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Theranostics 2022Colorectal cancer (CRC), mostly categorized as a low immunogenic microsatellite-stable phenotype bearing complex immunosuppressive tumor microenvironment (TME), is...
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. 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. 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. This study provides a promising self-assembled traditional Chinese nanomedicine to improve immunotherapy for CRC, which might be applicable for future clinical translation.
Topics: Carcinogens; China; Colorectal Neoplasms; Humans; Immunologic Factors; Immunotherapy; Lentinan; Nanomedicine; Oleanolic Acid; Tumor Microenvironment; Ursolic Acid
PubMed: 36168633
DOI: 10.7150/thno.72509 -
Scientific Reports Nov 2022Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of...
Gut microbiota dysbiosis is already a global problem after antibiotic overuse. This study was to investigate the therapeutic effect of lentinan and the mechanism of recovery of intestinal inflammation on broad-spectrum antibiotic-driven gut microbial dysbiosis in mice. Gut microbiota was elucidated by the Illumina MiSeq platform. Gas chromatography/mass spectrometry was used to investigate short-chain fatty acid content. Colon histology, expression of tight-junction associated proteins and pro-inflammatory cytokines levels were evaluated. The results showed that the gut microbiota of diversity and richness were reduced and various taxonomic levels of the gut microbiota were perturbed after antibiotics gavage. The abundance of Firmicutes and Bacteroidetes shifted to Proteobacteria and increased the relative abundance of harmful microbiota (Parabacteroides and Klebsiella) post-antibiotics, whereas lentinan administration reversed the dysbiosis and increased beneficial microbiota, including S24-7, Lactobacillus, Oscillospira, Ruminococcus and Allobaculum. The concentrations of propionic acid and butyric acid were significantly increased by treatment with lentinan. And lentinan improved colon tissue morphology and reduced pro-inflammatory cytokines via altering NF-κB signaling pathway in antibiotic-driven gut microbial dysbiosis mice. Taken together, the results proved that lentinan can be used as a prebiotic and the result provided a theoretical basis for improving the clinical treatment of broad-spectrum antibiotics side effects.
Topics: Mice; Animals; Dysbiosis; Lentinan; Anti-Bacterial Agents; Firmicutes; Bacteroidetes; Tight Junction Proteins; Cytokines; Inflammation; Mice, Inbred C57BL
PubMed: 36380080
DOI: 10.1038/s41598-022-23469-2 -
Pharmaceutics Dec 2022Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic...
Selenium nanoparticle (SeNP)-based nanotherapeutics have become an emerging cancer therapy, while effective drug delivery remains a technical hurdle. A theranostic approach, through which imaging companions are integrated with SeNPs, will allow image-guided drug delivery and, therefore, is highly desirable. Traditional methods require the chemical conjugation of imaging agents to the surface of nanoparticles, which may impede the later clinical translation. In this study, we developed a label-free strategy in which lentinan-functionalized SeNPs (LNT-SeNPs) are detected using MRI by the hydroxyl protons carried on LNT molecules. The in vitro phantom study showed that LNT and LNT-SeNPs have a strong CEST signal at 1.0 ppm apart from the water resonance, suggesting an in vivo detectability in the µM concentration range. Demonstrated on CT26 colon tumor cells, LNT-SeNPs exert a strong anticancer effect (IC50 = 4.8 μM), prominently attributed to the ability to generate intracellular reactive oxygen species. However, when testing in a mouse model of CT26 tumors, administration of LNT-SeNPs alone was found unable to deliver sufficient drugs to the tumor, leading to poor treatment responses. To improve the drug delivery, we co-injected LNT-SeNPs and TNF-α, a previously reported drug that could effectively damage the endothelial cells in the tumor vasculature, thereby increasing drug delivery to the tumor. Our results revealed a 75% increase in the intratumoral CEST MRI signal, indicating a markedly increased delivery efficiency of LNT-SeNPs when combined with TNF-α. The combination therapy also resulted in a significantly enhanced treatment outcome, as revealed by the tumor growth study. Taken together, our study demonstrates the first label-free, SeNP-based theranostic system, in which LNT was used for both functional surface coating and CEST MRI signal generating. Such a theranostic LNT-SeNP system is advantageous because it requires chemical labeling and, therefore, has high biocompatibility and low translatable barriers.
PubMed: 36678748
DOI: 10.3390/pharmaceutics15010120 -
Frontiers in Cellular and Infection... 2022Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has...
Influenza virus is a serious threat to global human health and public health security. There is an urgent need to develop new anti-influenza drugs. Lentinan (LNT) has attracted increasing attention in recent years. As potential protective agent, LNT has been shown to have anti-tumor, anti-inflammatory, and antiviral properties. However, there has been no further research into the anti-influenza action of lentinan , and the mechanism is still not fully understood. In this study, the anti-influenza effect and mechanism of Lentinan were studied in the Institute of Cancer Research (ICR) mouse model. The results showed that Lentinan had a high degree of protection in mice against infection with influenza A virus, delayed the emergence of clinical manifestations, improved the survival rate of mice, significantly prolonged the middle survival days, attenuated the weight loss, and reduced the lung coefficient of mice. It alleviated the pathological damage of mice infected with the influenza virus and improved blood indices. Lentinan treatment considerably inhibited inflammatory cytokine (TNF-α, IL-1β, IL-4, IL-5, IL-6) levels in the serum and lung and improved IFN-γ cytokine levels, which reduced cytokine storms caused by influenza virus infection. The underlying mechanisms of action involved Lentinan inhibiting the inflammatory response by regulating the TLR4/MyD88 signaling pathway. This study provides a foundation for the clinical application of Lentinan, and provides new insight into the development of novel immunomodulators.
Topics: Animals; Anti-Inflammatory Agents; Cytokines; Disease Models, Animal; Humans; Influenza, Human; Lentinan; Mice; Mice, Inbred ICR; Neoplasms; Orthomyxoviridae Infections
PubMed: 35669119
DOI: 10.3389/fcimb.2022.892864 -
Fungal Biology Apr 2016Despite the longstanding use of dried mushrooms and mushroom extracts in traditional Chinese medicine, there is no scientific evidence to support the effectiveness of... (Review)
Review
Despite the longstanding use of dried mushrooms and mushroom extracts in traditional Chinese medicine, there is no scientific evidence to support the effectiveness of these preparations in the treatment of human disease. Consumers should evaluate assertions made by companies about the miraculous properties of medicinal mushrooms very critically. The potential harm caused by these natural products is another important consideration. In a more positive vein, the presence of potent toxins and neurotropic compounds in basidiomycete fruit bodies suggests that secondary metabolites with useful pharmacological properties are widespread in these fungi. Major investment in controlled experiments and objective clinical trials is necessary to develop this natural pharmacopeia.
Topics: Agaricales; Biological Products; Humans
PubMed: 27020147
DOI: 10.1016/j.funbio.2016.01.006 -
Frontiers in Veterinary Science 2022The β-Glucans widely exist in plants and edible fungi, and their diverse bioactivities and good physicochemical properties have been widely reported. In addition,...
The β-Glucans widely exist in plants and edible fungi, and their diverse bioactivities and good physicochemical properties have been widely reported. In addition, β-glucan intravenous injections (such as lentinan and schizophyllan) have been clinically used as immunomodulators and antitumor polysaccharides. However, the pharmacokinetic studies of β-glucans only stay on the level of plasma concentration and biodistribution , and little is known about their metabolism and degradation , which severely limits the further application of β-glucans in the field of medicine and biomaterials. The aim of this paper is to explore the metabolism and degradation process of lentinan (as a representative of β-glucans) by labeling it with water-soluble fluorescein 5-([4, 6-Dichlorotriazin-2-yl]amino)fluorescein (DTAF). Fluorescently labeled lentinan (FLNT) was intravenously administered to rats at a single dose of 8 mg/kg. The degradation of LNT in blood, liver, kidney, and urine was evaluated by the gel permeation chromatography. Our results showed that although LNT could be degraded in blood, liver, kidney, and urine, there were still some prototypes until excreted in urine due to the incomplete degradation of LNT in each step. To the best of our knowledge, this is the first report to comprehensively study LNT metabolic degradation in rats. These results provide an important reference for further exploration and application of LNT and other β-glucans.
PubMed: 35720856
DOI: 10.3389/fvets.2022.889586 -
Anais Brasileiros de Dermatologia 2015Shiitake Dermatitis is a skin eruption that resembles whiplash marks and occurs after consumption of raw shiitake mushrooms. It is caused by a toxic reaction to...
Shiitake Dermatitis is a skin eruption that resembles whiplash marks and occurs after consumption of raw shiitake mushrooms. It is caused by a toxic reaction to lentinan, a thermolabil polysaccharide which decomposes upon heating. We report the second case of this dermatitis in Brazil. A 25-year-old man presented with linearly arranged erythematous, pruritic papules on the trunk and limbs, after ingestion of a salad containing raw shiitake mushrooms. The eruption was self-limited, resolving within 10 days of onset. The recognition of this entity gains importance due to the increased consumption of shiitake mushrooms in occidental countries.
Topics: Adult; Dermatitis; Erythema; Humans; Male; Mushroom Poisoning; Shiitake Mushrooms
PubMed: 25831007
DOI: 10.1590/abd1806-4841.20153396 -
Nutrients Jul 2021Exposure of individuals to radioactive material as a result of ingestion of contaminated food and water is an increasing public health concern. Unfortunately, there are...
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.
Topics: Cell Culture Techniques; Cesium; Chelating Agents; Cobalt; Curcumin; Dietary Exposure; Dietary Supplements; Elements, Radioactive; Food Contamination, Radioactive; Genistein; Humans; Lentinan; Plant Extracts; Quercetin; Strontium; Uranium
PubMed: 34444705
DOI: 10.3390/nu13082545 -
Cancer Immunology, Immunotherapy : CII Nov 2016Beta-glucans are large polysaccharides produced by a range of prokaryotic and eukaryotic organisms. They have potential immunostimulatory properties and have been used... (Review)
Review
Beta-glucans are large polysaccharides produced by a range of prokaryotic and eukaryotic organisms. They have potential immunostimulatory properties and have been used with therapeutic intent as anti-microbial and anti-tumour agents. A range of other potentially beneficial effects have been described, and oral forms of beta-glucans are widely available over-the-counter and online. Parenteral formulations are popular in parts of Asia and are the subject of ongoing trials, worldwide. Beta-glucans are also potential contaminants of pharmaceutical products, and high levels have been described in some blood products. However, little is known about the clinical effects of such contamination, considerable uncertainty exists over the level at which immunostimulation may occur, and there are no guidelines available on acceptable levels. We encountered beta-glucan contamination of one of our products, and we suspect that others may encounter similar issues since the origin of beta-glucan contamination includes commonly used filters and solutions applied in the manufacture of biotherapeutic agents. It is likely that regulators will increasingly enquire about beta-glucan levels in pharmaceutical products, especially those with an immunomodulatory mechanism of action. Here, we review the literature on beta-glucans in pharmaceutical products and propose an acceptable level for therapeutic agents for parenteral use.
Topics: Animals; Biosimilar Pharmaceuticals; Clinical Trials as Topic; Humans; Immunomodulation; Neoplasms; Pharmaceutical Preparations; Risk Assessment; Technology, Pharmaceutical; beta-Glucans
PubMed: 27473075
DOI: 10.1007/s00262-016-1875-9 -
Frontiers in Nutrition 2021The microbiota-gut-liver axis has emerged as an important player in developing nonalcoholic steatohepatitis (NASH), a type of nonalcoholic fatty liver disease (NAFLD)....
The microbiota-gut-liver axis has emerged as an important player in developing nonalcoholic steatohepatitis (NASH), a type of nonalcoholic fatty liver disease (NAFLD). Higher mushroom intake is negatively associated with the prevalence of NAFLD. This study examined whether lentinan, an active ingredient in mushrooms, could improve NAFLD and gut microbiota dysbiosis in NAFLD mice induced by a high-fat (HF) diet. Dietary lentinan supplementation for 15 weeks significantly improved gut microbiota dysbiosis in HF mice, evidenced by increased the abundance of phylum Actinobacteria and decreased phylum Proteobacteria and Epsilonbacteraeota. Moreover, lentinan improved intestinal barrier integrity and characterized by enhancing intestinal tight junction proteins, restoring intestinal redox balance, and reducing serum lipopolysaccharide (LPS). In the liver, lentinan attenuated HF diet-induced steatohepatitis, alteration of inflammation-insulin (NFκB-PTP1B-Akt-GSK3β) signaling molecules, and dysregulation of metabolism and immune response genes. Importantly, the antihepatic inflammation effects of lentinan were associated with improved gut microbiota dysbiosis in the treated animals, since the Spearman's correlation analysis showed that hepatic LPS-binding protein and receptor (Lbp and Tlr4) and pro- and antiinflammatory cytokine expression were significantly correlated with the abundance of gut microbiota of phylum Proteobacteria, Epsilonbacteraeota and Actinobacteria. Therefore, lentinan supplementation may be used to mitigate NAFLD by modulating the microbiota-gut-liver axis.
PubMed: 35127789
DOI: 10.3389/fnut.2021.803691