Tumor immune escape presents a significant challenge in cancer treatment, characterized by the upregulation of immune inhibitory molecules and dysfunction of immune cells. Tumor immunotherapy seeks to restore normal anti-tumor immune responses to control and eliminate tumors effectively. The active ingredients of traditional Chinese medicine (TCM) demonstrate a variety of anti-tumor activities and mechanisms, including the modulation of immune cell functions and inhibiting tumor-related suppressive factors, thereby potentially enhancing anti-tumor immune responses. Furthermore, nano-delivery systems function as efficient carriers to enhance the bioavailability and targeted delivery of TCM active ingredients, augmenting therapeutic efficacy. This review comprehensively analyzes the impact of TCM active ingredients on the immune system and explores the synergistic application of nano-delivery systems in combination with TCM active ingredients for enhancing tumor immunotherapy.

m6A methylation modification is an important genetic modification involved in biological processes such as sexual maturation, antibacterial, and antiviral in aquatic animals. However, few studies have been conducted in aquatic animals on the relationship between m6A methylation modification and autophagy-inflammation induced by lipid metabolism disorders. In the present study, a high-fat (HF) group and HF-MLP group (1 g mulberry leaf polysaccharides (MLPs)/1 kg HF diet) were set up. The mid-hind intestines of Megalobrama amblycephala juveniles from the two groups were collected for MeRIP-seq and RNA-seq after an 8-week feeding trial. The m6A peaks in the HF and HF-MLP groups were mainly enriched in the 3' Untranslated Region (3'UTR), Stop codon, and coding sequence (CDS) region. Compared with the HF group, the m6A peaks in the HF-MLP group were shifted toward the 5'UTR region. 'RRACH' was the common m6A methylation motif in the HF and HF-MLP groups. Methyltransferase mettl14 and wtap expression in the intestines of the HF-MLP group were significantly higher compared with the HF group (p < 0.05). A total of 21 differentially expressed genes(DEGs) with different peaks were screened by the combined MeRIP-seq and RNA-seq analysis. Kyoto encyclopedia of genes and genomes (KEGG) enrichment analysis enriched BCL2 interacting protein 3 (bnip3) to autophagy-animal and mitophagy-animal signaling pathways, etc., and nucleotide-binding domain leucine-rich repeat protein 1 (nlrp1) was enriched to the Nucleotide-binding oligomerization domain (NOD)-like receptor signaling pathway. Combined MeRIP-seq and RNA-seq analysis indicated that the expression pattern of bnip3 was hyper-up and that of nlrp1 was hyper-down. Gene Set Enrichment Analysis (GSEA) analysis confirmed that the intestinal genes of HF-MLP group positively regulate lysosomal and autophagy-animal signaling pathways. In the present study, we demonstrated that m6A methylation modification plays a role in regulating autophagy-inflammatory responses induced by HF diets by MLPs, and further explored the molecular mechanisms by which MLPs work from the epigenetic perspective.

Ganoderma lucidum (G. lucidum) has been widely used as adjuvant of anti-tumor therapy for variety tumors. The bioactive ingredients of G. lucidum mainly include triterpenes, such as Ganoderic acid A, Ganoderic acid B, Ganoderenic acid A, Ganoderenic acid B, Ganoderenic acid D, and Ganoderic acid X. However, the effects and underlying mechanisms of G. lucidum are often challenging in hepatocellular carcinoma (HCC) treatment.

To explore the potential role and mechanism of enhancer-associated lncRNAs (en-lncRNAs) in G. lucidum treated HCC through the in vivo and in vitro experiments.

Hepa1-6-bearing C57 BL/6 mice model were established to evaluate the therapeutic efficacy of G. lucidum treated HCC. Ki67 and TUNEL staining were used to detect the tumor cell proliferation and apoptosis in vivo. The Mouse lncRNA 4*180K array was implemented to identify the differentially expressed (DE) lncRNAs and mRNAs of G. lucidum treated tumor mice. The constructed lncRNA-mRNA co-expression network and bioinformatics analysis were used to selected core en-lncRNAs and its neighboring genes. The UPLC-MS method was used to identify the triterpenes of G. lucidum, and the in vitro experiments were used to verify which triterpene monomers regulated en-lncRNAs in tumor cells. Finally, a stable knockdown/overexpression cell lines were used to confirm the relationship between en-lncRNA and neighboring gene.

Ki67 and TUNEL staining demonstrated G. lucidum significantly inhibited tumor growth, suppressed cell proliferation and induced apoptosis in vivo. Transcriptomic analysis revealed the existence of 126 DE lncRNAs high correlated with 454 co-expressed mRNAs in G. lucidum treated tumor mice. Based on lncRNA-mRNA network and qRT-PCR validation, 6 core lncRNAs were selected and considered high correlated with G. lucidum treatment. Bioinformatics analysis revealed FR036820 and FR121302 might act as enhancers, and qRT-PCR results suggested FR121302 might enhance Popdc2 mRNA level in HCC. Furthermore, 6 main triterpene monomers of G. lucidum were identified by UPLC-MS method, and in vitro experiments showed FR121302 and Popdc2 were significantly suppressed by Ganoderenic acid A and Ganoderenic acid B, respectively. The knock/overexpression results demonstrated that FR121302 activating and enhancing Popdc2 expression levels, and Ganoderenic acid A and Ganoderenic acid B dramatically suppressed FR121302 and decreased Popdc2 level in Hepa1-6 cells.

Enhancer-associated lncRNA plays a crucial role as an enhancer during hepatocarcinogenesis, and triterpenes of G. lucidum significantly inhibited tumor cell proliferation and induced apoptosis by regulating en-lncRNAs. Our study demonstrated Ganoderenic acid A and Ganoderenic acid B suppressed en-lncRNA FR121302 may be one of the critical strategies of G. lucidum inhibit hepatocellular carcinoma growth.

To investigate the preliminary structural characteristics and functions of polysaccharides from Radix Tinosporae, a neutral α-glucan polysaccharide, RTP-W with a molecular weight of 14.248 kDa was obtained. The potential therapeutic effect of RTP-W on hepatocellular carcinoma was investigated in vivo. Structural analysis revealed that RTP-W comprises a backbone of (1 → 4)-linked α-D-Glcp units with the occasional occupancy of α-Glcp-(1 → at the O-6 position for every nine α (1 → 4)-D-Glcp unit. Studies showed that RTP-W significantly protects the liver against cancer, extends the survival of mice with liver cancer, and lowers ALT, AST, and GGT levels in their blood. Further investigation revealed that RTP-W reversed the exhaustion of CD8+ T cells by reducing PD-1 expression and promoting cell proliferation and cytokine expression, primarily through the activation of the Akt signaling pathway. These findings indicate that RTP-W has promising potential as an immunomodulatory agent with antitumor effects.

In recent years, a growing body of research has highlighted the significant influence of the microbiota on tumor immunity within the tumor microenvironment (TME). While much attention has been given to bacteria, emerging evidence suggests that fungi also play crucial roles in tumor development. The present review aimed to consolidate the latest findings on the mechanisms governing the interactions between fungi and the immune system or TME. By elucidating these intricate mechanisms, novel insights into the modulation of tumor immunity and therapeutic strategies may be uncovered. Ultimately, a deeper understanding of the interplay between fungi and the TME holds promise for the development of innovative management strategies and targeted drugs to enhance tumor therapy efficacy.

Regulatory immune cells regulate immune responses through various mechanisms, affecting the occurrence, development, and therapeutic effects of tumors. In this article, we reviewed the important roles of regulatory immune cells, such as regulatory T cells (Tregs), regulatory B cells (Bregs), myeloid-derived suppressor cells (MDSCs), regulatory dendritic cells (DCregs), and tumor-associated macrophages (TAMs), in the tumor microenvironment (TME). The immunomodulatory effects of natural products, such as polysaccharides, polyphenols, glycosides, alkaloids, terpenoids, quinones, and other compounds, which affect the functions of regulatory immune cells through molecular signaling pathways, thereby enhancing the potential of the antitumor immune response, are discussed. These findings provide new ideas and possibilities for the application of natural products in tumor treatment, which can help enhance the effectiveness of tumor treatment and improve patient prognosis.

Hepatocellular carcinoma (HCC) is one of the most common malignant tumors. Tumor immune microenvironment (TIME), angiogenesis, epithelial-mesenchymal transformation (EMT), invasion, metastasis, metabolism, and drug resistance are the main factors affecting the development and treatment of tumors. MiRNAs play crucial roles in almost all major cellular biological processes. Studies have been carried out on miRNAs as biomarkers and therapeutic targets. Their dysregulation contributes to the progression and prognosis of HCC. This review aims to explore the molecular cascades and corresponding phenotypic changes caused by aberrant miRNA expression and their regulatory mechanisms, summarize and analyze novel biomarkers from somatic fluids (plasma/serum/urine), and highlight the latent capacity of miRNAs as therapeutic targets.

Hepatocellular carcinoma (HCC) is the third leading cause of cancer mortality worldwide. HCC almost exclusively develops in patients with chronic liver disease, driven by a vicious cycle of liver injury, inflammation and regeneration that typically spans decades. A variety of new agents are in development for the treatment of the disease. Polysaccharide is important component of higher plants, membrane of the animal cell and the cell wall of microbes. It is also closely related to the physiological functions. Recently, there has been growing interest in polysaccharides as bioactive natural products, particularly in treating HCC. This paper provides a review of recent experimental and clinical studies on the effects and potential applications of polysaccharides in HCC treatment, aiming to offer theoretical insights and inspiration for further research on the bioactivity mechanisms of polysaccharides in HCC treatment.

Ganoderma lucidum polysaccharide (GLP) is a prebiotic with immunomodulatory effects. However, the therapeutic potential of GLP in tumor immunotherapy has not been fully explored, especially in T cell-mediated antitumor immunity. In this study, we found that GLP significantly inhibited tumor growth and activated antitumor immunity in colorectal cancer (CRC). In the spleens and tumor tissues, the proportion of cytotoxic CD8+T cells and Th1 helper cells increased, while immunosuppressive Tregs decreased. Additionally, microbiota dysbiosis was alleviated by GLP, and short-chain fatty acid production was increased. Meanwhile, GLP decreased the ratio of kynurenine and tryptophan (Kyn/Trp) in the serum, which contributed to antitumor immunity of T cells. More importantly, the combination of GLP and the immune checkpoint inhibitor anti-PD-1 monoclonal antibody further enhanced the efficacy of anti-PD-1 immunotherapy. Thus, GLP as a prebiotic has the potential to be used in tumor immunotherapy.

The tumor microenvironment (TME) can aid tumor cells in evading surveillance and clearance by immune cells, creating an internal environment conducive to tumor cell growth. Consequently, there is a growing focus on researching anti-tumor immunity through the regulation of immune cells within the TME. Various bioactive compounds in traditional Chinese medicine (TCM) are known to alter the immune balance by modulating the activity of immune cells in the TME. In turn, this enhances the body's immune response, thus promoting the effective elimination of tumor cells. This study aims to consolidate recent findings on the regulatory effects of bioactive compounds from TCM on immune cells within the TME. The bioactive compounds of TCM regulate the TME by modulating macrophages, dendritic cells, natural killer cells and T lymphocytes and their immune checkpoints. TCM has a long history of having been used in clinical practice in China. Chinese medicine contains various chemical constituents, including alkaloids, polysaccharides, saponins and flavonoids. These components activate various immune cells, thereby improving systemic functions and maintaining overall health. In this review, recent progress in relation to bioactive compounds derived from TCM will be covered, including TCM alkaloids, polysaccharides, saponins and flavonoids. This study provides a basis for further in-depth research and development in the field of anti-tumor immunomodulation using bioactive compounds from TCM.

PD-1/PD-L1 blockade therapy has brought great success to cancer treatment. Nevertheless, limited beneficiary populations and even hyperprogressive disease (HPD) greatly constrain the application of PD-1/PD-L1 inhibitors in clinical treatment. HPD is a special pattern of disease progression with rapid tumor growth and even serious consequences of patient death, which requires urgent attention. Among the many predisposing causes of HPD, regulatory T cells (Tregs) are suspected because they are amplified in cases of HPD. Tregs express PD-1 thus PD-1/PD-L1 blockade therapy may have an impact on Tregs which leads to HPD. Tregs are a subset of CD4+ T cells expressing FoxP3 and play critical roles in suppressing immunity. Tregs migrate toward tumors in the presence of chemokines to suppress antitumor immune responses, causing cancer cells to grow and proliferate. Studies have shown that deleting Tregs could enhance the efficacy of PD-1/PD-L1 blockade therapy and reduce the occurrence of HPD. This suggests that immunotherapy combined with Treg depletion may be an effective means of avoiding HPD. In this review, we summarized the immunosuppressive-related functions of Tregs in antitumor therapy and focused on advances in therapy combining Tregs depletion with PD-1/PD-L1 blockade in clinical studies. Moreover, we provided an outlook on Treg-targeted HPD early warning for PD-1/PD-L1 blockade therapy.

Primary liver cancer is a type of cancer that develops in the liver. Hepatocellular carcinoma is a primary liver cancer that usually affects adults. Liver cancer is a fatal global condition that affects millions of people worldwide. Despite advances in technology, the mortality rate remains alarming. There is growing interest in researching alternative medicines to prevent or reduce the effects of liver cancer. Recent studies have shown growing interest in herbal products, nutraceuticals, and Chinese medicines as potential treatments for liver cancer. These substances contain unique bioactive compounds with anticancer properties. The causes of liver cancer and potential treatments are discussed in this review. This study reviews natural compounds, such as curcumin, resveratrol, green tea catechins, grape seed extracts, vitamin D, and selenium. Preclinical and clinical studies have shown that these medications reduce the risk of liver cancer through their antiviral, anti-inflammatory, antioxidant, anti-angiogenic, and antimetastatic properties. This article discusses the therapeutic properties of natural products, nutraceuticals, and Chinese compounds for the prevention and treatment of liver cancer.

Traditional Chinese medicine polysaccharides (TCMPs) have gained increasing attention in the field of nanomedicine due to their diverse biological activities and favorable characteristics as drug carriers, including biocompatibility, biodegradability, safety, and ease of modification. TCMPs-based nano-drug delivery systems (NDDSs) offer several advantages, such as evasion of reticuloendothelial system (RES) phagocytosis, protection against biomolecule degradation, enhanced drug bioavailability, and potent therapeutic effects. Therefore, a comprehensive review of the latest developments in TCMPs-based NDDSs and their applications in disease therapy is of great significance. This review provides an overview of the structural characteristics and biological activities of TCMPs relevant to carrier design, the strategies employed for constructing TCMPs-based NDDSs, and the versatile role of TCMPs in these systems. Additionally, current challenges and future prospects of TCMPs in NDDSs are discussed, aiming to provide valuable insights for future research and clinical translation.

Hepatocellular carcinoma (HCC) is a prevalent malignancy, often associated with compromised immune function in affected patients. This can be attributed to the secretion of specific factors by liver cancer cells, which hinder the immune response and lead to a state of immune suppression. Polysaccharides derived from traditional Chinese medicine (TCM) are valuable constituents known for their immunomodulatory properties. This review aims to look into the immunomodulatory effects of TCM polysaccharides on HCC. The immunomodulatory effects of TCM polysaccharides are primarily manifested through the activation of effector T lymphocytes, dendritic cells, NK cells, and macrophages against hepatocellular carcinoma (HCC) both in vivo and in vitro settings. Furthermore, TCM polysaccharides have demonstrated remarkable adjuvant antitumor immunomodulatory effects on HCC in clinical settings. Therefore, the utilization of TCM polysaccharides holds promising potential for the development of novel therapeutic agents or adjuvants with advantageous immunomodulatory properties for HCC.

T helper (Th) cells have received extensive attention owing to their indispensable roles in anti-tumor immune responses. Th1 and Th2 cells are two key subsets of Th cells that exist in relative equilibrium through the secretion of cytokines that suppress their respective immune response. When the type of cytokine in the tumor microenvironment is altered, this equilibrium may be disrupted, leading to a shift from Th1 to Th2 immune response. Th1/Th2 imbalance is one of the decisive factors in the development of malignant tumors. Therefore, focusing on the balance of Th1/Th2 anti-tumor immune responses may enable future breakthroughs in cancer immunotherapy. Polysaccharides can regulate the imbalance between Th1 and Th2 cells and their characteristic cytokine profiles, thereby improving the tumor immune microenvironment. To our knowledge, this study is the most comprehensive assessment of the regulation of the tumor Th1/Th2 balance by polysaccharides. Herein, we systematically summarized the intrinsic molecular mechanisms of polysaccharides in the regulation of Th1 and Th2 cells to provide a new perspective and potential target drugs for improved anti-tumor immunity and delayed tumor progression.

Hepatocellular carcinoma (HCC) is a malignant tumor of the digestive system that poses a serious threat to human life and health. Chemotherapeutic drugs commonly used in the clinic have limited efficacy and heavy adverse effects. Therefore, it is imperative to find effective and safe alternatives, and natural polysaccharides (NPs) fit the bill. This paper summarizes in detail the anti-HCC activity of NPs in vitro, animal and clinical trials. Furthermore, the addition of NPs can reduce the deleterious effects of chemotherapeutic drugs such as immunotoxicity, bone marrow suppression, oxidative stress, etc. The potential mechanisms are related to induction of apoptosis and cell cycle arrest, block of angiogenesis, invasion and metastasis, stimulation of immune activity and targeting of MircoRNA. And on this basis, we further elucidate that the anti-HCC activity may be related to the monosaccharide composition, molecular weight (Mw), conformational features and structural modifications of NPs. In addition, due to its good physicochemical properties, it is widely used as a drug carrier in the delivery of chemotherapeutic drugs and small molecule components. This review provides a favorable theoretical basis for the application of the anti-HCC activity of NPs.

There has been a growing global interest in the potential health benefits of edible natural bioactive products in recent years. Ganoderma lucidum, a medicinal mushroom, has gained attention for its decadent array of therapeutic and pharmaceutical compounds. Notably, G. lucidum exhibits significant anti-cancer effects against various cancer types. Polysaccharides, a prominent component in G. lucidum, are pivotal in conferring its diverse biological and medicinal properties. The primary focus of this study was to investigate the anti-cancer activities of G. lucidum polysaccharides (GLPs), with particular attention to their potential to mitigate chemotherapy-associated toxicity and enhance targeted drug delivery. Our findings reveal that GLPs exhibit anti-cancer effects through diverse mechanisms, including cytotoxicity, antioxidative properties, apoptosis induction, reactive oxygen species (ROS) generation, and anti-proliferative effects. Furthermore, the potential of GLPs-based nanoparticles (NPs) as delivery vehicles for bioactive constituents was explored. These GLPs-based NPs are designed to target various cancer tissues, enhancing the biological activity of encapsulated compounds. As such, GLPs derived from G. lucidum represent a promising avenue for inhibiting cancer progression, minimizing chemotherapy-related side effects, and supporting their utilization in combination therapies as natural adjuncts.

Hepatocellular carcinoma (HCC) being a leading cause of cancer-related death, has high associated mortality and recurrence rates. It has been of great necessity and urgency to find effective HCC diagnosis and treatment measures. Studies have shown that microvascular invasion (MVI) is an independent risk factor for poor prognosis after hepatectomy. The abnormal expression of biomacromolecules such as circ-RNAs, lncRNAs, STIP1, and PD-L1 in HCC patients is strongly correlated with MVI. Deregulation of several markers mentioned in this review affects the proliferation, invasion, metastasis, EMT, and anti-apoptotic processes of HCC cells through multiple complex mechanisms. Therefore, these biomarkers may have an important clinical role and serve as promising interventional targets for HCC. In this review, we provide a comprehensive overview on the functions and regulatory mechanisms of MVI-related biomarkers in HCC.

Ganoderma lucidum (G. lucidum) has been known for many centuries in Asian countries under different names, varying depending on the country. The objective of this review is to investigate the scientific research on the natural active bio-compounds in extracts obtained from G. lucidum with significant biological actions in the treatment of cancer. This review presents the classes of bio-compounds existing in G. lucidum that have been reported over time in the main databases and have shown important biological actions in the treatment of cancer. The results highlight the fact that G. lucidum possesses important bioactive compounds such as polysaccharides, triterpenoids, sterols, proteins, nucleotides, fatty acids, vitamins, and minerals, which have been demonstrated to exhibit multiple anticancer effects, namely immunomodulatory, anti-proliferative, cytotoxic, and antioxidant action. The potential health benefits of G. lucidum are systematized based on biological actions. The findings present evidence regarding the lack of certainty about the effects of G. lucidum bio-compounds in treating different forms of cancer, which may be due to the use of different types of Ganoderma formulations, differences in the study populations, or due to drug-disease interactions. In the future, larger clinical trials are needed to clarify the potential benefits of pharmaceutical preparations of G. lucidum, standardized by the known active components in the prevention and treatment of cancer.

Gastrointestinal (GI) cancer is the most common cancer in the world and one of the main causes of cancer-related death. Clinically, surgical excision and chemotherapy are the main treatment methods for GI cancer, which is unfortunately accompanied with serious adverse reactions and drug toxicity, bringing irreversible damage to patients and seriously affecting the quality of life. Ganoderma lucidum (G. lucidum) has a long history of medicinal and edible use in China. Its bioactive compounds mainly include polysaccharides, triterpenes, and proteins, which have potential anti-tumor activities by inhibiting proliferation, inducing apoptosis, inhibiting metastasis, and regulating autophagy. Currently, there is no in-depth review on the anti-tumor effect of G. lucidum in GI cancer. Therefore, this review is an attempt to compile the basic characteristics, anti-GI caner mechanisms, and clinical application of G. lucidum, aiming to provide a reference for further research on the role of G. lucidum in the prevention and treatment of GI cancer from the perspective of traditional Chinese and western medicine.

Cancer immunotherapy has exhibited promising antitumor effects in various tumors. Infiltrated regulatory T cells (Tregs) in the tumor microenvironment (TME) restrict protective immune surveillance, impede effective antitumor immune responses, and contribute to the formation of an immunosuppressive microenvironment. Selective depletion or functional attenuation of tumor-infiltrating Tregs, while eliciting effective T-cell responses, represents a potential approach for anti-tumor immunity. Furthermore, it does not disrupt the Treg-dependent immune homeostasis in healthy organs and does not induce autoimmunity. Yet, the shared cell surface molecules and signaling pathways between Tregs and multiple immune cell types pose challenges in this process. Noncoding RNAs (ncRNAs), including microRNAs (miRNAs) and long noncoding RNAs (lncRNAs), regulate both cancer and immune cells and thus can potentially improve antitumor responses. Here, we review recent advances in research of tumor-infiltrating Tregs, with a focus on the functional roles of immune checkpoint and inhibitory Tregs receptors and the regulatory mechanisms of ncRNAs in Treg plasticity and functionality.

Ganoderma lucidum polysaccharides possess unique functional properties. Various processing technologies have been used to produce and modify G. lucidum polysaccharides to improve their yield and utilization. In this review, the structure and health benefits were summarized, and the factors that may affect the quality of G. lucidum polysaccharides were discussed, including the use of chemical modifications such as sulfation, carboxymethylation, and selenization. Those modifications improve the physicochemical characteristics and utilization of G. lucidum polysaccharides, and make them more stable that could be used as functional biomaterials to encapsulate active substances. Ultimate, G. lucidum polysaccharide-based nanoparticles were designed to deliver various functional ingredients to achieve better health-promoting effects. Overall, this review presents an in-depth summary of current modification strategies and offers new insights into the effective processing techniques to develop G. lucidum polysaccharide-rich functional foods or nutraceuticals.

Ganoderma lucidum (G. lucidum) has been widely used for its health benefits as an edible and traditional medicinal mushroom for thousands of years in Asian countries. It is currently used as a nutraceutical and functional food owing to its major bioactive compounds, polysaccharides and triterpenoids. G. lucidum exhibits a broad range of hepatoprotective impacts in various liver disorders, such as hepatic cancer, nonalcoholic fatty liver disease (NAFLD), alcohol-induced liver disease, hepatitis B, hepatic fibrosis, and liver injury induced by carbon tetrachloride (CCl4) and α-amanitin. G. lucidum protects the liver through a broad range of mechanisms that include the modulation of liver Phase I and II enzymes, the suppression of β-glucuronidase, antifibrotic and antiviral actions, the regulation of the production of nitric oxide (NO), the maintenance of hepatocellular calcium homeostasis, immunomodulatory activity, and scavenging free radicals. G. lucidum could signify an encouraging approach for the management of various chronic hepatopathies, and its potential mechanisms make it a distinctive agent when used alone or with other drugs and applied as a functional food, nutraceutical supplement, or adjuvant to modern medicine. This review summarizes the hepatoprotective properties of G. lucidum with its various mechanisms of action on different liver ailments. Biologically active substances derived from G. lucidum are still being studied for their potential benefits in treating different liver ailments.

In this study, we extracted the polysaccharides from Hizikia fusiforme (HFPs) and evaluated their effects on the immune response of the mud crab Scylla paramamosain. Compositional analysis revealed that HFPs were composed mainly of mannuronic acid (49.05%) and fucose (22.29%) as sulfated polysaccharides, and the sugar chain structure was β-type. These results indicated that HFPs have potential antioxidant and immunostimulation activity in vivo or in vitro assays. Through this research, we found that HFPs inhibited viral replication in white spot syndrome virus (WSSV)-infected crabs and promoted phagocytosis of Vibrio alginolyticus by hemocytes. Quantitative PCR results showed that HFPs up-regulated the expression levels of astakine, crustin, myosin, MCM7, STAT, TLR, JAK, CAP, and p53 in crab hemocytes. HFPs also promoted the activities of superoxide dismutase and acid phosphatase and the hemolymph antioxidant activities of crabs. HFPs maintained peroxidase activity after WSSV challenge, thereby providing protection against oxidative damage caused by the virus. HFPs also promoted apoptosis of hemocytes after WSSV infection. In addition, HFPs significantly enhanced the survival rate of WSSV-infected crabs. All results confirmed that HFPs improved the innate immunity of S. paramamosain by enhancing the expression of antimicrobial peptides, antioxidant enzyme activity, phagocytosis, and apoptosis. Therefore, HFPs have potential for use as therapeutic or preventive agents to regulate the innate immunity of mud crabs and protect them against microbial infection.

The response of macrophages to environmental signals demonstrates its heterogeneity and plasticity. After different forms of polarized activation, macrophages reach the M1 or M2 activation state according to their respective environment. Ganoderma lucidum polysaccharide (GLPS) is a major bioactive component of Ganoderma lucidum, a well-known medicinal mushroom. Although the immunomodulatory and anti-tumor effects of GLPS have been proven, GLPS's effect on inhibiting hepatocellular carcinoma (HCC) by regulating macrophage polarization is little known. Our data showed that GLPS notably inhibited the growth of a Hepa1-6 allograft. The expression of M1 marker CD86 was higher in the tumor tissue of the GLPS treatment group than in the control group in vivo. In vitro, the phagocytic activity and NO production of macrophages were increased by GLPS treatment. Moreover, it was discovered that GLPS was able to increase the expression of the M1 phenotype marker CD86, iNOS, and pro-inflammatory cytokines comprising IL-12a, IL-23a, IL-27 and TNF-α, but inhibited macrophage polarization towards the M2 phenotype by decreasing the expression of CD206, Arg-1, and inflammation-related cytokines comprising IL-6 and IL-10. The data suggest that GLPS may regulate macrophage polarization. Mechanistically, GLPS increased the phosphorylation of MEK and ERK. In addition, the phosphorylation of IκBα and P65 was increased by GLPS treatment. These data showed that GLPS can regulate the MAPK/NF-κB signaling pathway responsible for M1 polarization. In a nutshell, our research puts forward a new application of GLPS in anti-HCC treatment by regulating macrophage polarization through activating MAPK/NF-κB signaling.

Fueled by rapidly evolving comprehension of multifaceted nature of cancers, recently emerging preclinical and clinical data have supported researchers in the resolution of knowledge gaps to deepen the understanding of the molecular mechanisms. The extra-ordinary and bewildering chemical diversity encompassed by biologically active natural products continues to be of relevance to drug discovery. Accumulating evidence has spurred a remarkable evolution of concepts related to pharmacological target of oncogenic signaling pathways by polysaccharides in different cancers.

The objective of the current review is to provide new insights into study progress on anticancer effects of bioactive herbal polysaccharides.

PubMed, Scopus, Web of Science, Embase, and other databases were searched for articles related to anticancer effects of polysaccharides. Searches were conducted to locate relevant publications published up to October 2022.

Polysaccharides have been reported to pleiotropically modulate TGF/SMAD, BMP/SMAD, TLR4, mTOR, CXCR4 and VEGF/VEGFR cascades. We have also summarized how different polysaccharides regulated apoptosis and non-coding RNAs. Additionally, this mini-review describes increasingly sophisticated understanding related to polysaccharides mediated tumor suppressive and anti-metastatic effects in tumor-bearing mice. We have also provided an overview of the clinical trials related to chemopreventive role of polysaccharides.

Genomic and proteomic findings from these studies will facilitate 'next-generation' clinical initiatives in the prevention/inhibition of cancer.

Cancer has always been a focus of global attention, and the difficulty of treatment and poor prognosis have always plagued humanity. Conventional chemotherapeutics and treatment with synthetic disciplines will cause adverse side effects and drug resistance. Therefore, searching for a safe, valid, and clinically effective drug is necessary. At present, some natural compounds have proved to have the potential to fight cancer. Polysaccharides obtained from Chinese materia medica are good anti-cancer ingredients. Polysaccharides are macromolecular compounds of equal or distinct monosaccharides with an α- or β-glycosidic bonds. The anti-cancer activity has been fully demonstrated in vivo and in vitro. However, Chinese materia medica polysaccharides are only used as adjuvant therapy for cancer-related diseases. Hence, this review mainly discusses the chemical composition, biological activity, absorption in vivo, and clinical application of Chinese materia medica polysaccharides. Also, we discussed the anti-cancer mechanism. We also discussed the current research's limitations on treating cancer with Chinese materia medica polysaccharides and insights into future research.

Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.

Forkhead box protein 3 (FOXP3) is an important transcription factor for regulatory T cells (Tregs) and plays an important role in their immunosuppressive function. In recent years, studies have found that FOXP3 is expressed in many kinds of tumors and plays different roles in tumors' biological behaviors, including tumor proliferation, metastasis, drug resistance, and prognosis. However, the effects of FOXP3 on tumor metastasis and its interaction with traditional Chinese medicine (TCM) remain unclear. Therefore, in this review, we focus on the effects of FOXP3 on tumor metastasis and its relationship with TCM, which can provide evidence for further research and therapy in clinical settings.

Polysaccharides from Flos Sophorae Immaturus (FSI) are one of its pharmacological compounds that can perform effective activities. Aiming to extract the most effective polysaccharides against hepatocellular carcinoma (HCC), the polysaccharides were separated from FSI through ultrasonic microwave extraction, and the first comparison was carried out on the characterization of the structure and its cytotoxic properties on HCC SMMC 7721 cells of undeproteinized purified polysaccharides (PFSI-1) and papain-deproteinized polysaccharides (PFSI-2) from FSI. The findings indicated that PFSI-1 and PFSI-2 had characteristic absorption peaks of polysaccharides; PFSI-1 contained three monosaccharides and PFSI-2 contained ten; and SEM, AFM, and NMR were consistent with the verification of IR polysaccharide characteristics, suggesting probable additional latent activities. The pharmacotoxic effects of both PFSI-1 and PFSI-2 on SMMC 7721 cells (p < 0.05), attenuated the migration ability of SMMC 7721 cells (p < 0.05) and promoted apoptosis (p < 0.05), with an increase in G0/G1-phase cells and decrease in S-phase cells in the PFSI-1 as well as a decrease in G0/G1-phase cells, increase in S-phase cells, and decrease in apoptosis in the PFSI-2 (p < 0.05). The significant cytotoxic effect of PFSI-2 on SMMC 7721 cells (p < 0.05) and its protective effect on human hepatic L02 cells (HL-7702) at low concentrations (p > 0.05) could indicate its potential as a new drug for the treatment of HCC.

HCC is among the most common cancer. Ganoderma lucidum (G.lucidum) has been essential in preventing and treating cancer. The Nrf2 signaling cascade is a cell protective mechanism against further damage, such as cancer development. This signaling pathway upregulates the cytoprotective genes and is vital in eliminating xenobiotics and reactive oxygen. This study aimed to show the potential cytotoxic activity of G. lucidum aqueous extract in HCC.

MTT assay was used to detect cell viability. Nrf2-related proteins were measured by western blotting, and the flow cytometry method assayed cell population in different cycle phases. Cell viability was 49% and 47% following G. lucidum extract at 100 µg/ml at 24 and 48 h treatments, respectively. G. lucidum extract (aqueous, 100 or 50 µg/ml) treatments for 24, 48, or 72 h were able to significantly change the cytoplasmic/nuclear amount of Nrf2 and HO-1, NQO1 protein levels. Moreover, at both concentrations, arrest of the G0/G1 cell cycle was stimulated in HCC.

The activation of the Nrf2 signaling pathways seems to be among the mechanisms underlining the protective and therapeutic action of G. lucidum against HCC.

Carbohydrate polymers with unique chemical composition, molecular weight and functional chemical groups show multiple potentials in drug delivery. Most carbohydrate polymers such as plant polysaccharides exhibit advantages of biodegradability, ease of modification, low immunogenicity and low toxicity. They can be conjugated, cross-linked or functionally modified, and then used as nanocarrier materials. Polysaccharide drug delivery system can avoid the phagocytosis of the reticuloendothelial system, prevent the degradation of biomolecules, and increase the bioavailability of small molecules, thus exerting effective therapeutic effects. Therefore, they have been fully explored. In this paper, we reviewed the construction methods of drug delivery systems based on carbohydrate polymers (astragalus polysaccharide, angelica polysaccharide, lycium barbarum polysaccharide, ganoderma lucidum polysaccharide, bletilla polysaccharide, glycyrrhiza polysaccharide, and epimedium polysaccharides, etc). The application of polysaccharide drug delivery systems to deliver small molecule chemotherapeutic drugs, gene drugs, and metal ion drugs was also briefly introduced. At the same time, the role of the polysaccharide drug delivery system in tumor treatment, targeted therapy, and wound healing was discussed. In addition, the research of polysaccharide delivery systems based on the therapeutic efficacy of traditional Chinese medicine was also summarized and prospected.

The polysaccharides of the millenary mushroom Ganoderma lucidum (GL) have been shown for decades to present anti-tumor activities, but few studies evaluated its importance on cancer stem cells and EMT process. Cancer stem cells (CSC) drive the development of carcinoma and are also involved in cancer treatment failure, being a good target for treatment success. Also, the process of epithelial-mesenchymal transition (EMT) is involved in metastasis and cancer relapse. Besides that, the increasing incidence worldwide of oral squamous cell carcinoma (OSCC) became a public health issue with a high rate of metastasis and poor quality of life for patients during and after treatment.

to evaluate G. lucidum polysaccharides (GLPS) in vitro effects on OSCC, focusing on hallmarks associated with tumorigenesis using the SCC-9, a squamous cells carcinoma lineage from the tongue.

SCC-9 cells were treated in vitro for 72h with different GLPS concentrations. The controls cells were maintained with culture media only and cisplatin was used as treatment control. After the treatment period, the cells were evaluated.

GLPS treatment changed cell morphology and granularity, delayed migration, decreased colony, and impaired sphere formation, thereby leading to a non-invasive and less proliferative behavior of tumoral cells. Additionally, GLPS downregulated CSC, EMT, and drug sensitivity (ABC) markers.

These results show that the natural product GLPS has the potential to be an important ally for tongue squamous cell carcinoma treatment, bringing the millenary compound to modern therapy, providing a basis for future studies and the improvement of life quality for OSCC patients.

As a versatile Chinese herb, Ganoderma lucidum (Leyss. ex Fr.) Karst (G. lucidum) has been applied to treat multiple diseases in clinics and improve the quality of life of patients. Among all of its extracts, the main bioactive components are G. lucidum polysaccharides (GLPs), which possess many therapeutic effects, such as antitumor, immunoregulatory, anti-oxidant, antidiabetic, antibacterial, and antifungal effects and neuroprotection activities. This review briefly summarized the recent studies of the pharmacological rationales of GLPs and their underlying molecular signaling transmission mechanisms in treating diseases. Until now, the clear mechanisms of GLPs for treating diseases have not been reported. In this review, we used the keywords of "Ganoderma lucidum polysaccharides" and "tumor" to search in PubMed (years of 1992-2020), then screened and obtained 160 targets of antitumor activities in the literatures. The network pharmacology and mechanism framework were employed in this study as powerful approaches to systematically analyze the complicated potential antitumor mechanisms and targets of GLPs in cancer. We then found that there are 69 targets and 21 network pathways in "Pathways in cancer". Besides, we summarized the effects of GLPs and the models and methods used in the research of GLPs. In conclusion, GLPs have been studied extensively, but more in-depth research is still needed to determine the exact mechanisms and pathways. Therefore, this review might provide new insights into the vital targets and pathways for researchers to study the pharmacological mechanisms of GLPs for the treatment of diseases.

Immune checkpoints are the crucial regulators of immune system and play essential roles in maintaining self-tolerance, preventing autoimmune responses, and minimizing tissue damage by regulating the duration and intensity of the immune response. Furthermore, immune checkpoints are usually overexpressed in cancer cells or noninvasive cells in tumor tissues and are capable of suppressing the antitumor response. Based on substantial physiological analyses as well as preclinical and clinical studies, checkpoint molecules have been evaluated as potential therapeutic targets for the treatment of multiple types of cancers. In the last few years, extensive evidence has supported the immunoregulatory effects of traditional Chinese medicines (TCMs). The main advantage of TCMs and natural medicine is that they usually contain multiple active components, which can act on multiple targets at the same time, resulting in additive or synergistic effects. The strong immune regulation function of traditional Chinese medicine on immune checkpoints has also been of great interest. For example, Astragalus membranaceus polysaccharides can induce anti-PD-1 antibody responses in animals, and these antibodies can overcome the exhaustion of immune cells under tumor immune evasion. Furthermore, many other TCM molecules could also be novel and effective drug candidates for the treatment of cancers. Therefore, it is essential to assess the application of immune checkpoints in the development of new drugs and TCMs. In this review, we focus on research progress in the field of immune checkpoints based on three topics: (1) immune checkpoint targets and pathways, (2) development of novel immune checkpoint-based drugs, and (3) application of immune checkpoints in the development of TCMs.

Hepatocellular carcinoma (HCC) is one of the most common tumours worldwide, and identifying markers related to HCC is an important area of research. As a microRNA (miRNA), miRNA125b (miR-125b) plays an important role in the prediction and prognosis of HCC. In the past 10 years, with increasing research on miR-125b and HCC, the molecular mechanism of its relationship with the development of HCC has been elucidated. MiR-125b inhibits the development of HCC and is highly accurate in predicting HCC and is therefore a valuable predictive marker of HCC. This article summarizes the clinical application of miR-125b in HCC and the potential mechanism of its involvement in the progression of HCC.

Reishi owes an exceptional value in nutritional, cosmeceutical, and medical treatments; however, none of the studies has provided its future-driven critical assessment. This study documents an up-to-date review (2015-2020, wherever applicable) and provide valuable insights (preclinical and clinical evidence-based) with comprehensive and critical assessments. Various databases 'Google scholar', 'Web of Science', 'ScienceDirect', 'PubMed', 'Springer Link', books, theses, and library resources were used. The taxonomic chaos of G. lucidum and its related species was discussed in detail with solution-oriented emphasis. Reishi contains polysaccharides (α/β-D-glucans), alkaloids, triterpenoids (ganoderic acids, ganoderenic acids, ganoderol, ganoderiol, lucidenic acids), sterols/ergosterol, proteins (LZ-8, LZ-9), nucleosides (adenosine, inosine, uridine), and nucleotides (guanine, adenine). Some active drugs are explored at an optimum level to make them potential drug candidates. The pharmacological potential was observed in diabetes, inflammation, epilepsy, neurodegeneration, cancer, anxiety, sedation, cardiac diseases, depression, hepatic diseases, and immune disorders; however, most of the studies are preclinical with a number of drawbacks. In particular, quality clinical data are intensely needed to support pharmacological activities for human use. The presence of numerous micro-, macro, and trace elements imparts an essential nutritional and cosmeceutical value to Reishi, and various marketed products are available already, but the clinical studies regarding safety and efficacy, interactions with foods/drinks, chronic use, teratogenicity, mutagenicity, and genotoxicity are missing for Reishi. Reishi possesses many valuable pharmacological activities, and the number of patents and clinical trials is increasing for Reishi. Yet, a gap in research exists for Reishi, which is discussed in detail in the forthcoming sections.

Bioactive substances derived from natural products are valued for effective health-related activities. As extremely important component of plants, animal cell membrane and microbes cytoderm, polysaccharides have been applied as medications, foods and cosmetics stemming from their prominent biological functions and minor side-effects. Recent studies indicate that polysaccharides exert biological effects also through epigenetic mechanism. Through the intervention of DNA methylation, histone modification, and non-coding RNA, polysaccharides participatate in regulation of immunity/inflammation, glucose and lipid metabolism, antioxidant damage and anti-tumor, which presents novel mechanism of polysaccharide exerting various functions. In this review, the latest advances in the biological functions of dietary polysaccharides via epigenetic regulations were comprehensively summarized and discussed. From the view point of epigenetic regulation, investigating the relationship between polysaccharides and biological effects will enhance our understandings of polysaccharides and also means huge breakthrough of molecular mechanism in the polysaccharide research fields. The paper will provide important reference to these investigators of polysaccharide research and expand the applications of dietary polysaccharides in the functional food developments.

Traditional Chinese Medicine (TCM) is one of the ancient and most accepted alternative medicinal systems in the world for the treatment of health ailments. World Health Organization recognizes TCM as one of the primary healthcare practices followed across the globe. TCM utilizes a holistic approach for the diagnosis and treatment of cancers. The tumor microenvironment (TME) surrounds cancer cells and plays pivotal roles in tumor development, growth, progression, and therapy resistance. TME is a hypoxic and acidic environment that includes immune cells, pericytes, fibroblasts, endothelial cells, various cytokines, growth factors, and extracellular matrix components. Targeting TME using targeted drug delivery and nanoparticles is an attractive strategy for the treatment of solid tumors and recently has received significant research attention under precise medicine concept. TME plays a pivotal role in the overall survival and metastasis of a tumor by stimulating cell proliferation, preventing the tumor clearance by the immune cells, enhancing the oncogenic potential of the cancer cells, and promoting tumor invasion. Hepatocellular Carcinoma (HCC) is one of the major causes of cancer-associated deaths affecting millions of individuals worldwide each year. TCM herbs contain several bioactive phytoconstituents with a broad range of biological, physiological, and immunological effects on the system. Several TCM herbs and their monomers have shown inhibitory effects in HCC by controlling the TME. This study reviews the fundamentals and applications of targeting strategies for immunosuppressing TME to treat cancers. This study focuses on TME targeting strategies using TCM herbs and the molecular mechanisms of several TCM herbs and their monomers on controlling TME.

MiRNA is a type of small non-coding RNA, by regulating downstream gene expression that affects the progression of multiple diseases, especially cancer. MiRNA can participate in the biological processes of tumor, including proliferation, invasion and escape, and exhibit tumor enhancement or inhibition. The tumor immune microenvironment contains numerous immune cells. These cells include lymphocytes with tumor suppressor effects such as CD8+ T cells and natural killer cells, as well as some tumor-promoting cells with immunosuppressive functions, such as regulatory T cells and myeloid-derived suppressor cells. MiRNA can affect the tumor immune microenvironment by regulating the function of immune cells, which in turn modulates the progression of tumor cells. Investigating the role of miRNA in regulating the tumor immune microenvironment will help elucidate the specific mechanisms of interaction between immune cells and tumor cells, and may facilitate the use of miRNA as a predictor of immune disorders in tumor progression. This review summarizes the multifarious roles of miRNA in tumor progression through regulation of the tumor immune microenvironment, and provides guidance for the development of miRNA drugs to treat tumors and for the use of miRNA as an auxiliary means in tumor immunotherapy.