Xudong Wei

Although quercetin has anti‑allergic and anti‑inflammatory properties, its role in allergic rhinitis (AR) and its potential molecular mechanism, especially whether it acts through the Toll‑like receptor 4 (TLR4)/myeloid differentiation primary response 88 (MyD88)/interleukin‑1 receptor‑associated kinase 4 (IRAK4) signaling pathway, is currently unclear. Therefore, an ovalbumin (OVA)‑induced AR mouse model was established to investigate whether quercetin can treat AR by regulating the TLR4/MyD88/IRAK4 signaling pathway. OVA and aluminum hydroxide were injected intraperitoneally for sensitization, and OVA was dripped into the nose to establish a mouse model of AR. The mice were scored on behaviors such as scratching, sneezing and a runny nose to assess the success of the modeling. The treatment groups were given the relevant drugs (dexamethasone and quercetin) by gavage for 1 week after successful modeling. Following the completion of treatment, the serum OVA‑IgE, IL‑4, IL‑13, IL‑1β, IL‑17 and IL‑10 levels were measured; changes in the nasal mucosa were observed; protein and mRNA expression levels of TLR4, MyD88, IRAK4 and NF‑κB in lung tissue were determined; and changes in the percentages of regulatory T cells (Tregs) and T helper 17 (Th17) cells in the spleen were assessed. The results showed that compared with the normal control (NC) group, the allergic symptom scores were >10 points, and the serum levels of OVA‑IgE, IL‑4, IL‑13, IL‑1β and IL‑17 increased, whereas the serum level of IL‑10 decreased in the OVA group. Detachment and necrosis of the nasal mucosa, accompanied by tissue edema and inflammatory cell infiltration, were observed in the OVA group. Compared with the NC group, the relative expression mRNA and protein levels of TLR4, MyD88, IRAK4 and NF‑κB in lung tissues increased, the percentage of Tregs decreased and the percentage of Th17 cells increased in splenocytes of the OVA group. Based on these results, it was hypothesized that quercetin inhibits inflammatory responses and induces immune tolerance by regulating the TLR4/MyD88/IRAK4 signaling pathway in a mouse model of AR.

CXC chemokine ligand 8 (CXCL8) has emerged as a critical mediator in tumorigenesis. This study aims to elucidate the role of CXCL8 in the initiation and progression of papillary thyroid carcinoma (PTC). Comprehensive bioinformatic analyses were conducted to assess CXCL8 expression across pan-cancer datasets, clinical characteristics, biological functions, the tumor immune microenvironment, and single-cell RNA-sequencing data. The expression of CXCL8 and its association with clinicopathological features were validated using qRT-PCR and immunohistochemical analysis of tissue microarrays. The data revealed a significantly elevated expression of CXCL8 in PTC tissues compared to Paired non-cancerous thyroid tissues(PNTs), with CXCL8 expression showing a strong positive correlation with lymph node metastasis. These findings suggest that CXCL8 may function as a key molecular contributor to lymph node metastasis in PTC. CXCL8 is likely to promote tumor cell proliferation, migration, and invasion via the PI3K-Akt signaling pathway. Moreover, CXCL8 expression is closely associated with tumor-infiltrating immune cells, particularly exhibiting high expression levels in dendritic cells. In patients with low CXCL8 expression, anti-CTLA-4 immunotherapy may offer superior clinical benefit compared to anti-PD-1 treatment. Collectively, these findings indicate that CXCL8 represents a promising biomarker involved in the pathobiology of PTC and constitutes a potential therapeutic target, providing novel insights into immunotherapeutic strategies for PTC.

Head and neck cancer (HNC) is a common malignant disease in otorhinolaryngology; however, its pathogenesis remains to be fully elucidated. Currently, the treatment for HNC mainly comprises surgery assisted by other methods, including radiotherapy, chemotherapy and immunotherapy. After surgical treatment, the laryngeal function, and swallowing and breathing abilities of patients can be affected to a certain extent, and the loss of vocal ability can cause daily communication obstacles and affect the physical and mental health of patients. HNC recurrence makes retreatment challenging. Ferroptosis is a type of iron‑dependent regulated cell death caused by plasma membrane rupture and lipid peroxidation, and its occurrence is related to HNC. The present review aimed to describe the organelles that influence ferroptosis, the factors that activate and inhibit ferroptosis, and the role of ferroptosis in the pathogenesis, treatment and prognosis of HNC.

Laryngeal squamous cell carcinoma (LSCC) is a highly aggressive malignancy with a rising incidence over time. The tumor microenvironment (TME) plays a crucial role in LSCC development, yet the precise cellular characteristics of laryngeal cancer and its TME remain unclear. Here, we employed single-cell RNA sequencing analysis to uncover the heterogeneous populations of tumor and immune cells and investigate the role of the TME in LSCC. This analysis revealed significant heterogeneity among malignant cells, T cells, and macrophages. Notably, regulatory T cells were markedly increased at tumor sites, and macrophage analysis identified an increased presence of the Macrophage-C1-C1QC subset with up-regulated PPIF expression. Bulk RNA-seq further confirmed PPIF up-regulation in exosomes derived from LSCC tissues. Consistently, survival analysis indicated that high PPIF expression was associated with poor prognosis in LSCC. Further analyses suggested that PPIF up-regulation in Macrophage-C1-C1QC cells was associated with the enhancement of their anti-inflammatory phenotype and the promotion of F11R-F11R signaling with malignant cells, allowing LSCC cells to evade macrophage-mediated cytotoxicity. Our study provides new insights into the cellular dynamics of LSCC and highlights the critical role of Macrophage-C1-C1QC and PPIF in LSCC progression, offering potential therapeutic targets for treatment.

Background: Laryngeal cancer (LC) is characterized by high mortality and remains challenging in prognostic evaluation and treatment benefits. Ubiquitin-related genes (UbRGs) are widely involved in cancer initiation and progression, but their potential value in LC is unknown.Methods: RNA-seq and clinical data of LC were obtained from TCGA and GEO. UbRGs that independently influenced the overall survival (OS) of LC patients were screened with differential expression, COX and LASSO regression analyses. A prognostic signature was then established and assessed for its predictive value, stability and applicability using Kaplan-Meier analysis and receiver operating characteristic curves. The nomogram was further generated in combination with the signature and clinical characteristics. Characterization of immune properties and prediction of drug sensitivity were investigated on the signature-based subgroups using a panel of in silico platforms. Verification of gene expression was conducted with Western blot, qRT-PCR and ELISA, ultimately.Results: PPARG, LCK and LHX1 were identified and employed to construct the UbRGs-based prognostic signature, showing a strong ability to discriminate LC patients with distinct OS in TCGA-LC and GSE65858, and excellent applicability in most clinical conditions. The nomogram showed higher predictive value and net clinical benefit than traditional indicators. As evaluated, the low-risk group had a more activated immune function, higher infiltration of anti-cancer immune cells and stronger expression of immune-promoting cytokines than the high-risk group. Immune properties were also correlated with individual signature genes. PPARG and LHX1 were negatively correlated, whereas LCK positively correlated, with the immuno-promoting microenvironment. Additionally, chemotherapy would be more effective in high-risk patients, while immune checkpoint inhibitors would be more effective in low-risk patients. Finally, dysregulation of the signature genes was confirmed in LC cell lines by Western blot, and PPARG knockdown significantly reduced the expression of the immunosuppressive cytokines IL6, TGFB1, TGFB2 and VEGFC by qRT-PCR and ELISA.Conclusion: We have developed a UbRGs-based signature for LC prognostic evaluation that is valuable in clinical application, indicative of the immune microenvironment and beneficial for individualized treatment guidance.

Introduction: The aim of the study was to investigate how adipose-derived mesenchymal stem cells regulate the balance between regulatory T (Treg) cells and Th17 cells through the IL-2/JAK-3/STAT-5 signaling pathway in a rat model of allergic rhinitis (AR). Methods: Adipose-derived stem cells (ADSCs) were used to treat an ovalbumin (OVA)-induced AR rat model. The pathological changes and nasal symptoms were observed by HE staining and scanning electron microscopy. The concentrations of OVA-sIgE, IL-10, and IL-17 in serum were measured by enzyme-linked immunosorbent assay (ELISA). The mRNA expressions of JAK-3, STAT-5, forkhead box P3 (Foxp3), and retinoic acid-associated orphan receptor γt (RORγt) in nasal mucosa were detected by reverse transcription-polymerase chain reaction (RT-PCR). The expression of IL-2, JAK-3, and STAT-5 proteins in nasal mucosa was detected by Western blotting, and the expression patterns of these proteins were analyzed. Results: ADSCs significantly reduced nasal symptoms and histological abnormalities by significantly reducing the levels of OVA-sIgE, IL-17 and increasing IL-10 levels. The expressions of IL-2, JAK-3, STAT-5, Foxp3, and RORγt in the nasal mucosa of AR rats were abnormal, but ADSCs treatment significantly restored this change. Conclusion: ADSC can control the development of Treg/Th17 cells by the IL-2/JAK-3/STAT-5 signaling pathway and reduce OVA-induced allergic inflammation.

Trichoblastoma（TB） is a rare germ cell skin adnexal tumor of the hair, and it is a rare follicular tumor of the skin that differentiates from the hair germ epithelium and is often regarded as a benign skin tumorHowever, it is poorly confined and has a local infiltrative growth pattern. tb occurs in the head and neck region, especially in the face, and presents clinically as a slow growing, well-defined and elevated nodule. TB is routinely treated surgically. Due to the lack of universally accepted treatment guidelines or protocols, the recurrence rate after surgery is high, which makes clinical cure more difficult. In this study, a 65-year-old female patient was found to have a swelling with recurrent rupture and pus flow from the right external auditory canal opening and the auricular cavity. After initial misdiagnosis as otitis externa, she was treated with conventional anti-infective therapy, but her symptoms did not resolve and gradually worsened before coming to our hospital. The condition presented in this case is relativelyrare,therepre,timely and accurate diagnosis and treatment are crucial for prognosis improvement of such diseases.

Although surgery-based comprehensive therapy is becoming the main approach to treat laryngeal cancer, recurrence, metastasis, radiotherapy resistance and chemotherapy tolerance are still the main causes of death in patients. Targeted inhibition of laryngeal cancer stem cells has been considered as the consensus to cure laryngeal cancer. Our previous study has confirmed proto-oncogene Bmi-1 as a key regulator for self-renewal of laryngeal cancer stem cells. Targeted knockdown of Bmi-1 gene effectively inhibited the self-renewal and differentiation of laryngeal cancer stem cells, leading to the promoted sensitivity to chemotherapy including paclitaxel. However, due to off-target effects and quick degradation of the naked Bmi-1-RNAi small RNA oligo by nuclease in body fluids, it is urgently needed to develop a tumor-targeted delivery system with a protective shell. In this study, we designed and synthesized cRGD peptide-modified chitosan-polyethylene glycol slow-release nanoparticles (mPEG-CS-cRGD/Bmi-1RNAi-PTX) containing Bmi-1RNAi siRNA oligo and paclitaxel, which showed spherical in shape, 200 nm diameter in size, low cytotoxicity, strong DNA wrapping, resistance to nuclease degradation and high transfection efficiency to cells. Functional analysis indicated significant suppression of cell proliferation and migration and induction of apoptosis by the nanocomplex in laryngeal cancer cells in vitro. By application to the mouse model with laryngeal cancer, the nanocomplex inhibited tumor growth significantly in vivo. In addition, cRGD peptide, paclitaxel and Bmi-1 siRNA in the nanoparticles showed synergistic effects to suppress laryngeal cancer stem cells. In conclusion, this study not only developed a laryngeal tumor-targeted chemotherapeutic system, but also demonstrated a Bmi-1 RNAi-based chemotherapeutic strategy to inhibit cancer stem cells, having strong potential to treat laryngeal cancer patients suffering therapy resistance and/or tumor recurrence.

This study is to investigate the role and mechanism of RGD peptide in laryngeal cancer stem cells (CSCs). Laryngeal cancer CD133+Hep-2 CSCs were sorted by flow cytometry. RGD peptide was co-cultured with sorted laryngeal CSCs. Cell proliferation was detected with CCK-8 assay. The mRNA levels of VEGF/VEGFR2/STAT 3/HIF-1α were detected with RT-PCR. The proteins of VEGF/ VEGFR2/STAT 3/HIF-1α were detected with Western blot. The sorted CSCs were inoculated into nude mice. Tumor volume was measured. Integrin αvβ3 expression in tumor tissues was analyzed with immunohistochemistry. The results showed that the ratio of CD133+ CSCs to the total number of cells was 1.34±0.87 %, while CD133^-non-tumor stem cells accounted for 95.0±5.76 %. The sorted cancer stem cells grew well. The RGD peptide significantly inhibited the proliferation of CD133+Hep-2 laryngeal CSCs in a dose-dependent manner. The RGD peptide significantly inhibited the mRNA of VEGFR2, STAT3 and HIF-1α in laryngeal CSCs in a concentration-dependent manner. Consistently, the RGD peptide significantly inhibited the protein expression of VEGFR2, STAT3 and HIF-1α in laryngeal CSCs in a dose-dependent manner. At the same time, in vivo tumor experiments showed that the RGD peptide significantly inhibited tumor volume but not the body weight. Furthermore, RGD peptide significantly inhibited the expression of tumor angiogenesis-related protein integrin αvβ3. Our findings demonstrate that RGD peptide inhibits tumor cell proliferation and tumor growth. The underlying mechanism may that RGD inhibits tumor angiogenesis-related signaling pathways, thus affecting the tumor angiogenesis, and decreasing the progression of human laryngeal CSCs.