Exosomes serve as a crucial mode of communication between tumor-associated macrophages (TAMs) and cancer cells. This study attempted to explore the function of M1-derived exosomes and clarify their specific mechanism in head and neck squamous cell carcinoma (HNSCC). Moreover, the functional roles of M1-derived exosomes and their key molecule long noncoding RNA (lncRNA) HOXA transcript at the distal tip (HOTTIP) in HNSCC were investigated by conducting a series of in vitro and in vivo experiments. The dual-luciferase test was utilized to clarify the binding capacities between HOTTIP/mRNA and miRNAs. Accordingly, HOTTIP was found to be upregulated in M1-derived exosomes. Meanwhile, the in vitro experiments indicated that M1 exosomes suppressed proliferation, migration and invasion but induced apoptosis of cancer cells. This function was noted to be enhanced by HOTTIP-overexpressed M1 exosomes but was weakened by HOTTIP-knockdown ones, indicating that HOTTIP serves as a key molecule in M1 exosomes. Therefore, the function of HOTTIP in cancer cells was explored, for which overexpression of HOTTIP was found to inhibit proliferation, migration and invasion but induced apoptosis of cancer cells in vitro. A mechanism study further showed that M1 exosomes and HOTTIP activated the TLR5/NF-κB signaling pathway by competitively sponging miR-19a-3p and miR-19b-3p. Furthermore, cancer cells expressing HOTTIP were noted to induce the polarization of both local M1 and M2 macrophages; however, M1 exosomes were observed to reprogram local TAMs into M1 macrophages. More importantly, both cancer cells expressing HOTTIP and M1 exosomes reeducated circulating monocytes to express the M1 phenotype. The corresponding data demonstrated that the M1 exosomal lncRNA HOTTIP suppresses HNSCC progression by upregulating the TLR5/NF-κB signaling pathway through competitively sponging miR-19a-3p and miR-19b-3p. In particular, M1 exosomes and HOTTIP induce the polarization of M1 in circulating monocytes, thus providing novel insight into HNSCC immunotherapy.

Astaxanthine (AST) has important biological activities including antioxidant and anti-inflammatory effects that could alleviate neurological and heart diseases, but its role in the prevention of cisplatin-induced hearing loss (CIHL) is not yet well understood. In our study, a steady interaction between AST and the E3 ligase adapter Kelch-like ECH-associated protein 1, a predominant repressor of nuclear factor erythroid 2-related factor 2 (NRF2), was performed and tested via computer molecular docking and dynamics. AST protected against cisplatin-induced ototoxicity via NRF2 mediated pathway using quantitative PCR and Western blotting. The levels of reactive oxygen species (ROS) and mitochondrial membrane potential revealed that AST reduced ROS overexpression and mitochondrial dysfunction. Moreover, AST exerted anti-apoptosis effects in mouse cochlear explants using immunofluorescence staining and HEI-OC1 cell lines using quantitative PCR and Western blotting. Finally, AST combined with poloxamer was injected into the middle ear through the tympanum, and the protection against CIHL was evaluated using the acoustic brain stem test and immunofluorescent staining in adult mice. Our results suggest that AST reduced ROS overexpression, mitochondrial dysfunction, and apoptosis via NRF2-mediated pathway in cisplatin-exposed HEI-OC1 cell lines and mouse cochlear explants, finally promoting cell survival. Our study demonstrates that AST is a candidate therapeutic agent for CIHL.

Purpose: The authors studied the anatomic importance of the endoscopic prelacrimal recess approach (PLRA) to the pterygopalatine fossa (PPF) and infratemporal fossa (ITF). Methods: Ten adult heads (20 sides) from cadavers fixed in formalin were dissected using the PLRA. Anatomic dissections were detailed and several crucial landmarks measured. Results: Identification of the infraorbital neurovascular bundle is the crucial step for the detection of other branches of the maxillary artery. The distance from the base of columella to inferior orifice of the nasolacrimal duct, sphenopalatine foramen, pterygold canal, foramen rotundum, foramen ovale was (32.97 ± 3.44), (63.93 ± 4.52), (66.81 ± 3.44), (68.13 ± 4.43), and (85.23 ± 6.25) mm, respectively. The PLRA can be used to expose the entire maxillary sinus and PPF, most parts of the ITF (lateral pterygoid muscle, foramen ovale, mandibular division of the trigeminal nerve, and its divisions), maxillary artery and its branches, and the superior part of the medial pterygoid muscle (upon the floor of the maxillary sinus). The lateral boundary can be reached to visualize the temporomandibular joint and vertically oriented temporalis muscle. Conclusion: Use of the PLRA to the PPF and ITF offers a clear visual field, wide range of exposure, as well as preservation of the integrity of nasal structures.

Background. Thyroid cancer is the most common endocrine malignancy, with a recent global increase of 20% in age‐related incidence. Ultrasonography and ultrasonography‐guided fine‐needle aspiration biopsy (FNAB) are the most widely used diagnostic tests for thyroid nodules; however, it is estimated that up to 25% of thyroid biopsies are cytologically inconclusive. Molecular markers can help guide patient‐oriented and targeted treatment of thyroid nodules and thyroid cancer. Methods. Datasets related to papillary thyroid cancer (PTC) or thyroid carcinoma (GSE129562, GSE3678, GSE54958, GSE138042, and GSE124653) were downloaded from the GEO database and analysed using the Limma package of R software. For functional enrichment analysis, the Kyoto Encyclopedia of Genes and Genomes pathway analysis and Gene Ontology were applied to differentially expressed genes (DEGs) using the Metascape website. A protein‐protein interaction (PPI) network was built from the STRING database. Gene expression, protein expression, immunohistochemistry, and potential functional gene survival were analysed using the GEPIA website, the Human Protein Atlas website, and the UALCAN website. Potential target miRNAs were predicted using the miRDB and Starbase datasets. Results. We found 219 upregulated and 310 downregulated DEGs, with a cut‐off of p < 0.01 and ∣log FC | >1.5. The DEGs in papillary thyroid cancer were mainly enriched in extracellular structural organisation. At the intersection of the PPI network and Metascape MCODEs, the hub genes in common were identified as FN1, APOE, CLU, and SDC2. In the targeted regulation network of miRNA‐mRNA, the hsa‐miR‐424‐5p was found to synchronously modulate two hub genes. Survival analysis showed that patients with high expression of CLU and APOE had better prognosis. Conclusions. CLU and APOE are involved in the molecular mechanism of papillary thyroid cancer. The hsa‐miR‐424‐5p might have the potential to reverse the processes of papillary thyroid cancer by modulating the hub genes. These are potential targets for the treatment of patients with papillary thyroid cancer.

Emerging evidence of significant hearing loss occurring shortly after cisplatin administration in cancer patients has stimulated research into the causes and treatment of this side effect. Although the aetiology of cisplatin-induced hearing loss (CIHL) remains unknown, an increasing body of research suggests that it is associated with excessive generation of intracellular reactive oxygen species (ROS) in the cochlea. Astaxanthin, a xanthophyll carotenoid, has powerful anti-oxidant, anti-inflammatory, and anti-apoptotic properties based on its unique cell membrane function, diverse biological activities, and ability to permeate the blood-brain barrier. In this review, we summarize the role of ROS in CIHL and the effect of astaxanthin on inhibiting ROS production. We focus on investigating the mechanism of action of astaxanthin in suppressing excessive production of ROS.

Implantable middle ear hearing devices (IMEHDs) have been developed as a new technology to overcome the limitations of conventional hearing aids. The piezoelectric cantilever transducers currently used in the IMEHDs have the advantages of low power consumption and ease of fabrication, but generate less high-frequency output. To address this problem, we proposed and designed a new piezoelectric transducer based on a piezoelectric stack for the IMEHD. This new transducer, attached to the incus body with a coupling rod, stimulates the ossicular chain in response to the expansion-and-contraction of its piezoelectric stack. To test its feasibility for hearing loss compensation, a bench testing of the transducer prototype and a temporal bone experiment were conducted, respectively. Bench testing results showed that the new transducer did have a broad frequency bandwidth. Besides, the transducer was found to have a low total harmonic distortion (<0.75%) in all frequencies, and small release time (1 ms). The temporal bone experiment further proved that the transducer has the capability to produce sufficient vibrations to compensate for severe sensorineural hearing loss, especially at high frequencies. This property benefits the treatment of the most common sloping high-frequency sensorineural hearing loss. To produce a 100 dB SPL equivalent sound pressure at 1 kHz, its power consumption is 0.49 mW, which is low enough for the transducer to be utilized in the IMEHD.