RESUMO
BACKGROUND: Lenvatinib is a common systemic treatment for advanced hepatocellular carcinoma (HCC), the resistance to which presents a great challenge. However, the mechanism of lenvatinib resistance in HCC remains unclear. Therefore, elucidating the underlying and key regulatory molecular mechanisms of lenvatinib resistance is urgently needed. METHODS: Bioinformatic enrichment analysis was used to investigate the gene associated with lenvatinib resistance. RT-PCR, Western blot, immunohistochemistry, and luciferase assays were used to explore the mechanisms of lenvatinib resistance. The effects of the FGD5-AS1/miR-5590-3p/PINK1 axis on lenvatinib resistance were evaluated by colony formation assay, cell viability, apoptosis, mitochondrial homeostasis, and morphology analyses. RESULTS: Higher expression of PINK1 was observed in lenvatinib-resistant cells and tissues. PINK1 could be activated by increased FGD5-AS1 expression, thereby maintaining the mitochondrial structure and function and promoting the antioxidative stress response. FGD5-AS1/miR-5590-3p showed competitive regulation of PINK1, which affected lenvatinib sensitivity through regulation of mitochondrial structure and antioxidative stress. CONCLUSIONS: PINK1 was identified as a key gene leading to lenvatinib resistance by maintaining the mitochondrial structure and function. The FGD5-AS1/miR-5590-3p/PINK1 axis may be a promising strategy to overcome lenvatinib resistance in treatment-negative patients.
RESUMO
BACKGROUND: In the healthy body, the fascial system maintains elasticity and coordination of movements. If these functions are destroyed, facial paraly appears. Myofascial induction therapy (MIT), a manual physical therapy method that focuses on restoring altered fascial tissue, is prevalently and widely used in clinical treatment. OBJECTIVE: The study aimed to observe the application of MIT in the rehabilitation of patients with acute facial palsy. METHODS: Sixty-eight patients with acute facial palsy were divided into control group and manual treatment group. The control group received drug treatments, such as prednisone, methylcobalamin, and vitamin B1, and instrumental physical therapy, such as semiconductor laser, shortwave therapy, and facial muscle training. In addition to these treatments, the manual treatment group received MIT. Both groups were treated for 4 weeks. The patients were assessed using the following methods: the House-Brackmann facial nerve function evaluation, Sunnybrook facial grading system, facial nerve electrophysiological examination compound muscle action potential (CMAP) amplitude, and blink reflex (BR) R1 latency. RESULTS: House-Brackmann and Sunnybrook scores and CMAP amplitude and BRR1 latencies were significantly different between the two groups (pâ<â0.05). Furthermore, the manual treatment group showed greater improvement than the control group (pâ<â0.05). CONCLUSIONS: Treatment with MIT promoted better recovery of acute facial palsy and thus may be considered a valid rehabilitation intervention that is worthy of clinical application.