RESUMO
Tobacco mosaic virus (TMV) is extremely pathogenic and resistant to stress There are great needs to develop methods to reduce the virus in the environment and induce plant immunity simultaneously. Here, we report a multifunctional nano-protectant to reduce the virus in the environment and induce plant immunity simultaneously. The star polycation (SPc) nanocarrier can act as an active ingredient to interact with virus coat protein via electrostatic interaction, which reduces the proportion of TMV particles to 2.9% and leads to a reduction of the amount of virus in the environment by half. SPc can act as an adjuvant to spontaneously assemble with an immune inducer lentinan (LNT) through hydrogen bonding into nanoscale (142 nm diameter) LNT/SPc complex, which improves the physicochemical property of LNT for better wetting performance on leaves and cellular uptake, and further activates plant immune responses. Finally, the LNT/SPc complex displays preventive and curative effects on TMV disease, reducing TMV-GFP relative expression by 26% in the laboratory and achieving 82% control efficacy in the field We hope the strategy reported here would be useful for control of crop virus disease.
Assuntos
Nicotiana , Doenças das Plantas , Imunidade Vegetal , Vírus do Mosaico do Tabaco , Vírus do Mosaico do Tabaco/efeitos dos fármacos , Vírus do Mosaico do Tabaco/imunologia , Doenças das Plantas/virologia , Doenças das Plantas/prevenção & controle , Doenças das Plantas/imunologia , Imunidade Vegetal/efeitos dos fármacos , Nicotiana/virologia , Nicotiana/imunologia , Nanoestruturas/química , Lentinano/farmacologia , Folhas de Planta/virologia , Proteínas do Capsídeo/imunologia , Proteínas do Capsídeo/metabolismoRESUMO
Background: Iron-based nanocarriers have demonstrated potential in redirecting tumor associated macrophages (TAMs) polarization towards the M1 phenotype, critical for activating the tumor microenvironment (TME) in triple negative breast cancer (TNBC). However, their real-world effectiveness is curtailed by insufficient Fe2+/3+ exposure and the absence of suitable synergists in tumors. Methods: We introduce an air bag-embedded iron-based MIL-101 metal-organic frameworks (MOFMIL-101(Fe)) for igniting the TME in TNBC through bubble-driven tumoral codelivery of Fe2+/3+ and lentinan. This system, named HM/Ef/LNT-MOFMIL-101(Fe), features nano-sized MOFMIL-101(Fe) as the core, embedded NaHCO3 as a pH-triggered air bag, electrostatically-adsorbed lentinan forming the inner shell, and a shield shell with 4T1&red blood cell hybrid membrane. Results: HM/Ef/LNT-MOFMIL-101(Fe) can mitigate non-specific capture in the bloodstream but respond to the acidic tumor milieu, rapidly generating a burst of CO2 bubbles to disassemble MOFMIL-101(Fe). Upon entering tumors, lentinan-induced interferon-γ (IFN-γ) enable Fe2+/3+ facilitating an enhanced ferroptosis and Fenton-like reaction, pushing TAMs towards M1 polarization via the "IFN-γ-ferroptosis-ROS-Caspase-3" pathway. Moreover, HM/Ef/LNT-MOFMIL-101(Fe) increases the infiltration of T lymphocytes and decreases regulatory T cells. These cascading immune responses synergistically foster a loop of amplified TME activation based on TAMs M1 polarization, showcasing notable advancements in anticancer effectiveness and promise for various combination therapies. Conclusion: This study utilizes an "embedded air-bag" strategy to achieve strategic codelivery of Fe2+/3+ and lentinan, providing a new tool for engineering the TME.
Assuntos
Ferro , Lentinano , Estruturas Metalorgânicas , Microambiente Tumoral , Estruturas Metalorgânicas/química , Microambiente Tumoral/efeitos dos fármacos , Ferro/química , Ferro/metabolismo , Lentinano/química , Lentinano/farmacologia , Lentinano/administração & dosagem , Animais , Camundongos , Feminino , Linhagem Celular Tumoral , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Humanos , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Camundongos Endogâmicos BALB CRESUMO
Alzheimer's disease (AD) and Parkinson's disease (PD) are the two most common neurodegenerative diseases in the world. Misfolding of ß-amyloid (Aß) and α-synuclein (α-syn) and subsequent fibril formation are closely associated with the pathogenesis of AD and PD, respectively. Lentinan is a natural product commonly used in medicine and dietary supplements. It has potential antitumor, anti-inflammatory, and antiviral effects, but the underlying mechanism of its action on AD and PD remains unclear. In this study, lentinan inhibited the formation of Aß and α-syn fibers in a dose-dependent manner and disrupted their mature fibers. Lentinan inhibited the conversion of Aß and α-syn conformations to ß-sheet-rich conformations. Additionally, lentinan protected Caenorhabditis elegans against damage caused by the accumulation of Aß and α-syn aggregation and prolonged their lifespan. Notably, the beneficial effects of lentinan in AD and PD mice were also demonstrated, including ameliorating the cognitive and memory impairments in AD mice and behavioral deficits in PD mice. Finally, molecular interactions between lentinan and Aß/α-syn pentamers were also explored using molecular docking.
Assuntos
Doença de Alzheimer , Peptídeos beta-Amiloides , Caenorhabditis elegans , Lentinano , Doença de Parkinson , alfa-Sinucleína , Lentinano/farmacologia , Animais , alfa-Sinucleína/metabolismo , alfa-Sinucleína/antagonistas & inibidores , Peptídeos beta-Amiloides/metabolismo , Peptídeos beta-Amiloides/antagonistas & inibidores , Caenorhabditis elegans/efeitos dos fármacos , Camundongos , Doença de Parkinson/tratamento farmacológico , Doença de Parkinson/metabolismo , Doença de Alzheimer/tratamento farmacológico , Doença de Alzheimer/metabolismo , Humanos , Simulação de Acoplamento Molecular , Fármacos Neuroprotetores/farmacologia , Camundongos Endogâmicos C57BLRESUMO
Acute alcoholic liver injury (AALI) is a widespread disease that can develop into hepatitis, liver fibrosis, and cirrhosis. In severe cases, it can be life-threatening, while drug treatment presents various side effects. This study characterized the structure of natural lentinan (LNT) from the Qinba Mountain area and investigated the protective mechanism of different LNT doses (100 mg kg-1, 200 mg kg-1, and 400 mg kg-1) on AALI. The results showed that LNT was a glucose-dominated pyran polysaccharide with a triple-helical structure and a molecular weight (Mw) of 7.56 × 106 Da. An AALI mouse model showed that all the LNT doses protected liver function, reduced hepatic steatosis, alleviated oxidative stress and inflammatory response, and stimulated probiotic proliferation. Low-dose LNT increased anti-oxidant-associated beneficial bacteria, medium-dose LNT improved liver swelling and promoted anti-oxidant-associated probiotics, and high-dose LNT increased the probiotics that helped protect liver function and anti-oxidant and anti-inflammatory properties. All the LNT doses inhibited pathogenic growth, including Oscillospiraceae, Weeksellaceae, Streptococcaceae, Akkermansiaceae, Morganellaceae, and Proteus. These results indicated that the protective effect of LNT against AALI was mediated by the proliferation of various intestinal probiotics and was related to the consumption doses. These findings offer new strategies for comprehensively utilizing Lentinula edodes from the Qinba Mountain area and preventing AALI using natural food-based substances.
Assuntos
Lentinano , Hepatopatias Alcoólicas , Probióticos , Animais , Camundongos , Lentinano/farmacologia , Probióticos/farmacologia , Masculino , Hepatopatias Alcoólicas/prevenção & controle , Hepatopatias Alcoólicas/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Modelos Animais de Doenças , Fígado/efeitos dos fármacos , Fígado/metabolismo , Substâncias Protetoras/farmacologia , Substâncias Protetoras/administração & dosagem , Relação Dose-Resposta a DrogaRESUMO
Lentinan (LNT), a natural polysaccharide, has been reported to exhibit immunomodulatory effects in the intestine after oral administration. Herein, we aimed to investigate the lymphatic transport of LNT in Peyer's patches (PPs) by traceable fluorescent labeling and to explore whether/how LNT contacts related immune cells. Near-infrared imaging confirmed the absorption of LNT in the small intestinal segment and its accumulation within PPs after oral administration. Subsequently, tissue imaging confirmed that M cells are the main cells responsible for transporting LNT to PPs, and an M cell model was established to explore the involvement of Dectin-1 in the absorption process. Systematic in vitro and in vivo studies revealed that the Dectin-1 further mediates the uptake of LNT by mononuclear phagocytes in PPs. Moreover, LNT can promote the proliferation and differentiation of mononuclear phagocytes, thereby activating immune responses. In summary, this study elucidates the pharmacokinetic mechanisms by which LNT exerts oral immunomodulatory effects, providing a theoretical basis for the development and application of other polysaccharides.
Assuntos
Lectinas Tipo C , Lentinano , Nódulos Linfáticos Agregados , Nódulos Linfáticos Agregados/imunologia , Nódulos Linfáticos Agregados/efeitos dos fármacos , Nódulos Linfáticos Agregados/metabolismo , Animais , Lentinano/farmacologia , Lentinano/química , Lectinas Tipo C/metabolismo , Camundongos , Administração Oral , Fagócitos/efeitos dos fármacos , Fagócitos/metabolismo , Fagócitos/imunologia , Imunomodulação/efeitos dos fármacos , Masculino , Camundongos Endogâmicos BALB C , Células MRESUMO
BACKGROUND: Allergic asthma has been regarded as an inflammatory disease mediated by type 2 immunity. The treatment of progressive forms of asthma remains unsatisfactory despite substantial progress in drug development. Lentinan (LTN), a specific polysaccharide derived from Lentinus edodes, exhibits anti-inflammatory and immunomodulatory functions. Nevertheless, the effect and underlying mechanisms of Lentinan on asthma remain unclear. PURPOSE: This research investigated the regulatory role of Lentinan on allergic airway inflammation and epithelial barrier dysfunction in HDM (house dust mite)-induced asthma. STUDY DESIGN: HDM-induced C57BL/6 mice received different dosages of Lentinan through intraperitoneal injections, to observe the effect of Lentinan against allergic airway inflammation and epithelial barrier dysfunction in asthma. METHODS: Mice were intranasally administered HDM extract solution on days 0, 1, 2 and on days 8 to 12, establishing the allergic asthma model. On days 8 to 12, mice were intraperitoneally administered varying doses of Lentinan (5/10/20mg/kg) 1h before HDM challenge. On day 14, samples were harvested for analysis. Cell counting, flow cytometry, ELISA, HE and PAS staining, IF staining, western blotting, RT-PCR, and bioinformatic analysis were conducted to delve into the underlying functions and mechanisms of Lentinan in asthma. RESULTS: Our study revealed that the treatment of Lentinan significantly ameliorated allergic airway inflammation and improved epithelial barrier dysfunction in experimental mice. Following Lentinan treatment, there was a significant reduction in eosinophil counts, accompanied by a diminished presence of type 2 cytokines. Reversal of epithelial barrier dysfunction after treatment was also observed. The therapeutic mechanism involved suppression of the PI3K/AKT/ NF-κB pathway. CONCLUSION: Our research illuminated the protective role of Lentinan in allergic airway inflammation and impaired epithelial barrier, suggesting LTN could be an innovative and promising candidate for asthma treatment.
Assuntos
Asma , Lentinano , Transdução de Sinais , Animais , Feminino , Masculino , Camundongos , Asma/tratamento farmacológico , Líquido da Lavagem Broncoalveolar , Citocinas/metabolismo , Modelos Animais de Doenças , Inflamação/tratamento farmacológico , Lentinano/farmacologia , Pulmão/efeitos dos fármacos , Camundongos Endogâmicos C57BL , NF-kappa B/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Pyroglyphidae , Cogumelos Shiitake/química , Transdução de Sinais/efeitos dos fármacosRESUMO
Glioblastoma multiforme (GBM) exhibits a high mortality with an incidence rate of 3-5 per 100,000 each year, which demands existence of newer approach for its treatment. The current study focuses on synthesis of novel lipidic nanovesicles (LNs) loaded with highly potent macromolecule Lentinan (LNT) and surface modified with methoxy poly (ethylene glycol; PEG) amine (m-PEG-NH2)-grafted-chitosan (CS) for intranasal delivery. The grafting procedure was optimized using Box Behnken design (BBD) to limit the use of organic solvents. The fabricated polymer showed enhanced aqueous solubility, biodegradability and mucoadhesion, resulting in higher nasal mucosa permeation (z = 53.52 µm). The presence of PEG enabled the sustained release of LNT till 48 h and assisted in achieving higher accumulation of LNT in CSF (41.7 ± 3.1 µg/mL) and a higher brain targeting potential of 96.3 ± 2.31 % (p < 0.05). In-vitro cellular studies showed the enhanced anti-GBM effect of LNT on U87 MG cells by reducing the cell viability (~2 times reduction in IC50 value) accompanied with large number of cells undergoing late apoptosis and death (p < 0.05) because of the higher cellular uptake (63.22 ± 3.01 ng/100 cells) of novel formulation. The copolymer comprising LNs were biocompatible, stable and can be used as an effective tool in the management of GBM.
Assuntos
Administração Intranasal , Quitosana , Glioblastoma , Lentinano , Nanopartículas , Polietilenoglicóis , Glioblastoma/tratamento farmacológico , Glioblastoma/patologia , Quitosana/química , Humanos , Lentinano/química , Lentinano/farmacologia , Lentinano/administração & dosagem , Polietilenoglicóis/química , Linhagem Celular Tumoral , Nanopartículas/química , Portadores de Fármacos/química , Animais , Ratos , Sobrevivência Celular/efeitos dos fármacos , Apoptose/efeitos dos fármacosRESUMO
Cotton fabric has extensive application due to its comfort and breathability. However, the inherent flammability limits its wide application. Durable polysaccharide-based flame retardants with a low impact on the softness of fabrics are rarely reported. In this work, a novel flame retardant ammonium phosphate of lentinan (APLNT) was synthesized and grafted on the surface of cotton fabric. The treated cotton fabric had a high limiting oxygen index (LOI) value of 43.3 % and passed the vertical burning test (VBT) with a 21.1 % weight gain of APLNT. Compared with control cotton, the peak heat release rate and total heat release values of Cotton-APLNT2 decreased by 92.8 % and 50.9 %, respectively. In addition, the cotton fabric still passed the VBT and kept an LOI value of 27.0 % even after 50 laundering cycles, indicating that the fabric can be used for daily needs. More importantly, the treated fabric remains soft. This research provided a new strategy for preparing bio-based durable flame retardant cotton fabrics.
Assuntos
Fibra de Algodão , Retardadores de Chama , Lentinano , Retardadores de Chama/análise , Fibra de Algodão/análise , Lentinano/química , Têxteis , Fosfatos/químicaRESUMO
Pemetrexed is a folate analog metabolic inhibitor that is given for therapy of non-small cell lung cancer (NSCLC). Drug resistance affects the efficacy of pemetrexed in NSCLC. Lentinan is a polysaccharide extracted from Shiitake mushrooms which has antitumor roles in multiple cancers, including lung cancer. However, the effects of lentinan on pemetrexed resistance in NSCLC remain unclear. In present study, The pemetrexed-resistant NSCLC cells were established and exposed to pemetrexed and lentinan. Oxidative stress was investigated via mitochondrial membrane potential (JC-1 staining), levels of MDA and SOD.The phosphorylation and total of PI3K and Akt levels were actuated using specific activator 740Y-P and measured through western blot. We observed that Lentinan decreased IC50 of pemetrexed in resistant NSCLC cells. Lentinan aggravated pemetrexed-induced proliferation inhibition of resistant NSCLC cells via reducing PCNA levels. Lentinan exacerbated pemetrexed-triggered oxidative stress through increasing ROS and MDA levels, and reducing mitochondrial membrane potential and SOD levels. Lentinan inhibited PI3K/Akt signaling activation in pemetrexed-treated cells. Activated PI3K/Akt pathway using activator 740Y-P reversed the effects of lentinan on pemetrexed-mediated proliferation inhibition and oxidative stress. Our findings uncover that Lentinan mitigates pemetrexed resistance in NSCLC through inhibiting cell proliferation and inducing oxidative stress by suppressing PI3K/Akt signaling.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Resistencia a Medicamentos Antineoplásicos , Lentinano , Neoplasias Pulmonares , Estresse Oxidativo , Pemetrexede , Transdução de Sinais , Humanos , Antineoplásicos/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Resistencia a Medicamentos Antineoplásicos/efeitos dos fármacos , Lentinano/farmacologia , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Pemetrexede/farmacologia , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Transdução de Sinais/efeitos dos fármacos , Superóxido Dismutase/metabolismoRESUMO
BACKGROUND: Malignant pleural effusion (MPE) is a frequently observed complication in advanced malignant tumors. Clinical studies have shown that lentinan for injection (LNT) is beneficial for improving patients' quality of life and prolonging their survival. The purpose of this meta-analysis is to evaluate the efficacy and safety of LNT combining cisplatin in the treatment of MPE. METHODS: Randomized controlled trials (RCTs) of LNT combining cisplatin in the treatment of MPE were searched in 6 literature databases from the establishment time of each database by 2 researchers. According to the inclusion criteria, 2 researchers independently screened studies, assessed the risk of bias and conducted subgroup analyses for different outcome indicators according to the specific characteristics of the included literature. Analyzing the data by Revman software, and evaluating the stability of the results by Stata software. RESULTS: A total of 52 RCTs were included. The results showed that combined use of LNT and cisplatin could improve the treatment effect, and the difference between groups was statistically significant (RRâ =â 1.40, 95%CI: 1.33 ~ 1.46, Pâ <â .001). And the combined use of LNT could increase the quality of life (RRâ =â 1.45, 95%CI: 1.35 ~ 1.56, Pâ <â .001). The using of LNT could significantly decrease the incidence of gastrointestinal reactions (RRâ =â 0.86, 95%CI: 0.78 ~ 0.94, Pâ <â .001). Sensitivity analysis results showed that there were no qualitative changes in the indicator, and suggested the possibility of publication bias. CONCLUSIONS: Available evidence suggested the combined use of LNT and cisplatin showed better efficacy in treating MPE without increasing ADR incidence than using cisplatin alone. LNT is an ideal treatment for MPE, which has high clinical application value.
Assuntos
Antineoplásicos , Cisplatino , Lentinano , Derrame Pleural Maligno , Qualidade de Vida , Ensaios Clínicos Controlados Aleatórios como Assunto , Humanos , Cisplatino/administração & dosagem , Cisplatino/uso terapêutico , Derrame Pleural Maligno/tratamento farmacológico , Lentinano/administração & dosagem , Lentinano/uso terapêutico , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos , Resultado do TratamentoRESUMO
Marek's disease virus (MDV) is a significant tumorigenic virus that causes severe immunosuppression in chickens. Lentinan (LNT) is an immunomodulator containing ß-glucans and is widely used in areas such as antiviral, anticancer, and immune regulation. To investigate the immunomodulatory effects of LNT on specific pathogen-free (SPF) chicks and its potential to inhibit MDV infection, we conducted an MDV challenge experiment and observed the immune-enhancing effect of LNT on SPF chicks. The results showed that LNT promoted the growth and development of SPF chicks and induced the upregulation of cytokines such as Mx protein, interferon-γ (INF-γ), tumor necrosis factor-α (TNF-α), and interleukin-2 (IL-2). The specific gravity of CD4+ T-lymphocytes and CD8+ T-lymphocytes and their ratios were also significantly upregulated. Prophylactic use of LNT inhibited MDV replication in lymphocytes, liver, and spleen. It also alleviated MDV-induced weight loss and hepatosplenomegaly in SPF chicks. The present study confirms that LNT can enhance the levels of innate and cellular immunity in SPF chicks and contributes to the inhibition of MDV replication in vivo and mitigation of immune organ damage in chicks due to MDV infection. This provides an adjunctive measure for better control of MDV infection.
Assuntos
Galinhas , Herpesvirus Galináceo 2 , Lentinano , Doença de Marek , Doenças das Aves Domésticas , Animais , Doença de Marek/imunologia , Lentinano/farmacologia , Lentinano/administração & dosagem , Doenças das Aves Domésticas/virologia , Doenças das Aves Domésticas/imunologia , Doenças das Aves Domésticas/tratamento farmacológico , Herpesvirus Galináceo 2/fisiologia , Organismos Livres de Patógenos Específicos , Ração Animal/análise , Fatores Imunológicos/farmacologia , Fatores Imunológicos/administração & dosagem , Dieta/veterinária , Distribuição AleatóriaRESUMO
Non-small cell lung cancer (NSCLC) is an aggressive and devastating cancer due to its metastasis induced by increased invasion. Lentinan is a polysaccharide exerting antitumor roles in multiple cancers, including lung cancer. However, the influence of lentinan on cell invasion in NSCLC remains unclear. Cell invasion was detected by transwell analysis. Matrix metallopeptidase 9 (MMP9) levels were measured through immunofluorescence staining. The markers arginase-1 (Arg-1), CD206 and interleukin (IL)-10 (IL-10) of M2 macrophages, Wnt3a, and ß-catenin levels were measured by western blot or enzyme linked immunosorbent assay. Lentinan did not affect cell viability and proliferation in NSCLC cells. Lentinan suppressed cell invasion and reduced the expression and secretion of MMP9. Lentinan attenuated also M2 polarization of tumor-associated macrophages. Moreover, lentinan mitigated the M2 macrophage conditioned medium-mediated cell invasion and MMP9 alterations in NSCLC cells. Lentinan inhibited the activation of the Wnt/ß-catenin signaling in NSCLC cells. The activated Wnt/ß-catenin pathway reversed the suppressive effects of lentinan on cell invasion and MMP9 level in NSCLC cells. In conclusion, lentinan reduces cell invasion in NSCLC cells by inhibiting the M2 polarization of tumor-associated macrophages and the Wnt/ß-catenin signaling.
Assuntos
Carcinoma Pulmonar de Células não Pequenas , Lentinano , Neoplasias Pulmonares , Humanos , beta Catenina/metabolismo , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral/efeitos dos fármacos , Movimento Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Lentinano/farmacologia , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Metaloproteinase 9 da Matriz , Macrófagos Associados a Tumor/efeitos dos fármacos , Macrófagos Associados a Tumor/metabolismo , Macrófagos Associados a Tumor/patologiaRESUMO
The immune system acts as a vital defense barrier against pathogenic invasions, and its stable operation is crucial for maintaining body health. Nevertheless, various natural or artificial factors can compromise the body's immune function, leading to immunosuppression, which may interfere with the efficacy of vaccination and increase the susceptibility of the body to disease-causing pathogens. In an effort to ensure successful vaccinations and improve overall physical well-being, the search for appropriate immune regulators to enhance immunity is of paramount importance. Lentinan (LNT) has a significant role in immune regulation and vaccine adjuvants. In the present study, we constructed an immunosuppressive model using dexamethasone (DEX) and demonstrated that LNT could significantly improved antibody levels in immunosuppressive mice and stimulated T-lymphocyte proliferation and differentiation in intestinal Peyer's patches. LNT also increased the production of secretory immunoglobulin A (sIgA) in the duodenal fluid, the number of goblet cells, and the proportion of mucin area. Moreover, LNT modulated the intestinal microbiota and increased the production of short-chain fatty acids. Additionally, LNT promoted the proliferation, differentiation, and pro-inflammatory cytokines production of DEX-treated splenic T lymphocytes in vitro. Thus, the present study highlights the potential of LNT in reversing immunosuppression and avoiding the failure of vaccination.
Assuntos
Terapia de Imunossupressão , Lentinano , Animais , Camundongos , Lentinano/farmacologia , Tolerância Imunológica , Intestinos , Dexametasona/farmacologiaRESUMO
Diabetic wound healing is a substantial clinical challenge, characterized by delayed angiogenesis and unresolved inflammation. Lentinan, a polysaccharide extracted from shiitake mushrooms, has the potential to regulate both macrophage polarization and angiogenesis, though this aspect remains inadequately explored. To facilitate lentinan's clinical utility, we have developed a GelMA hydrogel encapsulated with lentinan (10 µM), offering a controlled release mechanism for sustained lentinan delivery at the wound site. Application of the lentinan-encapsulated delivery system topically significantly expedites wound closure compared to control groups. Furthermore, histological examination demonstrates enhanced neovascularization and reduced inflammation in lentinan-treated wounds, as evidenced by increased M2 macrophage infiltration. Moreover, our results indicated that lentinan-induced AMPK activation promotes DAF16 expression, enhancing the resistance of macrophages and HUVECs to oxidative stress in high-glucose environments, thereby promoting M2 macrophage polarization and angiogenesis. All these findings underscore lentinan's capacity to modulate macrophage polarization and angiogenesis via the AMPK/DAF16 pathway, ultimately facilitating the healing of diabetic wounds.
Assuntos
Diabetes Mellitus , Hidrogéis , Humanos , Lentinano/farmacologia , Proteínas Quinases Ativadas por AMP , Angiogênese , Cicatrização , Inflamação/patologiaRESUMO
Polysaccharides from natural products play multiple roles and have extensive bioactivities in life process. Bioactivities of polysaccharides (e.g., Lentinan, Schizophyllan, Scleroglucan, Curdlan, Cinerean) have a close relation to their chain conformation. Compared to other types of polysaccharides, the conformation of ß-glucan has been studied more. The major research methods of conformation of polysaccharides from natural products (Congo red experiment, circular dichroism spectrum, viscosity method, light scattering method, size exclusion chromatography, atomic force microscope), corresponding experimental schemes, and the external factors affecting polysaccharide conformation were reviewed in this paper. These research methods of conformation have been widely used, among which Congo red experiment and viscosity method are the most convenient ones to study the morphological changes of polysaccharide chains.
Assuntos
Produtos Biológicos , Vermelho Congo , Conformação Molecular , Lentinano/química , Polissacarídeos/química , Configuração de CarboidratosRESUMO
Shiitake mushrooms are a fungal food that has been recorded in Chinese medicine to nourish the blood and qi. Lentinan (lLNT) is an active substance extracted from shiitake mushrooms with powerful antioxidant, anti-inflammatory, anti-tumor functions. Inflammatory diseases and cancers are the leading causes of death worldwide, posing a serious threat to human life and health and posing enormous challenges to global health systems. There is still a lack of effective treatments for inflammatory diseases and cancer. LNT has been approved as an adjunct to chemotherapy in China and Japan. Studies have shown that LNT plays an important role in the treatment of inflammatory diseases as well as oncological diseases. Moreover, clinical experiments have confirmed that LNT combined with chemotherapy drugs has a significant effect in improving the prognosis of patients, enhancing their immune function and reducing the side effects of chemotherapy in lung cancer, colorectal cancer and gastric cancer. However, the relevant mechanism of action of the LNT signaling pathway in inflammatory diseases and cancer. Therefore, this article reviews the mechanism and clinical research of LNT in inflammatory diseases and tumor diseases in recent years.
Assuntos
Neoplasias Pulmonares , Neoplasias Gástricas , Humanos , Lentinano/uso terapêutico , Lentinano/farmacologia , Resultado do Tratamento , PrognósticoRESUMO
The development of hydrogels based on dextrans, pullulan and lentinan to be used in biomedical applications including tissue engineering is reported. Despite the fact that selected polysaccharides such as hyaluronic acid are well established, little is known, how these polysaccharides can be chemically modified to create hydrogels under controlled conditions. In this study we present a small library of chemically modified polysaccharides which are used for a divergent approach to achieve biomedical relevant hydrogels. In this case the crosslinking is based on thio ether formation between thiol modified donor and vinylsulfone or maleimide modified acceptor components. Successful synthesis of the linker systems and coupling at the polysaccharides, hydrogel formation takes place under physiological conditions. We extended the study by coupling small molecules like adhesion factors for increasing cell compatibility as well as a dye for further studies. The different hydrogels were studied to their rheological properties, water uptake, their permeability, biodegrability and their cytotoxicity.
Assuntos
Dextranos , Glucanos , Hidrogéis , Hidrogéis/química , Dextranos/química , Lentinano , Engenharia Tecidual , Polissacarídeos/químicaRESUMO
Current rabies vaccines require 5 doses to provide full protection from the deadly virus, which significantly reduce the compliance of recipients. To minimize the number of immunizations herein single injection vaccines were developed. First a single injection vaccine was designed using rabies virus glycoprotein (G protein) as antigen. A time-controlled release system which uses dynamic layer-by-layer films as erodible coating was employed to accomplish multiply pulsatile releases of G protein. The single-injection vaccine elicits potent humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of G protein. To further improve its performance, a second single injection vaccine, in which lentinan was added as adjuvant, was designed. This single-injection vaccine again elicits humoral and cellular immune responses comparable to the corresponding multi-dose ordinary vaccines because of their similar release pattern of antigen and adjuvant. In addition, the second single-injection vaccine elicits higher level immune response and provides higher efficiency on virus inhibition than the first one because lentinan can booster immune response.
Assuntos
Vacina Antirrábica , Raiva , Humanos , Raiva/prevenção & controle , Lentinano/farmacologia , Anticorpos Antivirais , Adjuvantes Imunológicos/farmacologia , Adjuvantes Farmacêuticos , Vacinas de Subunidades Antigênicas , Proteínas de Ligação ao GTPRESUMO
BACKGROUND: This study employed a meta-analysis to evaluate the efficacy and safety of adjunctive treatment with injectable Lentinan (LNT) in combination with chemotherapy for gastric cancer (GC). METHODS: Computer-based searches of 6 databases were performed to identify randomized controlled trials (RCTs) relevant to the treatment of GC with LNT through mid-March 2023. Two independent researchers performed risk of bias assessment and trial sequential analysis(TSA), extracted the data and used Revman 5.3 software for data analysis. The certainty of evidence was graded based on the GRADE (Grading of Recommendations Assessment, Development and Evaluation) approach. RESULTS: A total of 31 RCTs with 2729 patients were included in the analysis. The results revealed that adjunctive therapy with LNT was associated with improved treatment efficacy (RR = 1.48, 95%CI: 1.36 â¼ 1.61, p < 0.00001), improvement in clusters of differentiation (CD3+, CD4+, and CD4+/CD8+), natural killer (NK) cells, and quality of life assessment (RR = 1.32, 95%CI: 1.20 â¼ 1.45, p < 0.00001) compared to using chemotherapy alone. In addition, there was a reduction in CD8+ levels, incidence of white blood cell decline, gastrointestinal reactions, and platelet decline. TSA results indicated that there was sufficient evidence to draw firm conclusions about these outcomes, and the GRADE scores showed 'high' or 'moderate' quality of evidence for these outcomes. CONCLUSION: The efficacy of treatment of GC with LNT in combination with chemotherapy was found to be better than chemotherapy alone. And no serious adverse effects were observed. However, further RCTs are needed to further validate the results of this study.
Assuntos
Lentinano , Neoplasias Gástricas , Humanos , Lentinano/farmacologia , Neoplasias Gástricas/tratamento farmacológico , Resultado do TratamentoRESUMO
BACKGROUND: Toxoplasma gondii (T. gondii) is increasingly considered a risk factor for neurodegenerative diseases. However, there is only limited information on the development of drugs for T. gondii infection. Lentinan from Lentinula edodes is a bioactive ingredient with the potential to enhance anti-infective immunity. The present study aimed to investigate the neuroprotective effect of lentinan on T. gondii-associated cognitive deficits in mice. METHODS: A chronic T. gondii infection mouse model was established by administering 10 cysts of T. gondii by gavage. Lentinan was intraperitoneally administered 2 weeks before infection. Behavioral tests, RNA sequencing, immunofluorescence, transmission electron microscopy and Golgi-Cox staining were performed to assess the effect of lentinan on cognitive deficits and neuropathology in vivo. In vitro, the direct and indirect effects of lentinan on the proliferation of T. gondii tachyzoites were evaluated in the absence and presence of BV-2 cells, respectively. RESULTS: Lentinan prevented T. gondii-induced cognitive deficits and altered the transcriptome profile of genes related to neuroinflammation, microglial activation, synaptic function, neural development and cognitive behavior in the hippocampus of infected mice. Moreover, lentinan reduced the infection-induced accumulation of microglia and downregulated the mRNA expression of proinflammatory cytokines. In addition, the neurite and synaptic ultrastructural damage in the hippocampal CA1 region due to infection was ameliorated by lentinan administration. Lentinan decreased the cyst burden in the brains of infected mice, which was correlated with behavioral performance. In line with this finding, lentinan could significantly inhibit the proliferation of T. gondii tachyzoites in the microglial cell line BV2, although lentinan had no direct inhibitory effect on parasite growth. CONCLUSIONS: Lentinan prevents cognitive deficits via the improvement of neurite impairment and synaptic loss induced by T. gondii infection, which may be associated with decreased cyst burden in the brain. Overall, our findings indicate that lentinan can ameliorate T. gondii-related neurodegenerative diseases.