Molecular subtype identification and prognosis stratification based on golgi apparatus-related genes in head and neck squamous cell carcinoma.

BACKGROUND: Abnormal dynamics of the Golgi apparatus reshape the tumor microenvironment and immune landscape, playing a crucial role in the prognosis and treatment response of cancer. This study aims to investigate the potential role of Golgi apparatus-related genes (GARGs) in the heterogeneity and prognosis of head and neck squamous cell carcinoma (HNSCC). METHODS: Transcriptional data and corresponding clinical information of HNSCC were obtained from public databases for differential expression analysis, consensus clustering, survival analysis, immune infiltration analysis, immune therapy response assessment, gene set enrichment analysis, and drug sensitivity analysis. Multiple machine learning algorithms were employed to construct a prognostic model based on GARGs. A nomogram was used to integrate and visualize the multi-gene model with clinical pathological features. RESULTS: A total of 321 GARGs that were differentially expressed were identified, out of which 69 were associated with the prognosis of HNSCC. Based on these prognostic genes, two molecular subtypes of HNSCC were identified, which showed significant differences in prognosis. Additionally, a risk signature consisting of 28 GARGs was constructed and demonstrated good performance for assessing the prognosis of HNSCC. This signature divided HNSCC into the high-risk and low-risk groups with significant differences in multiple clinicopathological characteristics, including survival outcome, grade, T stage, chemotherapy. Immune response-related pathways were significantly activated in the high-risk group with better prognosis. There were significant differences in chemotherapy drug sensitivity and immune therapy response between the high-risk and low-risk groups, with the low-risk group being more suitable for receiving immunotherapy. Riskscore, age, grade, and radiotherapy were independent prognostic factors for HNSCC and were used to construct a nomogram, which had good clinical applicability. CONCLUSIONS: We successfully identified molecular subtypes and prognostic signature of HNSCC that are derived from GARGs, which can be used for the assessment of HNSCC prognosis and treatment responses.

Molecular subtyping and prognostic risk characterization of head and neck squamous cell carcinoma based on lysosome-related genes.

Lysosomes possess a multitude of biological functions and are known to play a crucial role in the proliferation and metastasis of head and neck squamous cell carcinoma (HNSCC). This study aims to systematically investigate the potential role of lysosomes-related genes (LRGs) in the development of heterogeneity and prognosis in HNSCC. Publicly available transcriptome and clinical data of HNSCC were obtained and analyzed using consensus clustering to identify molecular subtypes. A risk model based on LRGs was developed and evaluated, including its correlation with clinical features, immune infiltration, drug sensitivity, and response to immune therapy. Gene set enrichment analysis was conducted to explore relevant pathways, and a prognostic nomogram model for HNSCC was constructed and evaluated. In this study, we identified 542 LRGs that exhibited differential expression in HNSCC, with 116 of these being significantly associated with overall survival. Two LRGs-derived molecular subtypes were identified, which displayed significant differences in prognosis and immune cell infiltration. Additionally, a prognostic risk model was developed, which included 13 LRGs. This model successfully divided HNSCC into low-risk and high-risk groups with different prognoses and immune cell infiltrations. The LRGs-derived risk signature was associated with immune infiltration, clinical features, drug sensitivity and immunotherapy response. The good prognosis of the low-risk group was linked to the activation of immune response-related processes and the inhibition of pathways such as necroptosis and neutrophil extracellular trap formation. Patients in the low-risk group had better immune therapy response, while those in the high-risk group had higher drug sensitivity. Finally, our nomogram, which combines clinical N staging and LRG-derived model, demonstrated excellent prognostic evaluation performance as shown by decision curve analysis and calibration curve. The study provides a comprehensive analysis of the expression and prognostic significance of LRGs in HNSCC, leading to the identification of 2 distinct molecular subtypes and the development of a risk model based on LRGs.

Total glucosides of paeony ameliorates oxidative stress, apoptosis and inflammatory response by regulating the Smad7­TGF­ß pathway in allergic rhinitis.

Total glucosides of paeony (TGP), an active ingredient extracted from the root of Paeonia alba, has been reported to display an anti­inflammatory effect. However, the effect of TGP on allergic rhinitis (AR) is still unknown. The present study aimed to assess the role of TGP in an AR mouse model. An AR mouse model was established using the ovalbumin method. The expression levels of Smad7/TGF­ß pathway­related prtoeins in nasal mucosa tissues were determined by immunofluorescence, immunohistochemistry and western blotting. The severity of nasal allergic symptoms was detected by recording the frequency of sneezing and nose rubbing motions in all mice for 20 min. The levels of IgE and inflammatory cytokines, including IL­4, IL­5, IL­17 and IFN­Î³, in the serum were measured by conducting ELISAs. H&E staining, periodic acid­Schiff staining and Masson staining were used to detected histopathological changes in mice. The concentrations of malondialdehyde and glutathione, and the activities of superoxide dismutase and catalase in tissue supernatant and serum were quantified using commercial assay kits. Apoptosis of nasal tissue cells was detected by performing TUNEL assays and western blotting. The expression of Smad7 was upregulated and that of TGF­ß was downregulated in the nasal tissue of AR mice. Additionally, TGP regulated the Smad7/TGF­ß pathway in the nasal tissue of AR mice. TGP alleviated serum IgE, nasal symptoms and histopathological changes in AR mice. Moreover, TGP ameliorated oxidative stress, cell apoptosis and inflammatory response. Smad7 small interfering RNA intervention aggravated the symptoms of AR mice via activation of the TGF­ß pathway and reversed the protective effect of TGP in AR mice. TGP ameliorated oxidative stress, apoptosis and inflammatory response via the Smad7/TGF­ß pathway in AR.

MicroRNA-182-5p relieves murine allergic rhinitis via TLR4/NF-κB pathway.

Allergic rhinitis (AR) is one of the most common chronic diseases. This study examined whether microRNA (miR)-182-5p plays a role in AR by regulating toll-like receptor 4 (TLR4). First, data demonstrated that TLR4 was a target of miR-182-5p. Subsequently, AR mouse model was established to explore the role of miR-182-5p and TLR4 in AR in vivo. Initially, quantitative reverse transcription-PCR (qRT-PCR) analysis indicated that miR-182-5p was downregulated, while TLR4 expression was upregulated in AR mice. Then we found that miR-182-5p mimic reduced the frequency of sneezing and nose rubbing of the AR mice. In addition, miR-182-5p mimic significantly increased ovalbumin (OVA)-specific IgE and leukotriene C4 expression levels in nasal lavage fluid (NLF) and serum of AR mice. miR-182-5p mimic decreased the number of inflammatory cells in NLF of AR mice. It also reduced the levels of inflammatory factors in the serum of AR mice, such as interleukin (IL)-4, IL-5, IL-13, IL-17 and tumor necrosis factor (TNF)-α, while increasing the release of IFN-γ and IL-2. Finally, miR-182-5p mimic inhibited NF-κB signaling pathway activation in AR mice. However, all effects of miR-182-5p mimic on AR mice were reversed by TLR4-plasmid. In conclusion, miR-182-5p/TLR4 axis may represent a novel therapeutic target for AR.

Responses of soil specific enzyme activities to short-term land use conversions in a salt-affected region, northeastern China.

Soil enzyme activity is a sensitive indicator of soil quality changes. The response of soil enzyme activity to different land uses is important in addressing the issues of agricultural sustainability. The objectives of this study were to investigate the effects of short-term land use conversions on soil specific enzyme activity (per unit microbial biomass carbon) of sodic soils and compare the responses of soil absolute (per unit soil mass) and specific enzyme activities in northeastern China. Four specific enzyme activities, including catalase, invertase, urease and alkaline phosphatase were assayed at 0 to 20 cm depth under five land uses, including cropland (CL), alfalfa perennial forage (AF), monoculture grassland (AG), monoculture grassland for hay once a year (AG + M) and successional regrowth grassland (RG). The specific activities of catalase, urease and alkaline phosphatase at 10 to 20 cm depth were 117.3%, 40.0% and 35.6% higher than that in 0 to 10 cm depth, irrespective to the land uses. Conversion of cropland to re-vegetation land increased the specific activities of catalase (2.8%), invertase (99.0%), urease (14.3%) and alkaline phosphatase (14.0%). Under land uses of AF, AG + M, AG and RG, the geometric mean (0.2%, 32.8%, 65.7% and 24.3%, respectively) and sum (2.6%, 38.0%, 82.8% and 29.6%, respectively) of specific enzyme activities at 0 to 20 cm depth were higher than that under CL treatment. The soil specific enzyme activities showed the better discrimination to different land uses than the soil absolute enzyme activities. In conclusion, re-vegetation has a positive effect on the improvement of soil enzyme activity in northeastern China, and the responses of soil specific enzyme activities to short-term land-use conversions are more obvious than the absolute enzyme activities, which could be used as s suitable and sensitive indicator of land use change in semiarid agroecosystems.