasts (OBs) and macrophages (MØ) play essential roles in the bone restoration and regeneration processes in the bone and immune systems, respectively. The modulation of MØ on OBs has been extensively explored in the literature, whereas limited research has been conducted on the influence of OBs on the MØ phenotype and function. In the present study, OBs from the mandible and femur (MOBs and FOBs, respectively) promoted cranial defect regeneration in rats, with better outcomes noted in the MOBs-treated group. After MOBs transplantation, a significant inflammatory response was induced, accompanied by an early increase in IL-10 secretion. And then, there was an upregulation in M2-MØ-related cell markers and inflammatory factor expression. Condition media (CM) of OBs mildly inhibited apoptosis in MØ, enhanced their migration and phagocytic functions, and concurrently increased iNOS and Arg1 expression, with MOB-CM demonstrating more pronounced effects compared to FOB-CM. In conclusion, our investigation showed that MOBs and FOBs have the ability to modulate MØ phenotype and function, with MOBs exhibiting a stronger regulatory potential. These findings provide a new direction for improving therapeutic strategies for bone regeneration in autologous bone grafts from the perspective of the immune microenvironment.

Emerging role of NEDD8-mediated neddylation in age-related metabolic diseases.

Aging in humans is associated with abdominal distribution and remodeling of body fat and a parallel gradual increase in the prevalence of metabolic diseases such as obesity, type 2 diabetes mellitus and fatty liver disease, as well as the risk of developing metabolic complications. Current treatments might be improved by understanding the detailed mechanisms underlying the onset of age-related metabolic disorders. Neddylation, a post-translational modification that adds the ubiquitin-like protein NEDD8 to substrate proteins, has recently been linked to age-related metabolic diseases, opening new avenues of investigation and raising a potential target for treatment of these diseases. In this review, we will focus on the potential role of NEDD8-mediated neddylation in age-related metabolic dysregulation, insulin resistance, obesity, type 2 diabetes mellitus and fatty liver. We propose that alterations in NEDD8-mediated neddylation contribute to triggering insulin resistance and the development of age-related metabolic dysregulation, thus highlighting NEDD8 as a promising therapeutic target for preventing age-related metabolic diseases.

Machine learning-based radiomics for predicting BRAF-V600E mutations in ameloblastoma.

Background: Ameloblastoma is a locally invasive and aggressive epithelial odontogenic neoplasm. The BRAF-V600E gene mutation is a prevalent genetic alteration found in this tumor and is considered to have a crucial role in its pathogenesis. The objective of this study is to develop and validate a radiomics-based machine learning method for the identification of BRAF-V600E gene mutations in ameloblastoma patients. Methods: In this retrospective study, data from 103 patients diagnosed with ameloblastoma who underwent BRAF-V600E mutation testing were collected. Of these patients, 72 were included in the training cohort, while 31 were included in the validation cohort. To address class imbalance, synthetic minority over-sampling technique (SMOTE) is applied in our study. Radiomics features were extracted from preprocessed CT images, and the most relevant features, including both radiomics and clinical data, were selected for analysis. Machine learning methods were utilized to construct models. The performance of these models in distinguishing between patients with and without BRAF-V600E gene mutations was evaluated using the receiver operating characteristic (ROC) curve. Results: When the analysis was based on radiomics signature, Random Forest performed better than the others, with the area under the ROC curve (AUC) of 0.87 (95%CI, 0.68-1.00). The performance of XGBoost model is slightly lower than that of Random Forest, and its AUC is 0.83 (95% CI, 0.60-1.00). The nomogram evident that among younger women, the affected region primarily lies within the mandible, and patients with larger tumor diameters exhibit a heightened risk. Additionally, patients with higher radiomics signature scores are more susceptible to the BRAF-V600E gene mutations. Conclusions: Our study presents a comprehensive radiomics-based machine learning model using five different methods to accurately detect BRAF-V600E gene mutations in patients diagnosed with ameloblastoma. The Random Forest model's high predictive performance, with AUC of 0.87, demonstrates its potential for facilitating a convenient and cost-effective way of identifying patients with the mutation without the need for invasive tumor sampling for molecular testing. This non-invasive approach has the potential to guide preoperative or postoperative drug treatment for affected individuals, thereby improving outcomes.

Effect of platelet-rich plasma on the attachment of periodontal ligament fibroblasts to the diseased root surface and the attendant collagen formation.

OBJECTIVE: To investigate the effect of different concentrations of platelet-rich plasma (PRP) on collagen formation via periodontal ligament fibroblasts (PDLFs) on the surface of demineralised diseased tooth roots. METHODS: Various PDLFs were grown from tissue explants, with the cells between the fifth and eighth passage in the culture used. Human whole blood obtained from healthy subjects was collected in tubes containing an anticoagulant (acid-citrate-dextrose) and centrifuged (1300 rpm for 10 min) before the supernatant PRP layer was removed. A second spin at (2000 rpm for 10 min) produced the PRP fraction. The effect of PRP of various concentrations on the attachment of PDLFs on the diseased root surface of human teeth demineralised with ethylenediaminetetraacetic acid (EDTA) and treated with the PRP was then investigated in terms of PRP collagen formation, with the formation observed using the Sirius red staining method. RESULTS: The optical density values of the experimental groups were statistically significantly higher than those of the control groups (P < 0.05), while the Sirius red staining returned positive results for both the experimental group (A) and the control group (B). The images were analysed using a histogram, and a statistically significant difference was found (P < 0.05). CONCLUSION: While PRP could promote the attachment and collagen formation of PDLFs on the diseased root surface of human teeth demineralised with EDTA and treated with PRP, the effect is potentially reduced when the dose exceeds 20%.

SETD1A promotes the proliferation and glycolysis of nasopharyngeal carcinoma cells by activating the PI3K/Akt pathway.

Nasopharyngeal carcinoma is one of the common malignant tumors that the pathogenesis has not yet been completely defined. SETD1A (histone lysine methyltransferase SET domain-containing 1A) is related to the occurrence of various cancers. However, the role of SETD1A in nasopharyngeal carcinoma remains unclear. The SETD1A overexpression vector, si-NC, si-SETD1A#1, and si-SETD1A#2 were transfected into nasopharyngeal carcinoma cells to overexpress or knockdown SETD1A expression. The assay of biofunction was used to explore the role of SETD1A in nasopharyngeal carcinoma cells. The assay of glucose uptake, lactate release, ATP level, western blot, cell proliferation, and cellular apoptosis analysis were performed to investigate the potential mechanism of SETD1A regulation in nasopharyngeal carcinoma. This study was the first to show that SETD1A was upregulated in nasopharyngeal carcinoma cells and the overexpression of SETD1A significantly promoted the cell proliferation and glycolysis and suppressed the cellular apoptosis. Moreover, SETD1A enhances aerobic glycolysis and cell biological function of nasopharyngeal carcinoma cells via PI3K/AKT signaling pathway. SETD1A induced PI3K/AKT activation and subsequently prevented cellular apoptosis. In conclusion, this study identified overexpressed SETD1A as a positive regulator of proliferation that induced nasopharyngeal carcinoma cells' aerobic glycolysis via PI3K/AKT signaling activation in vitro. This study laid a strong foundation for unveiling the precise anticancer mechanism of SETD1A. The SETD1A may become a novel biomarker for further inhibitor design to obstruct the PI3K/AKT-dependent nasopharyngeal carcinoma progression.

Periodontitis-related salivary microbiota aggravates Alzheimer's disease via gut-brain axis crosstalk.

The oral cavity is the initial chamber of digestive tract; the saliva swallowed daily contains an estimated 1.5 × 1012 oral bacteria. Increasing evidence indicates that periodontal pathogens and subsequent inflammatory responses to them contribute to the pathogenesis of Alzheimer's disease (AD). The intestine and central nervous system jointly engage in crosstalk; microbiota-mediated immunity significantly impacts AD via the gut-brain axis. However, the exact mechanism linking periodontitis to AD remains unclear. In this study, we explored the influence of periodontitis-related salivary microbiota on AD based on the gut-brain crosstalk in APPswe/PS1ΔE9 (PAP) transgenic mice. Saliva samples were collected from patients with periodontitis and healthy individuals. The salivary microbiota was gavaged into PAP mice for two months. Continuous gavage of periodontitis-related salivary microbiota in PAP mice impaired cognitive function and increased ß-amyloid accumulation and neuroinflammation. Moreover, these AD-related pathologies were consistent with gut microbial dysbiosis, intestinal pro-inflammatory responses, intestinal barrier impairment, and subsequent exacerbation of systemic inflammation, suggesting that the periodontitis-related salivary microbiota may aggravate AD pathogenesis through crosstalk of the gut-brain axis. In this study, we demonstrated that periodontitis might participate in the pathogenesis of AD by swallowing salivary microbiota, verifying the role of periodontitis in AD progression and providing a novel perspective on the etiology and intervention strategies of AD.

Technical Note: Comparative Analysis and Evaluation of the Polymerase Chain Reaction and Rapid Urease Test for Diagnosing Helicobacter pylori Infection.

This study was conducted in order to compare the performance of the rapid urease test (RUT) with that of the polymerase chain reaction (PCR) for H. pylori diagnosis. Of 536 patients, 81% were concordant between RUT and PCR, 16% were concordant between two PCR assays but not between RUT and PCR, and the remaining 3% showed discrepant results between two PCR assays evaluated. Low bacterial load was shown to be a significant factor associated with false-negative diagnosis by RUT, and non-H. pylori urease activity or bacterial alkaline-generating activity was the cause of false-positive diagnosis. Disagreement between the PCR assays was due to single nucleotide polymorphisms in primers or probes causing decreased amplification efficiency and false-negative diagnosis when the bacterial load in the samples was low.

Experimental Periodontitis Deteriorates Cognitive Function and Impairs Insulin Signaling in a Streptozotocin-Induced Alzheimer's Disease Rat Model.

BACKGROUND: With advancements in periodontal medicine, the relationship between periodontitis and systemic diseases has garnered increasing attention. Recently, emerging evidence has indicated that periodontitis may be involved in the pathogenesis of Alzheimer's disease (AD). OBJECTIVE: To assess the impact of experimental periodontitis on cognitive function deficits in a rat model of streptozotocin-induced AD and determine the mechanisms underlying these effects. METHODS: Rats were randomly assigned to the control (C), experimental periodontitis (P), Alzheimer's disease (AD), and experimental periodontitis with streptozotocin-induced AD (AD-P) groups. Experimental periodontitis was induced using ligation and coating with Porphyromonas gingivalis. In the AD-P group, AD was induced by intracerebroventricular injection of streptozotocin after 6 weeks of experimental periodontitis induction. RESULTS: Compared with the group C rats, those in group P exhibited alveolar bone resorption, learning and memory function impairment, and decreased insulin sensitivity and insulin signaling-related protein expression. Glial cell activation and cognitive impairment in streptozotocin-induced groups with significantly increased phosphorylated tau levels were more pronounced relative to the C group. The number of neurons and insulin sensitivity and insulin signaling-related protein expression in group AD-P rats were lower than those in the AD alone group, while the expressions of glial fibrillary acidic protein, tau phosphorylation, interleukin-6, and cyclooxygenase-2 were significantly increased. CONCLUSION: Periodontitis may be a risk factor exacerbating cognitive deficits in an AD-like neurodegenerative context, possibly by impairing the insulin signaling pathway and stimulating gliosis and neuroinflammation.

Periodontitis Deteriorates Cognitive Function and Impairs Neurons and Glia in a Mouse Model of Alzheimer's Disease.

BACKGROUND: Although periodontitis is reportedly associated with increased cognitive decline in Alzheimer's disease, the mechanisms underlying this process remain unknown. Porphyromonas gingivalis lipopolysaccharide (P.g-LPS) is an endotoxin associated with periodontal disease. OBJECTIVE: We investigated the effect of periodontitis on learning capacity and memory of amyloid-ß protein precursor (AßPP)/presenilin (PS1) transgenic mice along with the mechanisms underlying these effects. METHODS: Mice were randomly assigned to three groups, namely AßPP/PS1 (control), P.g-LPS Injection, and P.g-LPS Injection + Ligation. Mice from the P.g-LPS Injection group were injected with P.g-LPS in the periodontal tissue three times per week for 8 weeks, while mice from the P.g-LPS Injection + Ligation group were injected with P.g-LPS and subjected to ligation of the gingival sulcus of the maxillary second molar. RESULTS: Expression of gingival proinflammatory cytokines as well as alveolar bone resorption in P.g-LPS-injected and ligatured mice was increased compared to that in control mice. Mice in the P.g-LPS Injection + Ligation group exhibited cognitive impairment and a significant reduction in the number of neurons. Glial cell activation in the experimental groups with significantly increased amyloid-ß (Aß) levels was more pronounced relative to the control group. Induction of periodontitis was concurrent with an increase in cyclooxygenase-2, inducible nitric oxide synthase, AßPP, and beta-secretase 1 expression and a decrease in A disintegrin and metalloproteinase domain-containing protein 10 expression. CONCLUSION: These findings indicated that periodontitis exacerbated learning and memory impairment in AßPP/PS1 mice and augmented Aß and neuroinflammatory responses. Our study provides a theoretical basis for risk prediction and early intervention of Alzheimer's disease and periodontitis.

Poor oral health conditions and cognitive decline: Studies in humans and rats.

BACKGROUND: The relationship between poor oral health conditions and cognitive decline is unclear. OBJECTIVE: To examine the association between oral health and cognition in humans and rats. METHODS: In humans: a cross-sectional study was conducted. Cognitive levels were evaluated by the Mini Mental State Examination (MMSE); oral conditions were reflected by the number of missing index teeth, bleeding on probing, and probing pocket depth (PD). In rats: a ligature-induced (Lig) periodontitis model and Aß25-35-induced model of Alzheimer's disease (AD) were established; tumor necrosis factor-α (TNF-α), interleukin 1 (IL-1), interleukin 6 (IL-6), and C-reactive protein levels in the hippocampus and cerebral cortex were detected. RESULTS: MMSE scores for the number of missing index teeth ≥ 7 group were significantly lower than those in the ≤ 6 group. A negative relationship (correlation coefficient ρ = -0.310, P = 0.002) was observed between MMSE scores and number of missing index teeth. More missing index teeth and lower education levels were independent risk factors for cognitive decline. A negative relationship (correlation coefficient ρ = -0.214, P = 0.031) was observed between MMSE scores and average PD. TNF-α and IL-6 levels in the hippocampus of the Lig+AD group were significantly higher than those of the AD group. IL-1 and IL-6 levels in the cerebral cortex of the Lig+AD group were significantly higher than those of the AD group. CONCLUSION: Poor oral health conditions including more missing index teeth and higher average PD may be risk factors for cognitive decline. Periodontitis may increase inflammatory cytokines in rat models of AD.