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1.
Chem Biol Drug Des ; 103(3): e14507, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38538070

RESUMO

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/patologia
2.
Eur J Med Res ; 29(1): 8, 2024 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-38172925

RESUMO

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 , Prognóstico
3.
Phytomedicine ; 123: 155242, 2024 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-38100922

RESUMO

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 ∼ 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 ∼ 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 Tratamento
4.
Parasit Vectors ; 16(1): 454, 2023 Dec 13.
Artigo em Inglês | MEDLINE | ID: mdl-38093309

RESUMO

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.


Assuntos
Doenças Neurodegenerativas , Toxoplasma , Toxoplasmose , Animais , Camundongos , Lentinano/metabolismo , Lentinano/farmacologia , Toxoplasmose/metabolismo , Encéfalo/patologia , Toxoplasma/genética , Doenças Neurodegenerativas/patologia , Cognição
5.
Anal Chim Acta ; 1278: 341752, 2023 Oct 16.
Artigo em Inglês | MEDLINE | ID: mdl-37709478

RESUMO

BACKGROUND: Lentinan medicament from Lentinus edodes has been considered as natural medicinal products with minimal side effects for cancer therapy, but Lentinus edodes are easily polluted by nonbiodegradable heavy metals, especially silver ion (Ag+). Therefore, it is highly desirable to monitor Ag + pollution in Lentinus edodes considering their adverse impact on lentinan medicament. Electrochemical sensor isn't affected from the interference of matrix turbidity and color, and offers a powerful means for determination of variant analytes. As for electrochemical sensing toward Ag+, there is a great need to design efficient signal probes for specific recognition and signal generation. RESULTS: We present an appropriate electrochemical aptasensor for Ag + assay based on biomimetic catalysis of porphyrin-encapsulated MOF (PorMOF) and allosteric switch of C-rich DNA. Thanks to the excellent biocompatibility, PorMOFs as nanozyme are used to design signal probes by loading duplex-like DNA scaffold. Owing to the specific recognition of Ag+ toward cytosine (C) base-rich DNA, PorMOF at the distal end was close to the underlying electrode via C-Ag+-C formation, leading to an enhanced current of catalytic hydroxylamine oxidation for signal generation. Using the positive correlation between current response and Ag+ level, the electrochemical system provides a promising means for on-line monitoring of Ag+ in Lentinus edodes with recoveries from 92.8% to 106.4% and relative standard deviation from 3.98% to 8.24%, verifying the applicability of the electrochemical aptasensor toward Ag+ in Lentinus edodes. SIGNIFICANCE AND NOVELTY: With merits of portability, simple operation, and rapid response, the electrochemical pattern offers a useful solution for on-line monitoring of Ag+ in Lentinus edodes. By altering the DNA sequence, the proposed aptasensor provides a powerful way for monitoring other heavy metals, capable of protecting medicament production from heavy metal pollution.


Assuntos
Produtos Biológicos , Estruturas Metalorgânicas , Metais Pesados , Cogumelos Shiitake , Lentinano , Prata
6.
Oncol Rep ; 50(1)2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37264970

RESUMO

Lentinan (LNT) isolated from Lentinus edodes is a vital host defense potentiator previously utilized as an adjuvant in cancer therapy. The present study investigated the effect of LNT on the mouse hepatocellular carcinoma (HCC) cell line Hepa1­6 and its possible mechanism. Mouse HCC apoptosis and its potential associated mechanism were then explored using in vitro and in vivo approaches. For in vitro approaches, the effect of LNT on the proliferation of Hepa1­6 cells was investigated by Cell Counting Kit­8 assay. Annexin V­FITC staining and flow cytometry were applied to explore HCC apoptosis. Western blotting was used to analyze related proteins, such as EGR1, phosphatase and tensin homolog (PTEN), phosphorylated protein kinase B (p­Akt), protein kinase B (Akt), B lymphocyte­2 (Bcl­2), Bcl2 family­associated X protein (Bax), etc. Cellular immunofluorescence staining was employed to assess the localization and expression of EGR1 and PTEN in nuclear and cytoplasmic fractions of Hepa1­6 cells. The association between EGR1 and PTEN was explored by EGR1 overexpression in cell lines. For in vivo methods, a mouse model of diethylnitrosamine (DEN)­induced primary liver cancer was established using C57BL/6 mice to investigate the inhibitory effect of LNT on liver cancer. Histopathology of liver tissue from mice was detected by hematoxylin­eosin staining and immunohistochemical assay. In vitro and in vivo results showed that LNT can inhibit the proliferation and promote the apoptosis of mouse HCC cells. Besides, LNT increased the expression of EGR1 in Hepa1­6 cells, which is translocated to the nucleus to function as a transcriptional factor. EGR1 then activates the expression of the tumor suppressor PTEN, thereby inhibiting the activation of the AKT signaling pathway. These data revealed a novel anti­tumor mechanism by which LNT can induce apoptosis to inhibit mouse HCC progression through the EGR1/PTEN/AKT axis. These results provide a scientific basis for the potential use of LNT in drug development and clinical applications associated with primary liver cancer.


Assuntos
Carcinoma Hepatocelular , Neoplasias Hepáticas , Camundongos , Animais , Proteínas Proto-Oncogênicas c-akt/metabolismo , Carcinoma Hepatocelular/tratamento farmacológico , Carcinoma Hepatocelular/genética , Carcinoma Hepatocelular/metabolismo , Lentinano/farmacologia , Neoplasias Hepáticas/tratamento farmacológico , Neoplasias Hepáticas/genética , Neoplasias Hepáticas/metabolismo , Linhagem Celular Tumoral , Camundongos Endogâmicos C57BL , Camundongos Endogâmicos , Transdução de Sinais , Apoptose , PTEN Fosfo-Hidrolase/genética , PTEN Fosfo-Hidrolase/metabolismo , Proliferação de Células , Proteína 1 de Resposta de Crescimento Precoce/genética , Proteína 1 de Resposta de Crescimento Precoce/metabolismo
7.
J Mater Chem B ; 11(20): 4475-4484, 2023 05 24.
Artigo em Inglês | MEDLINE | ID: mdl-37159051

RESUMO

Immunotherapies are a promising new class of anticancer treatments, but the immunosuppressive tumor microenvironment (TME) hinders their broader implementation. Here, we designed a '3C' strategy based on the conventional drug lentinan (LNT), applying the convertible material polylactic acid with controlled release of LNT (LNT@Mic). Our findings revealed that LNT@Mic exhibited effective biocompatibility coupled with controlled long-term release of LNT. Due to these characteristics, LNT@Mic reprogramed the immunosuppressive TME and demonstrated substantial antitumor activity in the MC38 tumor model. Furthermore, it served as a facile and generalizable cancer immunotherapy strategy for augmenting LNT bioavailability while enhancing the efficacy of anti-programmed death-ligand 1 therapy against the 'cold' 4T1 tumor model. These findings provide a reference for tumor immunotherapy strategies for the further study and application of LNT.


Assuntos
Lentinano , Neoplasias , Humanos , Lentinano/farmacologia , Lentinano/uso terapêutico , Microesferas , Microambiente Tumoral , Imunossupressores , Neoplasias/tratamento farmacológico
8.
Int J Biol Macromol ; 242(Pt 1): 124686, 2023 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-37146850

RESUMO

Environmental issues caused by plastic packaging materials have gotten increasingly severe, and substantial research has been conducted on environmentally friendly active packaging materials. In this study, the Litsea cubeba essential oil loaded soy protein isolate nanoparticles (LSNPs) with appropriate particle size, high storage stability and salt solution stability were fabricated. The LSNPs with the highest encapsulation efficiency of 81.76 % were added into the lentinan edible film. The microstructures of the films were observed by scanning electron microscopy. The physical properties of the films were measured. The results show that the lentinan film with LSNPs in the volume ratio of 4:1 (LF-4) had the highest elongation at break of 196 %, the lowest oxygen permeability of 12 meq/kg, and good tensile strength, water vapor barrier property, antibacterial property, oxidation resistance and thermal stability. The study suggested that LF-4 film could inhibit the growth of bacteria and delay the oxidation of lipid and protein on beef surface for 7 d.


Assuntos
Filmes Comestíveis , Litsea , Óleos Voláteis , Óleos Voláteis/farmacologia , Óleos Voláteis/química , Proteínas de Soja/química , Lentinano , Embalagem de Alimentos/métodos , Resistência à Tração , Permeabilidade
9.
Nutr Diabetes ; 13(1): 4, 2023 04 08.
Artigo em Inglês | MEDLINE | ID: mdl-37031163

RESUMO

BACKGROUND: Lentinan (LNT) is a complex fungal component that possesses effective antitumor and immunostimulating properties. However, there is a paucity of studies regarding the effects and mechanisms of LNT on type 1 diabetes. OBJECTIVE: In the current study, we investigated whether an intraperitoneal injection of LNT can diminish the risk of developing type 1 diabetes (T1D) in non-obese diabetic (NOD) mice and further examined possible mechanisms of LNT's effects. METHODS: Pre-diabetic female NOD mice 8 weeks of age, NOD mice with 140-160 mg/dL, 200-230 mg/dL or 350-450 mg/dL blood glucose levels were randomly divided into two groups and intraperitoneally injected with 5 mg/kg LNT or PBS every other day. Then, blood sugar levels, pancreas slices, spleen, PnLN and pancreas cells from treatment mice were examined. RESULTS: Our results demonstrated that low-dosage injections (5 mg/kg) of LNT significantly suppressed immunopathology in mice with autoimmune diabetes but increased the Foxp3+ regulatory T cells (Treg cells) proportion in mice. LNT treatment induced the production of Tregs in the spleen and PnLN cells of NOD mice in vitro. Furthermore, the adoptive transfer of Treg cells extracted from LNT-treated NOD mice confirmed that LNT induced Treg function in vivo and revealed an enhanced suppressive capacity as compared to the Tregs isolated from the control group. CONCLUSION: LNT was capable of stimulating the production of Treg cells from naive CD4 + T cells, which implies that LNT exhibits therapeutic values as a tolerogenic adjuvant and may be used to reverse hyperglycaemia in the early and late stages of T1D.


Assuntos
Diabetes Mellitus Tipo 1 , Lentinano , Estado Pré-Diabético , Linfócitos T Reguladores , Animais , Feminino , Camundongos , Diabetes Mellitus Experimental/imunologia , Diabetes Mellitus Experimental/prevenção & controle , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/imunologia , Diabetes Mellitus Tipo 1/prevenção & controle , Injeções Intraperitoneais , Lentinano/administração & dosagem , Lentinano/imunologia , Lentinano/farmacologia , Lentinano/uso terapêutico , Camundongos Endogâmicos NOD , Estado Pré-Diabético/tratamento farmacológico , Estado Pré-Diabético/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia
10.
J Control Release ; 356: 316-336, 2023 04.
Artigo em Inglês | MEDLINE | ID: mdl-36863692

RESUMO

Recently, lentinan (LNT) has been utilized for its diversified potential in research with an extended role from nutritional or medicinal applications to a novel biomaterial. LNT is a biocompatible, multifunctional polysaccharide employed as a pharmaceutical additive in engineering customized drug or gene carriers with an improved safety profile. Its triple helical structure containing hydrogen bonding offers more extraordinary binding sites for the attachments of dectin-1 receptors and polynucleotide sequences (poly(dA)). Hence, the diseases expressing dectin-1 receptors can be specifically targeted through so-designed LNT-engineered drug carriers. Gene delivery using poly(dA)-s-LNT complexes and composites has exhibited greater targetability and specificity. The achievement of such gene applications is assessed through the pH and redox potential of the extracellular cell membrane. The steric hindrance-acquiring behavior of LNT shows promise as a system stabilizer in drug carrier engineering. LNT shows viscoelastic gelling behavior temperature-dependently and therefore needs to explore more to meet topical disease applications. The immunomodulatory and vaccine adjuvant properties of LNT help in mitigating viral infections too. This review highlights the new role of LNT as a novel biomaterial, particularly in drug delivery and gene delivery applications. In addition, its importance in achieving various biomedical applications is also discussed.


Assuntos
Técnicas de Transferência de Genes , Lentinano , Lentinano/química , Terapia Genética , Portadores de Fármacos
11.
Eur J Pharmacol ; 946: 175631, 2023 May 05.
Artigo em Inglês | MEDLINE | ID: mdl-36863554

RESUMO

Oral administration of lentinan ameliorated dextran sulfate sodium (DSS)-induced colitis through Dectin-1 receptor on intestinal epithelial cells. However, it is unclear where lentinan affects in the intestine to prevent the inflammation. We found that the administration of lentinan has induced migration of CD4+ cells from the ileum to the colon by using Kikume Green-Red (KikGR) mice in this study. This result suggests that the oral lentinan treatment could accelerate the migration of Th cells in lymphocyte from ileum into the colon during lentinan intake. Then, C57BL/6 mice were administered 2% DSS to induce colitis. The mice were administered lentinan daily via oral or rectal route before DSS administration. Its rectal administration also suppressed DSS-induced colitis, but its suppressive effects were lower compared to when orally administered, indicating that the biological responses to lentinan in the small intestine contributed to the anti-inflammatory effects. In normal mice (without DSS treatment), the expression of Il12b was significantly increased in the ileum by the oral administration of lentinan, but not by rectal one. On the other hand, no change was observed in the colon by either administration method. In addition, Tbx21 was significantly increased in the ileum. These suggested that IL-12 was increased in the ileum and Th1 cells differentiated in dependence on it. Therefore, Th1 predominant condition in the ileum could influence immunity in the colon and improve the colitis.


Assuntos
Colite , Lentinano , Animais , Camundongos , Administração Oral , Colite/induzido quimicamente , Colite/tratamento farmacológico , Colo , Sulfato de Dextrana/efeitos adversos , Modelos Animais de Doenças , Íleo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lentinano/administração & dosagem , Lentinano/efeitos adversos , Camundongos Endogâmicos C57BL , Células Th1 , Antineoplásicos/administração & dosagem , Antineoplásicos/efeitos adversos
12.
Pol J Pathol ; 74(2): 136-140, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-36106424

RESUMO

AIM OF THE STUDY: Aim of the study is To investigate the effect of lentinan on proliferation and apoptosis of human astrocytoma U251 cells. Lentinan was dissolved in DMEM complete medium to form different concentrations (0, 25, 50, 100, 200, 400, 500, 600 µg/ml). CCK8 was used to detect the effect of lentinan with different concentrations on proliferation of human astrocytoma U251 cells, and the expression of Ki-67 was detected by immunofluorescence. In addition, the effect of different concentrations of lentinan on apoptosis of human astrocytoma U251 cells was detected by flow cytometry. Compared with the blank control group, 50 and 100 µg/ml lentinan significantly promoted proliferation of human astrocytoma U251 cells. When the concentration is more than 100 µg/ml, the cell activity gradually decreases, and the cell activity is the lowest when the concentration is 600 µg/ml. In addition, the low concentration lentinan (25, 50, and 100 µg/ml) had no significant effect on apoptosis of human astrocytoma U251 cells. However, lentinan above 200 µg/ml significantly promoted apoptosis of human astrocytoma U251 cells and had a concentration gradient effect, and the highest apoptosis rate was at 600 µg/ml. CONCLUSIONS: Lentinan can effectively inhibit proliferation and promote apoptosis of human astrocytoma U251 cells.


Assuntos
Astrocitoma , Lentinano , Humanos , Lentinano/farmacologia , Linhagem Celular Tumoral , Proliferação de Células , Apoptose
13.
Molecules ; 27(21)2022 Nov 02.
Artigo em Inglês | MEDLINE | ID: mdl-36364302

RESUMO

The papaya industry is mainly impacted by viral diseases, especially papaya ringspot disease (PRSD) caused by papaya ringspot virus (PRSV). So far, research on the interaction between Chitosan, Lentinan and Ningnanmycin on PRSD has not been reported. This research studied the controlled and interactive effect of three biological agents, namely, Chitosan (C), Lentinan (L) and Ningnanmycin (N), on PRSV in papaya, individually and collectively. The changes in disease index, controlled effect, Peroxidase (POD), Polyphenol oxidase (PPO), Superoxide dismutase (SOD), growth and development of plants were observed at the seedling stage, in pots, and at the fruiting stage, in the field. The appearance and nutrient contents of fruits were measured during the fruit stage. The disease index of PRSV, at seedling and fruiting stages, was significantly lower for chitosan, lentinan and ningnanmycin and their interactive effect, compared to a control check treatment. The activity of the defense enzymes could be improved by the three kinds of biological agents and their interactive effect, especially lentinan and ningnanmycin. The chlorophyll content, plant height, stem diameter and fruit quality rose significantly under chitosan, lentinan and ningnanmycin treatments. The interaction of LN could inhibit PRSV disease at the seedling and fruiting stages of papaya, and promote the growth of plants and the quality of fruit at the fruit stage. Hence, this study provides the theoretical foundation for the biological control of papaya ringspot disease.


Assuntos
Carica , Quitosana , Lentinano , Quitosana/farmacologia , Fatores Biológicos , Doenças das Plantas , Alérgenos , Verduras
14.
Int J Biol Macromol ; 222(Pt B): 2375-2391, 2022 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-36243161

RESUMO

Lentinan (LNT) has been reported to have a wide range of functions, including anti-inflammatory, antioxidant and anticancer properties. LNT may provide a protective effect in dairy cow mastitis. In this study, we investigated the effect of LNT on lipopolysaccharide (LPS)-induced injury of bovine mammary epithelial cells (BMECs) and the possible mechanism. First, we treated BMECs with different concentrations of LPS to study the effects of LPS on oxidative stress and inflammation in BMECs. Then, we examined the effects of LNT by dividing the cells into seven groups: the control group (CON), LPS treatment group (LPS), Acetyl-l-cysteine (NAC) pretreatment group (NAC + LPS), LNT pretreatment group (LNT + LPS), ML385 and LNT pretreatment group (ML385 + LNT + LPS), LNT treatment group (LNT) and NAC treatment group (NAC). The results showed that LPS-triggered intracellular ROS production and the downregulation of Nrf-2 and HO-1 in BMECs were blocked by LNT pretreatment. LNT inhibited the expression of inflammatory genes and proteins by inhibiting of NF-κB and MAPK. In addition, LNT attenuated LPS induced-apoptosis in BMECs. However, ML385 reversed the protective effect of LNT. Taken together, LNT can be used as a natural protective agent against LPS-triggered BMECs damage through its anti-inflammatory, antioxidant and antiapoptotic effects through modulation of the Nrf2 pathway.


Assuntos
Células Epiteliais , Lentinano , Fator 2 Relacionado a NF-E2 , Animais , Bovinos , Feminino , Anti-Inflamatórios/farmacologia , Antioxidantes/farmacologia , Apoptose , Células Epiteliais/efeitos dos fármacos , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Lentinano/farmacologia , Lipopolissacarídeos , Fator 2 Relacionado a NF-E2/metabolismo , NF-kappa B/metabolismo , Estresse Oxidativo , Transdução de Sinais , Glândulas Mamárias Animais/citologia
15.
Theranostics ; 12(14): 6088-6105, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36168633

RESUMO

Colorectal cancer (CRC), mostly categorized as a low immunogenic microsatellite-stable phenotype bearing complex immunosuppressive tumor microenvironment (TME), is highly resistant to immunotherapy. Seeking safe and efficient alternatives aimed at modulating tumor immunosuppressive TME to improve outcome of CRC is highly anticipated yet remains challenging. Methods: Enlightened from the drug complementary art in traditional Chinese medicine, we designed a self-assembled nanomedicine (termed LNT-UA) by the natural active ingredients of ursolic acid (UA) and lentinan (LNT) through a simple nano-precipitation method, without any extra carriers, for CRC immunotherapy. Results: UA induces immunogenic cell death (ICD), while LNT further promotes dendritic cell (DC) maturation and repolarizes tumor-associated macrophage (TAM) from a protumorigenic M2 to an antitumor M1 phenotype. Co-delivery of UA and LNT by LNT-UA effectively reshapes the immunosuppressive TME and mobilizes innate and adaptive immunity to inhibit tumor progression in the CT26 CRC tumor model. Following the principle of integrative theoretical system of traditional Chinese medicine (TCM) on overall regulation, the further combination of LNT-UA and anti-CD47 antibody (αCD47) would reinforce the antitumor immunity by promoting phagocytosis of dying tumor cells and tumor-associated antigens (TAAs), leading to effective suppression of both primary and distant tumor growth with 2.2-fold longer of median survival time in the bilateral tumor model. Most notably, this combination effect is also observed in the spontaneous CRC model induced by chemical carcinogens, with much less and smaller size of tumor nodules after sequential administration of LNT-UA and αCD47 through gavage and intraperitoneal injection, respectively. Conclusions: This study provides a promising self-assembled traditional Chinese nanomedicine to improve immunotherapy for CRC, which might be applicable for future clinical translation.


Assuntos
Neoplasias Colorretais , Microambiente Tumoral , Carcinógenos/farmacologia , China , Neoplasias Colorretais/genética , Humanos , Fatores Imunológicos/farmacologia , Imunoterapia/métodos , Lentinano/farmacologia , Nanomedicina , Ácido Oleanólico/análogos & derivados , Ácido Ursólico
16.
BMC Cancer ; 22(1): 918, 2022 Aug 25.
Artigo em Inglês | MEDLINE | ID: mdl-36008793

RESUMO

BACKGROUND: Selective activation of Delta-like 1 (DLL1)-Notch signaling is a new approach to activate CD8+ T cell and suppress tumor growth, while the efficacy remains modest. Lentinan (LNT) is a clinically used immunomodulation agent. Thus, we hypothesized that LNT could improve the efficacy of DLL1. METHODS: The effects of LNT combined with DLL1 on tumor growth were evaluated by growth curve and tumor weight in EO771 breast and LAP0297 lung tumor models. The impacts on immune cells and gene expression in tumor tissues were determined by flow cytometry, qPCR. Neutrophil depletion was used to investigate the mechanism of the combination therapy on tumor growth. The data sets were compared using unpaired student's t-test or ordinary one-way ANOVA. RESULTS:  LNT treatments additively improved the antitumor effects of DLL1 in EO771 breast tumor growth. Remarkably, LNT treatments synergistically enhanced the suppression of DLL1 on LAP0297 lung tumor growth, resulting in tumor regression. Mechanically, the combination of LNT and DLL1 interventions not only promoted the accumulation and activation of CD8+ T cells, but also increased intratumoral CD45+CD11b+Ly6G+ neutrophils. Reduced neutrophils by anti-Gr1 antibody administrations reversed the improved antitumor effects by LNT treatments in LAP0297 lung tumor. These results suggest that LNT treatments improve the inhibition of DLL1 on tumor growth via neutrophils. CONCLUSIONS: Our findings indicates that LNT and DLL1 may induce synergistical antitumor immunity via simultaneous modulating lymphoid and myeloid cell populations regardless of the type of tumor, providing a potential new strategy to potentiate cancer immunotherapy.


Assuntos
Neoplasias da Mama , Neoplasias Pulmonares , Neoplasias da Mama/tratamento farmacológico , Linfócitos T CD8-Positivos , Feminino , Humanos , Lentinano/farmacologia , Lentinano/uso terapêutico , Neoplasias Pulmonares/tratamento farmacológico , Neutrófilos
17.
Int J Biol Macromol ; 216: 779-788, 2022 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-35902021

RESUMO

The development of nanozymes with enhanced catalytic activity has been drawing great interest. Lentinan with special structure may be used to prepare bimetallic nanomaterials to enhance their catalytic activity. Herein, lentinan stabilized PdPt3 dendritic nanoparticles (PdPt3-LNT NDs) were prepared through reduction of Na2PdCl4 and K2PtCl4 with a molar ratio of 1:3 using lentinan as a biological template. PdPt3-LNT NDs had dendritic shape with size of 10.76 ± 1.82 nm. PdPt3-LNT NDs had the hydrodynamic size about 25.7 nm and the zeta potential between -1.4 mV and - 4.9 mV at different pH. Furthermore, PdPt3-LNT NDs catalyzed 3,3',5,5'-tetramethylbenzidine (TMB) to produce oxidized TMB, suggesting their oxidase-like property. The catalytic activity of PdPt3-LNT NDs was the highest when pH was 4 and the temperature was 40 °C. The catalytic mechanism was the generation of reactive oxygen species- from O2 catalyzed by PdPt3-LNT NDs. More importantly, L-cysteine detection method was set up based on the oxidase-like property of PdPt3-LNT NDs. This method had wide linear range for 0-200 µM and low detection limit for 3.099 µM. Taken together, PdPt3-LNT NDs have good potential applications in bio-related detection in the future.


Assuntos
Lentinano , Nanopartículas , Cisteína , Lentinano/química , Oxirredutases , Espécies Reativas de Oxigênio
19.
Front Immunol ; 13: 920065, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35812417

RESUMO

The effects of crude lentinan (CLNT) on the intestinal microbiota and the immune barrier were evaluated in rainbow trout (Oncorhynchus mykiss) infected by infectious hematopoietic necrosis virus (IHNV). The results showed that supplementary CLNT declined the rainbow trout mortality caused by IHNV, which suggested that CLNT has preventive effects on IHNV infection. IHNV destroyed intestinal integrity, as well as caused the intestinal oxidative and damage in rainbow trout. Supplementary CLNT significantly strengthened the intestinal immune barrier by declining intestinal permeability, as well as enhancing intestinal antioxidant and anti-inflammatory abilities in IHNV-infected rainbow trout (P<0.05). In addition, CLNT modified the aberrant changes of intestinal microbiota induced by IHNV, mainly represented by promoting the growths of Carnobacterium and Deefgea and inhibiting Mycobacterium and Nannocystis. Especially, supplementing with CLNT significantly promoted the growth of short-chain fatty acid-producing bacteria (P<0.05) and consequently increased the production of acetic acid, butanoic acid, and hexanoic acid in the intestine of IHNV-infected rainbow trout. Furthermore, it was speculated that CLNT could regulate the self-serving metabolic pathways of intestinal microbiota induced by IHNV, such as fatty acid metabolism and amino acid metabolism. Together, CLNT played the antiviral effects on IHNV infection through strengthening the intestinal immune barrier, as well as regulating intestinal microbiota and SCFA metabolism in rainbow trout. The present data revealed that CLNT exerted a promising prebiotic role in preventing the rainbow trout from IHNV infection.


Assuntos
Doenças dos Peixes , Microbioma Gastrointestinal , Vírus da Necrose Hematopoética Infecciosa , Oncorhynchus mykiss , Infecções por Rhabdoviridae , Animais , Suplementos Nutricionais , Lentinano
20.
Comput Math Methods Med ; 2022: 2296574, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-35844448

RESUMO

Objective: The focus of this research was to look at the effects of the combination of the lentinan (LNT) and oxaliplatin (Oxa) on the apoptosis of human esophageal cancer cells, as well as the underlying mechanism. Methods: LNT and Oxa were used to treat EC-109 human esophageal cancerous cells at various doses, and the cell survival rate was measured using the Cell Counting Kit-8 (CCK-8) assay. In addition, 24 h after treatment of EC-109 cells with a combination of LNT and Oxa, flow cytometry was used to analyze their apoptotic effect on these cells. Additionally, LNT on EC-109 cell apoptotic upshot was assessed via measuring the consequence of LNT on the mRNA and protein expression levels pertaining to immunogenic cell death factors CALR, HSP90, and HSP70 by qPCR (quantitative real-time polymerase chain reaction) and western blot analysis, correspondingly. Results: Cell proliferation was inhibited only when EC-109 cells were added with LNT at 1,200 µg/mL to the maximum concentrations, but the combination of LNT and Oxa at a low dose (800 µg/mL and 20 µM, respectively) significantly increased their sensitivity to Oxa and reduced their proliferation (P < 0.05), and their apoptosis was significantly increased by LNT (P < 0.05). The immunogenic cell death-related genes CALR, HSP90, and HSP70 had dramatically enhanced mRNA and protein expression levels after therapy with a combination of LNT and Oxa (P < 0.05). Conclusion: These data imply that LNT increases the susceptibility of esophageal cancerous cells to Oxa by driving EC-109 cells to display immunogenic death. Therefore, LNT combined with Oxa may be an effective method in esophageal cancer management.


Assuntos
Neoplasias Esofágicas , Lentinano , Neoplasias Esofágicas/tratamento farmacológico , Neoplasias Esofágicas/genética , Humanos , Morte Celular Imunogênica , Lentinano/farmacologia , Lentinano/uso terapêutico , Oxaliplatina/farmacologia , RNA Mensageiro/genética
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