Berberine inhibits the malignant cell phenotype by inactivating PI3K/AKT/mTOR signaling in laryngeal squamous cell carcinoma.

BACKGROUND: Berberine is an active compound found in different herbs used in Chinese medicine and is well-known for its potential anticancer properties. The study aimed to figure out the role of berberine in regulating the malignant behavior of laryngeal squamous cell carcinoma (LSCC) cells. METHODS: LSCC cell lines (SNU-899 and AMC-HN-8) were treated with different concentrations of berberine (0-200 µM) to determine its cytotoxicity. The migration, invasion, and apoptosis of LSCC cells were measured by wound healing assays, Transwell assays, and flow cytometry. Western blot was performed for the quantification of proteins involved in PI3K/AKT/mTOR signaling. RESULTS: The viability of LSCC cells was dose-dependently reduced by berberine. Berberine dampened LSCC cell migration and invasion while augmenting cell apoptosis, as evidenced by a reduced wound closure rate, a decrease in invaded cell number, and a surge in cell apoptosis in the context of berberine stimulation. Importantly, the effects of berberine on the cancer cell process were enhanced by LY294002 (an inhibitor for PI3K) treatment. Moreover, the protein levels of phosphorylated PI3K, AKT, and mTOR were markedly reduced in response to berberine treatment. CONCLUSION: Berberine inhibits cell viability, migration, and invasion but augments cell apoptosis by inactivating PI3K/AKT/mTOR signaling in LSCC.

IGF2BP2 promotes head and neck squamous carcinoma cell proliferation and growth via the miR-98-5p/PI3K/Akt signaling pathway.

Introduction: As a N6-methyladenosine reader protein, Insulin-like growth factor 2 mRNA-binding protein 2 (IGF2BP2) is a critical player in tumor progression and metastasis. However, its specific function in head and neck squamous carcinoma (HNSCC) has yet to be determined. The present study aimed to determine the role of IGF2BP2 in HNSCC. Methods: The expression of IGF2BP2 in HNSCC was analyzed using The Cancer Genome Atlas (TCGA) dataset and detected in HNSCC tissues and cells, respectively. Gain- and loss- of function methods were employed to study the effects of IGF2BP2 on HNSCC cell proliferation and tumorigenesis in vitro and in vivo. MicroRNAs (miRNAs) regulating IGF2BP2 were predicted using online tools and confirmed experimentally. Results: We showed augmented IGF2BP2 expression in HNSCC, which correlated with poor clinical outcomes. Functional studies showed that IGF2BP2 promoted HNSCC cell proliferation by facilitating cell cycle progression while inhibiting apoptosis. We further demonstrated that IGF2BP2 could enhance HNSCC cell tumorigenesis in vivo. Mechanistically, our data revealed that miR-98-5p could directly target IGF2BP2. The interplay between IGF2BP2 and miR-98-5p is essential to drive the progression of HNSCC via the phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)-protein kinase B (Akt) pathway signaling pathway. Discussion: The current study revealed the oncogenic role of IGF2BP2 and provided insights into its potential mechanism in HNSCC tumorigenesis. Additionally, IGF2BP2 might represent a promising therapeutic target and serve as prognostic biomarker in patients with HNSCC.

A multifaceted and feasible prognostic model of amino acid metabolism-related genes in the immune response and tumor microenvironment of head and neck squamous cell carcinomas.

We investigated the role of amino acid metabolism (AAM) in head and neck squamous cell carcinoma (HNSCC) tissues to explore its prognostic value and potential therapeutic strategies. A risk score based on four AAM-related genes (AMG) was constructed that could predict the prognosis of HNSCC. These four genes were up-regulated in HNSCC tissues and might act as oncogenes. Internal validation in The Cancer Genome Atlas (TCGA) by bootstrapping showed that patients with high-risk scores had a poorer prognosis than patients with low-risk scores, and this was confirmed in the Gene Expression Omnibus (GEO) cohort. There were also differences between the high-risk and low-risk groups in clinical information and different anatomical sites such as age, sex, TNM stage, grade stage, surgery or no surgery, chemotherapy, radiotherapy, no radiotherapy, neck lymph node dissection or not, and neck lymphovascular invasion, larynx, overlapping lesion of lip, and oral cavity and pharynx tonsil of overall survival (OS). Immune-related characteristics, tumor microenvironment (TME) characteristics, and immunotherapy response were significantly different between high- and low-risk groups. The four AMGs were also found to be associated with the expression of markers of various immune cell subpopulations. Therefore, our comprehensive approach revealed the characterization of AAM in HNSCC to predict prognosis and guide clinical therapy.

[Morphological changes of upper airway in patients with obstructive sleep apnea hypopnea syndrome after H-UPPP].

Objective:To investigate the morphological changes of the upper airway palatepharyngeal plane after modified uvulopalatopharyngoplasty（H-UPPP） in patients with obstructive sleep apnea hypopnea syndrome（OSAHS） and efficacy of the surgery. Methods:Thirty-six patients diagnosed as moderate to severe OSAHS in the Central Hospital of Wuhan from January 2016 to September 2019 were treated with H-UPPP. PSG and 64 slice spiral CT were performed before operation, 1 month, 3 months, 6 months, 1 year and 2 years after operation to evaluate the changes of AHI, LSaO2, CT90, BMI and the minimum anterior and posterior axis diameter, left and right axis diameter and cross-sectional volume of velopharyngeal plane, respectively. Results:The AHI, LSaO2, CT90, BMI were significantly improved, while the minimum anterior posterior axis diameter, left and right axis diameter and cross-sectional volume of velopharyngeal plane were enlarged in the maximum extent at one month after operation. The alteration of left and right axis diameter could be maintained until half a year after operation, but gradually retracted after 1 year after operation. The improvement of anterior and posterior axis diameter can only be maintained until 3 months after operation, and return to the preoperative level 2 years after operation; The minimum cross-sectional area improved significantly at 1 month after operation and decreased after 3 months, but there was still a significant improvement at 2 years after operation（P<0.05）. The change of AHI was similar to that of the minimum cross-sectional area, and there was still a significant difference at 2 years after operation（P<0.001）; The improvement of LSaO2 was the most significant at 1 month after operation, which could be maintained until 3 months after operation, and then gradually recovered. The improvement of CT90 could be maintained until half a year after operation, and decreased significantly at 1 year after operation. BMI was still better than that before operation at 1 year after operation, but returned to the preoperative level at 2 years after operation. The improvement of AHI was mainly related to the minimum anterior posterior axis diameter and cross-sectional area of velopharyngeal plane, but not to the left and right axis diameters. Conclusion:The morphological changes of upper airway in patients with OSAHS after H-UPPP are mainly the improvement of anterior posterior diameter, left and right diameter and minimum cross-sectional area caused by removing the anatomical load of upper airway within 3 months after operation, but the reduction of anterior posterior diameter and minimum cross-sectional area gradually occurs after 3 months, resulting in the weakening of surgical effect.

Impact of Vocal Fold Dehydration on Vocal Function and Its Treatment.

The change of vocal function after vocal fold dehydration due to dryness was discussed along with the treatment effect of different atomizing agents. Forty-eight staffs from The Central Hospital of Wuhan were recruited. All volunteers breathed dry air for vocal fold dehydration. After dry air inhalation, the subjects were randomly divided into four groups, with 12 cases each. Three groups were treatment groups, receiving 0.9% normal saline (IS), 5% hypertonic saline (HS) and double-distilled water (SW) atomizing inhalation therapy, respectively, and the last group was the control group without treatment. Voice data were collected for all subjects before and immediately after dry air inhalation using the Multi-Dimensional Voice Program (MDVP) system. Atomizing inhalation therapy was given 10 min after dry air inhalation, and voice data were collected using MDVP system at the following time points after atomizing inhalation treatment: 5 min, 20 min, 35 min, 50 min, 65 min, 80 min, 95 min, 110 min. In the control group, voice data were collected at the same time points and compared with those of treatment groups. The vocal function parameters collected before and after dry air inhalation as well as after treatment were subjected to test using SPSS 16.0 software. In the four groups, jitter (fundamental frequency perturbation), shimmer (amplitude perturbation), and amplitude perturbation quotient (APQ) were significantly increased after dry air inhalation (P<0.05). In IS, HS and SW groups, after atomizing inhalation treatment, there was an obvious reduction in jitter, shimmer and APQ, showing significant differences as compared with those after dry air inhalation (P<0.05). Moreover, these parameters were significantly lower than those in the control group (P<0.05). The jitter, shimmer and APQ in the IS group were significantly lower than those in the HS and SW groups (P<0.05). We are led to a conclusion: Vocal fold dehydration induced by dryness can reduce the stability of voice; such decreased voice stability can be improved by atomizing inhalation therapy; without proper treatment, voice stability caused by vocal fold dehydration cannot heal spontaneously; of three atomizing agents namely, IS, HS and SW, IS had the best treatment effect for decreased voice stability caused by vocal fold dehydration.