JDHY3 Inhibits Hypopharyngeal Carcinoma Cell Proliferation and Promotes Apoptosis by Inhibiting the PI3K/AKT Pathway.

BACKGROUND: Jieduhuayu No.3 (JDHY3) is a modified Chinese herbal formula beneficial for treating hypopharyngeal carcinoma (HC), but its pharmacological mechanism is unknown. OBJECTIVE: This study aimed to explore the mechanism of the herbal formula JDHY3 in inhibiting cell proliferation and promoting apoptosis in HC in vitro and in vivo. METHODS: In this study, HC cells were treated with cisplatin and different concentrations of JDHY3. The apoptosis rate was detected by flow cytometry. Western blotting was used to detect the proteins related to cell proliferation and apoptosis. Afterward, the xenograft mouse model was established and treated with cisplatin and JDHY3. Mouse tumour volume was measured, and the tumour tissues were assessed by HE staining and immunohistochemistry. RESULTS: JDHY3 significantly inhibited the proliferation of FaDu and Detroit-562 cells. In addition, JDHY3 significantly increased the apoptosis rate of HC cells and downregulated p-PI3K and p-Akt. In addition, JDHY3 upregulated the expression of the apoptosis-promoting proteins Bax, P53, and cleaved caspase-3. In addition, the expression of the antiapoptotic protein Bcl-2 was downregulated. Coincubation with SC79 attenuated the decrease in cell proliferation induced by JDHY3, further confirming that the proapoptotic effect of JDHY3 is associated with the inhibition of PI3K/Akt pathway activation. CONCLUSIONS: The results of in vivo experiments showed that JDHY3 could effectively inhibit the proliferation of HC cells, and HE staining showed that JDHY3 reduced the invasion of HC cells. Immunohistochemistry showed that the expression of P53 and cleaved caspase-3 was significantly increased in the tissues of the JDHY3-treated group.

Effect of momethasone furoate combined with loratadine and montelukast sodium on inflammatory factors and pulmonary function in children with allergic rhinitis.

OBJECTIVE: To compare the effects of mometasone furoate in combination with loratadine and montelukast sodium on inflammatory factors and pulmonary function in children with allergic rhinitis (AR). METHODS: In this retrospective study, a total of 89 children with AR admitted to our hospital from March 2020 to October 2021 were enrolled. Among them, 47 children who received mometasone furoate combined with loratadine were designated group A, while the other 42 with mometasone furoate combined with montelukast sodium were group B. The clinical efficacy of both groups was compared, and the levels of inflammatory factors IL-6 and TNF-α as well as the changes of pulmonary function levels were tested during the treatment. Adverse reactions during treatment were recorded. Finally, children were followed up for 3 months to record rhinitis recurrence after discontinuation of the treatment. RESULTS: There was no statistical difference in clinical treatment efficacy between both groups (P>0.05), while the levels of IL-6, TNF-α, and IgE were lower in children in group A than in group B at 2 weeks of treatment. Group A's lung function indexes, including forced expiratory volume in one second (FEV1%), forced expiratory volume in one second/forced vital capacity (FEV1/FVC) and peak expiratory flow (PEF), were higher than in group B (all P<0.05). The total incidence of adverse reactions was dramatically lower in group A than group B (P<0.05). Follow-up demonstrated no difference in the recurrence rate of rhinitis between both groups of children (P>0.05). Higher TNF-α after treatment, history of allergy, family history of rhinitis, combined asthma, and parental history of smoking were independent risk factors for relapse after discontinuation of the drug in children. CONCLUSION: Both mometasone furoate combined with either loratadine or montelukast sodium had good effects in AR, while the first option had a faster inhibitory effect on inflammatory factors and a better protection of lung function in children.

The deubiquitinase USP34 stabilizes SOX2 and induces cell survival and drug resistance in laryngeal squamous cell carcinoma.

Recent studies showed that the deubiquitinase ubiquitin-specific protease 34 (USP34) was involved in the tumorigenesis of several tumors, but its function and mechanism are still unclear in laryngeal squamous cell carcinoma (LSCC). In this study, we found that USP34 and SOX2 were elevated in LSCC tumor tissues, and we also found that USP34 expression was positively correlated with SOX2 expression. Our further studies showed that USP34 regulated the protein level of SOX2 in LSCC cells, but not the mRNA level, which suggested that USP34 stabilized SOX2. Moreover, USP34, as a deubiquitinase, could interact with SOX2, and reduce the polyubiquitination of SOX2. In addition, knockdown of USP34 could significantly inhibit LSCC cell growth, but overexpression of SOX2 could reverse this effect. Finally, we also found that USP34 and SOX2 were upregulated in cisplatin-resistant LSCC cells, but knockdown of USP34 could enhance the drug sensitivity of cisplatin in the resistant cells. Collectively, targeting USP34/SOX2 axis may be a promising strategy for the treatment of LSCC.