ABSTRACT
PURPOSE: This prospective study aims to provide further supportive evidence by assessing the sustained effectiveness and safety of sublingual immunotherapy (SLIT) using a vaccine containing house dust mite (HDM) extracts in patients diagnosed with allergic rhinitis (AR) with/without conjunctivitis (AR/C). MATERIALS AND METHODS: AR/C patients (n = 111, SLIT group: 57, control group: 54) allergic to HDM were treated with standardized SLIT drops or symptomatic drugs from October to December in 2020. The patients were directed by the investigators to attend annual hospital visits for the assessment of various parameters including the Rhinoconjunctivitis Quality of Life Questionnaire (RQLQ), visual analog scale (VAS), total nasal symptom score (TNSS), total ocular symptom score (TOSS) and total medication score (TMS). During the study period, all participants were mandated to maintain comprehensive records of any adverse events (AEs) on diary cards, which were then communicated to the investigators via telephone. RESULTS: At baseline (2020), TNSS, TOSS, TMS, VAS, and RQLQ scores were comparable between SLIT and control groups (P > 0.05). After one year of treatment (2021), significant reduction in all scores compared to the baseline for both groups (P < 0.001). At the end of the second year of treatment (2022), TNSS and RQLQ score in the SLIT group continued to decrease significantly compared to 2021 (P < 0.05). In the third year (2023), the control group showed a rebound in TNSS, TOSS, TMS, and RQLQ scores, significant differences compared to 2022 or 2021 (P < 0.05). Besides, the SLIT group had significantly lower scores across all domains of RQLQ compared to the control group (P < 0.001). Symptomatic treatment influenced the scores of Nasal Symptoms, Eye Symptoms, Practical Problems, and Emotions domains significantly in 2023 compared to 2021 or 2022 (P < 0.05). Within the SLIT group, no significant differences in TNSS, TMS, VAS, and RQLQ scores were observed between monosensitized and polysensitized patients throughout the three years of treatment (P > 0.05). All AEs were mild to moderate. CONCLUSION: The 3-year course of HDM-SLIT has shown significant therapeutic efficacy and a favorable safety profile in patients with AR/C. Importantly, our study presents initial evidence suggesting that the greater impact of AR/C on quality of life (QoL) may primarily stem from nasal symptoms, eye symptoms, practical issues, and emotional well-being.
ABSTRACT
LIM domain only 3 (LMO3) interacts with transcription factors to regulate target genes involved in embryonic development. The oncogenic role of LMO3 in hepatocellular carcinoma, gastric cancer, and neuroblastoma has been reported recently. However, little is known about the biological function of LMO3 in papillary thyroid carcinoma (PTC). First, expression of LMO3 was dramatically enhanced in the PTC tissues and cell lines. Second, knockdown of LMO3 in PTC cells repressed cell proliferation and promoted cell apoptosis with downregulated Bcl-2 and upregulated cleaved caspase-3/PARP. In vitro cell migration and invasion of PTC were also retarded by siRNA-mediated silence of LMO3. Third, protein expression of LIM kinase (LIMK) 1-mediated phosphorylation of cofilin and nuclear translocation of ß-catenin were reduced by the knockdown of LMO3. pcDNA-mediated overexpression of LIMK1 promoted cofilin phosphorylation and attenuated LMO3 silence-induced decrease of cofilin phosphorylation. Last, enhanced LIMK1 expression promoted PTC cell proliferation and metastasis and counteracted the suppressive effects of LMO3 silence on PTC cell proliferation and metastasis. In conclusion, LMO3 promoted PTC cell proliferation and metastasis by regulating LIMK1-mediated cofilin and the ß-catenin pathway.
ABSTRACT
Nasopharyngeal carcinoma (NPC) is a malignant tumor in nasopharynx tissues and lacks effective treatment strategies. Dysregulation of distal-less homeobox 4 (DLX4) participates in the development of tumors. Understanding the regulatory mechanism of DLX4 in NPC progression may address this issue. Here, we first identified an up-regulation of DLX4 in NPC cell lines compared to normal epithelial cells. Data from colony formation and transwell assays showed that knockdown of DLX4 inhibited cell proliferation and invasion of NPC, respectively. Moreover, DLX4 knockdown blocked the cell cycle of NPC at G1 phase, suggesting the antitumor effect of DLX4 knockdown on NPC. The downstream target of DLX4 was identified as Y-box binding protein 1 (YB-1), whose expression was increased by over-expression of DLX4, while decreased by knockdown of DLX4. The binding capacity between DLX4 and YB-1 was verified by chromatin immunoprecipitation (ChIP), and the result showed that DLX4 could not directly bind to the promoter of YB-1. Mechanically, YB-1 over-expression reversed the effects of DLX4 knockdown on cell proliferation, cell cycle arrest and cell invasion of NPC. In conclusion, our findings indicated that DLX4 promoted NPC progression via up-regulation of YB-1, which would shed light on therapeutic schedule in NPC.
