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1.
Cell Rep ; 42(12): 113437, 2023 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-37995679

RESUMO

Head and neck squamous cell carcinomas (HNSCCs) have high mortality and significant treatment-related morbidity. It is vital to discover effective, minimally invasive therapies that improve survival and quality of life. Bitter taste receptors (T2Rs) are expressed in HNSCCs, and T2R activation can induce apoptosis. Lidocaine is a local anesthetic that also activates bitter taste receptor 14 (T2R14). Lidocaine has some anti-cancer effects, but the mechanisms are unclear. Here, we find that lidocaine causes intracellular Ca2+ mobilization through activation of T2R14 in HNSCC cells. T2R14 activation with lidocaine depolarizes mitochondria, inhibits proliferation, and induces apoptosis. Concomitant with mitochondrial Ca2+ influx, ROS production causes T2R14-dependent accumulation of poly-ubiquitinated proteins, suggesting that proteasome inhibition contributes to T2R14-induced apoptosis. Lidocaine may have therapeutic potential in HNSCCs as a topical gel or intratumor injection. In addition, we find that HPV-associated (HPV+) HNSCCs are associated with increased TAS2R14 expression. Lidocaine treatment may benefit these patients, warranting future clinical studies.


Assuntos
Neoplasias de Cabeça e Pescoço , Infecções por Papillomavirus , Humanos , Paladar/fisiologia , Receptores Acoplados a Proteínas G/metabolismo , Carcinoma de Células Escamosas de Cabeça e Pescoço , Lidocaína/farmacologia , Qualidade de Vida , Neoplasias de Cabeça e Pescoço/tratamento farmacológico , Apoptose
2.
Acad Radiol ; 30(4): 765-770, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-35672236

RESUMO

INTRODUCTION: Medical imaging is integrated across all years in the medical programs at the Medical School, in our country. Little is known about this pedagogical approach from the perspective of those who participate in it. This study investigated how students and educators experience an integrated medical imaging curriculum. METHODS: One-on-one interviews were conducted with nine educators and three undergraduate medical students and analyzed using a reflexive thematic approach. Educators included radiologists, non-radiologists clinicians, and scientists and health professionals from the medical program. RESULTS: The integrated medical imaging curriculum appears to be incoherently experienced by educators and students as learning opportunities that were 'everywhere and nowhere'. Teaching events were 'repetitive and patchy' and featured a transmission-oriented pedagogy emphasizing 'exposure and absorption'. Educators expressed paradoxical views of their responsibility for teaching medical imaging reflected in this sentiment: 'I don't teach medical imaging… (but I do)'. DISCUSSION: When medical imaging is integrated into learning resources and course work across the undergraduate program, it may lose its visibility and importance as a distinct learning area despite its crucial role in medical practice. An integrated curriculum may inadvertently separate knowing about medical imaging from learning to apply medical imaging knowledge in clinical practice. CONCLUSIONS: Further work is required to construct an integrated medical imaging curriculum that explicitly emphasizes medical imaging learning outcomes, so they are experienced coherently and consistently by medical students and those who prepare them for practice as doctors.


Assuntos
Educação de Graduação em Medicina , Estudantes de Medicina , Humanos , Currículo , Aprendizagem , Atitude , Diagnóstico por Imagem , Ensino
3.
Pharmaceuticals (Basel) ; 15(4)2022 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-35455449

RESUMO

T2R bitter taste receptors in airway motile cilia increase ciliary beat frequency (CBF) and nitric oxide (NO) production. Polymorphisms in some T2Rs are linked to disease outcomes in chronic rhinosinusitis (CRS) and cystic fibrosis (CF). We examined the expression of cilia T2Rs during the differentiation of human nasal epithelial cells grown at air-liquid interface (ALI). The T2R expression increased with differentiation but did not vary between CF and non-CF cultures. Treatment with Pseudomonas aeruginosa flagellin decreased the expression of diphenhydramine-responsive T2R14 and 40, among others. Diphenhydramine increased both NO production, measured by fluorescent dye DAF-FM, and CBF, measured via high-speed imaging. Increases in CBF were disrupted after flagellin treatment. Diphenhydramine impaired the growth of lab and clinical strains of P. aeruginosa, a major pathogen in CF and CF-related CRS. Diphenhydramine impaired biofilm formation of P. aeruginosa, measured via crystal violet staining, as well as the surface attachment of P. aeruginosa to CF airway epithelial cells, measured using colony-forming unit counting. Because the T2R agonist diphenhydramine increases NO production and CBF while also decreasing bacterial growth and biofilm production, diphenhydramine-derived compounds may have potential clinical usefulness in CF-related CRS as a topical therapy. However, utilizing T2R agonists as therapeutics within the context of P. aeruginosa infection may require co-treatment with anti-inflammatories to enhance T2R expression.

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