Construction of a novel disulfidptosis-related lncRNAs signature for prognosis prediction and anti-tumor immunity in laryngeal squamous cell carcinoma.

Disulfidptosis, an innovative type of controlled cellular death linked to metabolic dysfunction, has garnered attention. However, there is limited knowledge regarding the involvement of disulfidptosisrelated lnRNAs (DRlncRNAs) in laryngeal squamous cell carcinoma (LSCC). The objective of our team in this study seeks to establish a DRlncRNAs signature, investigate their prognostic value in LSCC, and explore their associations with immune cell subpopulations, biological signaling pathways, and exploring implications for drug sensitivity. We accessed LSCC patients' RNA-seq data and pertinent clinical data for subsequent further analysis from The Cancer Genome Atlas (TCGA) portal. A literature search was conducted focusing on disulfidptosis-related genes. Pearson correlation coefficients were calculated to identify DRlncRNAs. Differential expression analysis of lncRNAs was performed. Utilizing univariate Cox regression analysis, we identified disulfidptosis-associated prognostic lncRNAs. The LASSO-Cox regression analysis was employed to refine this set of lncRNAs and construct a disulfidptosis-related lncRNAs signature. Various statistical techniques were employed to appraise model predictive performance. Subsequently, risk groups were stratified based on the risk score derived from the DRlncRNAs signature. The superiority of the risk score in prognostication over traditional clinicopathological features in LSCC patients was demonstrated. Evident distinctions emerged between risk groups, particularly in immune cell subpopulations like activated mast cells, eosinophils, and activated NK cells. Finally, the low-risk group demonstrated reduced IC50 values for specific chemotherapeutics like cisplatin and gemcitabine. The in vitro experiments indicated differential behavior of our DRlncRNAs. The DRlncRNAs signature can serve as a robust biomarker with the ability to predict both prognosis and therapeutic responses among patients with LSCC.

Association between the atherogenic index of plasma and hearing loss based on a nationwide cross-sectional study.

BACKGROUND: Hearing loss (HL) is a worldwide public health issue for which the role of dyslipidemia has not been fully elucidated. This study aimed to use the atherogenic index of plasma (AIP), a well-established serum lipid marker, to investigate the association of dyslipidemia with HL among the general population. METHODS: Participants (n = 3267) from the National Health and Nutrition Examination Survey database (2005-2012, 2015-2018) were included in the present study. The AIP was calculated based on the following formula: log10 (triglycerides/high-density lipoprotein cholesterol). HL was defined as a pure-tone average of at least 20 dBHL in the better ear. Weighted multivariable logistic regression, subgroup analysis, generalized additive model, and threshold analysis were adopted to reveal the association between the AIP and HL. RESULTS: In this study of US adults, a positive association was found between the AIP and high-frequency HL. However, the association between the AIP and low-frequency HL was not as strong. In addition, a reverse L-shaped curve with an inflection point located at -0.27 was detected between the AIP and high-frequency HL, followed by a significant positive association after the inflection point. CONCLUSIONS: The potential of the AIP as a bioindicator for high-frequency HL is noteworthy, and maintaining an AIP value below a certain threshold might provide beneficial outcomes in the management of high-frequency HL.

Mesenchymal Stem Cell-Derived Exosomes Promote Recovery of The Facial Nerve Injury through Regulating Macrophage M1 and M2 Polarization by Targeting the P38 MAPK/NF-Κb Pathway.

Facial nerve (FN) injury seriously affects human social viability and causes a heavy economic and social burden. Although mesenchymal stem cell-derived exosomes (MSC-Exos) promise therapeutic benefits for injury repair, there has been no evaluation of the impact of MSC-Exos administration on FN repair. Herein, we explore the function of MSC-Exos in the immunomodulation of macrophages and their effects in repairing FN injury. An ultracentrifugation technique was used to separate exosomes from the MSC supernatant. Administrating MSC-Exos to SD rats via local injection after FN injury promoted axon regeneration and myelination and alleviated local and systemic inflammation. MSC-Exos facilitated M2 polarization and reduced the M1-M2 polarization ratio. miRNA sequencing of MSC-Exos and previous literature showed that the MAPK/NF-κb pathway was a downstream target of macrophage polarization. We confirmed this hypothesis both in vivo and in vitro. Our findings show that MSC-Exos are a potential candidate for treating FN injury because they may have superior benefits for FN injury recovery and can decrease inflammation by controlling the heterogeneity of macrophages, which is regulated by the p38 MAPK/NF-κb pathway.

Prognostic Factors Affecting Hearing in Otitis Media With ANCA-Associated Vasculitis Patients: A Systematic Review and Meta-Analysis.

Objectives: To conduct a systematic review and meta-analysis of clinical studies describing the possible prognostic factors affecting hearing outcomes in Otitis media with antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis (OMAAV) patients. To provide guidance for clinical work, avoiding profound irreversible hearing loss affecting patients' lives. Methods: A literature search was performed in PubMed, MEDLINE, EMBASE, Cochrane, Scopus, and Web of Science to identify English articles published before December 1, 2022. After screening the articles, the Newcastle-Ottawa Scale (NOS) was used to assess the risk of bias of the extracted literature, and studies with high quality (score > 6) were included. Results: Four studies were included: 1 was a retrospective cohort study, and 3 were case-control studies. We performed a meta-analysis of 4 factors: facial palsy, hypertrophic pachymeningitis, ANCA-negative status, and the period from onset to diagnosis. The results showed that there was a significant association between facial palsy [odds ratio (OR) 1.51; 95% confidence interval (CI) 1.07-2.15; I2 = 0%; P = .02], hypertrophic pachymeningitis (OR 1.73; 95% CI 1.18-2.53; I2 = 24%; P = .005), ANCA negativity (OR 1.75; 95% CI 1.11-2.77; I2 = 33; P = .02), and poor hearing prognosis in OMAAV patients. However, the period from onset to diagnosis (SEM ± SD 2.54; 95% CI -1.56 to 6.64; I2 = 98%; P = .22) of OMAAV was not significantly associated with poor hearing outcomes. Conclusion: We found that OMAAV patients with facial palsy, hypertrophic pachymeningitis, and ANCA negativity have a significant association with poor hearing prognosis, which provides diagnosis and treatment guidance in protecting patients' hearing.

Effects of rosmarinic acid on the inflammatory response in allergic rhinitis rat models after PM2.5 exposure.

BACKGROUND: Studies have shown the promising prospects of rosmarinic acid (RosA) for the prevention and treatment of allergic diseases. OBJECTIVE: The aim of this study was to investigate the effects of RosA on inflammatory reaction in rat models of allergic rhinitis (AR) after PM2.5 exposure. METHODS: Allergic rhinitis rat models were established by ovalbumin sensitization, and PM2.5 was applied at a concentration of 1000 µg/m3 , 3 h a day for 30 consecutive days. RosA was administered via intraperitoneal injection (20 mg/kg/d) for seven consecutive days. Allergic nasal symptoms were recorded. The expressions of interleukin (IL)-4, IL-13, interferon (INF)-γ, and OVA-sIgE were determined by ELISA. Histopathological changes in nasal mucosa were observed by HE staining. mRNA expressions of T-bet and GATA-3 in nasal mucosa were detected by RT-PCR. NF-κBp65 in cell nuclei and IκBα in cytoplasm were analyzed by Western blot. RESULTS: PM2.5 exposure worsened allergic nasal symptoms in AR rats, while RosA ameliorated these symptoms. Histopathologically, AR rats exhibited disorganized nasal mucosal epithelium, cell exfoliation, eosinophilic infiltration of lamina propria, gland swelling, and submucosal vascular congestion, which were aggravated by PM2.5 exposure and alleviated by RosA. RosA decreased the expressions of IL-4, IL-13, and increased the level of IFN-γ in PM2.5-exposed AR rats. After RosA intervention, the expressions of GATA-3 mRNA and NF-κBp65 in PM2.5-exposed AR rats were significantly reduced, while those of T-bet mRNA and IκBα were markedly increased. CONCLUSION: Rosmarinic acid may alleviate symptoms of AR rat models exposed to PM2.5 through the modulation of the NF-κB pathway and Th1/Th2 balance.

miR-338-3p inhibits autophagy in a rat model of allergic rhinitis after PM2.5 exposure through AKT/mTOR signaling by targeting UBE2Q1.

Exposure to fine particulate matter (PM2.5) increases the incidence of allergic rhinitis (AR). microRNA (miRNA) can regulate cell proliferation, invasion and apoptosis. However, the mechanism of miR-338-3p in mediating PM2.5-induced autophagy in AR animal models remains unknown. To explore the mechanism of miR-338-3p in PM2.5-induced autophagy in AR, the human nasal epithelium cells and AR model exposed to PM2.5 were deployed. The results showed that miR-338-3p was down-regulated in both nasal mucosa of PM2.5-exacerbated AR rat models and PM2.5-treated RPMI-2650 cells. Forced expression of miR-338-3p could inhibit autophagy in vitro. miR-338-3p specifically bound to UBE2Q1 3'-untranslated region (3' UTR) and negatively regulated its expression. Overexpression of UBE2Q1 attenuated the inhibitory effects of miR-338-3p on PM2.5-induced autophagy of RPMI-2650 cells through AKT/mTOR pathway. Moreover, our in vivo study found that after administration of agomiR-338-3p in AR rats model, the expression of autophagy-related proteins decreased and nasal symptoms alleviated. In conclusion, this study revealed that miR-338-3p acts as an autophagy suppressor in PM2.5-exacerbated AR by directly targeting UBE2Q1 and affecting AKT/mTOR pathway.

Ozone inhalation induces exacerbation of eosinophilic airway inflammation and Th2-skew immune response in a rat model of AR.

BACKGROUND: Ozone (O3) exposure elicits allergic rhinitis (AR) exacerbations by mechanisms that remain poorly understood. We used a rat model to investigate the effects of O3 on eosinophilic airway inflammation and Th2-related response. METHODS: Sprague-Dawley (SD) rats were sensitized and challenged with ovalbumin (OVA) to make AR models. Three groups of AR rats were exposed respectively to 0.5, 1.0, 2.0 ppm of O3 for 2 h daily over 6 weeks consecutively and studied 24 h later. Normal rats exposed to O3 alone were used as controls. Nasal symptoms and OVA-specific immunoglobulin E (OVA-sIg E) in the serum were evaluated. Inflammatory cells in nasal lavage fluid (NLF) were classified and counted. Cytokines protein levels in NLF were assessed by ELISA. The pathological changes in the nasal mucosa were examined by histology. RESULTS: The combination of allergen and repeated O3 exposure in rats induced a significant increase of the number of sneezes, nasal rubs, amount of nasal secretion and OVA-sIgE in the serum, accompanied by enhancement of eosinophils in NLF and nasal mucosa. The increase of interleukin-5 (IL-5), IL-13, Eotaxin and decrease of INF-γ protein levels in NLF were detected in AR rats after O3 inhalation. Hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium and eosinophilic infiltration in a concentration-dependent manner. CONCLUSIONS: O3 inhalation deteriorated symptoms in AR rats, and the possible mechanism is that ozone co-exposure could enhance the expression of Th2 cytokines, eosinophilic airway inflammation dose-dependently. The observation is helpful for us to understand the synergistic effect of O3 in the air pollution and allergen on aggravating allergic rhinitis.

Ursolic Acid Alleviates Mucus Secretion and Tissue Remodeling in Rat Model of Allergic Rhinitis After PM2.5 Exposure.

BACKGROUND: According to recent epidemiologic studies, exposure to fine particulate matter (particulate matter 2.5 ≤ µm [PM2.5]) in the air increases the incidence and severity of allergic rhinitis (AR). Ursolic acid (UA) has activities in immune regulation and anti-inflammatory. However, the role of UA intervention on PM2.5-exposed AR remains unknown. In this study, we investigated the effects of UA on tissue remodeling and mucus hypersecretion in a rat model of AR after PM2.5 exposure. METHODS: AR was induced in rats with ovalbumin (OVA) and they were exposed to ambient PM2.5(200 µg/m3) via a PM2.5 inhalation exposure system for 30 days(ARE group). Ursolic acid intervention was administrated in the AR model after PM2.5 exposure (UA group). Hyperplasia of goblet cells was detected by periodic acid-Schiff (PAS) staining and collagen deposition in the nasal mucosa was detected by Masson trichrome (MT) staining.MUC5AC expression was measured by immunohistochemistry. RESULTS: UA group showed reduced goblet cell hyperplasia and collagen deposition in the nasal mucosa which exacerbated after PM2.5 exposure, as reflected by PAS and MT staining when compared with the ARE group. Immunohistochemical results showed that the expression of MUC5AC in the UA group was lower than that in the ARE group. CONCLUSION: Analysis of our data indicated that UA could attenuate nasal remodeling and mucus hypersecretion in aggravation of AR after PM2.5 exposure, which may be the pathophysiologic mechanisms for the prevention of AR exacerbated by exposure to PM2.5.

Effects of N-acetylcysteine on oxidative stress and inflammation reactions in a rat model of allergic rhinitis after PM2.5 exposure.

Particulate matter 2.5 (PM2.5) exposure can increase the prevalence of allergic rhinitis (AR), the mechanism underlying which may include oxidative stress and inflammatory response. As a ROS quenching agent, N-acetylcysteine (NAC) can attenuate the accumulation of inflammatory cells and hyper-responsiveness in animal asthma models. To explore the effect of NAC on the oxidative stress and inflammatory reactions in AR rats exposed to PM2.5, we analyzed the components of PM2.5 and examined the nasal symptoms, redox level in nasal mucosa, Th1/Th2-related serum cytokines, nasal mucosal histopathology and ultrastructure in AR rat models with NAC intervention after PM2.5 exposure. The results showed that the high concentrations of metal cations and PAHs in PM2.5 could aggravate Th2-dominant allergic inflammation in AR model and cause redox imbalance, accompanied by nasal epithelial cell stripping and eosinophil infiltration, while NAC intervention could alleviate the clinical symptoms of AR model after PM2.5 exposure, correct the redox imbalance, reduce the Th2 cytokines, reduce eosinophil infiltration, and promote the moderate regeneration of epithelial cells. The mechanism of NAC reversing PM2.5-mediated action may be related to its anti-oxidant and anti-inflammatory effects, which may provide some new insights for the prevention of AR exacerbated by exposure to PM2.5.

Effects of Ursolic Acid on the Expression of Th1-Th2-related Cytokines in a Rat Model of Allergic Rhinitis After PM2.5 Exposure.

BACKGROUND: Allergic rhinitis (AR) is a global health problem and closely related to environmental factors. Ursolic acid (UA) has potential in the treatment of allergic inflammation. The effects of UA intervention on PM2.5-induced AR remain uncertain. OBJECTIVE: To assess the effects of UA on nasal symptoms and the expression of T-helper (Th)1-Th2-related cytokines in a rat model of AR after fine particulate matter (particulate matter ≤ 2.5 µm [PM2.5]) exposure. METHODS: A total of 40 healthy female Sprague-Dawley rats were randomly divided into 4 groups: normal control group (NC group), ovalbumin (OVA)- induced AR model (AR group), PM2.5-exposed AR group exposed to 200 g/m3 PM2.5 for 30 days via inhalation (ARE group), and a group with UA intervention to the AR model after PM2.5 exposure (UA group). UA intervention was adopted after PM2.5 exposure in the UA group. Nasal symptoms and levels of Th1-Th2 cytokines in the serum were detected in each individual rat. The pathological changes and expression of Eotaxin in the nasal mucosa of each individual rat were examined by histology. RESULTS: PM2.5 significantly increased the number of sneezes and nasal rubs in the rats with AR, and UA alleviated these symptoms. UA decreased interleukin (IL)-4, IL-5, IL-13, Eotaxin-1, and OVA Immunoglobulin E (IgE) protein levels. In the AR group, hematoxylin and eosin staining showed disordered arrangement of the nasal mucosa epithelium, cell shedding, eosinophilic infiltration, swelling of the glands, and submucosal vascular congestion. UA group showed reduced eosinophilic infiltration and orderly arrangement of the mucosal epithelium when compared with the ARE group. Immunohistochemical results showed that the expression of Eotaxin in the UA group was lower than that in the ARE group. CONCLUSION: UA could relieve nasal symptoms caused by PM2.5 exposure, the possible mechanism of which is to inhibit the expression of Th2 cytokines, eosinophilic infiltration, and specific IgE production.

Effects of PM2.5 on mucus secretion and tissue remodeling in a rabbit model of chronic rhinosinusitis.

BACKGROUND: According to epidemiologic studies, fine particulate matter (particulate matter ≤2.5 µm, PM2.5) is closely associated with increases in the incidence and severity of chronic rhinosinusitis (CRS). However, the role of PM2.5 in the pathophysiology of CRS remains largely unknown. In this study, we investigated the effects of PM2.5 on nasal cilia, tissue remodeling, and mucus hypersecretion in a rabbit model of CRS. METHODS: CRS rabbits were exposed to ambient PM2.5 via a PM2.5 inhalation exposure system. The degree of ciliary damage was evaluated using scanning electron microscopy (SEM). Histopathologic changes were determined using periodic acid-Schiff (PAS) staining of goblet cells and Masson trichrome (MT) staining for collagen in the nasal mucosa. MUC5AC expression was assessed by immunohistochemistry. RESULTS: PM2.5 exposure substantially aggravated ciliary disruption in rabbits with CRS. PM2.5 also significantly increased goblet cell hyperplasia and collagen deposition, as reflected by PAS and MT staining. The nasal mucosa of CRS rabbits displayed markedly elevated MUC5AC expression after PM2.5 exposure. CONCLUSION: Increases in ciliary disruption, nasal remodeling, and mucus hypersecretion may be the pathophysiologic mechanisms underlying the PM2.5-induced aggravation of CRS.