JOURNAL OF CELLULAR AND MOLECULAR MEDICINE最新文献

Periodontitis is one of the most common oral inflammatory diseases. Baiyaojian decoction, known for its prominent immunomodulatory and anti-inflammatory properties, shows significant potential in treating periodontitis, though its molecular mechanisms remain unknown. The active ingredients and therapeutic targets were determined by integrating multiple databases. The protein–protein interaction network was constructed by the STRING platform. Bulk RNA seq data of GSE16134 were included and GO enrichment, GSEA and CIBERSORT algorithm were employed to investigate the immune microenvironment in periodontitis. Single-cell RNA seq data of GSE152042 and GSE171213 were integrated by harmony; the cell–cell communication network was analysed by CellChat, and the differentiation trajectory was constructed by monocle3. Molecular docking was carried out using AutoDockTools, AutoDock Vina and PyMOL. Experimental validation was performed via qRT-PCR, CCK-8 assay, flow cytometry and ELISA. Twenty-seven active ingredients and 207 therapeutic targets were obtained. Thirty-one core therapeutic targets were identified. The infiltration of plasma cells, neutrophils, macrophages and mast cells was significantly enhanced in periodontitis tissues. Twenty-eight of 31 core therapeutic targets were involved in their infiltration, differentiation and pro-inflammatory activities. Molecular docking suggested stable bindings between ingredients and therapeutic targets. Experimental validation confirmed the elevated infiltration of above immune cells and demonstrated the anti-inflammatory properties and target modulation capabilities of key ingredients including Coumestrol, Diosmetin and Gallicin. Baiyaojian decoction may exert immunomodulatory and anti-inflammatory effects to treat periodontitis through multi-ingredient and multi-target mechanisms.

Growth factors, including recombinant human bone morphogenetic protein-2 (rhBMP2), have been clinically utilised for large bone augmentation with good outcomes. Nevertheless, long-term healing, swelling, safety concerns, and high cost limit their use. Exosomes, nanoscale extracellular vesicles, have emerged as promising regenerative alternatives. This study assessed the osteogenic potential of periodontal-specific exosomes (Px) on bone marrow mesenchymal stem cells (BMSCs) compared to rhBMP2. Px were morphologically characterised by TEM and quantified via BCA assay. BMSCs were treated with Px at 1:10, 1:50, and 1:100 dilutions (100, 20, and 10 μg/mL) and compared to rhBMP2 (100 ng/mL). Px uptake was evaluated using PKH26 labeling. Functional assays included viability, migration, alkaline phosphatase (ALP) activity, alizarin red (ARS) mineralization, collagen, osteocalcin secretion, and RT-PCR analysis of osteogenic genes. Px exhibited spheroidal to cup-shaped morphology and internalisation in BMSCs up to 18 days. Compared to rhBMP2, Px promoted viability (1.14-fold), migration (1.78-fold) up to 1.14 and 1.78-fold, ALP (1.48-, 4.11-fold), ARS (1.43-, 14.71-fold), collagen (1.40-, 3.58-fold), and osteocalcin (1.86-, 5.2-fold). Gene expression demonstrated significant upregulation of ALP (1.73-fold), RUNX2 (1.70-fold), OCN (1.36-fold), and OPN (1.35-fold). Overall, Px significantly enhanced BMSC osteogenesis compared to rhBMP2, highlighting their potential as a cell-free nanotherapeutic in bone tissue engineering.

The AT-Rich Interaction Domain (ARID) family plays critical roles in malignancies. Although numerous members have been shown to influence cancer processes, there is a lack of a general understanding of the ARID family in colon cancer. To address this gap, we used bioinformatic technologies to investigate the role of the ARID family as a whole and to identify the crucial member. Subsequently, cell growth assays, transwell assays, and animal models were employed to validate the key member's effect on colon cancer growth and metastasis. Furthermore, bioinformatics and immunohistochemistry were utilised to explore the potential mechanisms and evaluate the efficacy of a targeted intervention strategy. Our results showed that the ARID family was upregulated in colon cancer, with ARID3A being the main component that promoted colon cancer development. Specifically, ARID3A enhanced colon cancer cell proliferation, migration, and invasion both in vivo and in vitro. Mechanistically, this promotional effect could be associated with ARID3A promoting PGE2 synthesis and triggering macrophage infiltration. Notably, aspirin treatment reduced the PGE2 level, which significantly inhibited the malignant behaviour of ARID3A-overexpressing cells. In conclusion, ARID3A was a key member of the ARID family in the development of colon cancer. ARID3A was an underlying biomarker for aspirin administration.

TRPM8 is a cold temperature-sensitive and non-selective Ca²⁺-channel. Previously we have observed that TRPM8 is endogenously expressed and affects T cell activation process. Now, we report that TRPM8 regulates functions of mitochondria and ER, two important sub-cellular compartments. Pharmacological modulation of TRPM8 and/or due to TCR-treatment regulates mitochondrial Ca²⁺, ATP, membrane potential, cardiolipin level and mitochondrial temperature in a context-dependent manner. In addition, TRPM8 alters the relative temperature of mitochondria and ER, ER-mitochondrial contact points, mainly at the immunological synapse (IS), and thus TRPM8 has the potential to affect the overall cellular functions. Our data suggests both, i.e., the presence and enrichment of TRPM8 in the IS of T cells. We suggest that TRPM8 is a crucial regulator of Ca²⁺-signalling in T cells and significantly contributes to Ca²⁺-buffering by modulating cellular and sub-cellular organelle functions. These findings are useful to understand the functions of T cells in different pathological conditions.

Cervical cancer has become a glaring concern for women's health globally. The use of single-cell RNA sequencing (scRNA-seq) contributes to a comprehensive understanding of cellular heterogeneity and the immune cell landscape in the TME of cervical cancer. This study is to investigate the distribution pattern of immune cell subsets and their correlation with some gene expression based on single-cell RNA sequencing (scRNA-seq) data in patients with cervical cancer. We collected cervical cancer single-cell RNA sequencing data and explored the quality of the data using the violin plots, scatter plots, variance plots and elbow plots, as well as a search for highly variable genes. We clustered cells with UMAP and t-SNE clustering analyses and then labelled cell populations via flow cytometry and immunohistochemistry. We also analysed the biological functions of critical genes using GO enrichment analysis, and the expression patterns of individual genes at the single-cell level. Lastly, we calculated the shift of immune cell proportion and explored the relationship between key genes like TNFRSF18 and immune cell subgroups. We identified 12 unique cell populations in cervical cancer samples and stained positive for epithelial cells, T cells and macrophages. Functional enrichment analysis revealed the gene expression pattern associated with multiple biological processes and molecular interactions in the tumour microenvironment. Certain genes, such as 16 FOXP3 and CD8A, displayed different expression patterns across the immune cell subsets. Additionally, the expression of TNFRSF18 was directly related to the proportions of most of the immune cells and inversely related to a few T and B lymphocyte subsets. This study offers a comprehensive landscape of immune cell proportions within the cervical cancer TME and uncovers a complexity in the relationships between gene expression and tumour-infiltrating immune cell subsets. These results will provide valuable clues for the study of the immune microenvironment in cervical cancer and will shed some light into novel therapeutic approaches.

This retrospective study aimed to investigate the risk factors influencing the 28-day clinical prognosis of sepsis patients and evaluate their predictive efficacy. Clinical data of patients diagnosed with sepsis between January 1, 2019, and December 31, 2023, were collected from the Hospital Information System (HIS) of Beijing Hospital of Traditional Chinese Medicine, Capital Medical University. Based on 28-day outcomes, patients were divided into survival (n = 146) and death (n = 81) groups. Statistical analysis was performed using SPSS 20, employing univariate and multivariate logistic regression to identify prognostic risk factors. Receiver operating characteristic (ROC) curve analysis was conducted to assess the predictive performance of these factors, with the area under the curve (AUC) calculated for evaluation. Although blood stasis syndrome was not included in the final model due to collinearity with critical indicators, univariate analysis demonstrated its significant prognostic value (OR = 2.49, 95% CI 1.199–5.17, p = 0.014), and ROC curve analysis confirmed its fundamental discriminatory capacity (AUC > 0.5). Multivariable logistic regression identified CRP, TT, disease severity, CA and ARDS as independent risk factors for sepsis mortality. ROC analysis showed all individual indicators and the combined model had AUC > 0.5, with the combined model achieving the highest AUC. The combined model demonstrated good stability via Hosmer-Lemeshow testing (p = 0.067). This study established CRP, TT, disease severity, CA and ARDS as independent mortality risk factors in sepsis, with the combined model showing optimal performance. It demonstrated consistency between TCM macro-pattern differentiation and Western medical indicators, providing a framework for integrated prognostic models that combines both medical approaches.

To explore the causal relationship between monocytes and osteoporosis by Mendel randomization, and to verify it through subsequent experiments. Data regarding osteoporosis and immune cell phenotypes were sourced from the GWAS-Catalogue database. We utilised several Mendelian randomization methods, including the inverse variance weighted method, MR-Egger, weighted median method, and simple median method, complemented by Cochran's Q, MR-Egger regression and Leave-One-Out analysis. Clinical samples were classified into healthy and osteoporosis groups, and blood samples from both cohorts were analysed using flow cytometry. In vitro cell experiments were performed to investigate the effect of si-CD14 on the differentiation of monocytes into osteoclasts, employing western blotting, qPCR and TRAP staining techniques. In addition, we assessed the impact of CD14+ monocytes on the proliferation and mineralisation of osteoblasts through western blotting, qPCR and Alizarin Red staining, and further investigated the underlying mechanisms. Cochran's Q results indicated that the Mendelian randomization findings exhibited heterogeneity; therefore, the conclusions of this study were derived from the inverse variance weighting method. The weighted results of this method demonstrated a positive causal relationship between CD14+ monocyte count and osteoporosis (β = 0.096599, 95% CI: 1.06246, 1.141806, p = 1.46E−07). Additionally, the CD14+/CD16− monocyte count was found to have a positive causal relationship with osteoporosis (β = 0.097927, 95% CI: 1.065098, 1.142008, p = 3.67E−08). Mouse monocytes are activated through the NF-kB pathway under RANKL stimulation, leading to their differentiation into osteoclasts; however, si-CD14 transfection can inhibit this differentiation. Similarly, glucocorticoid stimulation can inhibit the proliferation and mineralisation of osteoblasts, while co-culturing with CD14+ monocytes exacerbates the glucocorticoid-induced biological activity, which is regulated by the TGF-β/SMAD3 pathway. Increased levels of CD14+ monocytes or CD14+/CD16− monocytes are recognised as risk factors for osteoporosis. CD14 plays a crucial role in this process. Inhibition of CD14 expression in monocytes can prevent their differentiation into osteoclasts by suppressing the NF-kB pathway. Additionally, the co-culture of CD14+ monocytes with osteoblasts has been shown to inhibit the TGF-β/SMAD3 pathway, thereby suppressing the proliferation and mineralisation of osteoblasts.

There have been reports that overexpression of mitochondrial ribosomal protein S16 (MRPS16) can greatly improve the growth of tumour cells, migration and invasion abilities in many ways. However, the role of MRPS16 in glioma cell proliferation, which is closely associated with tumour malignancy, remains unclear. The study applied a human gene expression array to investigate the expression levels of genes within glioma tissues in comparison with normal brain tissue. By RT-PCR, cell counting, flow cytometry, MTT assays, colony formation and injection of mice, we deeply explored the role of MRPS16 in glioma cell growth and the underlying mechanism. MRPS16 expression was significantly higher in glioma tissues compared with normal brain tissues. In the cultured glioma cells, glioma cell proliferation was inhibited, and cell cycle arrest and cell apoptosis were induced after MRPS16 knockdown. In BALB/c mice inoculated with glioma cells knocked down for MRPS16, it was found that tumour proliferation and growth were relatively slower than the control. Through further prediction and gene transformation of cultured cells, it is confirmed that the presence of MRPS16 promotes the proliferation of glioma cells through the Wnt/β-catenin/NFATC2 pathway. MRPS16 and NFATC2 promote glioma cell proliferation, which was confirmed by in vivo BALB/c mice inoculation. The Wnt/β—Catenin/NFATC2 pathway plays a role in promoting glioma cell proliferation by MRPS16, which is shown in our experimental data. Inhibition of MRPS16 may be a promising and effective treatment option for gliomas.

Cystatin B (CSTB) is highly expressed in hepatocellular carcinoma (HCC) tissues and serum, indicating its potential as an early diagnostic biomarker. Given the known tumour-suppressive effects of all-trans retinoic acid (ATRA) in solid tumours, this study investigated whether ATRA inhibits HCC progression by modulating CSTB expression. Bioinformatics analyses of databases revealed the elevated CSTB expression in HCC, correlating with poor patient prognosis. These findings were validated in human HCC tissues and HepG2 cells. Through in vitro and in vivo functional assays, ATRA treatment was shown to significantly inhibit HCC cell proliferation, migration, and invasion, concomitantly with reduced CSTB expression. Proteomic sequencing identified cytochrome b (CYTB), a core component of mitochondrial respiratory chain complex III, as a downstream target of CSTB. Further experiments demonstrated that ATRA decreases mitochondrial membrane potential, complex III activity, and cellular ATP levels, these above effects were partially reversed upon CSTB overexpression. In vivo, ATRA administration effectively suppressed subcutaneous tumour growth. Collectively, these results indicated that ATRA exerts anti-tumour activity in HCC by targeting the CSTB/CYTB axis, thereby impairing mitochondrial function and inhibiting tumour progression.

The liver executes essential metabolic functions including energy homeostasis, lipid biosynthesis, cholesterol regulation and xenobiotic detoxification. While hepatocyte metabolic activity forms the foundation of these processes, their precise regulation is achieved through chromatin remodelling mechanisms, with the SWI/SNF complex emerging as a central epigenetic orchestrator. Accumulating evidence positions this ATP-dependent chromatin remodeler as a critical regulator of hepatic development, homeostatic maintenance and pathological transformation. Through nucleosome repositioning and histone-DNA interaction modulation, the SWI/SNF complex governs transcriptional programs controlling cellular proliferation, differentiation and metabolic adaptation. This review synthesises current understanding of SWI/SNF-mediated epigenetic regulation in hepatic biology and explores its therapeutic potential for liver disorders.