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1.
Biochem Biophys Res Commun ; 577: 45-51, 2021 11 05.
Artigo em Inglês | MEDLINE | ID: mdl-34507064

RESUMO

Liver cancer is one of the most common malignancies that is difficult to treat due to late diagnosis and chemo-resistance. In the present study, we developed and validated a cell based split nanoLuc biosensor to monitor the Apaf1-Apaf1 interactions in response to apoptosis-inducing drugs such as cisplatin. We showed that the activity of split nanoLuc is reconstituted only in response to apoptotic inducer, cisplatin and in a dose-dependent manner. Apaf1 mutants which were unable to oligomerize failed to recover nanoLuc activity while constitutively active variant increased the nanoLuc activity. Generation of Apaf1 knockout HepG2 and treatment with cisplatin showed dramatic reduction in cell death suggesting that cisplatin mainly targets liver cancer cells through apoptosis. As the natural products are potent sources of compounds for adjuvant therapy, we screened a collection of natural products and identified lentinan as an inducer of apoptosome formation, a key step for induction of apoptosis. Lentinan is a polysaccharide with antitumor, pro-apoptotic properties that functions with poorly understood mechanisms. Lentinan was shown to have cytotoxic effects with the IC50 of 650 µM. Sub-lethal lentinan concentration doubled the nanoLuc activity when co-treated with cisplatin. We also showed that lentinan hugely reduced the dose of cisplatin to induce certain amount of death and that lentinan co-treatment with cisplatin enhanced the Apaf1 transcription in HepG2 cells while lentinan or cisplatin alone failed to alter the transcription. In addition, lentinan and cisplatin co-treatment induced mitochondrial depolarization. This suggested that lentinan combinatorial therapy with cisplatin engaged a different signalling pathway to kill the liver cancer cells and that adjuvant therapy with lentinan can reduce the dose of cisplatin and thus reduce the possibility of chemo-resistance.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Fator Apoptótico 1 Ativador de Proteases/metabolismo , Técnicas Biossensoriais/métodos , Carcinoma Hepatocelular/tratamento farmacológico , Neoplasias Hepáticas/tratamento farmacológico , Apoptose/efeitos dos fármacos , Apoptose/genética , Fator Apoptótico 1 Ativador de Proteases/genética , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Cisplatino/administração & dosagem , Sinergismo Farmacológico , Células Hep G2 , Humanos , Lentinano/administração & dosagem , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Mutação
2.
Nutrients ; 13(8)2021 Jul 25.
Artigo em Inglês | MEDLINE | ID: mdl-34444705

RESUMO

Exposure of individuals to radioactive material as a result of ingestion of contaminated food and water is an increasing public health concern. Unfortunately, there are limited treatment modalities for dealing with these types of potentially toxic exposures. Recent research suggests that many plant-based nutraceuticals may possess metal-binding properties. This preliminary study investigated the ability of genistein, curcumin, quercetin, and lentinan to bind metals considered internal contamination risks, namely cesium, uranium, cobalt, and strontium, in a variety of matrices. The efficacy of these nutraceuticals in protecting cultured cells from metal-induced toxicity was also explored. Results showed that none of the compounds bound cesium or strontium. However, genistein, curcumin, and quercetin could bind uranium. Curcumin and quercetin also bound cobalt and could also protect cultured cells from metal-induced cytotoxicity. Lentinan did not bind any of the metals tested. Metal binding was also pH dependent, with no binding observed at lower pH values. This project showed that nutraceuticals could function as chelators for metals considered internal radionuclide contamination hazards. Further investigations are required in order to determine whether these compounds will become a new nontoxic arsenal of pharmaceutical compounds with which to treat radionuclide contamination.


Assuntos
Quelantes/farmacologia , Exposição Dietética/prevenção & controle , Suplementos Nutricionais/análise , Elementos Radioativos/toxicidade , Extratos Vegetais/farmacologia , Técnicas de Cultura de Células , Césio/toxicidade , Cobalto/toxicidade , Curcumina/farmacologia , Exposição Dietética/efeitos adversos , Contaminação Radioativa de Alimentos/análise , Contaminação Radioativa de Alimentos/prevenção & controle , Genisteína/farmacologia , Humanos , Lentinano/farmacologia , Quercetina/farmacologia , Estrôncio/toxicidade , Urânio/toxicidade
3.
J Agric Food Chem ; 69(26): 7344-7352, 2021 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-34132531

RESUMO

Lentinan (LNT), a typical triple helix ß-glucan extracted from Lentinus edodes, has been widely used as a functional food and an orally administered drug. However, its oral pharmacokinetics has been rarely reported. The aim of this work is to systematically study the pharmacokinetics and intestinal absorption mechanism of LNT after oral administration. Radioactive 99m-technetium (99mTc) was introduced to label LNT to determine the plasma concentration, tissue distribution, and excretion of the ß-glucan in rats after oral administration. The results confirmed the absorption of LNT, with the maximal plasma concentration reached at 1 h. 5-([4,6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF) was used to label LNT to explore the absorption mechanism of LNT, utilizing both a Ussing chamber and a monolayer of Caco-2 cells. These transport assays showed that LNT could penetrate through the intestine and epithelial monolayer, which was mediated by macropinocytosis and clathrin-mediated endocytosis. These findings provide a pharmacokinetic reference for LNT and help provide a greater understanding of the absorption of ß-glucans in general.


Assuntos
Endocitose , Lentinano , Animais , Células CACO-2 , Clatrina , Humanos , Absorção Intestinal , Ratos
4.
Int J Biol Macromol ; 184: 101-108, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119545

RESUMO

Lentinan is a natural ß-glucan with various bioactivities and is combined with chemotherapy drugs for cancer treatment. Regorafenib is an oral multi-kinase inhibitor approved by FDA for treatment of metastatic colorectal cancer, advanced hepatocellular carcinoma, and metastatic gastrointestinal stromal tumors. Regorafenib has poor water solubility and multiple toxicities. We report drug-drug nanosuspensions of regorafenib and lentinan. Results of dynamic light scattering and scanning electron microscopy showed that the mean particle size of the regorafenib-lentinan nanosuspensions was approximately 200 nm and was uniformly distributed. Transmission electron microscopy findings indicated that lentinan stabilized the nanosuspensions by steric manner. Hydrogen bonds and hydrophobic interactions were found between regorafenib and lentinan by molecular dynamics simulation. The results of cytotoxicity assay and pharmacokinetics study in rats showed that the regorafenib-lentinan nanosuspensions reduced the toxicity and enhanced the in vitro anticancer activity and oral bioavailability of regorafenib. Lentinan as a natural stabilizer has the potential using for drug nanosuspensions. Drug-drug nanosuspensions are a new form of combination therapies that can reduce the number of drugs taken by patients and improve their compliance.


Assuntos
Antineoplásicos/administração & dosagem , Lentinano/administração & dosagem , Compostos de Fenilureia/administração & dosagem , Piridinas/administração & dosagem , Administração Oral , Animais , Antineoplásicos/química , Antineoplásicos/farmacocinética , Disponibilidade Biológica , Composição de Medicamentos , Células HCT116 , Células HEK293 , Humanos , Lentinano/química , Lentinano/farmacocinética , Simulação de Dinâmica Molecular , Nanopartículas , Tamanho da Partícula , Compostos de Fenilureia/química , Compostos de Fenilureia/farmacocinética , Piridinas/química , Piridinas/farmacocinética , Ratos , Ratos Sprague-Dawley , Solubilidade , Suspensões
5.
Carbohydr Polym ; 267: 118154, 2021 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-34119128

RESUMO

Lentinan (SLNT) has been shown to be directly cytotoxic to cancer cells. However, this direct antitumour effect has not been thoroughly investigated in vivo, and the mechanism remains unclear. We aimed to examine the direct antitumour effect of SLNT on human colon cancer and the mechanism in vivo and in vitro. SLNT significantly inhibited tumour growth and induced autophagy and endoplasmic reticulum stress (ERS) in HT-29 cells and tumour-bearing nonobese diabetic (NOD)/severe combined immunodeficiency (SCID) mice. Experiments with the autophagy inhibitors chloroquine (CQ) and 3-methyladenine (3-MA) showed that autophagy facilitated the antitumour effect of SLNT. Moreover, ERS was identified as the common upstream regulator of SLNT-induced increases in Ca2+concentrations, autophagy and apoptosis by using ERS inhibitors. In summary, our study demonstrated that SLNT exerted direct antitumour effects on human colon cancer via ERS-mediated autophagy and apoptosis, providing a novel understanding of SLNT as an anti-colon cancer therapy.


Assuntos
Antineoplásicos/uso terapêutico , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Estresse do Retículo Endoplasmático/efeitos dos fármacos , Lentinano/uso terapêutico , Neoplasias/tratamento farmacológico , Animais , Linhagem Celular Tumoral , Humanos , Masculino , Camundongos Endogâmicos NOD , Camundongos SCID , Transdução de Sinais/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
6.
DNA Cell Biol ; 40(5): 683-693, 2021 May.
Artigo em Inglês | MEDLINE | ID: mdl-33902331

RESUMO

PM2.5 plays an important role in the physiological and pathological progression of lung cancer. Lentinan exerts antitumor activity in many kinds of human cancers. Plasmacytoma variant translocation 1 (PVT1) exerts antitumor activity in many kinds of human cancers. However, the role and underlying molecular mechanism of PVT1 in the role of lentinan in PM2.5-exposed lung cancer are still largely unknown. Our study confirmed that PM2.5 exposure induced the production of inflammatory factors, epithelial-mesenchymal transition (EMT) and migration of lung cancer cells. Lentinan exerted antitumor effects by inhibiting the production of inflammatory factors, EMT, and migration of lung cancer cells. Lentinan suppressed PM2.5 exposure-induced cellular progression by inhibiting the PM2.5 exposure-induced elevation of PVT1 expression. PVT1 absorbed miR-199a, and miR-199a inhibited caveolin1 expression and thus formed the PVT1/miR-199a/caveolin1 signaling pathway in lung cancer cells. Our study revealed that silencing of the PVT1/miR-199a/caveolin1 signaling pathway affected the role of lentinan in PM2.5-exposed lung cancer cells. Thus, this study first investigated the role of lentinan in PM2.5-exposed lung cancer cells and further displayed the underlying molecular mechanism, providing a potential treatment for PM2.5-exposed lung cancer.


Assuntos
Movimento Celular , Transição Epitelial-Mesenquimal , Inflamação/patologia , Lentinano/farmacologia , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Material Particulado/efeitos adversos , Transdução de Sinais , Sequência de Bases , Caveolina 1/metabolismo , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Transição Epitelial-Mesenquimal/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Interleucina-6/biossíntese , MicroRNAs/genética , MicroRNAs/metabolismo , RNA Longo não Codificante/genética , RNA Longo não Codificante/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fator de Necrose Tumoral alfa/biossíntese
7.
Medicine (Baltimore) ; 100(12): e25220, 2021 Mar 26.
Artigo em Inglês | MEDLINE | ID: mdl-33761711

RESUMO

BACKGROUND: A growing number of studies suggest that lentinan combined with cisplatin thoracic injection for the treatment of lung cancer is an effective combination of traditional Chinese and Western medicine, which has a continuous and beneficial effect on eliminating clinical symptoms and improving cachexia in lung cancer patients. However, whether this treatment is effective and safe for lung cancer patients or not, evidence supporting the effectiveness and safety of this treatment is still incomplete. Besides, there is lack of systematic review to assess the detailed situation (including risk of bias and methodology) of current related clinical studies. OBJECTIVE: This study aimed to evaluate the effectiveness and safety of lentinan combined with cisplatin thoracic injection in the treatment of lung cancer. METHODS: The major databases (Embase, PubMed, the Cochrane Library, China National Knowledge Infrastructure, Chinese Scientific Journals Database [VIP] Database, Chinese Biomedical Literature Service System [SinoMed], and Wanfang Database) were searched from inception to March 1, 2020. Randomized controlled trials (RCTs) of lentinan combined with cisplatin chest injection on patients with non-small cell lung cancer (NSCLC) were identified. Two assessors reviewed each trial independently. The methodological quality of the eligible studies was evaluated according to the Cochrane Collaboration's tool for assessing risk of bias. Both the data extraction and the literature quality screening evaluation were conducted independently by 2 researchers. RESULTS: Totally 17 clinical RCTs were included in this study, involving 1390 patients. Meta-analysis results showed that the clinical efficacy (risk ratio [RR] = 1.34, 95% confidence interval [CI] 1.21-1.48), effective subgroup analysis (RR = 1.51, 95% CI 1.3-1.77), and quality of life (RR = 1.48, 95% CI 1.27-1.72), the differences are statistically significant. In terms of adverse reactions, mainly related to gastrointestinal reactions and bone marrow suppression, the incidence and degree of adverse reactions of lentinan combined with cisplatin thoracic injection group were lower than those of cisplatin thoracic injection group alone. CONCLUSIONS: The current evidence prompted that Lentinan combined with cisplatin in thoracic injection might benefit patients with NSCLC on a certain extent; this systematic review revealed some definite conclusions about the application of Lentinan combined with cisplatin in thoracic injection for NSCLC. Due to the low methodological quality, high risk of bias, and inadequate reporting on clinical data, these results still require verification by a large number of well designed, heterogeneous RCT studies. More rigorous, multicenter, sufficient-sample, and double-blind RCTs are warranted.


Assuntos
Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Cisplatino/farmacologia , Lentinano/farmacologia , Antineoplásicos/farmacologia , Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/patologia , Medicamentos de Ervas Chinesas/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Ensaios Clínicos Controlados Aleatórios como Assunto , Resultado do Tratamento
8.
Carbohydr Polym ; 261: 117847, 2021 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-33766343

RESUMO

Surface functionalization of mesoporous silica nanoparticles (MSNs) has been proposed as an efficient strategy for enhancing the biocompatibility and efficiency of an MSN-based carrier platform. Herein, natural polyelectrolyte multilayers composed of poly-l-ornithine (PLO) and carboxymethyl lentinan (LC) were coated on the surface of MSNs through a layer-by-layer (LbL) self-assembly technique, and were characterized by ζ-potential, FTIR, 13C NMR, SEM, TEM, XRD, and TG. The prepared carrier presented alternating positive and negative potentials when coated with the polyelectrolytes, and the surface of MSN-PLO/LC was rougher compared to the naked MSNs. The biocompatibility tests, including cytocompatibility, hemocompatibility, and histocompatibility, showed that MSNs biocompatibility could be improved by modifying LC. A high loading and sustained release drug delivery system was constructed after loading doxorubicin (DOX) into the prepared MSN-PLO/LC, which exhibited significant anti-proliferative efficiency in human cervical cancer cell lines (Hela). Therefore, the PLO/LC LbL NPs (layer-by-layer self-assembled nanoparticles coated with PLO/LC layers) based on MSNs, which is easily prepared by electrostatic interactions, can be considered a promising drug chemotherapeutic platform and delivery technique for future human cervical cancer therapy.


Assuntos
Antineoplásicos/administração & dosagem , Portadores de Fármacos , Lentinano , Animais , Antineoplásicos/farmacocinética , Células Cultivadas , Portadores de Fármacos/síntese química , Portadores de Fármacos/química , Portadores de Fármacos/uso terapêutico , Composição de Medicamentos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Feminino , Células HeLa , Humanos , Lentinano/análogos & derivados , Lentinano/síntese química , Lentinano/química , Lentinano/uso terapêutico , Masculino , Teste de Materiais , Camundongos , Nanopartículas/química , Nanopartículas/uso terapêutico , Polimerização , Polímeros/síntese química , Polímeros/química , Polímeros/uso terapêutico , Porosidade , Coelhos , Dióxido de Silício/química , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Int J Biol Macromol ; 172: 289-298, 2021 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-33450341

RESUMO

The sensitive colorimetric detection of glucose using nanomaterials has been attracting considerable attention. To improve the detection sensitivity, highly stable lentinan stabilized platinum nanoclusters (Pt-LNT NCs) were prepared, in which lentinan was employed as a mild reductant and stabilizer. The size of platinum nanoclusters (Pt NCs) was only 1.20 ± 0.29 nm. Pt-LNT NCs catalyzed the oxidation of substrate 3,3',5,5'-tetramethylbenzidine (TMB) in the presence of hydrogen peroxide (H2O2) to produce a blue oxidation product with absorption peak at 652 nm, indicating their peroxidase-like properties. Their enzymatic kinetics followed typical Michaelis-Menten theory. In addition, fluorescence experiments confirmed their ability to efficiently catalyze the decomposition of H2O2 to generate •OH, which resulted in the peroxidase-like mechanism of Pt-LNT NCs. Moreover, a colorimetric method for highly selective and sensitive detection of glucose was established by using Pt-LNT NCs and glucose oxidase. The linear range of glucose detection was 5-1000 µM and the detection limit was 1.79 µM. Finally, this method was further used for detection of glucose in human serum and human urine. The established colorimetric method may promote the development of biological detection and environmental chemistry in the future.


Assuntos
Glicemia/análise , Colorimetria/métodos , Glicosúria/diagnóstico , Lentinano/química , Nanopartículas Metálicas/química , Platina/química , Benzidinas/química , Glucose Oxidase/química , Glicosúria/sangue , Glicosúria/urina , Química Verde , Humanos , Peróxido de Hidrogênio/química , Radical Hidroxila/química , Cinética , Limite de Detecção , Nanopartículas Metálicas/ultraestrutura , Oxirredução , Tamanho da Partícula
11.
Int J Biol Macromol ; 171: 527-538, 2021 Feb 28.
Artigo em Inglês | MEDLINE | ID: mdl-33428957

RESUMO

Lentinan, a ß-1,3-D-glucan, is clinically used as an immune enhancement drug for tumor therapy. Dectin-1 is a cell-surface immune receptor, which plays an important role in immunological defense against fungal pathogens and ß-glucan-mediated immune modulation. Herein we attempted to study the advanced structure of lentinan and how lentinan interacts with dectin-1 for its immune enhancement effect. We firstly used MD simulation and rigid macromolecule docking, combining some spectral techniques, to uncover the complex 3D conformation of a typical polysaccharide - lentinan, and the detailed interaction mode of lentinan with dectin-1. We proved by computational simulation that lentinan can maintain its triple-helix through hydrogen network and disclosed some structural properties of lentinan. We also characterized the affinity of lentinan to dectin-1 by LSPR and binding free energy calculation, and we found out that hydrogen bonds and CH-π interaction are the major contributors for lentinan's binding to dectin-1. Besides, after bound with lentinan, dectin-1 might surprisingly go through a conformational change. In summary, our work provided insights into lentinan's advanced structure and ß-glucan recognition by dectin-1.


Assuntos
Lectinas Tipo C/efeitos dos fármacos , Lentinano/farmacologia , Animais , Configuração de Carboidratos , Sequência de Carboidratos , Análise por Conglomerados , Ligação de Hidrogênio , Proteínas Imobilizadas , Lectinas Tipo C/química , Lentinano/química , Camundongos , Simulação de Acoplamento Molecular , Simulação de Dinâmica Molecular , Conformação Proteica , Espectrometria de Fluorescência , Ressonância de Plasmônio de Superfície , Água
13.
Int Arch Allergy Immunol ; 182(3): 167-181, 2021.
Artigo em Inglês | MEDLINE | ID: mdl-33378763

RESUMO

INTRODUCTION: Biological rhythm is inextricably linked to the physiological mechanisms of allergic diseases, but the exact mechanisms are still poorly understood. Clinical studies have reported rhythmic fluctuations in allergic diseases. The search for natural and harmless active ingredients based on biological rhythm with which to regulate allergic diseases is essential for the control of food allergy. METHODS: In this study, mice were treated at different time points to determine the link between the severity of allergic reactions and the circadian clock genes. The mice were treated with lentinan, either continuously or discontinuously, to assess their clinical symptoms, vascular permeability, immune cells, cytokines, and clock genes. Specifically, rat basophilic leukemia (RBL-2H3) cells were treated with lentinan and the rhythmic changes of cell degranulation were measured. RESULTS: The results in different models showed that the allergic reactions in mice treated at different time points were significantly different and thus related to fluctuations in biological rhythm. Treatment with lentinan was found to reduce the amplitude of changes in the clock genes, such as the activation of Per and Cry proteins in allergic mice, as well as to regulate biological rhythm in cells, inhibit the activation of Th2 cells, and alleviate allergic reactions. Furthermore, lentinan changed the rhythm of degranulation in RBL-2H3 cells. CONCLUSION: Lentinan was, therefore, determined to successfully alleviate allergic reactions by reducing the amplitude of changes in the body's biological rhythm, inhibiting the activation of Th2 cells, and affecting the immune microenvironment.


Assuntos
Hipersensibilidade/etiologia , Lentinano/farmacologia , Ativação Linfocitária/efeitos dos fármacos , Ativação Linfocitária/imunologia , Periodicidade , Células Th2/efeitos dos fármacos , Células Th2/imunologia , Animais , Biomarcadores , Degranulação Celular/efeitos dos fármacos , Degranulação Celular/genética , Degranulação Celular/imunologia , Relógios Circadianos/genética , Modelos Animais de Doenças , Suscetibilidade a Doenças , Expressão Gênica , Hipersensibilidade/diagnóstico , Hipersensibilidade/tratamento farmacológico , Hipersensibilidade/metabolismo , Camundongos , Índice de Gravidade de Doença , Células Th2/metabolismo
14.
Carbohydr Polym ; 253: 117255, 2021 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-33279005

RESUMO

Lentinan (LNT), a typical triple helix ß-glucan, has been widely used as drug and biomaterial. However, its pharmacokinetics in vivo is rarely reported, which severely limits its further development and application. The aim of this study is to establish a sensitive method for detecting LNT in biosamples and to evaluate the plasma level, tissue distribution and metabolic degradation of LNT in rats. 5-([4,6-Dichlorotriazin-2-yl] amino) fluorescein (DTAF) was labelled to LNT. After purification and identification, FLNT was intravenously administered to rats at dose of 32 mg/kg. LNT was predominantly incorporated into the liver and liver microsomes were used to study the degradation mechanism of LNT in the liver. The results showed that two cytochrome P450 (CYP450) enzymes subtypes (CYP2D6 and CYP2C9), as well as epoxide hydrolase, were involved in the metabolic degradation of LNT. These findings provide a pharmacokinetic reference for further study and application of LNT and other ß-glucans.


Assuntos
Citocromo P-450 CYP2D6/metabolismo , Sistema Enzimático do Citocromo P-450/metabolismo , Epóxido Hidrolases/metabolismo , Carpóforos/química , Lentinano/sangue , Fígado/enzimologia , Cogumelos Shiitake/química , Administração Intravenosa , Animais , Feminino , Fluoresceínas/administração & dosagem , Fluoresceínas/metabolismo , Lentinano/administração & dosagem , Microssomos Hepáticos/enzimologia , Ratos , Ratos Sprague-Dawley , Distribuição Tecidual
15.
Carbohydr Polym ; 254: 117476, 2021 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-33357929

RESUMO

Herein the nucleic acid aptamers were attached to the polydeoxyadenylic acid (poly(dA)) tail for improving the tumor-targetability and cellular internalization of s-LNT/poly(dA) composite composed of two single chains of triple helical ß-glucan lentinan (s-LNT) and one poly(dA) chain. The in vitro results demonstrate that the cellular uptake of s-LNT/poly(dA) composites in MCF-7 cancer cells was enhanced effectively after attaching the aptamer. The as-prepared fluorescin isothiocyanate (FITC)-labelled LNT (LNT-FITC) through grafting was used for tracing the enhanced tumor-targetability of the composites. As a result, the cellular internalization of the LNT-FITC into MCF-7 and 4T1 cancer cells was further increased by the aptamer conjugated to poly(dA). Meanwhile, the in vivo experiments further demonstrate more s-LNT/poly(dA)-aptamer composites were effectively accumulated at the tumor site compared with s-LNT alone. This work provides a novel strategy for fabricating triplex ß-glucan as delivery vectors with active tumor-targetability.


Assuntos
Antineoplásicos/farmacologia , Aptâmeros de Nucleotídeos/administração & dosagem , Lentinano/farmacologia , Neoplasias Mamárias Experimentais/terapia , Terapia de Alvo Molecular/métodos , Poli A/administração & dosagem , Animais , Antineoplásicos/química , Aptâmeros de Nucleotídeos/química , Aptâmeros de Nucleotídeos/genética , Linhagem Celular Tumoral , Portadores de Fármacos , Feminino , Fluoresceína-5-Isotiocianato/química , Corantes Fluorescentes/química , Humanos , Injeções Intravenosas , Lentinano/química , Células MCF-7 , Neoplasias Mamárias Experimentais/metabolismo , Neoplasias Mamárias Experimentais/patologia , Camundongos , Poli A/química , Poli A/genética , Coloração e Rotulagem/métodos
16.
PLoS Negl Trop Dis ; 14(9): e0008632, 2020 09.
Artigo em Inglês | MEDLINE | ID: mdl-32976511

RESUMO

There is an urgent need for the development of new, improved vaccine adjuvants against T. spiralis infection. Polysaccharides are effective, safe, and biodegradable as adjuvant. In our study, we first observed the protective efficacy of lentinan as adjuvant against helminth T. spiralis infection. Recombinant T. spiralis Serpin (rTs-Serpin) immunoscreened from a cDNA library of T. spiralis, as a vaccine, protect host against Trichinella infection. The reduction rate of helminth burden of rTs-Serpin+lentinan-immunized mice was significantly increased compared with rTs-Serpin+FCA -immunized mice. rTs-Serpin+lentinan induced IgG1-dominant immune response and higher levels of IFN-γ and IL-4. rTs-Serpin+lentinan displayed a lower reduction rate of parasite burden in NLRP3-/- mice than that in WT mice and lower level of IgG1 than that in WT mice. The level of IL-4, but not IFN-γ, from NLRP3-/- mice immunized by rTs-Serpin+lentinan was significantly lower than that from WT mice, suggesting that NLRP3 is associated with rTs-Serpin+lentinan -triggering Th2 protective immunity against T. spiralis infection. In summary, we revealed that lentinan was a novel adjuvant against T. spiralis infection via NLRP3. NLRP3 therefore represents an important target for adjuvant discovery and the control of T. spiralis infection.


Assuntos
Adjuvantes Imunológicos , Lentinano/imunologia , Proteína 3 que Contém Domínio de Pirina da Família NLR/imunologia , Trichinella spiralis/efeitos dos fármacos , Trichinella spiralis/imunologia , Triquinelose/imunologia , Vacinas/imunologia , Animais , Anticorpos Anti-Helmínticos , Antígenos de Helmintos/genética , Antígenos de Helmintos/imunologia , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Imunização , Camundongos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/metabolismo , Serpinas/genética , Serpinas/imunologia , Trichinella spiralis/genética , Triquinelose/prevenção & controle
17.
Drug Des Devel Ther ; 14: 2819-2829, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32764881

RESUMO

Background: Chondrocyte-mediated inflammation is an important pathological component of osteoarthritis (OA) development. There are currently no therapies that completely reverse the development of OA. Lentinan, a type of polysaccharide derived from Lentinus edodes, has been demonstrated to possess significant anti-viral, anti-cancer, and anti-inflammatory effects, and has been recently used in the treatment of several inflammatory diseases. However, little research has focused on the pharmacological effect of lentinan in human OA. Materials and Methods: We evaluated the anti-inflammatory and anti-ROS effects of lentinan in SW1353 chondrocytes treated with AGEs using real-time polymerase chain reaction (PCR), enzyme-linked immunosorbent assay (ELISA), and the nitro oxide-specific stain DAF-FM DA. The regulatory effects of lentinan on NF-κB and MAPK p38 signaling were investigated via promoter assay and Western blot analysis. Results: We found that lentinan inhibits the production of pro-inflammatory cytokines, including IL-1ß, TNF-α, IL-8 and the secretion of PGE2 and NO, by reducing the expression of COX-2 and iNOS in AGE-challenged chondrocytes. Lentinan also reduces AGE-induced increased expression of matrix metalloproteinases-1, -3, and -13 (MMP-1, MMP-3, MMP-13). Furthermore, lentinan has a similar effect on a disintegrin and metalloproteinase with thrombospondin motifs-4 and -5 (ADAMTS-4, ADAMTS-5). Mechanistically, lentinan reduces the activation of NF-κB. Conclusion: Our findings indicate that lentinan shows a protective effect against AGE-induced inflammatory response in chondrocytes. These findings suggest that lentinan is a promising agent for the treatment of OA that could be used as a dietary supplement for patients with OA.


Assuntos
Anti-Inflamatórios/farmacologia , Condrócitos/efeitos dos fármacos , Produtos Finais de Glicação Avançada/antagonistas & inibidores , Inflamação/tratamento farmacológico , Lentinano/farmacologia , Metaloproteinases da Matriz/metabolismo , Células Cultivadas , Condrócitos/metabolismo , Citocinas/antagonistas & inibidores , Citocinas/biossíntese , Produtos Finais de Glicação Avançada/metabolismo , Humanos , Inflamação/metabolismo , Metaloproteinases da Matriz/genética , Osteoartrite/tratamento farmacológico , Osteoartrite/metabolismo
18.
Int J Biol Macromol ; 163: 1384-1392, 2020 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-32758599

RESUMO

In recent years, the high prevalence of avian influenza viruses especially H5N1 subtype isolated from poultry and human has become a major public health concern. Vaccination is still a major strategy for preventing H5N1 infections. Lentinan (LNT), a ß-1,3-glucohexaose with ß-1,6-branches, is extracted from Lentinus edodes and has been extensively studied for its immunoenhancement effects. In this study, we synthesized and characterized calcium carbonate (CaCO3) microparticles which modified with LNT as an adjuvant for H5N1 vaccine and investigated their ability to enhance immune responses. We prepared spherical and uniform CaCO3-LNT microparticles with a mean hydrodynamic size was around 2 µm. The H5N1 antigen-loaded CaCO3-LNT particles were injected into mice to evaluate their effectiveness as an adjuvant for H5N1 vaccines. The results demonstrated that CaCO3-LNT/H5N1 significantly enhanced the expression of MHC-II and CD86 in lymph node dendritic cells, and increased the ratio of CD4+ to CD8+ T cells in lymphocytes. Moreover, CaCO3-LNT/H5N1 surprisingly increased the HI titers and induced the secretion of IgG subtypes (IgG1 and IgG2b) and Th-associated cytokines (TNF-α, IFN-γ and IL-4) in immunized mice. Therefore, by combining with the immunostimulatory activity of LNT and the drug/antigen delivery capabilities of CaCO3, the CaCO3-LNT/H5N1 could induce a stronger cellular and humoral immune response and could be a potential adjuvant for the H5N1 vaccine.


Assuntos
Carbonato de Cálcio/imunologia , Virus da Influenza A Subtipo H5N1/imunologia , Vacinas contra Influenza/imunologia , Lentinano/imunologia , Adjuvantes Imunológicos/administração & dosagem , Animais , Anticorpos Antivirais/imunologia , Antígenos Virais/imunologia , Linfócitos T CD4-Positivos/imunologia , Linfócitos T CD8-Positivos/imunologia , Células Dendríticas/imunologia , Feminino , Imunidade/imunologia , Imunoglobulina G/imunologia , Linfonodos/imunologia , Camundongos , Camundongos Endogâmicos ICR , Vacinação/métodos
19.
Int J Med Mushrooms ; 22(5): 407-415, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32749096

RESUMO

Lentinus edodes (=Lentinula edodes) is a culinary-medicinal mushroom with a long tradition of use in Asia. The major active substance in L. edodes is a beta-(1-3,1-6)-glucan (lentinan). GlycaNova produces Lentinex®, which contains this beta-glucan from L. edodes mycelia, in a proprietary process that maintains the triple helix molecular structure and high molecular weights. This study was carried out to investigate the effect of Lentinex supplementation on the well-being of adults. We evaluated the effect of Lentinex in healthy adult subjects in a randomized, placebo-controlled, double-blind trial. Sixty-three subjects, randomly allocated to two groups, took orally either 1-2 mL/day Lentinex (1-2 mg beta-glucan) or placebo for four weeks. The participants completed a well-being questionnaire prior to commencing supplementation and again at the end of the in-home study. The results showed an important and statistically significant improvement in well-being over the period in the treated group compared with the placebo group. The degree of improvement in the treated group, including relative to placebo, was higher for subjects who had lower initial well-being than for subjects with higher initial well-being. In conclusion, the lower an individual's initial well-being, the more Lentinex helped.


Assuntos
Lentinano/administração & dosagem , Cogumelos Shiitake , beta-Glucanas/análise , Adulto , Suplementos Nutricionais , Método Duplo-Cego , Feminino , Humanos , Fatores Imunológicos , Lentinano/uso terapêutico , Masculino , Micélio/química , Qualidade de Vida , Inquéritos e Questionários
20.
Integr Cancer Ther ; 19: 1534735420946823, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32735179

RESUMO

Background: Lentinan (LNT), an isolated traditional Chinese herbal component, has antitumor potential. In the current study, the intrinsic mechanism of LNT-induced immunity against bladder cancer was explored in a mouse model. Methods: In the mouse model of bladder cancer, we used flow cytometry to detect the LNT caused population changes of T cells, macrophages, MDSC cells, and Treg cells. ELISA was used to evaluate cytokines expression in the supernatant of splenocytes. Results: We found that the administration of LNT increased the proportions of CD3+CD4+ and CD3+CD8+ T cell subsets as well as CD11b+F480+ macrophages, whereas it diminished the subpopulations of CD4+CD25+Foxp3+ regulatory T cells (Tregs) and Gr-1+CD11b+ myeloid-derived suppressor cells (MDSCs). LNT also upregulated the expression of interferon (IFN)-γ and interleukin (IL)-12, accompanied by a significant reduction in IL-10 and tumor growth factor (TGF)-ß (P < .05). Our research further confirmed the synergy between LNT and gemcitabine (GEM) to activate immunity and inhibit the growth of bladder tumors in mouse model. Conclusions: LNT induced macrophage activation, followed by the enhanced proliferation of CD4+ and CD8+ T cells, and the upregulated expression of IFN-γ and IL-2. Meanwhile, the proportions of MDSCs and Tregs were downregulated, leading to a reduced expression of the anti-inflammatory cytokines IL-10 and TGF-ß. The synergy between LNT and GEM provides additional evidence supporting the application of this traditional Chinese herbal component for bladder cancer therapy.


Assuntos
Lentinano , Neoplasias da Bexiga Urinária , Animais , Linfócitos T CD8-Positivos , Imunomodulação , Lentinano/farmacologia , Camundongos , Linfócitos T Reguladores , Neoplasias da Bexiga Urinária/tratamento farmacológico
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