RESUMO
AIMS: To identify an effective strategy for promoting microvascular endothelial cells (MECs) to phagocytize myelin debris and reduce secretion of inflammatory factors following spinal cord injury (SCI). METHODS: We established a coculture model of myelin debris and vascular-like structures. The efficiency with which MECs phagocytize myelin debris under different conditions was examined via ELISA, flow cytometry, and immunofluorescence. Tubastatin-A was used to interfere with the coculture model. The anti-inflammatory effects of Tubastatin-A were observed by HE staining, flow cytometry, immunofluorescence, and ELISA. RESULTS: MECs phagocytized myelin debris via IgM opsonization, and phagocytosis promoted the secretion of inflammatory factors, whereas IgG-opsonized myelin debris had no effect on inflammatory factors. Application of the HDAC6 inhibitor Tubastatin-A increased the IgG levels and decreased the IgM levels by regulating the proliferation and differentiation of B cells. Tubastatin-A exerted a regulatory effect on the HDAC6-mediated autophagy-lysosome pathway, promoting MECs to phagocytize myelin debris, reducing the secretion of inflammatory factors, and accelerating the repair of SCI. CONCLUSIONS: Inhibition of HDAC6 to regulate the immune-inflammatory response and promote MECs to phagocytize myelin debris may represent a novel strategy in the treatment of SCI.
Assuntos
Bainha de Mielina , Traumatismos da Medula Espinal , Humanos , Células Endoteliais/metabolismo , Desacetilase 6 de Histona/antagonistas & inibidores , Desacetilase 6 de Histona/metabolismo , Imunoglobulina G/farmacologia , Imunoglobulina M/metabolismo , Macrófagos , Bainha de Mielina/metabolismo , Medula Espinal/metabolismo , Traumatismos da Medula Espinal/tratamento farmacológico , Traumatismos da Medula Espinal/metabolismoRESUMO
BACKGROUND: Hypersecretion of mucin 5AC (MUC5AC) is a prominent feature of chronic rhinosinusitis with nasal polyps (CRSwNP) and autophagy plays a pivotal role in this process. TNF receptor-associated factor 6 (TRAF6) functions as a signal transducer in many inflammation diseases, whereas the correlation between TRAF6 and autophagy in CRSwNP remains unclear. OBJECTIVE: To investigate the role of TRAF6 in the human neutrophil elastase (HNE)-induced autophagy and mucin MUC5AC over-expression in CRSwNP. METHODS: Tissue specimens were obtained from control subjects and patients with CRSwNP. The relationships between HNE, TRAF6, autophagy, and MUC5AC were investigated. The effect of TRAF6 on HNE-mediated autophagy and hypersecretion of MUC5AC was assessed by in-vitro culture of HNECs treated with human recombinant HNE. RESULTS: Patients with CRSwNP had more protein expression of HNE, MUC5AC, TRAF6, and light chain (LC3B), and increased levels of Beclin-1(BECN1) and autophagy-related gene 5 (ATG5) in mRNA level. Treatment of nasal epithelial cells with recombinant HNE induced the upregulation of TRAF6, autophagy, and MUC5AC. Alternatively, si-TRAF6 or autophagy inhibitor treatment mitigates the hyperexpression of MUC5AC before incubating with recombinant HNE. CONCLUSION: HNE promotes autophagy through TRAF6, resulting in hyperexpression of MUC5AC in CRSwNP.
Assuntos
Elastase de Leucócito , Pólipos Nasais , Rinite , Sinusite , Autofagia , Proteína Beclina-1/metabolismo , Doença Crônica , Humanos , Elastase de Leucócito/metabolismo , Mucina-5AC/genética , Mucina-5AC/metabolismo , Pólipos Nasais/metabolismo , RNA Mensageiro , Rinite/metabolismo , Sinusite/metabolismo , Fator 6 Associado a Receptor de TNF/genética , Fator 6 Associado a Receptor de TNF/metabolismoRESUMO
The laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma continues to be a challenge for surgeons. In this article, we describe our experience with laryngopharyngeal reconstruction in patients with pyriform sinus carcinoma using the modified infrahyoid myocutaneous flap (IHMCF). The modified incision design for the modified IHMCF and clinical outcomes are also detailed here. Between January 2012 and February 2018, 10 patients with hypopharyngeal squamous cell carcinoma who underwent laryngopharyngeal reconstruction using the modified IHMCF after hemicricolaryngopharyngectomy were included in this study. The drainage vessels of the modified IHMCF, oncological outcomes, and functional reservation of the larynx were recorded. All of the flaps survived well. No flap necrosis or other major complications occurred during follow-up. None of the patients remained on nasogastric feeding for more than 4 weeks postoperatively. The follow-up period ranged from 12 to 73 months (mean, 36 months). In our series, 6 patients were successfully decannulated and 5 had received radiation therapy. We roughly assessed the speech and swallowing functions, and the outcomes seemed acceptable in all of the patients after surgery. Laryngoscopic examination showed that the modified IHMCF survived well and the new glottis provided excellent function and good ventilation results. In our experience, the modified IHMCF is a safe and viable procedure that can serve as a valid alternative to free flaps and the pectoralis major myocutaneous flap to reconstruct laryngopharyngeal defects.
Assuntos
Carcinoma de Células Escamosas/cirurgia , Neoplasias Hipofaríngeas/cirurgia , Laringoplastia/métodos , Retalho Miocutâneo , Procedimentos de Cirurgia Plástica/métodos , Adulto , Idoso , Feminino , Humanos , Osso Hioide/cirurgia , Hipofaringe/cirurgia , Laringe/cirurgia , Masculino , Pessoa de Meia-Idade , Resultado do TratamentoRESUMO
The study evaluated the ability of long intergenic noncoding RNA LINC00312 (LINC00312) to influence the proliferation, invasion, and migration of thyroid cancer (TC) cells by regulating miRNA-197-3p. TC tissues and adjacent normal tissues were collected from 211 TC patients. K1 (papillary TC), SW579 (squamous TC), and 8505C (anaplastic TC) cell lines were assigned into a blank, negative control (NC), LINC00312 overexpression, miR-197-3p inhibitors, and LINC00312 overexpression + miR-197-3p mimics group. The expression of LINC00312, miR-197-3p, and p120 were measured using quantitative real-time PCR (qRT-PCR) and Western blotting. Cell proliferation was assessed via CCK8 assay, cell invasion through the scratch test, and cell migration via Transwell assay. In comparison with adjacent normal tissues, the expression of LINC00312 is down-regulated and the expression of miR-197-3p is up-regulated in TC tissues. The dual luciferase reporter gene assay confirmed that P120 is a target of miR-197-3p The expression of LINC00312 and p120 was higher in the LINC00312 overexpression group than in the blank and NV groups. However, the expression of miR-197-3p was lower in the LINC00312 overexpression group than in the blank and NC groups. The miR-197-3p inhibitors group had a higher expression of miR-197-3p, but a lower expression of p120 than the blank and NC groups. The LINC00312 overexpression and miR-197-3p inhibitor groups had reduced cell proliferation, invasion and migration than the blank and NC groups. These results indicate that a LINC00312 overexpression inhibits the proliferation, invasion, and migration of TC cells and that this can be achieved by down-regulating miR-197-3p.