Open Life Sciences最新文献

Allergic rhinitis (AR) is a frequent respiratory condition characterized by elevated immunoglobulin E (IgE) levels and nasal mucosal inflammation. Atractylenolide I (ATL-I), a bioactive ingredient in medicinal plants, is known for its ability to alleviate tissue damage by inhibiting inflammatory and oxidative stress responses. In this study, we aimed to investigate the protective roles of ATL-I in AR and reveal the potential mechanism involved. The AR model was developed in mice by intraperitoneal sensitization followed by intranasal exposure to ovalbumin. The effects of ATL-I on allergic responses were evaluated by recording sneezing and rubbing frequencies and measuring the serum concentrations of Th1 and Th2 cytokines following the intragastric administration of ATL-I. The activation of the Toll-like receptor 4/nuclear factor κB (TLR4/NF-κB) pathway and the NOD-like receptor 3 (NLRP3) inflammasome was assessed via Western blotting and immunohistochemistry. The results showed that ATL-I administration alleviated allergic responses in AR mice, as evidenced by significant decreases in the frequencies of sneezing and rubbing and in the serum concentrations of histamine and IgE. Compared with control mice, AR mice presented downregulated Th1 cytokines and upregulated Th2 cytokines, whereas the Th1/Th2 imbalance was improved by ATL-I. ATL-I reduced the mucosal layer thickness and alleviated goblet cell hyperplasia in AR mice. Furthermore, ATL-I inhibited TLR4/NF-κB pathway activation in mucosal tissues, which resulted in the inactivation of the downstream NLRP3 inflammasome. In summary, our results indicate that ATL-I alleviates allergic responses by inhibiting the TLR4/NF-κB/NLRP3 pathway, providing a promising therapeutic strategy for AR.

Traditional serrated adenomas (TSAs) and sessile serrated adenomas (SSAs) are known precursors to colorectal cancer (CRC), but differentiating between them morphologically can be challenging. This study developed an immune molecule-based model to distinguish TSA from SSA using RNA sequencing data from the GEO datasets (GSE117606, GSE45270, GSE117607). Gene expression profiling was conducted with the R package GEOquery, and immune cell infiltration was assessed using CIBERSORTx. Differential expression analysis of immune-related genes was performed with the "limma" package. Enrichment analysis of differentially expressed genes (DEGs) was conducted using "clusterProfiler" for Gene Ontology and kyoto encyclopedia of genes and genomes pathways, identifying protein-protein interaction networks to find core hub genes. Notable differences in immune cell infiltration were observed among SSA, TSA, CRC, and healthy tissues, involving various immune cell types. A total of 45 DEGs (34 upregulated, 11 downregulated) were identified, with CCL2 and CXCL11 emerging as key hub genes. Their diagnostic potential was validated through receiver operating characteristic analysis in GEO datasets and clinical samples, while immunohistochemistry revealed decreased expression of CCL2 and CXCL11 in SSA compared to TSA and normal tissues, indicating their role in SSA pathogenesis and potential as molecular diagnostic markers. The diagnostic value of CCL2 is superior to that of CXCL11, while the diagnostic value of CXCL11 requires further experimental verification.

This study investigates the previously unexplored role of CXC chemokine receptor 6 (CXCR6) in hepatic fibrosis, where excessive extracellular matrix deposition by activated hepatic stellate cells (aHSCs) drives disease progression. Through analysis of gene expression omnibus datasets and human fibrotic liver samples, we identified significant CXCR6 upregulation, subsequently validated in murine fibrosis models. Using quantitative real-time polymerase chain reaction, western blotting, and immunohistochemistry, we demonstrated that CXCR6 silencing in vitro promoted aHSC senescence - as confirmed by senescence-associated β-galactosidase staining and Cell Counting Kit-8 assays - while simultaneously restricting the pro-inflammatory senescence-associated secretory phenotype (SASP). Mechanistically, the enzyme-linked immunosorbent assay revealed this process involves modulation of the interleukin-1 alpha/nuclear factor-kappa beta feedback loop. Our findings position CXCR6 inhibition as a promising therapeutic strategy that uniquely targets both fibrogenesis (through hepatic stellate cell senescence induction) and inflammation (via SASP regulation) in hepatic fibrosis.

Diabetic foot ulcer (DFU) is a severe and prevalent complication of diabetes mellitus, posing substantial risks to patient health and increasing healthcare burdens globally. These chronic wounds often result from a complex interplay of factors, including neuropathy, ischemia, infection, immune dysregulation, and vascular dysfunction, leading to significant morbidity and, in severe cases, amputation. Effective management of DFUs necessitates a comprehensive understanding of their risk factors and prognostic indicators. This review provides an in-depth examination of the various risk factors and prognostic markers associated with DFUs, integrating insights from cellular mechanisms, emerging biomarkers, omics-based research, serological studies, and clinical assessments. We explore the underlying biological processes, such as the impact of chronic hyperglycemia, oxidative stress, inflammation, impaired angiogenesis, and the role of the microbiome in DFU development. The role of serological markers, including inflammatory and glycemic indicators, in predicting DFU risk and progression is discussed. Additionally, clinical markers and advanced assessment tools, such as ulcer grading systems and imaging technologies, used to evaluate DFU severity and healing are reviewed. By synthesizing these diverse perspectives, this review aims to offer a holistic view of DFU management, highlighting how understanding the interplay of risk factors and prognostic markers can lead to improved prevention strategies and personalized therapeutic interventions.

The current work has further elucidated the expression and functional implication of cysteine desulfurase (NFS1) in gastric cancer (GC), the prognostic value, and therapeutic target because of the interaction with tumor immune infiltration and ferroptosis. Transcriptomic data from TCGA and GTEX were analyzed to assess mRNA expression and survival correlation with NFS1 among GC patients. A total of 152 GC cases were retrospectively analyzed. The level of NFS1 expression was upregulated in GC tissues compared to non-tumor gastric tissues, which was related to clinical characteristics and poor prognosis. Downregulation of the NFS1 protein in the GC cell line had an adverse effect on the migration, invasion, and proliferation of cells. In addition, NFS1 and immune correlation analysis showed that the level of NFS1 expression was related to a variety of immune cells and characteristics of the immune microenvironment. Based on functional enrichment analysis, NFS1 may have a role in ferroptosis and the tumor microenvironment (TME), such as epithelial-mesenchymal transition control, and the stromal and immunologic responses. NFS1 is a potential diagnostic and prognostic biomarker linked to ferroptosis and the TME, and provides a novel target for cancer treatment and immunotherapy.

Determining the critical elements in melanoma stem cell growth could aid in preventing the development of malignant cancer. The purpose of this study was to illustrate how FBXO31 affects the stemness, invasion, and migratory properties of melanoma stem cells. Side population (SP) cells with tumor stem cell characteristics were sorted from A375 melanoma cells. The mRNA and protein expression levels of FBXO31 in SP cells were detected using molecular techniques. FBXO31 was then transfected into SP cells, and the proportion of CD147 (+) cells in SP cells was detected by flow cytometry. FBXO31 was also transfected into CD147 (+) cells, and their spheroid formation, migration, and invasion ability were measured. Additionally, CD147 (-) and CD147 (+) cells were inoculated into nude mice to assess the effect of FBXO31 on tumor growth and metastasis. The findings demonstrate that FBXO31 is downregulated in SP cells. Upon FBXO31 transfection, the proportion of CD147 (+) cells sorted from SP cells decreased. CD147 (+) cells exhibit higher stemness characteristics, migration, and invasion abilities than CD147 (-) cells. However, these characteristics were markedly suppressed following FBXO31 transfection in CD147 (+) cells. In vivo experiment further showed that CD147 (+) cells promoted tumor growth and metastasis, while after transfection with FBXO31, tumor proliferation and metastatic abilities were inhibited. Overall, FBXO31 inhibits the migration, invasion, and stemness characteristics of CD147 (+) melanoma stem cells.

The purpose of this study was to explore the potential mechanism of SATB2 and phosphatidylinositol 3-kinase/protein kinase B (PI3K/AKT) pathway promoting fracture healing in vivo. An SD model of humeral fracture in rats was established and treated. Following a 6-week treatment period, the morphology of the fracture was assessed. Serum interleukin 6 (IL-6), tumor necrosis factor-α (TNF-α), osteocalcin, C-telopeptide of type I collagen (CTX-I), and bone morphogenetic protein 2 (BMP-2) were determined. Alkaline phosphatase (ALP), receptor activator of nuclear factor-kappa B ligand (RANKL), osteoprotegerin (OPG), and other relevant molecules such as PI3K and p-AKT were measured. The results showed that SATB2 overexpression repaired humeral fracture and bone continuity. SATB2 overexpression resulted in a significant reduction in RANKL, IL-6, TNF-α, and CTX-I expression, while simultaneously increasing OPG, ALP, osteocalcin, and BMP-2. This indicates that SATB2 inhibits osteoclast activity and promotes osteoblast function. Additionally, SATB2 overexpression increased PI3K and p-AKT protein expression in humerus. Furthermore, the inhibitory effect of the PI3K/AKT inhibitor on PI3K and p-AKT protein expression was counterbalanced by upregulating SATB2. In conclusion, SATB2 promotes fracture healing in humeral fracture rats by stimulating the proliferation and differentiation of osteoblasts, which is related to the activation of PI3K/AKT signaling pathway.

Pancreaticoduodenectomy is the standard surgical treatment for a range of malignant and some benign diseases. The mortality rate associated with this procedure has decreased to less than 3% in recent years, although the morbidity remains high at 6-40%. Common complications may include delayed gastric emptying, pancreatic fistula, intra-abdominal abscess, and gastrointestinal or intra-abdominal bleeding, among others. Bleeding and pseudoaneurysm formation are likely to be the most significant complications. This is a case report about gastrointestinal bleeding following a Whipple procedure from an aberrant hepatic artery originating from the superior mesenteric artery (SMA), treated by endovascular means. The SMA was cannulated under local anesthesia and direct puncture of the common femoral artery. Catheterization and angiogram of the aberrant right hepatic artery identified the pseudoaneurysm and bleeding site at its bifurcation. Coil embolization resulted in pseudoaneurysm occlusion and bleeding management. Hepatic perfusion was not affected as the main vasculature of the liver, namely the common hepatic artery, remained intact. The management of hemorrhage following pancreatectomy represents a significant challenge, particularly given the vulnerability of the patient cohort and the necessity for re-operation in an anatomically challenging environment. Endovascular intervention is the preferred method of treatment when applicable, as it can be performed under local anesthesia and is associated with less morbidity.

Metastasis remains a major challenge to improve the survival of patients with hepatocellular carcinoma (HCC). Artesunate is an antimalarial drug that also has anti-cancer properties. Additionally, O-GlcNAcylation has been implicated in cancer progression. In this study, we investigated whether artesunate regulated HCC cell migration and invasion and explored its impact on protein O-GlcNAcylation. Cellular functions, including viability, migration, and invasion, were evaluated using the cell counting kit-8, scratch assay, and Transwell analysis. Molecular docking and biolayer interferometry were employed to assess the binding interaction between artesunate and OGA. Furthermore, the O-GlcNAcylation of ZEB1 was examined using immunoprecipitation, cycloheximide chase assay, and immunoblotting. Our results demonstrated that artesunate significantly inhibited HCC cell viability, migration, and invasion. OGA expression was increased in HCC cells after artesunate treatment. Artesunate directly bound to OGA, and OGA knockdown reversed the inhibition of malignant behaviors induced by artesunate. Additionally, OGA suppressed the O-GlcNAcylation of ZEB1 at the Ser670 site, decreasing protein stability. Knockdown of ZEB1 inhibited HCC cellular behaviors. In conclusion, artesunate inhibits HCC cell migration and invasion by binding to OGA, which removes the O-GlcNAcylation of ZEB1 at the Ser670 site. These findings provide a new action mechanism for artesunate to treat HCC.

In a cross-sectional analysis of 14,973 adults from North China, thyroid nodules (TNs) were detected via high-resolution ultrasonography in 8,104 participants (54.1%), with a higher prevalence among women. The mean age of those with TNs was significantly higher (51.39 ± 15.41 vs 41.83 ± 12.43 years, p < 0.001). Univariate analyses indicated that female sex (OR ≈ 2.0), older age (OR ≈ 1.03 per year), elevated low-density lipoprotein cholesterol, low high-density lipoprotein cholesterol, and higher BMI were significantly linked to TNs. In contrast, total cholesterol and uric acid did not reach significance in the final model. A nomogram incorporating these risk factors demonstrated moderate predictive performance (AUC = 0.84 in the training set; 0.78 in the validation set). While the study's large sample size is a strength, its cross-sectional design limits conclusions about causality, and potential overfitting cannot be excluded. Future research should include thyroid hormone measurements, external validation of the nomogram, and longitudinal follow-up to clarify the role of metabolic factors. These findings highlight the importance of age, sex, and metabolic profiles - particularly dyslipidemia and obesity - in screening for TNs during routine health examinations.