-
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 -
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 -
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 -
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 -
Food Chemistry Advances Oct 2022The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020, because of its widespread transmission and infection rates. The unique severe... (Review)
Review
The World Health Organization (WHO) declared COVID-19 as a pandemic on March 11, 2020, because of its widespread transmission and infection rates. The unique severe disease was found in Wuhan, China, since December 2019, and swiftly spread throughout the world. Natural chemicals derived from herbal medicines and medicinal mushrooms provide a significant resource for the development of novel antiviral drugs. Many natural drugs have been proven to have antiviral properties against a variety of virus strains, such as the coronavirus and the herpes simplex virus (HSV).. In this research, successful dietary treatments for different COVID illnesses were compared to potential of mushroom products in its therapy. In Google Scholar, Science Direct, PubMed, and Scopus, search keywords like COVID, COVID-19, SARS, MERS, mushrooms, and their compounds were utilized. In this review of the literature we foucsed popular mushrooms such as Peck Murill, (Berk.) Sacc. (Curtis.) P. Karst. (Dicks.) Gray (Bull.) Pers. (Arch. Ex Pers.) Pilát. (Berk.) Pegler (Jacq.) P. Kumm. F.A. Wolf, and (L.) Lloyd.,. Changed forms of β-Glucan seem to have a good impact on viral replication suppression and might be used in future studies. However, the results seems terpenoids, lectins, glycoproteins, lentinan, galactomannan, and polysaccharides from mushrooms are promising prophylactic or therapeutic agents against COVID-19.
PubMed: 36686330
DOI: 10.1016/j.focha.2022.100023 -
International Journal of Molecular... Nov 2023No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this... (Review)
Review
No matter what treatment is used after nerve transection, a complete cure is impossible, so basic and clinical research is underway to find a cure. As part of this research, autophagy is being investigated for its role in nerve regeneration. Here, we review the existing literature regarding the involvement and significance of autophagy in peripheral nerve injury and regeneration. A comprehensive literature review was conducted to assess the induction and role of autophagy in peripheral nerve injury and subsequent regeneration. Studies were included if they were prospective or retrospective investigations of autophagy and facial or peripheral nerves. Articles not mentioning autophagy or the facial or peripheral nerves, review articles, off-topic articles, and those not written in English were excluded. A total of 14 peripheral nerve studies that met these criteria, including 11 involving sciatic nerves, 2 involving facial nerves, and 1 involving the inferior alveolar nerve, were included in this review. Studies conducted on rats and mice have demonstrated activation of autophagy and expression of related factors in peripheral nerves with or without stimulation of autophagy-inducing factors such as rapamycin, curcumin, three-dimensional melatonin nerve scaffolds, CXCL12, resveratrol, nerve growth factor, lentinan, adipose-derived stem cells and melatonin, basic fibroblast growth factor, and epothilone B. Among the most studied of these factors in relation to degeneration and regeneration of facial and sciatic nerves are LC3II/I, PI3K, mTOR, Beclin-1, ATG3, ATG5, ATG7, ATG9, and ATG12. This analysis indicates that autophagy is involved in the process of nerve regeneration following facial and sciatic nerve damage. Inadequate autophagy induction or failure of autophagy responses can result in regeneration issues after peripheral nerve damage. Animal studies suggest that autophagy plays an important role in peripheral nerve degeneration and regeneration.
Topics: Rats; Mice; Animals; Peripheral Nerve Injuries; Melatonin; Prospective Studies; Retrospective Studies; Peripheral Nerves; Sciatic Nerve; Nerve Regeneration; Autophagy
PubMed: 38003409
DOI: 10.3390/ijms242216219 -
International Journal of Molecular... Aug 2023Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ... (Review)
Review
Sepsis is associated with high rates of mortality in the intensive care unit and accompanied by systemic inflammatory reactions, secondary infections, and multiple organ failure. Biological macromolecules are drugs produced using modern biotechnology to prevent or treat diseases. Indeed, antithrombin, antimicrobial peptides, interleukins, antibodies, nucleic acids, and lentinan have been used to prevent and treat sepsis. In vitro, biological macromolecules can significantly ameliorate the inflammatory response, apoptosis, and multiple organ failure caused by sepsis. Several biological macromolecules have entered clinical trials. This review summarizes the sources, efficacy, mechanism of action, and research progress of macromolecular drugs used in the prevention and treatment of sepsis.
Topics: Humans; Multiple Organ Failure; Sepsis; Antibodies; Anticoagulants; Antimicrobial Peptides; Macromolecular Substances
PubMed: 37629199
DOI: 10.3390/ijms241613017 -
Journal of Leukocyte Biology Aug 2020A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the... (Review)
Review
A wealth of evidence supports the role of tumor immunotherapy as a vital therapeutic option in cancer. In recent decades, accumulated studies have revealed the anticancer activities of natural products and their derivatives. Increasing interest has been driven toward finding novel potential modulators of tumor immunotherapy from natural products, a hot research topic worldwide. These works of research mainly focused on natural products, including polyphenols (e.g., curcumin, resveratrol), cardiotonic steroids (e.g., bufalin and digoxin), terpenoids (e.g., paclitaxel and artemisinins), and polysaccharide extracts (e.g., lentinan). Compelling data highlight that natural products have a promising future in tumor immunotherapy. Considering the importance and significance of this topic, we initially discussed the integrated research progress of natural products and their derivatives, including target T cells, macrophages, B cells, NKs, regulatory T cells, myeloid-derived suppressor cells, inflammatory cytokines and chemokines, immunogenic cell death, and immune checkpoints. Furthermore, these natural compounds inactivate several key pathways, including NF-κB, PI3K/Akt, MAPK, and JAK/STAT pathways. Here, we performed a deep generalization, analysis, and summarization of the previous achievements, recent progress, and the bottlenecks in the development of natural products as tumor immunotherapy. We expect this review to provide some insight for guiding future research.
Topics: Animals; Antineoplastic Agents, Phytogenic; Biological Products; Humans; Immunologic Factors; Immunomodulation; Immunotherapy; Neoplasms; Treatment Outcome
PubMed: 32678943
DOI: 10.1002/JLB.3MR0320-444R -
3 Biotech Dec 2019Diabetes and obesity are the most frequently found disease worldwide. Several factors are responsible for obesity, i.e., imbalance in energy expenditure, environmental... (Review)
Review
Diabetes and obesity are the most frequently found disease worldwide. Several factors are responsible for obesity, i.e., imbalance in energy expenditure, environmental factors, feeding habit, lifestyle, etc., which can also be responsible for type 2 diabetes mellitus. There are several synthetic drugs available to combat these diseases which have some side effects on sufferers. Therefore, people are shifting towards inexpensive, effective, widely available natural and herbal medicines. Edible mushrooms, which have been used from ancient time to cure these diseases, contain anti-oxidant, fibers, triterpenoids, alkaloid, and other phytochemicals. Comatin, β-glucan, Tremellastin, and Lentinan KS-2 are active chemicals of mushrooms which show great effect on diabetes mellitus and obesity by modulating either cellular function or biochemical pathways. Here, in this review, we have discussed the potential role of edible mushrooms and its biochemicals in control of diabetes and obesity. Using Bioinformatics, we can find the specific targets of theses biochemicals, so that these can be more effective.
PubMed: 31832297
DOI: 10.1007/s13205-019-1982-3