Mining of antioxidant sesquiterpene lactones from the aerial parts of Saussurea involucrata with feature-based molecular network strategy.

Sesquiterpene lactones (SLs) are a class of natural products with diverse structural scaffoldings and biological activities, making them intriguing objects in the fields of pharmaceutical industry, drug development, and pharmacology. Herein, fifteen SLs, including eleven undescribed SLs compounds sauruintones A-K (1-8 and 13-15), were isolated and identified from the aerial parts of Saussurea involucrata. Their structures were characterized by using mass spectrometry, spectroscopic methods, computational calculations, and single crystal X-ray diffraction.

Corydecusines A-H, new phthalideisoquinoline hemicetal alkaloids from the bulbs of Corydalis decumbens inhibit Tau pathology by activating autophagy mediated by AMPK-ULK1 pathway.

Twelve phthalideisoquinoline hemiacetal alkaloids including eight new ones (1-8) and one natural alkaloid characterized by an aziridine moiety with unassigned NMR data (9), were isolated and identified from the bulbs of Corydalis decumbens. Their structures were established by comprehensive analyses of HRESIMS, NMR, X-ray crystallography, and ECD analyses. The unambiguously established structures of the phthalideisoquinoline hemiacetal alkaloids indicated that the absolute configurations of C-1, C-9, and C-7' were confusable only relied on coupling constants.

Myeloid Cell-Triggered In Situ Cell Engineering for Robust Vaccine-Based Cancer Treatment.

Following the success of the dendritic cell (DC) vaccine, the cell-based tumor vaccine shows its promise as a vaccination strategy. Except for DC cells, targeting other immune cells, especially myeloid cells, is expected to address currently unmet clinical needs (e.g.

Cardiac glycosides from the roots of Streblus asper Lour. with activity against Epstein-Barr virus lytic replication.

Cardiac glycosides (CGs) show potential broad-spectrum antiviral activity by targeting cellular host proteins. Herein are reported the isolation of five new (1-5) and eight known (7-13) CGs from the roots of Streblus asper Lour. Of these compounds 1 and 7 exhibited inhibitory action against EBV early antigen (EA) expression, with half-maximal effective concentration values (EC) being less than 60 nM, and they also showed selectivity, with selectivity index (SI) values being 56.

STING and TLR7/8 agonists-based nanovaccines for synergistic antitumor immune activation.

Unlabelled: Immunostimulatory therapies based on pattern recognition receptors (PRRs) have emerged as an effective approach in the fight against cancer, with the ability to recruit tumor-specific lymphocytes in a low-immunogenicity tumor environment. The agonist cyclic dinucleotides (CDNs) of the stimulator of interferon gene (STING) are a group of very promising anticancer molecules that increase tumor immunogenicity by activating innate immunity. However, the tumor immune efficacy of CDNs is limited by several factors, including relatively narrow cytokine production, inefficient delivery to STING, and rapid clearance.

Prophylactic and Therapeutic EBV Vaccines: Major Scientific Obstacles, Historical Progress, and Future Direction.

The Epstein-Barr virus (EBV) infects more than 95% of adults worldwide and is associated with various malignant tumors and immune diseases, imparting a huge disease burden on the human population. Available EBV vaccines are imminent. Prophylactic vaccines can effectively prevent the spread of infection, whereas therapeutic vaccines mainly stimulate cell-mediated immunity and kill infected cells, thus curbing the development of malignant tumors.

Black phosphorous nanosheet: A novel immune-potentiating nanoadjuvant for near-infrared-improved immunotherapy.

Intrinsic immune behaviors of nanomaterials and immune systems promote research on their adjuvanticity and the design of next generation nanovaccine-based immunotherapies. Herein, we report a promising multifunctional nanoadjuvant by exploring the immune-potentiating effects of black phosphorus nanosheets (BPs) in vitro and in vivo. The facile coating of BPs with phenylalanine-lysine-phenylalanine (FKF) tripeptide-modified antigen epitopes (FKF-OVAp@BP) enables the generation of a minimalized nanovaccine by integrating high loading capacity, efficient drug delivery, comprehensive dendritic cell (DC) activation, and biocompatibility for cancer immunotherapy.

A novel STING agonist for cancer immunotherapy and a SARS-CoV-2 vaccine adjuvant.

A novel STING agonist, CDG, ipsilaterally modified with phosphorothioate and fluorine, was synthesized. The phosphorothioate in CDG might be a site for covalent conjugation. Injection of CDG generated an immunogenic ("hot") tumor microenvironment to suppress melanoma, more efficiently than dithio CDG.

PamCSK-CDG Augments Antitumor Immunotherapy by Synergistically Activating TLR1/2 and STING.

Cyclic dinucleotides (CDNs), agonists of stimulator of interferon genes (STING), are promising agents for immunotherapy. However, the application of CDNs has been limited by their instability and low transmembrane efficiency. Here, we introduced a conjugated adjuvant of STING and TLR1/2, PamCSK-CDG.

Cardiac glycosides from the roots of Streblus asper Lour. and their apoptosis-inducing activities in A549 cells.

Phytochemical investigation of the roots of Streblus asper Lour. resulted in the isolation of six previously undescribed cardiac glycosides, designated 2'-de-O-methylstrebloside (1), cannogenol-3α-O-β-D-gluopyranosyl-(1 → 4)-6-deoxy -2,3-dimethoxyl-β-D-fucopyranoside (2), periplogenin-3-O-α-L-rhamnopyranosyl -(1 → 4)-6-deoxy-β-D-allopyranoside (3), 5-de-O-hydroxylstrebloside (4), 5βH-16β-hydroxylkamaloside (5), and 17S, 21R-21-hydroxylstrebloside (6), and three known analogues (7-9). The structures were elucidated using NMR spectroscopic techniques, mass spectrometry, and comparison of the spectroscopic data with previously reported data.

Sauropus androgynus L. Merr.-A phytochemical, pharmacological and toxicological review.

Ethnopharmacological Relevance: Sauropus androgynus L. Merr is an underexploited perennial shrub traditionally used as a medicinal plant in South Asia and Southeast Asia. The plant is regarded as not just a green vegetable for diet, but as a traditional herb for certain aliments.

Fully Synthetic Invariant NKT Cell-Dependent Self-Adjuvanting Antitumor Vaccines Eliciting Potent Immune Response in Mice.

Constructing an effective therapeutic cancer vaccine is very attractive and promising for cancer immunotherapy. However, the poor immunogenicity of tumor antigens and suppression of the immune system in the tumor microenvironment are two major obstacles for developing effective cancer vaccines. Invariant NKT cells (iNKT cells), which are essential bridges between the innate and adaptive immune systems, can be rapidly activated by their agonists and, consequently, evoke whole immune systems.

Regulation of Immune Activation by Optical Control of TLR1/2 Heterodimerization.

The activation of toll-like receptors (TLRs) plays important roles in the immune response. The ability to control the activities of TLRs could be usable as a switch for immune response. Here we have rationally designed and synthesized a photoswitchable Pam CSK derivative-P10-to control the activation of TLR1/2.

Traditional uses, phytochemistry, and pharmacology of Ficus hispida L.f.: A review.

Ethnopharmacological Relevance: Ficus hispida L.f. (Moraceae) has long been used as a traditional medicine in India, China, Sri Lanka, Australia, and Myanmar in the treatment of diarrhea, ulcer, anemia, diabetes, inflammation, and cancer.

Novel Mannitol-Based Small Molecules for Inhibiting Aggregation of α-Synuclein Amyloids in Parkinson's Disease.

The aggregation of the amyloidogenic protein α-synuclein (α-Syn) into toxic oligomers and mature fibrils is the major pathological hallmark of Parkinson's disease (PD). Small molecules that inhibit α-Syn aggregation thus may be useful therapeutics for PD. Mannitol and naphthoquinone-tryptophan (NQTrp) have been shown in the past to inhibit α-Syn aggregation by different mechanisms.

Targeting STING with cyclic di-GMP greatly augmented immune responses of glycopeptide cancer vaccines.

Cyclic di-GMP (CDG) was applied to MUC1 glycopeptide-based cancer vaccines with physical mixing and built-in (at 2'-OH of CDG) strategies for activating the STING pathway. CDG in both strategies behaved as a potent immunostimulant and contributed to high titers of IgG antibodies and the expression of multiple cytokines.

Designable Immune Therapeutical Vaccine System Based on DNA Supramolecular Hydrogels.

Immunotherapy is believed to be an ideal method to treat cancer because it can break the immunotolerance of tumor and induce robust immunoresponse. However, constructing a wide antigen-adaptive, easy-handling, and biodegradable system that can recruit and activate antigen-presenting cells (APCs) much effectively is still a challenge. Herein, we show an injectable DNA supramolecular hydrogel vaccine (DSHV) system which could efficiently recruit and activate APCs in vitro and in vivo.

Self-Assembled Nano-Immunostimulant for Synergistic Immune Activation.

Immunotherapy has become one of the most promising therapies for the treatment of diseases. Synthetic immunostimulants and nanomaterial immunostimulant systems are indispensable for the activation of the immune system in cancer immunotherapy. Herein, a strategy for preparing self-assembled nano-immunostimulants (SANIs) for synergistic immune activation is reported.