Effect of Blocking the OX40/OX40L Signaling Pathway by siRNA Interference on Animal Experimental Study of Allergic Rhinitis.

BACKGROUND: The identification of new approaches and intervention targets for the treatment of AR is urgently needed. We aimed to investigate the effect of blocking the OX40/OX40L signaling pathway by small interfering RNA (siRNA) on ovalbumin (OVA)-induced AR in a mouse model. METHODS: After establishment of the AR model, the mice were interfered by siRNA-OX40L (experimental group), siRNA-C (negative control group), or PBS (control group). Nose scratching, sneezing and nasal discharge were observed. OX40L mRNA and protein and the IL-5, TNF-α, regulatory T cell (Treg) -specific marker Foxp3, and eosinophil (EOS) levels were analyzed. RESULTS: The numbers of nose scratching and sneezing were significantly lower in the siRNA-OX40L-treated group (p <0.05). After the intervention of siRNA-OX40L, OX40L mRNA and protein levels were significantly inhibited (p <0.05), but the Foxp3 level was significantly increased in the experimental group (p <0.05). The IL-5 and TNF-α levels were significantly lower in the experimental group (p <0.05), and the reduction was more evident for the Th2-type cytokine IL-5 than for the Th1-type cytokine TNF-α. Few or no EOSs were found in the nasal mucosal epithelium of the experimental group (p <0.05), whereas EOS infiltration was significant in the other two groups. CONCLUSIONS: Blockage of the OX40/OX40L signaling pathway with siRNA-OX40L interference can inhibit allergic reactions and relieve allergic symptoms in AR mice. The underlying mechanism may be related to correcting Th2 immune deviation, inducing immune tolerance, and promoting Treg production.

Silencing of FANCD2 enhances the radiosensitivity of metastatic cervical lymph node-derived head and neck squamous cell carcinoma HSC-4 cells.

Fanconi anemia complementation group D2 (FANCD2) is involved in the key steps of the Fanconi anemia (FA) pathway, which plays a role in the repair of DNA crosslink damage. However, the role of FANCD2 during radiotherapy for head and neck squamous cell carcinoma (HNSCC) is unclear. In this study, the HNSCC cell line HSC-4 was used. Western blotting was used to evaluate the expression of the FANCD2 in HSC-4 cells. We investigated the impact of FANCD2 on the radiosensitivity of HSC-4 cells in vitro and in vivo. TUNEL, western blotting and immunohistochemistry were used to analyze the apoptosis and proteins involved in apoptosis-related pathways after radiotherapy to investigate the relevant mechanism. The present study showed that shRNA interference could effectively and stably silence FANCD2 expression in HSC-4 cells. In vitro, the silencing of FANCD2 inhibited cell proliferation, decreased the survival rate, increased apoptosis and induced S phase arrest in HSC-4 cells after radiotherapy. In vivo, the silencing of FANCD2 could prolong the tumor-forming time and slow tumor growth. In addition, the tumor volume was significantly reduced, the weight was deceased, and the tumor inhibition rate was increased after radiotherapy. TUNEL showed that the silencing of FANCD2 significantly increased apoptosis in HSC-4 cells induced by radiotherapy. Both in vitro and in vivo esperiments revealed that the expression of the Bax and p-p38 proteins in HSC-4 cells, in which FANCD2 had been silenced, was increased after radiotherapy, whereas the expression of the p38 and Bcl2 proteins was decreased. Our results suggested that the silencing of FANCD2 enhanced the radiosensitivity of HSC-4 cells, and its mechanism involves the activation of the p38 MAPK signaling pathway and the regulation of the expression of Bax and Bcl2 proteins. This study provides a novel candidate target for HNSCC therapy.

Scalp junctional nevus with malignant transformation (melanoma) metastatic to parotid lymph node region, cervical lymph nodes and the back: a case report and review of literature.

Parotid malignancy may occur as a primary neoplasm of the salivary tissue or as metastatic involvement of the parotid lymph nodes. Primary tumors of squamous cell carcinoma and malignant melanoma involving the skin of the head and neck have the potential to spread to lymph nodes of the parotid gland. Metastatic malignant melanoma to the back was exceptionally rare and no such reports have been noted in the literature. We reported an exceptional case of intraparotid lymph nodes metastasis of the right scalp junctional nevus with malignant transformation to malignant melanoma in a 48-year-old man. The patient presented with a mass in the parotid gland area, which was misdiagnosed as a primary parotid tumor and surgical removal was performed. Unfortunately, recurrence with newly developed metastatic lesions in the back and cervical lymph nodes occurred 1 year after initial surgical management. This case is presented highlighting the unusual features of metastatic junctional nevus with malignant transformation to malignant melanoma of intraparotid lymph nodes, cervical lymph nodes and the back, which should help us to reduce misdiagnosis and obtain the best results.

Rosai-Dorfman disease (RDD) in the paraglottic space: report of a case and review of literature.

Sinus histiocytosis with massive lymphadenopathy is also known as Rosai-Dorfman disease (RDD) and is characterized by painless bilateral cervical lymphadenopathy. In the present case report, a 67-year-old Chinese woman presented with a 3-month history of progressive voice hoarseness, progressive dyspnea on exertion and a foreign body sensation. MRI revealed a lesion involving the right side of the paraglottic space. The lesion was totally resected. Based on the histologic features and immunoreactivity for the S-100 protein and CD68, a diagnosis of RDD was made. We described an extremely unique case of RDD that was observed in the paraglottic space and discussed its clinical and histopathologic features, differential diagnoses and treatment options.