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Background: Accumulation of immunosuppressive protein programmed death-ligand 1 (PD-L1) has been documented in several cancers and contributes to the evasion of the host immune system. However, cancer cellintrinsic signaling-dependent control of PD-L1 expression remains to be elucidated. Herein, we aimed to identify the let-7 family of microRNAs as candidates that up-regulate tumor cell PD-L1 expression and mediates immune evasion of head and neck squamous cell carcinoma (HNSCC). Methods: The expression of let-7 family and PD-L1 was quantified in HNSCC tissues and adjacent normal tissues. PD-L1 degradation was evaluated in HNSCC cells in response to elevated expressions of let-7a or let-7b. The regulation of let-7 family on PD-L1 degradation through a mechanism involving T-cell factor-4 (TCF-4) control of βcatenin/STT3 pathway was evaluated. Immune recognition of HNSCC in vivo was examined in subcutaneous tumorbearing C3H mice in the presence of let-7a/b and/or CTLA-4 antibody. Results: The let-7 family were significantly down-regulated in the context of HNSCC, sharing a negative correlation with PD-L1 expression. Glycosylated PD-L1 was detected in HNSCC cells, which was reduced by let-7a/b overexpression. TCF-4, the target of let-7a/b, activated the β-catenin/STT3 pathway and promoted PD-L1 degradation. In vivo analysis demonstrated that let-7a/b over-expression potentiated anticancer immunotherapy by CTLA-4 blockade. Conclusions: Taken together, our findings highlight targeting let-7 family as a potential strategy to enhance immune checkpoint therapy for HNSCC.

Chronic obstructive pulmonary disease (COPD) is the major leading cause of disease with high-mortality worldwide. Cigarette smoke (CS) is a major factor for COPD. CS causes chronic inflammation and oxidative stress, which contributes to lung dysfunction in COPD. Isoliquiritigenin (ILG), a natural flavonoid derived from the root of liquorice, has been reported to possess antiinflammatory and antioxidant activity. In the present study, we tested the mechanism and protective effects of ILG on CS-induced COPD. Mice were exposed to CS for 2 h twice a day for 4 weeks. ILG was given orally 1 h before CS exposure twice a day for 4 weeks. The bronchial alveolar lavage fluid was collected to test the levels of inflammatory cytokines and the number of inflammatory cells. The lung tissues were obtained to evaluate the pathological changes, lung edema, myeloperoxidase (MPO) activity, malondialdehyde (MDA) level, as well as the expression of the nuclear factor-erythroid 2 (Nrf2) and nuclear factor κB (NF-κB) signaling pathways. The results showed that ILG reduced the infiltration of inflammatory cells and the production of inflammatory cytokines. ILG also reversed CS-induced lung pathological injuries, wet/dry ratio, MPO activity, and MDA level. Further research also showed that ILG dose-dependently up-regulated the expression of Nrf2 and down-regulated the expression of NF-κB signaling pathways induced by CS. In conclusion, ILG protected against CS-induced COPD by inhibiting inflammatory and oxidative stress via the regulation of the Nrf2 and NF-κB signaling pathways.

Endoscopy is essential for the diagnosis and treatment of cancers derived from the larynx. However, a laryngoscope with conventional white light (CWL) has technical limitations in detecting small or superficial lesions on the mucosa. Narrow band imaging especially combined with magnifying endoscopy (ME) is useful for the detection of superficial squamous cell carcinoma (SCC) within the oropharynx, hypopharynx, and oral cavity. A total of 3675 patients who have come to the outpatient clinic and complained of inspiratory stridor, dyspnea, phonation problems or foreign body sensation, were enrolled in this study. We describe the glottic conditions of the patients. All 3675 patients underwent laryngoscopy equipped with conventional white light (CWL) and NBI system. 1149 patients received a biopsy process. And 1153 lesions were classified into different groups according to their histopathological results. Among all the 1149 patients, 346 patients (312 males, 34 females; mean age 62.2±10.5 years) were suspected of having a total of 347 precancerous or cancerous (T1 or T2 without lymphnode involvement) lesions of the larynx under the CWL. Thus, we expected to attain a complete vision of what laryngeal lesions look like under the NBI view of a laryngoscope. The aim was to develop a complete description list of each laryngeal conditions (e.g. polyps, papilloma, leukoplakia, etc.), which can serve as a criteria for further laryngoscopic examinations and diagnosis.

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Glioma with poor prognosis is accepted as a lethal, malignant intracranial tumor among central nervous system diseases. It has been frequently exhibited that long noncoding RNAs (lncRNAs) exert indispensable functions in glioma through regulating gene expression through various molecular mechanisms. To unveil a novel lncRNA functioning in glioma, we browsed the cancer genome atlas dataset and chose the lncRNA PC‐esterase domain containing 1B antisense RNA 1 (PCED1B‐AS1) for further investigations. Loss‐of‐function experiments depicted that the proliferation ability was restrained and apoptosis ability was induced in glioma cells by PCED1B‐AS1 silencing and this phenomenon was also observed when PCED1B was knocked down. In view of the position of PCED1B‐AS1 in the cytoplasm, we produced the Venn diagram and discovered one shared microRNA of PCED1B‐AS1 and PCED1B. The competing endogenous RNA network formed by PCED1B‐AS1, miR‐194‐5p, and PCED1B was attested by mechanism assays. Rescue experiments reconfirmed that miR‐194‐5p suppression or PCED1B overexpression neutralized the obstructive impacts of PCED1B‐AS1 silence on proliferation and the promoting effects of PCED1B‐AS1 silence on apoptosis. The modulation mechanism of the PCED1B‐AS1/miR‐194‐5p/PCED1B axis in glioma was investigated and affirmed, which supports researchers with a new insight into the therapy of patients with glioma.

Mesoporous silica nanoparticles (MSNs) represent a new form of drug nanocarrier with thermo/pH-coupling sensitivity and site-specificity. CD133(+) Hep-2 laryngeal cancer cells are responsible for multidrug resistance due to elevated expression of ABCG2. Since positively charged nanoparticles could easily uptake nucleic acids, we examined the possibility of using this new drug delivery system to simultaneously deliver different chemotherapeutic drugs and siRNA targeting ABCG2. Our results demonstrated that both antitumor drugs and siRNA against ABCG2 were successfully delivered into CD133(+) cancer cells by loaded MSNs. Down-regulation of ABCG2 significantly enhanced the efficacy of chemotherapeutic drug-induced apoptosis in laryngeal carcinoma cells. Furthermore, the chemotherapeutic drug and siRNA loaded nanoparticles inhibited tumor growth in vivo in a laryngeal cancer mouse model.