Nanoparticle-mediated immunogenic cell death for cancer immunotherapy.

The field of cancer therapy is witnessing the emergence of immunotherapy, an innovative approach that activates the body own immune system to combat cancer. Immunogenic cell death (ICD) has emerged as a prominent research focus in the field of cancer immunotherapy, attracting significant attention in recent years. The activation of ICD can induce the release of damage-associated molecular patterns (DAMPs), such as calreticulin (CRT), adenosine triphosphate (ATP), high mobility group box protein 1 (HMGB1), and heat shock proteins (HSP). Subsequently, this process promotes the maturation of innate immune cells, including dendritic cells (DCs), thereby triggering a T cell-mediated anti-tumor immune response. The activation of the ICD ultimately leads to the development of long-lasting immune responses against tumors. Studies have demonstrated that partial therapeutic approaches, such as chemotherapy with doxorubicin, specific forms of radiotherapy, and phototherapy, can induce the generation of ICD. The main focus of this article is to discuss and review the therapeutic methods triggered by nanoparticles for ICD, while briefly outlining their anti-tumor mechanism. The objective is to provide a comprehensive reference for the widespread application of ICD.

Stability of tryptophan-containing LOs in flaxseed oil and their response towards γ-tocopherol.

Linusorbs (LOs), significantly influence oil quality and sensory properties of flaxseed oil. Trp-containing LOs exhibit distinct oxidative behavior when γ-tocopherol (γ-T) is present. Polar fractions of crude flaxseed oil were stripped via silica absorption, and reintroduced (LO and γ-T) separately into the oil matrix to investigate their interaction during storage. Compared with crude oil, LOs account for 18.49% reduction of p-anisidine value, while LOs with γ-T contributed to most of the endogenous antioxidant effect in crude oil. γ-T was found to suppress oxidation of Trp-containing LO at early stage (Met form), while facilitate oxidation while at their mid-stage (MetO form, Methionine sulfoxide). In vitro oxidation shows that CLD more likely cleaved into peptide fragments, while few products retain intact ring structures. LC-MS/MS analysis and silicon simulation revealed proximity between MetO and Trp residues, facilitating inter- or intra-molecular reactions and ring structure rupture. Remarkably, the presence of γ-T facilitate these phenomena.

Effects of traditional Chinese medicine on treatment outcomes in severe COVID-19 patients: a single-centre study.

As the search for effective treatments for COVID-19 continues, the high mortality rate among critically ill patients in Intensive Care Units (ICU) presents a profound challenge. This study explores the potential benefits of traditional Chinese medicine (TCM) as a supplementary treatment for severe COVID-19. A total of 110 critically ill COVID-19 patients at the Intensive Care Unit (ICU) of Vulcan Hill Hospital between Feb., 2020, and April, 2020 (Wuhan, China) participated in this observational study. All patients received standard supportive care protocols, with a subset of 81 also receiving TCM as an adjunct treatment. Clinical characteristics during the treatment period and the clinical outcome of each patient were closely monitored and analysed. Our findings indicated that the TCM group exhibited a significantly lower mortality rate compared with the non-TCM group (16 of 81 vs 24 of 29; 0.3 vs 2.3 person/month). In the adjusted Cox proportional hazards models, TCM treatment was associated with improved survival odds (P < 0.001). Furthermore, the analysis also revealed that TCM treatment could partially mitigate inflammatory responses, as evidenced by the reduced levels of proinflammatory cytokines, and contribute to the recovery of multiple organic functions, thereby potentially increasing the survival rate of critically ill COVID-19 patients.

Research progress of organic photothermal agents delivery and synergistic therapy systems.

Cancer is currently one of the leading causes of mortality worldwide. Due to the inevitable shortcomings of conventional treatments, photothermal therapy (PTT) has attracted great attention as an emerging and non-invasive cancer treatment method. Photothermal agents (PTAs) is a necessary component of PTT to play its role. It accumulates at the tumor site through appropriate methods and converts the absorbed light energy into heat energy effectively under near-infrared light irradiation, thus increasing the temperature of the tumor area and facilitating ablation of the tumor cells. Compared to inorganic photothermal agents, which have limitations such as non-degradability and potential long-term toxicity in vivo, organic photothermal agents exhibit excellent biocompatibility and biodegradability, thus showing promising prospects for the application of PTT in cancer treatment. And these organic photothermal agents can also be engineered into nanoparticles to improve their water solubility, extend their circulation time in vivo, and specifically target tumors. Moreover, further combination of PTT with other treatment methods can effectively enhance the efficacy of cancer treatment and alleviate the side effects associated with single treatments. This article briefly introduces several common types of organic photothermal agents and their nanoparticles, and reviews the applications of PTT based on organic photothermal agents in combination with chemotherapy, photodynamic therapy, chemodynamic therapy, immunotherapy, and multimodal combination therapy for tumor treatment, which expands the ideas and methods in the field of tumor treatment.

Structural insights into ligand recognition and subtype selectivity of the human melanocortin-3 and melanocortin-5 receptors.

Members of the melanocortin receptor (MCR) family that recognize different melanocortin peptides mediate a broad spectrum of cellular processes including energy homeostasis, inflammation and skin pigmentation through five MCR subtypes (MC1R-MC5R). The structural basis of subtype selectivity of the endogenous agonist γ-MSH and non-selectivity of agonist α-MSH remains elusive, as the two agonists are highly similar with a conserved HFRW motif. Here, we report three cryo-electron microscopy structures of MC3R-Gs in complex with γ-MSH and MC5R-Gs in the presence of α-MSH or a potent synthetic agonist PG-901. The structures reveal that α-MSH and γ-MSH adopt a "U-shape" conformation, penetrate into the wide-open orthosteric pocket and form massive common contacts with MCRs via the HFRW motif. The C-terminus of γ-MSH occupies an MC3R-specific complementary binding groove likely conferring subtype selectivity, whereas that of α-MSH distances itself from the receptor with neglectable contacts. PG-901 achieves the same potency as α-MSH with a shorter length by rebalancing the recognition site and mimicking the intra-peptide salt bridge in α-MSH by cyclization. Solid density confirmed the calcium ion binding in MC3R and MC5R, and the distinct modulation effects of divalent ions were demonstrated. Our results provide insights into ligand recognition and subtype selectivity among MCRs, and expand the knowledge of signal transduction among MCR family members.

Polysaccharides derived from Chinese medicinal herbs: A promising choice of vaccine adjuvants.

Adjuvants have been used in vaccines for a long time to promote the body's immune response, reducing vaccine dosage and production costs. Although many vaccine adjuvants are developed, the use in human vaccines is limited because of either limited action or side effects. Therefore, the development of new vaccine adjuvants is required. Many studies have found that natural polysaccharides derived from Traditional Chinese medicine (TCM) possess good immune promoting effects and simultaneously improve humoral, cellular and mucosal immunity. Recently polysaccharide adjuvants have attracted much attention in vaccine preparation because of their intrinsic characteristics: immunomodulation, biocompatibility, biodegradability, low toxicity and safety. This review article systematically analysed the literature on polysaccharides possessing vaccine adjuvant activity from TCM plants, such as Astragalus polysaccharide (APS), Rehmannia glutinosa polysaccharide (RGP), Isatis indigotica root polysaccharides (IRPS), etc. and their derivatives. We believe that polysaccharide adjuvants can be used to prepare the vaccines for clinical use provided their mechanisms of action are studied in detail.

Ameliorative effects of ginsenosides on myelosuppression induced by chemotherapy or radiotherapy.

BACKGROUND: and ethnopharmacological relevance: As the major side effect of radiotherapy or chemotherapy, myelosuppression usually leads to anemia, hemorrhage, immunosuppression, and even fatal infections, which may discontinue the process of cancer treatment. As a result, more and more attention is paid to the treatment of myelosuppression. Ginseng, root of Panax ginseng Meyer (Panax ginseng C. A. Mey), is considered as the king of herbs in the Orient, particularly in China, Korea and Japan. Ginsenosides, the most important active ingredients of ginseng, have been shown to have a variety of therapeutic effects, such as neuroprotective, anti-cancer and anti-diabetic properties. Considering that ginsenosides are closely associated with the pathogenesis of myelosuppression, researchers have carried out a few experiments on ginsenosides to attenuate myelosuppression induced by chemotherapy or radiotherapy in recent years. AIM OF THE STUDY: To summarize previous studies about the effects of ginsenosides on alleviating myelosuppression and the mechanisms of action. METHODS: Literatures in this review were searched in PubMed, China National Knowledge Infrastructure (CNKI), Web of Science, and ScienceDirect. RESULTS: Ginsenosides play an important role in relieving myelosuppression predominantly by restoring hematopoiesis and immunity. CONCLUSION: Ginsenosides might be potential candidates for the treatment of myelosuppression induced by chemotherapy or radiotherapy.

The Prebiotic-Like Effects of Coprinus comatus Polysaccharides on Gut Microbiota in Normal Mice and Those with Acute Alcoholic Liver Injury: A Comparative Study.

This study aims to investigate the prebiotic-like effects of Coprinus comatus polysaccharides (CCP) on gut microbiota. Mice were divided into four groups: normal group (NG), alcohol group (AG), polysaccharides group (PG), and alcohol + polysaccharides group (APG). The gut microbiota structure of feces was analyzed by determining the V3-V4 region sequence in 16S rDNA. The results showed CCP could increase the diversity of gut microbiota. Compared with NG, PG had a significantly higher relative abundance of Firmicutes and Lactobacillaceae and a lower abundance of Rikenellaceae. These changes in gut microbiota result in positive effects on gut due to a series of prebiotic-like effects of CCP. At the same time, CCP could improve some adverse changes in gut microbiota caused by acute alcohol intake, such as the increased proportion of Firmicutes, Bacteroidetes, Muribaculaceae, and Lachnospiraceae and the decreased proportion of Rikenellaceae. In conclusion, the CCP has certain prebiotic effects not only on normal mice but also on mice with acute alcoholic liver injury.

Correction to "A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts".

[This corrects the article DOI: 10.1021/acscentsci.9b01125.].

A Novel G Protein-Biased and Subtype-Selective Agonist for a G Protein-Coupled Receptor Discovered from Screening Herbal Extracts.

Subtype selectivity and functional bias are vital in current drug discovery for G protein-coupled receptors (GPCRs) as selective and biased ligands are expected to yield drug leads with optimal on-target benefits and minimal side-effects. However, structure-based design and medicinal chemistry exploration remain challenging in part because of highly conserved binding pockets within subfamilies. Herein, we present an affinity mass spectrometry approach for screening herbal extracts to identify active ligands of a GPCR, the 5-HT2C receptor. Using this method, we discovered a naturally occurring aporphine 1857 that displayed strong selectivity for activating 5-HT2C without activating the 5-HT2A or 5-HT2B receptors. Remarkably, this novel ligand exhibited exclusive bias toward G protein signaling for which key residues were identified, and it showed comparable in vivo efficacy for food intake suppression and weight loss as the antiobesity drug, lorcaserin. Our study establishes an efficient approach to discovering novel GPCR ligands by exploring the largely untapped chemical space of natural products.

Substolides A-G, germacrane sesquiterpenoids from Salvia substolonifera.

Chemical investigation of the whole plants of Salvia substolonifera E.Peter yielded seven germacrane sesquiterpenoids, substolides A-G (1-7), an ethoxylated artifact (8), and two known analogues, 6ß-tigloyloxyglechomafuran (9) and castanin F (10). Four germacrane 8-acetylation derivatives (1a-4a) were obtained by chemical transformation. Their structures and relative or absolute configurations were elucidated by intensive spectroscopic methods, and single-crystal X-ray diffraction analysis. Compounds 1a-4a, and 5-10 were evaluated for their in vitro anti-angiogenic effects. Compounds 7 and 9 significantly inhibited VEGF-induced human umbilical vein endothelial cell (HUVEC) proliferation in vitro, with IC50 values of 16.15 ± 0.19, and 4.03 ± 0.26 µM, respectively. The structure activity relationship of these compounds is discussed.

Curcumolide, a unique sesquiterpenoid with anti-inflammatory properties from Curcuma wenyujin.

Curcumolide, a novel sesquiterpenoid with a unique 5/6/5 tricyclic skeleton, was isolated from Curcuma wenyujin. The structure and absolute configuration were elucidated by extensive NMR, ECD data analysis, and a single-crystal X-ray study. This molecule exhibited significant anti-inflammatory effects in LPS-induced RAW 264.7 macrophages. It suppressed LPS-induced NF-κB activation, including the nuclear translocation and DNA binding activity of NF-κB, and decreased tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), interleukin-1ß (IL-1ß), nitric oxide (NO) and reactive oxygen species (ROS) production. Therefore, Curcumolide may have therapeutic potential for treating inflammatory diseases by inhibiting NF-κB activation and pro-inflammatory mediator production.

Simplified bicyclic pyridinol analogues protect mitochondrial function.

Bicyclic pyridinol antioxidants have been reported to suppress the autoxidation of methyl linoleate more effectively than α-tocopherol in benzene solution. A few novel lipophilic analogues have recently been synthesized by conjugating a pyridinol core with the phytyl side chain of α-tocopherol; these have been shown to possess potent antioxidant activity. However, the complexity of the synthetic routes has hampered their further development. Herein, we describe a facile approach, involving only five synthetic steps, to simplified analogues (1a-1c) and their acetate ester precursors (2a-2c). Simple alkyl chains of different lengths were attached to the 6-methyl group of the antioxidant core via regioselective metalation. These analogues were found to retain biological activity and exhibit protective behaviour under conditions of induced oxidative stress, which could lead to the development of more readily accessible analogues as potential antioxidants capable of preserving mitochondrial function.