The Effectiveness of Traditional Chinese Medicine in Treating Malignancies via Regulatory Cell Death Pathways and the Tumor Immune Microenvironment: A Review of Recent Advances.

Traditional Chinese Medicine (TCM) has achieved high clinical efficacy in treating malignancies in recent years and is thus gradually becoming an important therapy for patients with advanced tumor for its benefits in reducing side effects and improving patients' immune status. However, it has not been internationally recognized for cancer treatment because TCM's anti-tumor mechanism is not fully elucidated, limiting its clinical application and international promotion. This review traced the mechanism of the TCM-mediated tumor cell death pathway and its effect on remodeling the tumor immune microenvironment, its direct impact on the microenvironment, its anti-tumor effect in combination with immunotherapy, and the current status of clinical application of TCM on tumor treatment. TCM can induce tumor cell death in many regulatory cell death (RCD) pathways, including apoptosis, autophagy, pyroptosis, necroptosis, and ferroptosis. In addition, TCM-induced cell death could increase the immune cells' infiltration with an anti-tumor effect in the tumor tissue and elevate the proportion of these cells in the spleen or peripheral blood, enhancing the anti-tumor capacity of the tumor-bearing host. Moreover, TCM can directly affect immune function by increasing the population or activating the sub-type immune cells with an anti-tumor role. It was concluded that TCM could induce a pan-tumor death modality, remodeling the local TIME differently. It can also improve the systemic immune status of tumor-bearing hosts. This review aims to establish a theoretical basis for the clinical application of TCM in tumor treatment and to provide a reference for TCM's potential in combination with immunotherapy in cancer treatment.

Carbohydrate regulation response to cold during rhizome bud dormancy release in Polygonatum kingianum.

BACKGROUND: The rhizome of Polygonatum kingianum Coll. et Hemsl (P. kingianum) is a crucial traditional Chinese medicine, but severe bud dormancy occurs during early rhizome development. Low temperature is a positive factor affecting dormancy release, whereas the variation in carbohydrates during dormancy release has not been investigated systematically. Therefore, the sugar content, related metabolic pathways and gene co-expression were analysed to elucidate the regulatory mechanism of carbohydrates during dormancy release in the P. kingianum rhizome bud. RESULTS: During dormancy transition, starch and sucrose (Suc) exhibited opposing trends in the P. kingianum rhizome bud, representing a critical indicator of dormancy release. Galactose (Gal) and raffinose (Raf) were increased in content and synthesis. Glucose (Glc), cellulose (Cel), mannose (Man), arabinose (Ara), rhamnose (Rha) and stachyose (Sta) showed various changes, indicating their different roles in breaking rhizome bud dormancy in P. kingianum. At the beginning of dormancy release, Glc metabolism may be dominated by anaerobic oxidation (glycolysis followed by ethanol fermentation). After entering the S3 stage, the tricarboxylic acid cycle (TCA) and pentose phosphate pathway (PPP) were may be more active possibly. In the gene co-expression network comprising carbohydrates and hormones, HYD1 was identified as a hub gene, and numerous interactions centred on STS/SUS were also observed, suggesting the essential role of brassinosteroids (BRs), Raf and Suc in the regulatory network. CONCLUSION: We revealed cold-responsive genes related to carbohydrate metabolism, suggesting regulatory mechanisms of sugar during dormancy release in the P. kingianum rhizome bud. Additionally, gene co-expression analysis revealed possible interactions between sugar and hormone signalling, providing new insight into the dormancy release mechanism in P. kingianum rhizome buds.

In vivo antimalarial activity of synthetic hepcidin against Plasmodium berghei in mice.

The present study was designed to investigate the antimalarial activity of synthetic hepcidin and its effect on cytokine secretion in mice infected with Plasmodium berghei. The mice were infected with P. berghei intravenously and treated with hepcidin according to 4-day suppression test and Rane's test. The serum levels of interleukins (IL-1ß, IL-2, IL-6, IL-10, IL-12p70, and IL-17A), tumor necrosis factor-α (TNF-α), and interferon-γ (IFN-γ) in the experimental mice were determined using a cytometric bead array (CBA) kit. The survival rate of the infected mice was also registered. Additionally, the serum iron, alanine transaminase (ALT), aspartate transaminase (AST), and total bilirubin (BIL) were detected to evaluate liver functions. Hepcidin exerted direct anti-malarial function in vivo and increased survival rate in a dose-dependent manner. In addition, the secretion of T helper cell type 1 (Th1), Th2, and Th17 cytokines, TNF-α, and IFN-γ were inhibited by hepcidin. In conclusion, our results demonstrated that synthetic hepcidin exerts in vivo antimalarial activity and possesses anti-inflammatory function, which provides a basis for future design of new derivatives with ideal anti-malarial activity.

Phenolic acids isolated from the fungus Schizophyllum commune exert analgesic activity by inhibiting voltage-gated sodium channels.

The present study was designed to search for compounds with analgesic activity from the Schizophyllum commune (SC), which is widely consumed as edible and medicinal mushroom world. Thin layer chromatography (TLC), tosilica gel column chromatography, sephadex LH 20, and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify compounds from SC. Structural analysis of the isolated compounds was based on nuclear magnetic resonance (NMR). The effects of these compounds on voltage-gated sodium (NaV) channels were evaluated using patch clamp. The analgesic activity of these compounds was tested in two types of mouse pain models induced by noxious chemicals. Five phenolic acids identified from SC extracts in the present study included vanillic acid, m-hydroxybenzoic acid, o-hydroxybenzeneacetic acid, 3-hydroxy-5-methybenzoic acid, and p-hydroxybenzoic acid. They inhibited the activity of both tetrodotoxin-resistant (TTX-r) and tetrodotoxin-sensitive (TTX-s) NaV channels. All the compounds showed low selectivity on NaV channel subtypes. After intraperitoneal injection, three compounds of these compounds exerted analgesic activity in mice. In conclusion, phenolic acids identified in SC demonstrated analgesic activity, facilitating the mechanistic studies of SC in the treatment of neurasthenia.

Identification and characterization of a novel neuropeptide (neuropeptide Y-HS) from leech salivary gland of Haemadipsa sylvestris.

The present study was designed to identify immunomodulatory components from the leech salivary gland of Haemadipsa sylvestris. The Sephadex G-50, Resource(TM) S column chromatography and reverse-phase high performance liquid chromatography (RP-HPLC) were used to isolate and purify the salivary gland extracts (SGE). Structural analysis of isolated compounds was based on Edman degradation and matrix assisted laser desorption ionization time-of-flight mass spectrometer (MALDI-TOF-MS). The cDNA encoding the precursor of the compound was cloned from the cDNA library of the salivary gland of H. sylvestris. The levels of inflammatory mediators, including tumor necrosis factor-α (TNF-α), interferon γ (IFN-γ), interleukin-6 (IL-6), and monocyte chemotactic protein-1 (MCP-1) were assayed using an enzyme-linked immunosorbent assay (ELISA). The effects on cell proliferation and cell viability were observed using MTT assay. A novel neuropeptide Y (Neuropeptide Y-HS) from the leech salivary gland of H. sylvestris was purified and characterized. It was composed of 36 amino acid residues and the amino acid sequence was determined to be FLEPPERPAVFTSVEQMKSYIKALNDYYLLLGRPRF-NH2, containing an amidated C-terminus. It showed significant inhibitory effects on the production of inflammatory cytokines including TNF-α, IFN-γ, IL-6, and MCP-1. Neuropeptide Y was identified from leeches for the first time. The presence of neuropeptide Y-HS in leech salivary gland may help get blood meal from hosts and inhibit inflammation.

A Designed Tryptophan- and Lysine/Arginine-Rich Antimicrobial Peptide with Therapeutic Potential for Clinical Antibiotic-Resistant Candida albicans Vaginitis.

New therapeutic agents for Candida albicans vaginitis are urgently awaiting to be developed because of the increasing antibiotic resistance of C. albicans. Antimicrobial peptides (AMPs) are one of the most promising choices for next-generation antibiotics. In this study, novel peptides were designed based on snake venom antimicrobial peptide cathelicidin-BF to promote anti-C. albicans activity and decrease side-effects. The designing strategies include substitutions of charged or hydrophobic amino acid residues for noncharged polar residues to promote antimicrobial activity and insertion of a hydrophobic residue in the hydrophilic side of the helix structure to reduce hemolysis. A designed tryptophan and lysine/arginine-rich cationic peptide 4 (ZY13) (VKRWKKWRWKWKKWV-NH2) exhibited excellent antimicrobial activity against either common strain or clinical isolates of antibiotic-resistant C. albicans with little hemolysis. Peptide 4 showed significant therapeutic effects on vaginitis in mice induced by the infection of clinical antibiotic-resistant C. albicans. The approaches herein might be useful for designing of AMPs.

Inhibitory effect of Lycium barbarum polysaccharides on cell apoptosis and senescence is potentially mediated by the p53 signaling pathway.

Lycium barbarum (L. barbarum) fruit or extract has been regarded as a superior-grade Chinese medicine, used to modulate body immunity and for anti-aging purposes. However, the underlying molecular mechanisms behind these effects remain unclear. In the present study, L. barbarum polysaccharides (LBPs), considered a major contributor of L. barbarum effects, were used to elucidate its mechanism of action by phenotypic and senescence associated-ß-galactosidase (SA-ß-gal) assays, evaluation of survival rates in vivo and expression profiling of genes related to the p53 signaling pathway in a zebrafish model. Zebrafish embryos were continuously exposed to various concentrations of LBPs (1.0, 2.0, 3.0 and 4.0 mg/ml) for 3 days. The results of fluorescent acridine orange and SA-ß-gal staining indicated that cell apoptosis and senescence mainly occur in the head at 24 hours post fertilization (hpf) and 72 hpf. In addition, resistance to replicative senescence was observed at low doses of LBPs, especially at the 3.0 mg/ml concentration. Furthermore, the expression of genes that relate to aging, such as p53, p21 and Bax, was decreased, while that of Mdm2 and TERT genes was increased after treatment with LBPs. The results demonstrated that the effects of LBPs on cell apoptosis and aging might be mediated by the p53-mediated pathway.