Proteomic and single-cell analysis shed new light on the anti-inflammatory role of interferonß in chronic periodontitis.

Periodontitis, a condition that results in periodontal attachment loss and alveolar bone resorption, contributes to the global burden of oral disease. The underlying mechanism of periodontitis involves the dysbiosis and dyshomeostasis between host and oral microbes, among which the macrophage is one of the major innate immune cell players, producing interferon ß (IFNß) in response to bacterial infection. The objective of this research was to examine the interaction of macrophages with periodontitis and the role and mechanism of IFNß on macrophages. IFNß has been shown to have the potential to induce the differentiation of M1 to M2 macrophages, which are stimulated by low levels of lipopolysaccharide (LPS). Additionally, IFNß has been demonstrated to promote the production of ISG15 by macrophages, which leads to the inhibition of the innate immune response. Moreover, our investigation revealed that IFNß has the potential to augment the secretion of ISG15 and its downstream cytokine, IL10, in LPS-stimulated macrophages. Single-cell analysis was conducted on the gingival tissues of patients with periodontitis, which revealed a higher proportion of macrophages in the periodontitis-diseased tissue and increased expression of IFNß, ISG15, and IL10. Gene Set Enrichment Analysis indicated that bacterial infection was associated with upregulation of IFNß, ISG15, and IL10. Notably, only IL10 has been linked to immunosuppression, indicating that the IFNß-ISG15-IL10 axis might promote an anti-inflammatory response in periodontitis through IL10 expression. It is also found that macrophage phenotype transitions in periodontitis involve the release of higher levels of IFNß, ISG15, and IL10 by the anti-inflammatory M2 macrophage phenotype compared to the pro-inflammatory M1 phenotype and myeloid-derived suppressor cells (MDSCs). This implies that the IFNß-induced production of IL10 might be linked to the M2 macrophage phenotype. Furthermore, cell communication analysis demonstrated that IL10 can promote fibroblast proliferation in periodontal tissues via STAT3 signaling.

MARCO is a potential prognostic and immunotherapy biomarker.

BACKGROUND: Macrophage receptor with collagenous structure (MARCO), a novel immune checkpoint expressed on tumor-associated macrophages, has antitumor therapeutic properties. However, the association between MARCO and patient prognosis, immune infiltration, and ICI immunotherapy needs to be studied urgently. METHODS: MARCO distribution in cancer tissues was investigated using the TCGA and GTEx databases. The PrognoScan and KM Plotter databases was used to assess the MARCO prognosis. TIMER2.0, GEPIA, cBioPortal, and GSEA all confirmed the link between MARCO and immune infiltration, mutation profile, and enrichment pathway analysis. Data visualization was implemented by R language. RESULTS: In general, MARCO had a substantial impact on the prognosis of cancer patients and was expressed differently in cancer and adjacent normal tissues. High expression of MARCO was associated with poorer OS in bladder urothelial carcinoma (BLCA), breast invasive carcinoma (BRCA), lung squamous cell carcinoma (LUSC), colon adenocarcinoma (COAD), and prostate adenocarcinoma (PRAD). However, high expression of MARCO had a better PFI in brain lower-grade glioma (LGG) and skin cutaneous melanoma (SKCM). We discovered that MARCO expression was lowest in pancreatic adenocarcinoma (PAAD) and rectum adenocarcinoma (READ) stage 1, BLCA stage 2, LUSC and stomach adenocarcinoma (STAD) stage 3, and liver hepatocellular carcinoma (LIHC) stage 4. Subsequently, we analyzed the correlation between MARCO and 47 immune checkpoints and observed that MARCO was positively connected with CD80, CD86, and leukocyte-associated immunoglobulin-like receptor 1(LAIR1) in most cancers. In COAD, MARCO has the most microsatellite instability (MSI). In addition, we discovered that high expression of MARCO patients had a better prognosis after immune checkpoint inhibitor (ICI) treatment in SKCM. Finally, GSEA revealed a significant correlation between MARCO and TNF/NFκB signaling, KRAS signaling, PI3K/AKT/mTOR pathway, IL-6-STAT3 signaling, TGFß pathway, and p53 pathway. CONCLUSION: This study comprehensively investigated the relationship between MARCO and clinical prognosis, immune infiltration, and ICI immunotherapy in various cancers. We demonstrated the potential of MARCO as an emerging biomarker, exploring new avenues for future tumor immunotherapy.

The Role of Cartilage Stem/Progenitor Cells in Cartilage Repair in Osteoarthritis.

Osteoarthritis (OA) is a degenerative joint disease characterized by the loss of cartilage, which seriously affects the quality of patient's life and may even cause permanent sequelae. The treatment of OA is diversified, mostly limited to relieving clinical symptoms. Less invasive treatments that can cure OA are still lacking. With the rise of tissue-cell engineering, stem cell therapy has gradually aroused great interest in treating OA. Cartilage stem/progenitor cells (CSPCs), a type of stem cell found on the surface of articular cartilage, have many similarities with mesenchymal stem cells (MSCs). These cells can be isolated and cultured from animals and humans and exist in articular cartilage over the body, such as the knee joint, patellofemoral joint, and temporomandibular joint. Due to their strong proliferative and chondrogenic differentiation abilities, CSPCs may contribute a lot to cartilage regeneration and repair in OA. We will provide an overview of the biological characteristics of CSPCs and their role in OA in combination with the research progress. Despite some existing limitations, CSPCs still offer an innovative idea for OA treatment with great advantages.

Single-cell analysis reveals that cancer-associated fibroblasts stimulate oral squamous cell carcinoma invasion via the TGF-ß/Smad pathway.

Although substantial progress has been made in cancer biology and treatment, the prognosis of oral squamous cell carcinoma (OSCC) is still not satisfactory because of local tumor invasion and frequent lymph node metastasis. The tumor microenvironment (TME) is a potential target in which cancer-associated fibroblasts (CAFs) are of great significance due to their interactions with cancer cells. However, the exact mechanism is still unclear. Therefore, we focus on the crosstalk between cancer cells and CAFs and discover that CAFs are the main source of TGF-ß1. Transwell assays and western blot analysis further prove that CAFs activate the TGF-ß1/Smad pathway to promote OSCC invasion. Through survival analysis, we confirm that CAF overexpression is correlated with poor overall survival in OSCC. To further elucidate the origin and role of CAFs in OSCC, we analyze single-cell RNA sequencing (scRNA-seq) data from 14 OSCC tumor samples and identify four distinct cell types, including CAFs, in the TME, indicating high intratumoral heterogeneity. Then, two subtypes of CAFs, namely, myofibroblasts (mCAFs) and inflammatory CAFs (iCAFs), are further distinguished. Based on the differentially upregulated genes of mCAFs and iCAFs, GO enrichment analysis reveals their different roles in OSCC progression. Furthermore, the gene expression pattern is dynamically altered across pseudotime, potentially taking part in the transformation from epithelial to mCAFs or iCAFs through the epithelial to mesenchymal transition.

Epigenetic Therapeutics Targeting NRF2/KEAP1 Signaling in Cancer Oxidative Stress.

The transcription factor nuclear factor erythroid 2-related factor 2 (NRF2) and its negative regulator kelch-like ECH-associated protein 1 (KEAP1) regulate various genes involved in redox homeostasis, which protects cells from stress conditions such as reactive oxygen species and therefore exerts beneficial effects on suppression of carcinogenesis. In addition to their pivotal role in cellular physiology, accumulating innovative studies indicated that NRF2/KEAP1-governed pathways may conversely be oncogenic and cause therapy resistance, which was profoundly modulated by epigenetic mechanism. Therefore, targeting epigenetic regulation in NRF2/KEAP1 signaling is a potential strategy for cancer treatment. In this paper, the current knowledge on the role of NRF2/KEAP1 signaling in cancer oxidative stress is presented, with a focus on how epigenetic modifications might influence cancer initiation and progression. Furthermore, the prospect that epigenetic changes may be used as therapeutic targets for tumor treatment is also investigated.

Comprehensive analysis of INHBA: A biomarker for anti-TGFß treatment in head and neck cancer.

Inhibin subunit ßA (INHBA) is a protein-coding gene belonging to the transforming growth factor ß (TGFß) superfamily, which is associated with the development of a variety of cancers. However, the role of INHBA in head and neck squamous cell carcinoma (HNSC) remains unclear. The expression profile and prognostic significance of INHBA in HNSC were assessed using a variety of informatics methods. The level of INHBA expression was significantly higher in patients with HNSC, and it was correlated with sex, tumor-node-metastasis (TNM) stage, histological grade, and human papillomavirus (HPV) status. Kaplan-Meier (K-M) analysis indicated that poor overall survival (OS) and disease-free survival (DFS) were significantly associated with INHBA upregulation in HNSC. INHBA overexpression was validated as an independent poor prognostic factor by multivariate Cox regression, and including INHBA expression level in the prognostic model could increase prediction accuracy. In addition, copy number alterations (CNAs) of INHBA and miR-217-5p downregulation are potential mechanisms for elevated INHBA expression in HNSC. In conclusion, INHBA may represent a promising predictive biomarker and candidate target for anti-TGFß therapy in HNSC.

Research progress on psychotherapy for dental anxiety / 口腔疾病防治

@#Dental anxiety refers to the unique tension, worry and even fear of dental treatment, which may lead to patients refusing to receive treatment and missing the best time for treatment. With the development of bio-psycho-social medical models, psychotherapy has gradually become the optimal treatment for dental anxiety. This article reviewed the etiology, evaluation and psychotherapy of dental anxiety. Research has shown that uncomfortable dental treatment experience is the main cause of dental anxiety, which is commonly assessed using questionnaires in clinical practice. Psychotherapy for dental anxiety is a noninvasive, widely applicable treatment without side effects, mainly including improving the treatment environment and service attitude, behavior therapy, and cognitive therapy, which has been shown to effectively alleviate dental anxiety in patients. However, psychotherapy for dental anxiety is highly demanding for dentists, which hinders its promotion and application. At the same time, the psychotherapeutic mechanism of dental anxiety is not clear and remains to be further elucidated by large-scale and high-quality randomized controlled studies.

Circular RNA: A promising new star for the diagnosis and treatment of colorectal cancer.

BACKGROUND: Colorectal cancer (CRC) is one of the most common malignant tumors of the digestive tract. According to the research of circular RNAs in the CRC field, compared with linear RNAs, circular RNAs are a special type of noncoding RNA that are covalently closed circular structures, which have no 5' cap structure and 3' polyA tail and are not affected by RNA exonuclease and actinomycin D. BIOLOGICAL FUNCTIONS: Notably, circular RNAs have a high degree of stability and potential effect on gene regulation. Meanwhile, circular RNAs are involved in the sponge action of microRNAs and mediate protein translation and direct binding, alternative splicing, and histone modification. RELATIONSHIPS WITH CRC: Studies have shown that circular RNAs are related to the proliferation, invasion, recurrence, metastasis, ferroptosis, apoptosis, and chemotherapy resistance of CRC. CONCLUSIONS: This article provides a brief review based on the source, structural characteristics, mechanisms, biological functions of circular RNAs, and the relationships between CRC.

Gold standard for nutrition: a review of human milk oligosaccharide and its effects on infant gut microbiota.

Human milk is the gold standard for nutrition of infant growth, whose nutritional value is mainly attributed to human milk oligosaccharides (HMOs). HMOs, the third most abundant component of human milk after lactose and lipids, are complex sugars with unique structural diversity which are indigestible by the infant. Acting as prebiotics, multiple beneficial functions of HMO are believed to be exerted through interactions with the gut microbiota either directly or indirectly, such as supporting beneficial bacteria growth, anti-pathogenic effects, and modulation of intestinal epithelial cell response. Recent studies have highlighted that HMOs can boost infants health and reduce disease risk, revealing potential of HMOs in food additive and therapeutics. The present paper discusses recent research in respect to the impact of HMO on the infant gut microbiome, with emphasis on the molecular basis of mechanism underlying beneficial effects of HMOs.

A novel methylation signature predicts inferior outcome of patients with PDAC.

Pancreatic ductal adenocarcinoma (PDAC) will become the second most common cause of death in North America and Europe over the next 10 years owing to the lack of early diagnosis, poor treatment, and poor prognosis. This study evaluated the methylation array data of 184 patients with PDAC in The Cancer Genome Atlas database to explore methylation biomarkers related to patient outcome. Using Univariable Cox regression analysis and Lasso regression analysis method in the training dataset, it was found that the four DNA methylation markers (CCNT1, ITGB3, SDS, and HMOX2) were significantly correlated with the overall survival of patients with PDAC. Kaplan-Meier analysis showed that these four DNA methylation markers could significantly distinguish high-risk and low-risk patients. Receiver operating characteristic analysis further confirmed that the four DNA methylation markers had high sensitivity and specificity, which could predict the prognosis of patients. Moreover, there was a difference in the genetic mutations between high-risk and low-risk patients distinguished by the four-DNA methylation model, which can provide information for clinical treatment. Finally, compared with known biomarkers, the model was more accurate in predicting the prognosis of PDAC. This four-DNA methylation model has potential as a new independent prognostic indicator, and could be used for the diagnosis, monitoring, and precision medicine of pancreatic cancer.

Beyond regulations at DNA levels: A review of epigenetic therapeutics targeting cancer stem cells.

In the past few years, the paramount role of cancer stem cells (CSCs), in terms of cancer initiation, proliferation, metastasis, invasion and chemoresistance, has been revealed by accumulating studies. However, this level of cellular plasticity cannot be entirely explained by genetic mutations. Research on epigenetic modifications as a complementary explanation for the properties of CSCs has been increasing over the past several years. Notably, therapeutic strategies are currently being developed in an effort to reverse aberrant epigenetic alterations using specific chemical inhibitors. In this review, we summarize the current understanding of CSCs and their role in cancer progression, and provide an overview of epigenetic alterations seen in CSCs. Importantly, we focus on primary cancer therapies that target the epigenetic modification of CSCs by the use of specific chemical inhibitors, such as histone deacetylase (HDAC) inhibitors, DNA methyltransferase (DNMT) inhibitors and microRNA-based (miRNA-based) therapeutics.