The optimal therapeutic strategy for periodontitis aims to eliminate pathogenic bacteria within periodontal pockets while promoting periodontal tissue regeneration. However, treatment efficacy remains limited due to anatomical constraints within the periodontal environment. Furthermore, antibiotic resistance presents a persistent challenge in clinical management, notwithstanding the status of antibiotics as first-line therapeutics. To thoroughly eliminate bacteria and reduce drug resistance, we prepared a polyphenol-metal coordination hydrogel, namely EGCG-Zn@FG, which consists of a plasma-derived fibrin gel wrapped with epigallocatechin gallate (EGCG) coordinated with zinc ions. The antibacterial efficacy was synergistically enhanced by the intrinsic antimicrobial properties of EGCG combined with the sustained release of zinc ions. Of particular note, EGCG-Zn@FG demonstrated superior antibacterial activity against Porphyromonas gingivalis compared to EGCG-Zn alone. Meanwhile, EGCG-Zn@FG was also shown to have anti-inflammatory effects by reducing the expression of inflammatory factors (IL-1β and IL-6). It is worth mentioning that EGCG-Zn@FG was also verified to upregulate the expression of osteogenic factors (Col-1, ALP, and Runx-2) through the release of EGCG, promoting alveolar bone repair. In rat models, EGCG-Zn@FG in the treatment area was slowly and continuously released for 24 h after administration. Notably, the administration of EGCG-Zn@FG not only exhibited remarkable capability in mitigating dental inflammation and facilitating bone repair, but also ensured favorable biosafety in periodontitis rat models, thereby highlighting its dual advantages in therapeutic efficacy and biocompatibility. Collectively, these findings validate EGCG-Zn@FG as a promising antibiotic-alternative strategy to address antibiotic resistance in periodontitis while possessing substantial potential for clinical treatment of periodontal disease.

Macrophage polarization and inflammation play a pivotal role in bone healing disorders in diabetes. This study aimed to investigated the effect and mechanism of circANKRD36 on M1 polarization and inflammatory response in LPS-stimulated macrophages under high glucose conditions. Our results showed that high glucose promoted circANKRD36 expression, the proportion of CD11b+CD86+ cells, and mRNA and protein levels of M1-type pro-inflammatory factors IL-1β, TNF-α, and iNOS in LPS-stimulated macrophages, while reducing miR-498 expression. The interaction between circANKRD36 and miR-498 was predicted by ENCORI and proved by the luciferin experiment. circANKRD36 knockdown downregulated the proportion of CD11b+CD86+ cells and the expression of IL-1β, TNF-α, and iNOS in LPS-stimulated macrophages under high glucose conditions, whereas miR-498 knockdown reversed these effects. Moreover, high-throughput mRNA sequencing and bioinformatic analysis revealed that, compared to LPS-stimulated macrophages under high glucose conditions, the differentially expressed genes (DEG) in those with circANKRD36 knockdown were enriched in AGE-RAGE signaling pathway, while the DEG in those with miR-498 knockdown were enriched in NF-κB, MAPK, and TNF signaling pathways. Based on sequencing data and bioinformatics prediction, we identified TXNRD1 as the downstream target gene. TXNRD1 expression decreased with circANKRD36 knockdown but increased with miR-498 knockdown in LPS-stimulated macrophages under high glucose conditions. TXNRD1 overexpression reversed the effects of circANKRD36 knockdown in LPS-stimulated macrophages under high glucose conditions. In conclusion, circANKRD36 knockdown could inhibit M1 polarization and inflammatory response via miR-498/TXNRD1 in macrophages under high glucose and inflammatory conditions.

To identify key genes and metabolites that promote the progression of periodontitis in the context of hypertension through combined transcriptomic and metabolomic analyses. Rat models of periodontitis and periodontitis combined with hypertension were established, with healthy rats serving as the control group. Periodontal tissues from each group were collected for transcriptomic and metabolomic sequencing. Subsequently, differential genes and metabolites were analyzed in the periodontitis with hypertension group compared to the control group, as well as in the periodontitis with hypertension group compared to the periodontitis group. Gene Ontology and KEGG enrichment analyses were performed, and a joint analysis of differential genes and metabolites was conducted. A total of 631 differential mRNAs and 67 differential metabolites were identified in the periodontitis with hypertension group compared to the control group. The differential genes and metabolites were mainly enriched in the pathways of phenylalanine, tyrosine, and tryptophan biosynthesis, phenylalanine metabolism, arginine biosynthesis, and arginine and proline metabolism. In the periodontitis with hypertension group compared to the periodontitis group, 135 differential mRNAs and 24 differential metabolites were identified. The differential genes and metabolites were primarily enriched in the pathways of arginine biosynthesis, cysteine and methionine metabolism, and biosynthesis of amino acids. Citrulline significantly suppresses the production of reactive oxygen species and the expression of the inflammatory cytokine interleukin-8 (IL-8) in gingival fibroblasts. Hypertension may promote the development of periodontitis by altering interferon-inducible genes and the arginine metabolism-related pathway. Citrulline represents a potential therapeutic option for periodontitis.

Background: Mogroside V (MV), a triterpene glycoside, exhibits diverse biological functions. However, its ability to promote the osteogenic differentiation of bone marrow mesenchymal stem cells (BMSCs) under diabetic conditions is yet to be elucidated. Objective: To study the regulation of osteogenic differentiation of BMSCs in diabetic mice by MV and determine the potential mechanism. Methods: BMSCs were isolated from both normal (referred to as N-BMSCs) and diabetic (referred to as DM-BMSCs) C57BL/6 mice. DM-BMSCs were treated with different concentrations of MV for varying durations, and cell viability was detected using the cell counting kit-8 assay. Following 2 weeks of osteogenic induction, osteogenic differentiation capability was evaluated using alizarin red S staining, alkaline phosphatase (ALP) activity analysis, and quantitative real-time reverse transcription polymerase chain reaction. Furthermore, the microRNA (miRNA) expression profiles of N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV were tested using high-throughput sequencing. Results: Treatment with MV enhanced the viability of DM-BMSCs and mitigated the reduction of calcium nodule deposition, ALP activity, and mRNA expression of ALP, osteocalcin, and runt-related transcription factor 2. Of the analyzed miRNAs, miR-10b-5p was the only one that exhibited differential expression in N-BMSCs, DM-BMSCs, and DM-BMSCs treated with MV. An analysis of the top four protein clusters based on KEGG suggested that the target genes of differentially expressed miRNAs were closely linked to the PI3K/AKT pathway. Conclusion: MV significantly enhances the viability and osteogenic differentiation of BMSCs under diabetic conditions. The alteration of miRNA profiles provides a foundation for further research into the regulatory role of miRNAs and MV in this process.

Maxillofacial trauma is an infection and oxidative stress-induced damage to maxillofacial area related cells. Increasing evidences have suggested that therapeutic strategies with controllable anti-infective and anti-inflammatory capabilities hold great potentials in the clinical treatment of maxillofacial trauma. Herein, we reported an infectious microenvironment responsive bimetallic sulfide (FeCuSx, FCS) combining with near infrared (NIR) irradiation for maxillofacial trauma therapy. In cellular levels, FCS exhibited the most efficient antioxidant and anti-inflammatory, cell migration, and angiogenesis behaviors through down-regulating the inflammatory factor (iNOS) expression level, up-regulating anti-inflammatory factors (Arg-1 and TGF-β) expression level, inducing macrophages M2 polarization (CD86 down-regulation and CD206 up-regulation), and promoting tissue repair factors (CD31) expression level. Besides, it presented the excellent antibacterial ability of Escherichia coli (99.74

Mogroside V (MV) is a triterpene glucoside that reportedly exhibits an array of antitumor, anti-inflammatory, hypolipidemic, and hypoglycemic properties. In prior studies, our group determined that MV was able to readily enhance osteogenic bone marrow mesenchymal stem cells (BMSCs) differentiation under high-glucose conditions through mechanisms potentially associated with miR-10b-5p and PI3K/Akt signaling activity. The precise molecular basis for these effects, however, remains to be fully elucidated. This study aims to explore the potential mechanisms by which MV regulates the osteogenic differentiation of BMSCs under hyperglycemic conditions. Femoral and tibial BMSCs were isolated from control and diabetic C57BL/6J mice. qRT-PCR was used to quantify miR-10b-5p levels. Putative miR-10b-5p target genes were predicted through bioinformatics assays and validated in a luciferase reporter assay system. miR-10b-5p expression was inhibited with an antagomiR-10b-5p construct, while PI3K/Akt pathway signaling was inhibited with LY294002. Western blotting was used to detect PI3K/Akt pathway and target gene protein levels, while Alizarin red staining was used to detect calcium nodule deposition by BMSCs. miR-10b-5p upregulation was noted in BMSCs exposed to hyperglycemic conditions. HOXD10 was identified as a cell differentiation-related miR-10b-5p target gene in bioinformatics analyses, and the targeting relationship between the two was confirmed in a luciferase reporter assay. MV treatment elicited significantly higher levels of miR-10b-5p expression, PI3K phosphorylation, and calcium deposition, while antagomiR-10b-5p or LY294002 treatment reversed these changes, and the opposite trends were observed with respect to HOXD10 protein levels. MV favors BMSCs osteogenic differentiation under high-glucose conditions through the upregulation of miR-10b-5p and the activation of PI3K/Akt signaling.

Acute lung injury (ALI) was characterized by excessive reactive oxygen species (ROS) levels and inflammatory response in the lung. Scavenging ROS could inhibit the excessive inflammatory response, further treating ALI. Herein, we designed a novel nanozyme (P@Co) comprised of polydopamine (PDA) nanoparticles (NPs) loading with ultra-small Co, combining with near infrared (NIR) irradiation, which could efficiently scavenge intracellular ROS and suppress inflammatory responses against ALI. For lipopolysaccharide (LPS) induced macrophages, P@Co + NIR presented excellent antioxidant and anti-inflammatory capacities through lowering intracellular ROS levels, decreasing the expression levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) as well as inducing macrophage M2 directional polarization. Significantly, it displayed the outstanding activities of lowering acute lung inflammation, relieving diffuse alveolar damage, and up-regulating heat shock protein 70 (HSP70) expression, resulting in synergistic enhanced ALI therapy effect. It offers a novel strategy for the clinical treatment of ROS related diseases.

Tooth loss represents the most prevalent form of dental agenesis. Anterior tooth loss primarily impacts aesthetics and psychological well-being, whereas posterior tooth loss influences bone growth patterns and masticatory function. Prolonged tooth loss can significantly hinder subsequent restorative procedures. Genetic factors are among the principal contributors to tooth loss, as genes dictate the location, quantity, and morphology of teeth; mutations at specific gene loci may result in underdevelopment or even complete absence of teeth. Investigating the relationship between gene polymorphisms and tooth loss could yield novel insights for future clinical interventions aimed at addressing this issue. Consequently, this study aims to elucidate the correlation between PAX9 and MSX1 gene polymorphisms and instances of tooth loss. We searched Cochrane, PubMed, Web of Science, MEDLINE, EMBASES, and CNKI journal databases for articles up to April 1, 2024 to determine the association of PAX9 and MSX1 genes with the risk of dental development. Used STATA version 11.2 to calculate the odds ratio (OR) and 95% confidence interval (CI). Analyzed meta-regression, sensitivity, and publication bias. Used Bayesian measures of the false positive reporting probability and false discovery probability to examine the reliability of the calculation. Finally, 12 eligible reports were included in this study, including 7 reports on PAX9 rs2073247, with 873 cases of polymorphism and 812 cases of control; 5 reports on PAX9 rs2073244, with 668 cases of polymorphism and 668 cases of control; 7 reports on MSX1 rs12532, with 762 cases of polymorphism and 1,544 cases of control. The ORs and 95% CIs showed a statistically significant relationship between PAX9 rs2073247 or PAX9 rs2073244 polymorphism and tooth agenesis risk. Moreover, there was no association observed for the MSX1 rs12532 polymorphism. In further subgroup analysis of the polymorphisms (PAX9 rs2073247, PAX9 rs2073244), we found an increased risk of tooth loss in the Caucasian and Hungarian groups. This article concludes that the PAX9 rs2073247 and PAX9 rs2073244 polymorphism might help to increase the risk of tooth agenesis. Understanding the mechanisms of genetic mutations will enable clinical physicians and human geneticists to develop new strategies for future therapeutic research and preventive treatments.

The delayed healing of alveolar bone defects caused by periodontitis remains a thorny problem. Here, we developed a kind of natural hydrogel, Cu/Zn-FG, synthesized based on the formation of a hydrogel network triggered by thrombin and the coordination bond between the fibrin and metal ions. The characteristics of Cu/Zn-FG were evaluated using the following methods: morphological observation, scanning electron microscopy (SEM), Fourier-transform infrared spectroscopy (FTIR), and X-ray photoelectron spectroscopy (XPS). The anti-inflammatory effect and osteogenic differentiation potential of Cu/Zn-FG were also assessed on the RAW264.7 and MC3T3-E1 cells. Moreover, Cu/Zn-FG's in vivo therapeutic efficacy was evaluated in a rat model of periodontitis. The results demonstrated that Cu/Zn-FG could release copper and zinc ions for 26 hours as the protease activity increases in the infection microenvironment, and these ions can maintain their biological activity in vitro. Furthermore, we found that Cu/Zn-FG can effectively inhibit the growth activity of Porphyromonas gingivalis (P. gingivalis), promote osteogenic differentiation of MC3T3-E1 and regulate the expression of inflammatory factors of RAW264.7. In the process of the in vivo experiment, periodontitis rats treated with Cu/Zn-FG revealed that bone regeneration was accelerated. Our study confirms that Cu/Zn-FG is an innovative material that could promote alveolar bone regeneration in a rat model of periodontitis, exhibiting its translational potential for clinical application and providing a new therapeutic strategy in the treatment of periodontitis.

Background:Liriopesides B (LPB), a steroidal saponin derived from Liriope spicata, demonstrates potent anti-tumor activity across multiple malignancies. Nevertheless, its influence on oral squamous cell carcinoma (OSCC) has not been investigated. This study aims to evaluate the anti-OSCC properties of LPB and elucidate the underlying mechanisms. Methods:Proliferation of OSCC cells treated with LPB was evaluated via Cell Counting Kit-8 (CCK-8) and colony formation assays. Cell migration, invasion, and apoptosis were analyzed, along with measuring related gene expression utilizing quantitative reverse transcription polymerase chain reaction (qRT-PCR). Transcriptomic analysis of LPB-treated cells was performed, and protein levels within the PI3K/Akt/mTOR cascade were examined by Western blotting. In vivo anti-cancer activity of LPB was assessed through xenograft tumor models, with messenger RNA (mRNA) levels of MMP-2/9, Bcl-2, Bax, and Bad assessed by qRT-PCR, and PI3K/Akt/mTOR pathway protein expression analyzed via immunohistochemistry (IHC). Biological safety was evaluated by body weight changes of nude mice, Hematoxylin and Eosin (H&E) staining and serum biochemical markers. Results:LPB suppressed OSCC cell growth, colony formation, motility, and invasiveness while promoting apoptosis. High-throughput sequencing suggested that the PI3K/Akt cascade is a potential target of LPB in OSCC. Treatment with LPB markedly suppressed key protein levels within the PI3K/Akt/mTOR cascade. In xenograft models, LPB treatment led to considerable decreases in tumor volume and weight. Furthermore, mRNA levels of MMP-2/9 and proteins such as PI3K, Akt, p-mTOR, and S6 were markedly downregulated in LPB-treated tumors, while Bax and Bad expression were upregulated. No substantial variations in body weight, histological morphology, or organ function were observed between the control and LPB-treated cohorts. Conclusions:LPB exerts anti-OSCC properties by modulating the PI3K/Akt/mTOR cascade with minimal biological toxicity, highlighting its potential as a therapeutic agent for OSCC.

Periodontitis, a chronic inflammatory disease of the supporting tissue around teeth, is triggered by periodontal pathogens. Clinical treatments face the problem of bacterial resistance and most therapies focus on a single function, lacking the multifunctional treatment of antibacterial, antioxidant, anti-inflammatory, and osteogenic properties. In our study, we developed a copper-cerium bimetallic oxide (CuCeOx) nanozyme with near-infrared (NIR) light responsiveness for the periodontitis therapy. Under the excitation of 808 nm NIR light, CuCeOx displayed excellent photodynamic and photothermal activities, efficiently generating reactive oxygen species (ROS) and heat. After the treatment of the CuCeOx/NIR system, the inhibition rate of Porphyromonas gingivalis (P. gingivalis), the main periodontitis pathogen, reached 98.69 ± 0.23 % in vitro. Without the NIR light irradiation, CuCeOx, acting as a nanozyme, exhibited enzyme-like activity in scavenging ROS, effectively alleviating the cellular oxidative stress. Furthermore, CuCeOx significantly mitigated the cellular inflammatory response induced by lipopolysaccharide (LPS) and promoted osteogenesis under the oxidative stress condition. Notably, the CuCeOx exhibited excellent blood compatibility (hemolysis < 5 %). The efficacy of the CuCeOx/NIR system in vivo was also investigated. H&E staining results demonstrated a significant reduction in periodontal tissue inflammation following treatment. Micro-CT analysis revealed that CuCeOx effectively inhibited the alveolar bone loss. Additionally, we found CuCeOx regulated the Nrf2/HO-1 signaling pathway both in vitro and in vivo. In conclusion, the multifunctional nanomaterial CuCeOx provides a promising strategy for the treatment of periodontitis.

Background: Mogroside V (MV) has anti-inflammatory properties. However, its impact on macrophage polarization under diabetic condition is yet unclear. This study aimed to investigate effects and underlying mechanisms of MV on inflammatory response and M1 polarization of bone marrow-derived macrophages (BMDMs) from diabetic mice. Methods: BMDMs were isolated from normal and diabetic C57BL/6 mice. LPS and IFN-gamma were used to produce M1-polarized BMDMs. MV treatment was administered throughout the M1 polarization process with or without SB203580 or PDTC. Surface markers CD11b, F4/80 and CD86 of macrophages were identified using flow cytometry or immunofluorescence staining. Inflammatory cytokines IL-1 beta and IL-6 and phosphorylation levels of p65 and p38 were examined by western blot. Results: High glucose increased proportion of CD11b(+)F4/80(+)CD86(+) cells, protein levels of inflammatory cytokines IL-1 beta and IL-6 and phosphorylation levels of p65 and p38 in LPS+IFN-gamma-induced BMDMs, while they were decreased upon MV treatment. Additionally, these effects were further downregulated when MV was co-added with SB203580 or PDTC. Conclusions: MV suppressed M1 macrophage polarization and inflammatory response, which was partially through NF-kappa B and p38 MAPK in LPS+IFN-gamma induced BMDMs under high glucose condition, implying the potential of MV in treatment for inflammatory complications of diabetes.

Background: This meta-analysis aimed to systematically summarize the association between cancer risks and glutathione s-transferases (GSTs) among smokers and drinkers. Methods: Literature was searched through PubMed, Web of Science, CNKI, and WANFANG published from 2001 to 2022. Stata was used with fixed-effect model or random-effect model to calculate pooled odds ratios (ORs) and the 95% confidence interval (95% CI). Sensitivity and heterogeneity calculations were performed, and publication bias was analyzed by Begg and Egger's test. Regression analysis was performed on the correlated variables about heterogeneity, and the false-positive report probabilities (FPRP) and the Bayesian False Discovery Probability (BFDP) were calculated to assess the confidence of a statistically significant association. Results: A total of 85 studies were eligible for GSTs and cancer with smoking status (19,604 cases and 23,710 controls), including 14 articles referring to drinking status (4409 cases and 5645 controls). GSTM1-null had significant associations with cancer risks (for smokers: OR = 1.347, 95% CI: 1.196-1.516, P < .001; for nonsmokers: OR = 1.423, 95% CI: 1.270-1.594, P < .001; for drinkers: OR = 1.748, 95% CI: 1.093-2.797, P = .02). GSTT1-null had significant associations with cancer risks (for smokers: OR = 1.356, 95% CI: 1.114-1.651, P = .002; for nonsmokers: OR = 1.103, 95% CI: 1.011-1.204, P = .028; for drinkers: OR = 1.423, 95% CI: 1.042-1.942, P = .026; for nondrinkers: OR = 1.458, 95% CI: 1.014-2.098, P = .042). Negative associations were found between GSTP1rs1695(AG + GG/AA) and cancer risks among nondrinkers (OR = 0.840, 95% CI: 0.711-0.985, P = .032). Conclusions: GSTM1-null and GSTT1-null might be related cancers in combination with smoking or drinking, and GSTP1rs1695 might be associated with cancers among drinkers.

Background: The analysis of single-cell transcriptome profiling of tumour tissue isolates helps to identify heterogeneous tumour cells, neighbouring stromal cells and immune cells. Local metastasis of lymph nodes is the most dominant and influential biological behaviors of oral squamous cell carcinoma (OSCC) in terms of treatment prognosis. Understanding metastasis initiation and progression is important for the discovery of new treatments for OSCC and prediction of clinical responses to immunotherapy. However, the identity of metastasis-initiating cells in human OSCC remains elusive, and whether metastases are hierarchically organized is unknown. Therefore, this study was conducted to understand the cellular origins and gene expression signature of OSCC at the single-cell level. Methods: Single-cell RNA sequencing (scRNA-seq) was used to analyze cells from tissue of para-carcinoma (PCA: adjacent normal tissue not less than 2 cm from the tumour), carcinoma (CA), lymph node metastasis (LNM) from patients with OSCC and PCA and CA tissue from patients with second primary OSCC (SPOSCC) after radiotherapy of nasopharyngeal carcinoma (NPC). The cell types and their underlying functions were classified. The comparisons were then conducted between the homology and heterogeneity from cell types and both conservative and heterogeneous aspects of evolution were identified. Immunohistochemistry was performed to verify the makers of cell clusters and the expression level of novel genes. Results: A single-cell transcriptomic map of OSCC was created, including 16 clusters of PCA cells, 17 clusters of CA cells, 14 clusters of left LNM cells, and 14 clusters of right LNM cells. We also discovered two novel types of cells including CD1C-CD141-dendritic cells and CD1C+_B dendritic cells. Most of the non-cancer cells are immune cells, with two distinct clusters of T lymphocytes, B lymphocytes, CD1C-CD141-dendritic cells+ and CD1C+_B dendritic cells. We also classified cells into 15 clusters for SPOSCC after radiotherapy of NPC. Determining the upregulated expression levels of IL1RN and C15orf48 as novel markers using immunohistochemistry facilitated the correct classification of OSCC including SPOSCC after radiotherapy of NPC and the prediction of their prognosis. Conclusions: The findings provided an unprecedented and valuable view of the functional states and heterogeneity of cell populations in LNM of OSCC and SPOSCC after radiotherapy of NPC at single-cell genomic resolution. Moreover, this transcriptomic map discovered new cell types in mouth, and novel tumour cell-specific markers/oncogene.

To develop new antimicrobial strategy or agents has always been an eternal topic for the researchers. In this study, we have found that the visible light can enhance the antibacterial action of gold ions because of the photo-reduction and thus the visible light energy can be used to kill bacteria. The electron accepting ability of Au ions exposed to the visible light can strengthen, so their damage capability for the organic compounds from bacteria simultaneously enhances. The products of light-triggering Au ions, Au nanoparticles (Au NPs), also can bind protein and other bacterial cell wall components to further enhance the antibacterial ability. With the aid of the penetrating capacity of Au ions and light, light can also enhance the antibacterial action of Au ion in the biofilm and dentinal tubules and their products have the ability to crosslink the collagens to protect them from the degradation of collagenase. The toxicity of Au ions limits its application in clinic treatment, but the toxicity can decrease significantly after Au ions kills bacteria and the light can further reduce the toxicity as well. High concentration of Au ions and long-exposure light for dentin-pulp complex also are safe in vivo. Hence, light-enhancing the antibacterial treatment of Au ions has the potential to be used in the prevention and cure of the caries.

Programmed response, carrier-free, and multimodal therapy drug delivery systems (DDS) are promising solutions to multidirectional cytotoxic effects, inefficient antitumor, and severe side effects for cancer therapy. Here, three widely used clinical drugs, interferon a1b (IFNa1b), indocyanine green (ICG), and doxorubicin (DOX), were prepared into carrier-free DDS IFNa1b-ICG-DOX (IID) by a simple one-step method without additional any reagents. IID can achieve smart and programmed DDS by combining low pH and near-infrared (NIR) light stimuli-responsive controlled release. In pH = 7.4 environments, our IID is about 380 nm in size with negative charge rounded particles; while they enter into the acid environment (pH < 7), hydrogen ions (H+) trigger DOX release, their size becomes larger and the surface charge turns positive. These larger particles are rapidly disintegrated after exposure to NIR light and then the remaining DOX, IFNa1b, and ICG are released. In vivo, the IID with larger size and positive charge resulting from low pH is is easy to accumulate in tumor tissue. Tumors can be exposed to NIR light when needed to control the release of these three drugs. Hence, DOX, ICG, and IFNa1b can be enriched in the tumor to the high efficiency of combined chemotherapy, photothermal therapy, and immunotherapy. (c) 2023 Elsevier Inc. All rights reserved.

目的:通过网络药理学理论及分子对接探究黄芪治疗口腔鳞状细胞癌(Oral Squamous Cell Carcinoma,OSCC)的可能机制.方法:从中药系统药理学数据库与分析平台(TCMSP)下载黄芪的有效成分及对应靶点,并通过癌症基因组图谱获取OSCC的差异表达基因集,筛选出的共同靶点即为黄芪治疗OSCC的潜在靶点.利用STRING数据库获取潜在靶点的相互作用关系,用Cytoscape软件构建黄芪治疗OSCC的潜在靶点相互作用网络图,并获得关键靶点.通过注释可视化和集成发现数据库(DAVID)和KOBAS数据库分别对潜在靶点进行基因本体论功能和京都基因与基因组百科全书通路富集分析并构建"靶点-信号通路"网络图.借助Schrodinger软件对关键靶点及相应的黄芪有效成分进行分子对接.结果:黄芪可通过66个潜在靶点治疗OSCC,包括周期蛋白依赖激酶1(Cyclin Dependent Kinase 1,CDK1)、信号转导和转录活化因子1(Signal Transducer and Activator of Transcription 1,STAT1)、雄激素受体蛋白(Androgen Receptor,AR)、表皮生长因子受体(Epidermal Growth Factor Receptor,EGFR)和微囊蛋白1(Caveolin-1,CAV1).黄芪治疗OSCC的潜在靶点富集最显著的是肿瘤坏死因子(Tumor Necrosis Factor,TNF)信号通路、细胞衰老和p53信号通路.关键靶点AR和黄芪相关有效成分均有良好的结合活性.结论:研究证明了黄芪治疗OSCC的多组分、多靶点和多通路特征,并为黄芪治疗OSCC的深入验证及黄芪在临床的合理应用提供科学依据.

BackgroundMetastasis is the major cause of high recurrence and mortality of hepatocellular carcinoma (HCC). Unfortunately, there are few reports on effective biomarkers of HCC metastasis. Previous studies have reported that SAA1 may be a predictor and prognostic biomarker for multiple malignant tumors. However, the role of SAA1 in HCC has not yet been investigated.MethodsWe applied RNA sequencing and proteomics analysis to investigate the expression landscape of HCC cell lines and patient serum, respectively. SAA1 is a common key gene and listed as a candidate biomarker of HCC metastasis. It was validated in two cell lines, 107 participants serum, and 63 matched HCC and adjacent non-tumorous liver tissues. Human Protein Atlas (HPA), Genotype-Tissue Expression (GTEx), and The Cancer Genome Atlas (TCGA) datasets were integrated to explore SAA1 expression among various cell types and organs. The diagnostic and prognostic value of SAA1 in HCC were determined through receiver operating characteristic (ROC) and Kaplan–Meier curves. Gene Ontology (GO), Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analysis, and protein-protein interaction (PPI) network were constructed for SAA1, as well as for its co−expressed genes. We further analyzed the correlation between SAA1 and co-expression genes.ResultsWe found 7 differentially expressed genes (DEGs) and 14 differentially expressed proteins (DEPs) were related to HCC metastasis. SAA1, a key candidate biomarker, was highly enriched in hepatocytes and liver organ, and it was also highly expressed in HCC cells and the serum and tissues of HCC patients. The results of ROC curve analysis indicated that SAA1 had better predictive values for distinguishing HCC metastasis from non-metastasis. Kaplan-Meier curve analysis revealed that HCC patients with higher SAA1 expression had worse overall survival.ConclusionsOur findings provide new insights into HCC metastasis by identifying candidate gene prediction biomarkers for HCC metastasis.

In an attempt to search for new natural product-based antitumor agents, a series of novel thiazolidinone derivatives of dehydroabietic acid-based B ring-fused-thiazole were designed and synthesized. The primary antitumor tests showed that compounds 5 m exhibited almost the best inhibitory activity against the tested cancer cells. The computational study suggested NOTCH1, IGF1R, TLR4, and KDR were the core targets of the title compounds, and the IC50 of SCC9 and Cal27 is strong correlation with the binding ability of TLR4 and compounds.