Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 55
Filtrar
1.
J Laryngol Otol ; 138(5): 540-547, 2024 May.
Artigo em Inglês | MEDLINE | ID: mdl-38348656

RESUMO

OBJECTIVE: Retropharyngeal lymphadenectomy is challenging. This study investigated a minimally invasive approach to salvage retropharyngeal lymphadenectomy in patients with nasopharyngeal carcinoma. METHODS: An anatomical study of four fresh cadaveric heads was conducted to demonstrate the relevant details of retropharyngeal lymphadenectomy using the endoscopic transoral medial pterygomandibular fold approach. Six patients with nasopharyngeal cancer with retropharyngeal lymph node recurrence, who underwent retropharyngeal lymphadenectomy with the endoscopic transoral medial pterygomandibular fold technique at the Eye and ENT Hospital of Fudan University from July to December 2021, were included in this study. RESULTS: The anatomical study demonstrated that the endoscopic transoral medial pterygomandibular fold approach offers a short path and minimally invasive approach to the retropharyngeal space. The surgical procedure was well tolerated by all patients, with no significant post-operative complications. CONCLUSION: The endoscopic transoral medial pterygomandibular fold approach is safe and efficient for retropharyngeal lymphadenectomy.


Assuntos
Excisão de Linfonodo , Carcinoma Nasofaríngeo , Neoplasias Nasofaríngeas , Humanos , Excisão de Linfonodo/métodos , Masculino , Neoplasias Nasofaríngeas/cirurgia , Neoplasias Nasofaríngeas/patologia , Carcinoma Nasofaríngeo/cirurgia , Carcinoma Nasofaríngeo/patologia , Feminino , Pessoa de Meia-Idade , Terapia de Salvação/métodos , Cirurgia Endoscópica por Orifício Natural/métodos , Cadáver , Adulto , Faringe/cirurgia , Idoso , Recidiva Local de Neoplasia/cirurgia , Recidiva Local de Neoplasia/patologia , Resultado do Tratamento
2.
Front Immunol ; 14: 1211730, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37449203

RESUMO

Intracellular recognition of self and non-self -nucleic acids can result in the initiation of effective pro-inflammatory and anti-tumorigenic responses. We hypothesized that macrophages can be activated by tumor-derived nucleic acids to induce inflammasome activation in the tumor microenvironment. We show that tumor conditioned media (CM) can induce IL-1ß production, indicative of inflammasome activation in primed macrophages. This could be partially dependent on caspase 1/11, AIM2 and NLRP3. IL-1ß enhances tumor cell proliferation, migration and invasion while coculture of tumor cells with macrophages enhances the proliferation of tumor cells, which is AIM2 and caspase 1/11 dependent. Furthermore, we have identified that DNA-RNA hybrids could be the nucleic acid form which activates AIM2 inflammasome at a higher sensitivity as compared to dsDNA. Taken together, the tumor-secretome stimulates an innate immune pathway in macrophages which promotes paracrine cancer growth and may be a key tumorigenic pathway in cancer. Broader understanding on the mechanisms of nucleic acid recognition and interaction with innate immune signaling pathway will help us to better appreciate its potential application in diagnostic and therapeutic benefit in cancer.


Assuntos
Inflamassomos , Neoplasias , Humanos , Inflamassomos/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Caspase 1/metabolismo , Microambiente Tumoral , Proteínas de Ligação a DNA/metabolismo , Macrófagos , DNA/metabolismo , Neoplasias/metabolismo , Carcinogênese/metabolismo
3.
Food Chem ; 420: 136110, 2023 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-37105086

RESUMO

Soy protein isolates (SPI) exhibit weaker emulsifying properties than those of animal proteins, thereby limiting their wide applicability. In this study, a novel plant-based antioxidant emulsifier was developed using SPI and young apple polyphenols (YAP), and its underlying interaction mechanisms were discovered using multispectral technology and molecular docking. YAP physically bound to SPI through hydrogen bonds and hydrophobic interactions, which significantly enhanced the free radicals scavenging, reducing, and metal ion chelating abilities of SPI by introducing free hydroxyl groups. Moreover, SPI modified by YAP exerted better emulsifying performance owing to a looser protein structure, reflected by a higher random coil and a lower α-helix content. In addition, YAP may bridge adjacent SPI molecules, promoting the adsorption and anchoring of SPI at the oil-water interface. SPI-YAP complexes are promising antioxidant emulsifiers that can be used to nano-deliver functional oils and nutrients, thereby broadening SPI and YAP applications in the food industry.


Assuntos
Antioxidantes , Proteínas de Soja , Emulsões , Proteínas de Soja/química , Polifenóis/química , Simulação de Acoplamento Molecular
4.
Int J Med Robot ; 19(1): e2474, 2023 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-36331902

RESUMO

BACKGROUND: Transoral robotic surgery (TORS) is a reliable, minimally invasive approach for treating recurrent nasopharyngeal carcinoma (rNPC). However, tumours involving the internal carotid artery (ICA) are considered to be unsuitable for TORS. This paper presents the first case of transoral robotic resection of advanced rNPC involving the ICA. MATERIALS AND METHODS: This case is a 55 year-old male patient who received radiotherapy 27 years ago. This patient underwent a standard TORS resection 2 weeks after ipsilateral ICA embolization. RESULTS: Postoperative Magnetic resonance imaging and biopsy results indicated total resection. During the 2 month follow-up, no severe complications were found, and the primary site was tumour-free. CONCLUSION: This study preliminarily presents the feasibility and efficiency of advanced rNPC resection with TORS. TORS can potentially provide better quality of life for patients as a less invasive approach than current endoscopic surgery. Even so, the surgical approach should be selected strictly according to the tumour's location.


Assuntos
Neoplasias Nasofaríngeas , Procedimentos Cirúrgicos Robóticos , Masculino , Humanos , Pessoa de Meia-Idade , Procedimentos Cirúrgicos Robóticos/métodos , Carcinoma Nasofaríngeo/cirurgia , Artéria Carótida Interna/diagnóstico por imagem , Artéria Carótida Interna/cirurgia , Qualidade de Vida , Neoplasias Nasofaríngeas/diagnóstico por imagem , Neoplasias Nasofaríngeas/cirurgia
5.
Theranostics ; 12(8): 3794-3817, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35664067

RESUMO

Background: High emotional or psychophysical stress levels have been correlated with an increased risk and progression of various diseases. How stress impacts the gut microbiota to influence metabolism and subsequent cancer progression is unclear. Methods: Feces and serum samples from BALB/c ANXA1+/+ and ANXA1-/- mice with or without chronic restraint stress were used for 16S rRNA gene sequencing and GC-MS metabolomics analysis to investigate the effect of stress on microbiome and metabolomics during stress and breast tumorigenesis. Breast tumors samples from stressed and non-stressed mice were used to perform Whole-Genome Bisulfite Sequencing (WGBS) and RNAseq analysis to construct the potential network from candidate hub genes. Finally, machine learning and integrated analysis were used to map the axis from chronic restraint stress to breast cancer development. Results: We report that chronic stress promotes breast tumor growth via a stress-microbiome-metabolite-epigenetic-oncology (SMMEO) axis. Chronic restraint stress in mice alters the microbiome composition and fatty acids metabolism and induces an epigenetic signature in tumors xenografted after stress. Subsequent machine learning and systemic modeling analyses identified a significant correlation among microbiome composition, metabolites, and differentially methylated regions in stressed tumors. Moreover, silencing Annexin-A1 inhibits the changes in the gut microbiome and fatty acid metabolism after stress as well as basal and stress-induced tumor growth. Conclusions: These data support a physiological axis linking the microbiome and metabolites to cancer epigenetics and inflammation. The identification of this axis could propel the next phase of experimental discovery in further understanding the underlying molecular mechanism of tumorigenesis caused by physiological stress.


Assuntos
Anexina A1 , Microbiota , Neoplasias , Animais , Carcinogênese/genética , Epigênese Genética , Ácidos Graxos/farmacologia , Metaboloma , Metabolômica , Camundongos , Neoplasias/genética , RNA Ribossômico 16S/genética
6.
J Clin Lab Anal ; 36(7): e24526, 2022 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-35657334

RESUMO

BACKGROUND: We aimed to analyze the level of carcinoembryonic antigen-related cell adhesion molecule 1 (CEACAM1) in neutrophils of ischemic stroke (IS) patients at different stages, together with its roles in neutrophils. PATIENTS AND METHODS: Sixty-seven patients were classified into acute phase group (n = 19), subacute phase group (n = 28), and stable phase group (n = 20), and 20 healthy individuals who had received physical examination at the same time period as healthy control. We then analyzed the expression level of CEACAM1 and cell viability in CEACAM1 positive and CEACAM1 negative neutrophils by flow cytometry and the content of plasma CEACAM1, neutrophil gelatinase-associated lipocalin (NGAL), matrix metalloproteinases-9 (MMP-9) was measured using enzyme-linked immunosorbent assay (ELISA), while that of interleukin-10 (IL-10) and tumor necrosis factor (TNF) was determined using a Human Enhanced Sensitivity Flex set. RESULTS: Compared with healthy control, the percentage of CEACAM1 positive neutrophils in IS patients showed a significant increase, and a significant increase was also noticed in the content of plasma CEACAM1 at the subacute stage. Reduction in cell viability was observed in CEACAM1 positive neutrophils compared with CEACAM1 negative counterparts. There was a positive correlation between CEACAM1 expression rate in neutrophils and plasma CEACAM1 and IL-10 content in the subacute group. Compared with acute group and healthy control group, there was an instinct increase in the level of plasma MMP-9 and NGAL in subacute group. CONCLUSIONS: Our data showed that there was a rapid increase of CEACAM1 in neutrophils at the acute stage of IS. We speculated that CEACAM1 may serve as an inhibitory regulator involving in the progression of IS.


Assuntos
Antígenos CD , Antígeno Carcinoembrionário , Moléculas de Adesão Celular , AVC Isquêmico , Antígenos CD/metabolismo , Antígeno Carcinoembrionário/metabolismo , Moléculas de Adesão Celular/metabolismo , Humanos , Mediadores da Inflamação , Interleucina-10/metabolismo , Lipocalina-2 , Metaloproteinase 9 da Matriz/metabolismo
7.
Zhen Ci Yan Jiu ; 46(12): 1016-22, 2021 Dec 25.
Artigo em Chinês | MEDLINE | ID: mdl-34970878

RESUMO

OBJECTIVE: To observe the effect of acupuncture of "Yinlingquan"(SP9) and "Sanyinjiao"(SP6) on expression of phosphatidylinositol-3 kinase/protein kinase B/mammalian target protein of rapamycin (PI3K/Akt/mTOR) signaling in adjuvant arthritis (AA) rats, so as to explore its mechanism underlying improvement of AA. METHODS: Forty-eight male Wistar rats were randomly divided into normal control, AA model, acupuncture and medication (tripterygium wilfordii) groups, with 12 rats in each group. The AA model was established by putting the rats in a windy, cold and wet environment for 12 h, once every day for 21 days and injection of Freund's complete adjuvant (CFA) into the sole of the right hindlimb on the 21st day. Manual acupuncture stimulation was applied at SP9 and SP6 for 30 min/time, once a day for 21 days. Rats of the medication group received gavage of tripterygium wilfordii tablets solution (8 mg/kg), once a day for 21 days, and those of the normal control group and model group received gavage of the same amount of normal saline, once a day for 21 days. The degree of joint swelling and arthritis index (AI) were detected 1 day before modeling, 3 days after modeling, and 21 days after the treatment. Twenty-four hours after the last treatment, the contents of serum cytokines interleukin (IL)-17, IL-6 and tumor necrosis factor (TNF)-α were detected by enzyme-linked immunosorbent assay (ELISA); and changes of synovial ultrastructure were observed under electron microscope. Western blot was used to detect the expression levels of PI3K, Akt, phosphorylated protein kinase B (p-Akt), phosphorylated mammalian rapamycin target protein (p-mTOR), mTOR, microtubule associated protein 1 light chain 3B (LC3-Ⅱ) and mammalian atg6 homologous protein (Beclin-1) in the synovial membrane tissue. RESULTS: Compared with the normal control group, the joint swel-ling degree and AI, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR in the synovium were increased in the model group (P<0.05), while the expression levels of LC3-Ⅱ and Beclin-1 proteins in the synovium were significantly decreased (P<0.05). Compared with the model group, the joint swelling degree and AI, contents of serum TNF-α, IL-6 and IL-17, and the expression levels of PI3K, Akt, p-Akt, mTOR and p-mTOR were significantly decreased in the acupuncture and medication groups (P<0.05), while the expresion levels of LC3-Ⅱ and Beclin-1 proteins were significantly increased (P<0.05). Comparison between the two treatment groups showed that the therapeutic effects of acupuncture were obviously weaker than those of medication in down-regulating TNF-α and IL-6, Akt, p-Akt and mTOR levels (P<0.05) and in up-regulating Beclin-1 expression (P<0.05). Outcomes of electron microscope displayed widened nuclear membrane space, some fractured mitochondrial cristae with vacuoles, expanded rough endoplasmic reticulum, reduction of autophagosomes in the cytoplasm and ruptured synovial cell membrane in the model group, and increase of autophagosomes, deformed organelles in the acupuncture and medication groups. CONCLUSION: Acupuncture can relieve the inflammatory reactions and joint synovial injury of the affected joint in AA rats which may be associated with its effects in inhibiting PI3K/Akt/mTOR signaling and increasing the auto-phagy level of synovial cells.


Assuntos
Terapia por Acupuntura , Artrite Experimental , Animais , Artrite Experimental/genética , Artrite Experimental/terapia , Autofagia , Masculino , Fosfatidilinositol 3-Quinases/genética , Proteínas Proto-Oncogênicas c-akt/genética , Ratos , Ratos Sprague-Dawley , Ratos Wistar , Serina-Treonina Quinases TOR/genética
8.
Cell Transplant ; 30: 963689721996217, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33845643

RESUMO

COVID-19 has spread worldwide, including the United States, United Kingdom, and Italy, along with its site of origin in China, since 2020. The virus was first found in the Wuhan seafood market at the end of 2019, with a controversial source. The clinical symptoms of COVID-19 include fever, cough, and respiratory tract inflammation, with some severe patients developing an acute and chronic lung injury, such as acute respiratory distress syndrome (ARDS) and pulmonary fibrosis (PF). It has already claimed approximately 300 thousand human lives and the number is still on the rise; the only way to prevent the infection is to be safe till vaccines and reliable treatments develop. In previous studies, the use of mesenchymal stem cells (MSCs) in clinical trials had been proven to be effective in immune modulation and tissue repair promotion; however, their efficacy in treating COVID-19 remains underestimated. Here, we report the findings from past experiences of SARS and MSCs, and how SARS could also induce PF. Such studies may help to understand the rationale for the recent cell-based therapies for COVID-19.


Assuntos
COVID-19/complicações , Transplante de Células-Tronco Mesenquimais , Fibrose Pulmonar/etiologia , Animais , COVID-19/sangue , COVID-19/patologia , COVID-19/terapia , Coronavirus/isolamento & purificação , Humanos , Transplante de Células-Tronco Mesenquimais/métodos , Fibrose Pulmonar/sangue , Fibrose Pulmonar/patologia , Fibrose Pulmonar/terapia , Sistema Renina-Angiotensina , SARS-CoV-2/isolamento & purificação , Síndrome Respiratória Aguda Grave/sangue , Síndrome Respiratória Aguda Grave/complicações , Síndrome Respiratória Aguda Grave/patologia , Síndrome Respiratória Aguda Grave/terapia , Fator de Crescimento Transformador beta/sangue
9.
J Vis Exp ; (168)2021 02 26.
Artigo em Inglês | MEDLINE | ID: mdl-33720129

RESUMO

The technique of maxillectomy has been revised since it was first described in the 1820s. During the past decade, the endoscopic approach has been widely practiced for resecting maxilla. Compared with the traditional approaches, the combined endoscopic and transoral approach has many advantages such as avoiding facial incisions and postoperative scars and better visualization of the surgical margin. However, this technique is complicated to master and possess several challenges. Here, we demonstrate this approach step-by-step to show how to perform a total maxillectomy. We also reported nine cases with malignant tumors originating from the maxilla, and for all of them total maxillectomy was performed with combined endoscopic and transoral approach. Our data showed that the combination of the endoscopic and transoral approach could be used to resect the total maxilla successfully, though the tumor extended to the infratemporal and pterygopalatine fossa should be treated very carefully to avoid its spread in the local area. Furthermore, besides denture, other reconstruction methods should be attempted to improve the postoperative quality of life after the total maxillectomy.


Assuntos
Endoscopia , Maxila/cirurgia , Adolescente , Adulto , Idoso , Craniotomia , Feminino , Humanos , Masculino , Maxila/diagnóstico por imagem , Pessoa de Meia-Idade , Qualidade de Vida , Adulto Jovem
10.
Biomed Pharmacother ; 135: 111169, 2021 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-33433359

RESUMO

The long noncoding RNAs (lncRNAs) are non-coding RNAs that are more than 200 nucleotides in length, and one of several types of non-coding RNAs (ncRNAs). The lncRNAs function in diverse biological processes in normal cells, such as cellular differentiation and cell cycle regulation. There is also evidence that some aberrantly regulated lncRNAs function as oncogenes or tumor suppressor genes in various cancers. For example, TTN-AS1 is a lncRNA that binds to titin mRNA (TTN) and has pro-oncogenic effects in many cancers. Overexpression of TTN-AS1 correlates with poor prognosis in breast cancer, lung cancer, digestive system neoplasms, reproductive system cancers, and other cancers. Furthermore, increased TTN-AS1 expression correlates with more advanced pathology and tumor malignancy. In this review, we comprehensively summarize recent studies on the molecular mechanisms of TTN-AS1 regulation and the role of TTN-AS1 in the carcinogenesis and progression of numerous tumors.


Assuntos
Biomarcadores Tumorais/metabolismo , Neoplasias/metabolismo , RNA Longo não Codificante/metabolismo , Animais , Biomarcadores Tumorais/genética , Regulação Neoplásica da Expressão Gênica , Humanos , Neoplasias/genética , Prognóstico , RNA Longo não Codificante/genética , Transdução de Sinais
11.
Cell Transplant ; 29: 963689720927394, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32854518

RESUMO

Mammalian fat comprises white and brown adipose tissue (WAT and BAT, respectively). WAT stores energy, whereas BAT is used for thermogenesis. In recent years, the incidence of obesity and its associated disorders have increased tremendously. Considering the thermogenic capacity and decreased levels of BAT with increasing age, BAT can be used as a suitable therapeutic target for the treatment of obesity and diabetes. In several studies, using positron emission tomography and computed tomography images, adult humans have been shown to have functional BAT in interscapular fat. Results of these basic research studies on BAT have shed light on the new components of transcriptional regulation and the role of hormones in stimulating BAT growth and differentiation. In this review article, we have summarized the thermogenic regulators identified in the past decades by focusing on peroxisome proliferator-activated receptor gamma/uncoupling protein 1 activators, branched-chain amino acids, fatty acids (lipokine), and adenosine monophosphate-activated protein kinase mediators. We have also presented the progress of a few ongoing clinical trials aimed at the treatment of obesity and its associated metabolic disorders. The main purpose of this review was to provide a comprehensive introduction to the latest knowledge of the representative thermogenic regulators for the treatment of obesity. The fat combustion capacity of BAT may have great potential and can be considered as a suitable target for the therapeutic application of drugs from bench-to-bed treatment of obesity and the associated diseases.


Assuntos
Tecido Adiposo Marrom/efeitos dos fármacos , Obesidade/tratamento farmacológico , Obesidade/terapia , Bibliotecas de Moléculas Pequenas/farmacologia , Termogênese/efeitos dos fármacos , Animais , Humanos , Metabolismo dos Lipídeos/efeitos dos fármacos , Obesidade/metabolismo , Bibliotecas de Moléculas Pequenas/uso terapêutico
12.
Int J Mol Sci ; 21(12)2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32575820

RESUMO

Although butylidenephthalide (BP) is an efficient anticancer drug, its poor bioavailability renders it ineffective for treating drug-resistant brain tumors. However, this problem is overcome through the use of noninvasive delivery systems, including intranasal administration. Herein, the bioavailability, drug stability, and encapsulation efficiency (EE, up to 95%) of BP were improved by using cyclodextrin-encapsulated BP in liposomal formulations (CDD1). The physical properties and EE of the CDD1 system were investigated via dynamic light scattering, transmission electron microscopy, UV-Vis spectroscopy, and nuclear magnetic resonance spectroscopy. The cytotoxicity was examined via MTT assay, and the cellular uptake was observed using fluorescence microscopy. The CDD1 system persisted for over 8 h in tumor cells, which was a considerable improvement in the retention of the BP-containing cyclodextrin or the BP-containing liposomes, thereby indicating a higher BP content in CDD1. Nanoscale CDD1 formulations were administered intranasally to nude mice that had been intracranially implanted with temozolomide-resistant glioblastoma multiforme cells, resulting in increased median survival time. Liquid chromatography-mass spectrometry revealed that drug biodistribution via intranasal delivery increased the accumulation of BP 10-fold compared to oral delivery methods. Therefore, BP/cyclodextrin/liposomal formulations have potential clinical applications for treating drug-resistant brain tumors.


Assuntos
Antineoplásicos/farmacocinética , Encéfalo/metabolismo , Sistemas de Liberação de Medicamentos , Anidridos Ftálicos/farmacocinética , Animais , Antineoplásicos/administração & dosagem , Disponibilidade Biológica , Encéfalo/efeitos dos fármacos , Neoplasias Encefálicas/tratamento farmacológico , Neoplasias Encefálicas/metabolismo , Ciclodextrinas/química , Glioblastoma/tratamento farmacológico , Glioblastoma/metabolismo , Lipossomos/química , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Anidridos Ftálicos/administração & dosagem , Distribuição Tecidual
13.
Cell Transplant ; 29: 963689720907565, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32233795

RESUMO

Stem cell transplantation is a fast-developing technique, which includes stem cell isolation, purification, and storage, and it is in high demand in the industry. In addition, advanced applications of stem cell transplantation, including differentiation, gene delivery, and reprogramming, are presently being studied in clinical trials. In contrast to somatic cells, stem cells are self-renewing and have the ability to differentiate; however, the molecular mechanisms remain unclear. SOX2 (sex-determining region Y [SRY]-box 2) is one of the well-known reprogramming factors, and it has been recognized as an oncogene associated with cancer induction. The exclusion of SOX2 in reprogramming methodologies has been used as an alternative cancer treatment approach. However, the manner by which SOX2 induces oncogenic effects remains unclear, with most studies demonstrating its regulation of the cell cycle and no insight into the maintenance of cellular stemness. For controlling certain critical pathways, including Shh and Wnt pathways, SOX2 is considered irreplaceable and is required for the normal functioning of stem cells, particularly neural stem cells. In this report, we discussed the functions of SOX2 in both stem and cancer cells, as well as how this powerful regulator can be used to control cell fate.


Assuntos
Fatores de Transcrição SOXB1/metabolismo , Transplante de Células-Tronco/métodos , Animais , Diferenciação Celular/genética , Diferenciação Celular/fisiologia , Proliferação de Células/genética , Proliferação de Células/fisiologia , Reprogramação Celular/genética , Reprogramação Celular/fisiologia , Humanos , Células-Tronco Neurais/citologia , Células-Tronco Neurais/metabolismo , Fatores de Transcrição SOXB1/genética
14.
Int J Nanomedicine ; 14: 3601-3613, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31190814

RESUMO

Introduction: Kolliphor® EL (K-EL) is among the most useful surfactants in the preparation of emulsions. However, it is associated with low hydrophobic drug loading in the resulting emulsified formulation. Methods: In this study, a formulation for intranasal administration of butylidenephthalide (Bdph), a candidate drug against glioblastoma (GBM), was prepared. Physical characteristics of the formulation such as particle size, zeta potential, conductivity, and viscosity were assessed, as well as its cytotoxicity and permeability, in order to optimize the formulation and improve its drug loading capacity. Results: The optimized formulation involved the integration of polyethylene glycol 400 (PEG 400) in K-EL to encapsulate Bdph dissolved in dimethyl sulfoxide (DMSO), and it exhibited higher drug loading capacity and drug solubility in water than the old formulation, which did not contain PEG 400. Incorporation of PEG 400 as a co-surfactant increased Bdph loading capacity to up to 50% (v/v), even in formulations using Kolliphor® HS 15 (K-HS15) as a surfactant, which is less compatible with Bdph than K-EL. The optimized Bdph formulation presented 5- and 2.5-fold higher permeability and cytotoxicity, respectively, in human GBM than stock Bdph. This could be attributed to the high drug loading capacity and the high polarity index due to DMSO, which increases the compatibility between the drug and the cell. Rats bearing a brain glioma treated with 160 mg/kg intranasal emulsified Bdph had a mean survival of 37 days, which is the same survival time achieved by treatment with 320 mg/kg stock Bdph. This implies that the optimized emulsified formulation required only half the Bdph dose to achieve an efficacy similar to that of stock Bdph in the treatment of animals with malignant brain tumor.


Assuntos
Neoplasias Encefálicas/tratamento farmacológico , Sistemas de Liberação de Medicamentos , Emulsões/química , Nanopartículas/química , Mucosa Nasal/fisiologia , Polietilenoglicóis/química , Animais , Neoplasias Encefálicas/patologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Glioma/tratamento farmacológico , Glioma/patologia , Humanos , Concentração Inibidora 50 , Masculino , Nanopartículas/ultraestrutura , Tamanho da Partícula , Permeabilidade , Anidridos Ftálicos/química , Ratos Endogâmicos F344 , Solubilidade , Tensoativos/química , Análise de Sobrevida , Carga Tumoral , Viscosidade
15.
J Clin Anesth ; 56: 119-125, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-30771713

RESUMO

INTRODUCTION: Whether anesthesia depth affects postoperative mortality remains uncertain. MEASUREMENTS: Several databases were systematically searched to identify all articles studying the relationship between depth of anesthesia and postoperative mortality. Post hoc subgroup analyses were conducted for follow-up period (30 days vs. longer than 90 days) and type of surgery. MAIN RESULTS: The analysis included 38,722 patients from nine studies. We observed a significant relationship between low bispectral index (BIS) and mortality (pooled aHR, 1.22;95% CI, 1.08 to 1.38; P = 0.001; I2 = 85.4%). Post hoc subgroup analyses indicated low BIS to be linked with significantly elevated mortality risk in patients with ≥90 days follow-up (pooled adjusted hazard ratio [aHR], 1.09; 95% CI, 1.00-1.19; P = 0.01; I2 = 79.4%), but this association did not achieve significance in those with a 30 day follow-up duration (pooled aHR, 1.52; 95% CI, 0.97-2.38; P = 0.28; I2 = 79.0%). In addition, this link between postoperative mortality and low BIS was significant in those who had undergone cardiac surgery (pooled aHR, 1.30; 95% CI, 1.14 to 1.49; P < 0.001; I2 = 0.0%), but not in patients that had received other forms of surgery (pooled aHR, 1.06; 95% CI, 0.98 to 1.14; P = 0.14; I2 = 73.2%). CONCLUSIONS: We observed a significant relationship between deep anesthesia and long-term mortality, though this was not significant 30 days following surgery. In patients who had received cardiac surgery, deep anesthesia may increase mortality. However, this trend was not observed in patients who had undergone other forms of surgery.


Assuntos
Anestesia/efeitos adversos , Procedimentos Cirúrgicos Cardíacos/efeitos adversos , Monitorização Intraoperatória/métodos , Complicações Pós-Operatórias/mortalidade , Anestesia/métodos , Monitores de Consciência , Mortalidade Hospitalar , Humanos , Monitorização Intraoperatória/instrumentação , Estudos Observacionais como Assunto , Complicações Pós-Operatórias/etiologia
16.
J Zhejiang Univ Sci B ; 20(1): 23-31, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30614227

RESUMO

With the rapid development of immunology, molecular biology, and associated technologies such as next-generation sequencing, cellular immunotherapy has recently become the fourth major cancer treatment. Immunotherapies based on T cells, natural killer cells, and dendritic cells play key roles in cancer immunotherapy. However, their application in clinical practice raises several ethical issues. Thus, studies should focus on proper adherence to basic ethical principles that can effectively guide and solve related clinical problems in the course of treatment, improve treatment effects, and protect the rights and interests of patients. In this review, we discuss cellular immunotherapy-related ethical issues and highlight the ethical practices and current status of cellular immunotherapy in China. These considerations may supplement existing ethical standards in cancer immunotherapy.


Assuntos
Imunoterapia/ética , Neoplasias/terapia , China , Células Dendríticas/imunologia , Humanos , Imunidade Celular , Imunoterapia/métodos , Células Matadoras Naturais/imunologia , Neoplasias/imunologia , Seleção de Pacientes/ética , Linfócitos T/imunologia
17.
Pharmacol Res ; 139: 50-61, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30385365

RESUMO

Annually, 48,000 people die from pancreatic ductal adenocarcinoma (PDAC), ranking it the fourth among cancer-related deaths in the United States. Currently, anti-cancer drugs are not effective against PDAC, and only extends survival by 3 months. Aberrant DNA methylation has been shown to play an important role during carcinogenesis in PDAC, with approximately 80% of tumor overexpressing the DNA methyltransferase 1 (DNMT1) protein. In the present study, we used DNMTs as a screening platform to find a new DNMT inhibitor, n-butylidenephthalide (n-BP), which is identified from a Chinese herbal drug. n-BP could inhibit DNMT1 expression in both dose-dependent and time-dependent manner. It also displays an effect in suppressing growth of PDAC cells and inducing cell cycle arrest at G0/G1 phase leading apoptosis. Growth suppression can be restored by the overexpression of DNMT1 in PDAC cells. Furthermore, we found n-BP-mediated DNMT1 suppression influenced the protein stability rather than changing the RNA expression. Through microarray studies, we found that the patched domain contained 4 (PTCHD4) is the potential downstream gene of DNMT1. Following silencing of PTCHD4 expression by siRNA, n-BP decreased tumor growth inhibition. Finally, in vivo, two animal models were used to evaluate the efficacy and survival after n-BP treatment by interstitial control release polymer delivery. The results show that n-BP could effectively inhibit PDAC tumor volume growth and extend animal survival. In summary, n-BP may inhibit the growth of human PDAC cells though reducing DNMT1 and increasing the expression of PTCHD4 both in vitro and in vivo.


Assuntos
Carcinoma Ductal Pancreático/tratamento farmacológico , Metilases de Modificação do DNA/antagonistas & inibidores , Proteínas Hedgehog/antagonistas & inibidores , Neoplasias Pancreáticas/tratamento farmacológico , Anidridos Ftálicos/farmacologia , Anidridos Ftálicos/uso terapêutico , Animais , Carcinoma Ductal Pancreático/genética , Carcinoma Ductal Pancreático/metabolismo , Linhagem Celular Tumoral , Metilases de Modificação do DNA/genética , Metilases de Modificação do DNA/metabolismo , Epigênese Genética , Humanos , Masculino , Camundongos Endogâmicos BALB C , Camundongos Nus , Neoplasias Pancreáticas/genética , Neoplasias Pancreáticas/metabolismo , Polímeros/farmacologia , Polímeros/uso terapêutico , RNA Interferente Pequeno/genética , Proteínas Repressoras/genética
18.
Int Forum Allergy Rhinol ; 8(11): 1233-1241, 2018 11.
Artigo em Inglês | MEDLINE | ID: mdl-30281941

RESUMO

BACKGROUND: Postoperative care is an important factor affecting the outcome of endoscopic sinus surgery (ESS) in patients with chronic rhinosinusitis (CRS). The aim of this study was to test the effect of mometasone furoate (MF)-soaked biodegradable nasal dressings (BNDs) on endoscopic appearance in CRS patients with nasal polyps (CRSwNP) after ESS. METHODS: This study was a prospective, randomized, double-blinded, placebo-controlled study. A total of 64 CRSwNP patients with bilateral ESS were enrolled and randomly given 4 mL or 8 mL of MF-soaked BNDs (NasoPore) in 1 nasal cavity and the same amount of normal saline-soaked BNDs in the contralateral side. The BNDs were removed on the 7th or 14th postoperative day. Perioperative sinus endoscopy (POSE) and Lund-Kennedy scores were collected, on the 7th or 14th postoperative days and at 1, 2, and 3 postoperative months. RESULTS: The POSE and Lund-Kennedy scores showed that in the 4-mL, 1-week group, no significant differences between the sides treated with MF-soaked BNDs and the normal saline-soaked control were observed at any postoperative visits. In the 4-mL, 2-week group, significant differences were found at the 2-week and 1-month postoperative visits but not at the 2-month and 3-month visits. In the 8-mL, 1-week group, significant differences were found at the 1-week, 1-month, and 2-month postoperative visits but not at the 3-month visit. In the 8-mL, 2-week group, significant differences were found at all postoperative visits. CONCLUSION: This study reveals that MF-impregnated BNDs improve the endoscopic appearance in the healing process of CRSwNP after ESS.


Assuntos
Anti-Inflamatórios/administração & dosagem , Bandagens , Furoato de Mometasona/administração & dosagem , Pólipos Nasais/tratamento farmacológico , Rinite/tratamento farmacológico , Sinusite/tratamento farmacológico , Administração Intranasal , Adulto , Idoso , Doença Crônica , Método Duplo-Cego , Endoscopia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pólipos Nasais/cirurgia , Procedimentos Cirúrgicos Nasais , Seios Paranasais/efeitos dos fármacos , Seios Paranasais/cirurgia , Rinite/cirurgia , Sinusite/cirurgia , Cicatrização/efeitos dos fármacos , Adulto Jovem
19.
Exp Ther Med ; 16(3): 1987-1993, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30186429

RESUMO

Moist exposed burn ointment (MEBO) is becoming increasingly popular in China as it shortens wound-healing time and reduces scar formation. However, its exact mechanism in mediating the wound-healing process is not yet clear. In the present study a total of 90 healthy adult male Wistar rats of specific-pathogen-free grade were divided equally into a control group, wound group, MEBO group, recombinant bovine basic fibroblast growth factor (rb-bFGF) group and sham operation group. Wound healing was observed from the extracted granulation tissues and recorded at three time points on 3, 7 and 14 days. Different levels of tumor necrosis factor α (TNF-α) and interleukin-6 (IL-6) in tissue homogenate were detected using ELISA. Western blot analysis and quantitative PCR were used to detect the expression of nerve growth factor (NGF), substance P (SP) as well as tyrosine kinase A (TrkA) receptor protein and the corresponding mRNA levels in granulation tissue. It was observed that the wound healing progressed faster in the MEBO and rb-bFGF groups compared with the wound group (P<0.01). TNF-α and IL-6 had an upward-downward trend at three time points, with the wound group demonstrating the most obvious increase (P<0.01). NGF and SP mRNA and protein levels in granulation tissue in MEBO, rb-bFGF and sham operation groups reached their highest levels on day 7 and then decreased on day 14. The expression level of TrkA was also measured simultaneously and its expression pattern was similar to that of NGF and SP. These results suggested that MEBO may promote nerve repair and accelerate wound healing through mediating the expression levels of NGF and SP, as well as TrkA.

20.
J Vis Exp ; (136)2018 06 20.
Artigo em Inglês | MEDLINE | ID: mdl-29985371

RESUMO

Endoscopic septoplasty is a surgical procedure in otolaryngology that is commonly performed to treat nasal airway obstruction caused by nasal septal deviation. It has a long history with multiple variations. In this article, a modified endoscopic septoplasty procedure using the limited two-line resection (2LoRs) technique at the posterior and inferior junction of the cartilaginous and bony septum is presented based on embryologic and anatomic knowledge of the nasal septum and the biomechanics of cartilaginous behavior. With this procedure, the quadrangular cartilage can be preserved as much as possible, which is helpful in retaining the supporting framework and rigidness of the septum. 2LoRs has been proven effective and sound for the correction of nasal septal deviation with rare complications. This modified procedure can be applied to correct the deviated nasal septum in the absence of any external nasal deformity to improve nasal patency or to improve access to the middle meatus or to the axillary region of the middle turbinate. It may also be used to expand the indications of septoplasty to children and adolescents because of its minimally invasive approach.


Assuntos
Endoscopia/métodos , Septo Nasal/patologia , Deformidades Adquiridas Nasais/cirurgia , Rinoplastia/métodos , Adolescente , Criança , Feminino , Humanos , Masculino , Obstrução Nasal
SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA