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Rheumatoid arthritis (RA) is an essential cause of labor loss and disability for people worldwide. Acanthopanax senticosus polysaccharide (ASPS) is one of the most important active components from A. senticosus, which exhibits various pharmacological activities such as antioxidation and immunomodulation. However, no studies have reported the application of ASPS in treating RA. This study aims to investigate the therapeutic effect of ASPS on RA and reveal its underlying mechanism. The potential therapeutic effect of ASPS against RA is initially verified in this study using the collagen‐induced arthritis model. Moreover, the protective benefits of ASPS are transmitted through the fecal microbiota and blocked by simultaneous antibiotic cocktail treatment, indicating that gut microbiota may be correlated with ASPS. The 16S rRNA sequencing using feces samples and untargeted UPLC‐MS metabolomics using serum samples further reveal that ASPS reprograms the arthritic progression triggered dysbiosis, enhances the expression of γ‐glutamylcysteine (GGC) synthetase, and enriches the serum concentration of GGC. Furthermore, metabolites GGC is found to be able to effectively interrupt NLRP3 inflammasome activation via inhibiting ASC nucleation and therefore attenuate inflammatory arthritis. Taken together, this work highlights ASPS's therapeutic potential against RA, which mainly exhibits its effects via modulating gut microbiota and regulating GGC production. [ABSTRACT FROM AUTHOR]

Introduction: Numerous research works have shown that serum Gal-deficient (Gd) IgA1 levels are increased in IgA nephropathy (IgAN) patients and these levels are a dangerous risk factor for IgAN. A relationship between the gut microbiota and IgAN has been reported. Whether the gut microbiota participates in the pathogenesis of IgAN was still controversial. Methods: We evaluated changes in the gut flora and the levels of Gd-IgA1 in IgAN patients and healthy controls (HCs). We investigated the Gd-IgA1 levels in both blood and urine specimens. C57BL/6 mice were given a broad-spectrum antibiotic cocktail to deplete the endogenous gut flora. We established a model of IgAN in pseudosterile mice and investigated the expression of the markers of intestinal permeability, inflammation, and local immune responses. Results: Studies have shown that the levels of certain gut flora differ between IgAN patients and HCs. Moreover, elevated Gd-IgA1 levels were found in both the serum and urine. Interestingly, Coprococcus, Dorea, Bifidobacterium, Blautia, and Lactococcus, selected from 10 candidate biomarkers to predict risk in IgAN patients according to random forest analysis, were inversely associated with urinary Gd-IgA1 levels. Notably, the urine level of Gd-IgA1 could best distinguish IgAN patients from HCs. Additionally, the degree of kidney damage in pseudosterile mice with IgAN was more severe than that in mice with IgAN. Furthermore, the markers of intestinal permeability were significantly elevated in pseudosterile IgAN mice. Moreover, the inflammation responses (TLR4, MyD88, and NF-κB in intestinal and renal tissues; TNF-α and IL-6 in serum) and local immune responses (BAFF and APRIL in intestinal tissue) were upregulated in pseudosterile IgAN mice. Conclusions: The urine Gd-IgA1 level may be as a biomarker for the early screening of potential IgAN, and gut microbiota dysbiosis was demonstrated in IgAN, which might involve the dysfunction of the mucosal barrier, inflammation, and local immune responses. [ABSTRACT FROM AUTHOR]

Mountain Zizania latifolia is produced at scale in China, and the edible swollen culm is exported to many countries, but little attention has been paid to its functional components. In this work, microwave‐assisted enzymatic extraction (MAEE) is used for the first time to extract polysaccharides from mountain Z. latifolia swollen culm (PMZL). MAEE conditions optimized by Box–Behnken design‐response surface methodology were as follows: 2.4% cellulase, microwaving for 6.0 min at 607 W, with a liquid‐to‐solid ratio of 63:1 ml g−1. Under these conditions, a notably high yield of 60.43% ± 1.12% for PMZL was achieved, which was significantly higher (p < 0.01) than from plain‐grown varieties. PMZL are naturally occurring sulfated polysaccharide–protein complexes containing 8.46% ± 0.18% proteins and 7.86% ± 0.73% sulfates. PMZL comprises mannose, glucosamine, rhamnose, glucose, galactose, and arabinose at molar ratios of 3.80:2.68:1.00:17.41:5.12:2.91, with a weight‐average molecular weight of 1569,219 Da and a number‐average molecular weight of 364,088 Da. The surface morphology of PMZL is composed of tightly packed oval particles, and this kind of promising polysaccharides preferentially scavenges reactive nitrogen species. Practical Application: Due to global warming, the land available for planting vegetables is likely to expand to higher areas, so greater attention should now be paid to mountain‐grown vegetables. This study provides an efficient way to obtain novel polysaccharides from mountain Zizania latifolia using microwave‐assisted enzymatic extraction with a remarkably high yield of 60.4%. This promising source of natural carbohydrates has potential uses in pharmaceutical, nutraceutical, functional foods, cosmetics, and functional materials industries. [ABSTRACT FROM AUTHOR]

Infantile hemangioma (IH) is a common benign endothelial cell tumor in infants and young children, sometimes accompanied by potential complications, and may develop into malignant tumors. Hemangioma endothelial cells (HemECs) are one of the main components of IH. Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially anti‐tumor, but its high toxicity, poor water solubility, and serious gastrointestinal side effects limit its clinical application. In this study, we have designed and synthesized 20 ester derivatives by introducing Boc‐amino acids or organic acids at the C‐4 position of podophyllotoxin through esterification reactions. The cytotoxicity of these compounds was evaluated on HemECs. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, measurement of reactive oxygen species (ROS) levels flow cytometry, and Western blot analysis. We found that eight of the compounds were more potent than PPT. Of these, compound V‐31 was the most active (IC50 = 0.079 ± 0.0049 µM). Further research indicated that compound V‐31 inhibited its proliferation and migration, increased the level of ROS in cells, and induced apoptosis by downregulating p‐PI3K, p‐Akt, and Bcl‐2, and upregulating cleaved caspase‐3 and Bax. Our research provides the first insight into the application of PPT derivatives in HemECs, may provide an effective medicine for IH treatment. [ABSTRACT FROM AUTHOR]

A rich of 3,4-seco-lupane triterpenoids (3,4-SLT), including chiisanoside (CSS), divaroside (DVS), sessiloside-A1 (SSA), chiisanogenin (CSG), sessiligenin (SSG), were isolated from the ethanol extract of the leaves of Eleutherococcus sessiliflorus (LES). The present study was performed to explore the cytotoxic and anti-tumor effects of the isolated five ones, as well as potential molecular mechanisms. The results of a CCK-8 assay demonstrated that these 3,4-SLT can inhibit the growth of HepG2 cells, and SSG showed the most significant cytotoxicity. Hoechst 33258 fluorescence staining and Annexin V-FITC/PI staining indicated that 3,4-SLT in LES can induce HepG2 cell apoptosis effectively. The AutoDock Vina program was used to simulate molecular docking of drugs and targets to discuss possible pharmacological mechanisms. Besides, western blot and qRT-PCR results indicated that SSG can inhibit PI3K/AKT signaling pathway through controlling multi-targets. This study suggested that 3,4-SLT might become a new research hotspot for antineoplastic drugs. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of novel α-mangostin derivatives. • Compound 5 has a strong cardioprotective effect on myocardial cells. • Compound 5 may be used as a potential cardioprotective agent. In this study, 17 α-mangostin Boc amino acid/organic acid ester derivatives 1–17 were synthesized and subjected to cytotoxicity and cell viability screening assays. A hypoxia/reoxygenation model of cardiomyocyte injury was selected and compound 5 was found to have a better protective effect against hypoxia/reoxygenation-induced myocardial injury by prophylactic administration screening. The levels of LDH and CK-MB in extracellular fluid were detected by ELISA; apoptosis was detected by Hoechst3358/PI double staining, Annexin V-FITC/PI double staining and mitochondrial membrane potential; the expression of key proteins in PI3K/Akt signaling pathway was detected by western blot. The result showed that compound 5 was non-toxic and has a significant cytoprotection effect at concentrations of 1 μM and 10 μM, and reduced the levels of LDH and CK-MB in the extracellular fluid. Hoechst 33,258/PI double staining results showed that compound 5 treatment significantly reduced bright blue cell nuclei and had anti-apoptotic effects; flow cytometry results showed that compound 5 improved hypoxia/reoxygenation-induced mitochondrial membrane potential and thus apoptosis. The western blot results showed that compound 5 upregulated the levels of p-PI3K and p-Akt, decreased the expression of cleaved caspase-3, cleaved caspase-9 and increased the Bcl-2/Bax ratio in a concentration-dependent manner. In addition, compound 5 reversed the effect of the LY294002 inhibitor. The present study suggests that compound 5 may serve as a potential PI3K activator and a safe and effective lead compound for the treatment of cardiovascular disease. [ABSTRACT FROM AUTHOR]

Eleocharis dulcis, an aquatic plant belonging to Cyperaceae family, is indigenous to Asia, and also occurs in tropical Africa and Australia. The edible corm part of E. dulcis is a commonly consumed aquatic vegetable with a planting area of 44.46 × 103 hm2 in China. This work aims to explore the potential of E. dulcis corm for use as a new food source for sufficient nutrients and health benefits by reviewing its nutrients, phytochemicals, functions, processing and food products. Eleocharis dulcis corm contains starches, dietary fibers, non‐starch polysaccharides, proteins, amino acids, phenolics, sterols, puchiin, saponins, minerals and vitamins. Among them, phenolics including flavonoids and quinones could be the major bioconstituents that largely contribute to antioxidant, anti‐inflammatory, antibacterial, antitumor, hepatoprotective, neuroprotective and hypolipidemic functions. Peel wastes of E. dulcis corm tend to be enriched in phenolics to a much higher extent than the edible pulp. Fresh‐cut E. dulcis corm can be consumed as a ready‐to‐eat food or processed into juice for beverage production, and anti‐browning processing is a key to prolonging shelf life. Present food products of E. dulcis corm are centered on various fruit and vegetable beverages, and suffer from single categories and inadequate development. In brief, underutilized E. dulcis corm possesses great potential for use as a new food source for sufficient nutrients and health benefits. © 2021 Society of Chemical Industry. [ABSTRACT FROM AUTHOR]

[Display omitted] • Synthesis of novel camptothecin derivatives. • All compounds showed good in vitro cytotoxicity against five tumour cell lines. • 3D-QSAR, molecular docking to explore conformational relationships. Malignant tumors are increasing the human mortality rate year by year, so there is an urgent need to develop novel and highly effective drugs. Camptothecin (CPT) is a natural medicinal product with broad-spectrum antitumor activity. In this study, 11 CPT derivatives were synthesized. Their antitumor activities were evaluated by CCK-8, morphological observation, plate cloning, scratching, DAPI staining, cell cycle, and apoptosis. The conformational relationships were also analyzed by molecular docking and 3D-QSAR. The results showed that the CPT derivatives showed significant inhibitory effects on all five tumor cell lines, A549, HepG2, MCF-7, HemECs, and PC-3M, with the best inhibitory ability against PC-3M in prostate cancer. Among all derivatives, compound 5 had the lowest IC50 value of 0.0881 μM. In addition, compound 5 regulated the downstream cascade response by inhibiting the PI3K-Akt signaling pathway, causing cycle arrest and apoptosis. The predicted results of molecular docking and 3D-QSAR were consistent with those of the experimental group. This demonstrates the anti-tumor potential of compound 5. [ABSTRACT FROM AUTHOR]

Sagittaria trifolia is an aquatic plant that is distributed worldwide. The edible tuber part of S. trifolia is a very common and popular vegetable in China. The aim of the present review is to discuss the discovery of nutraceuticals from S. trifolia tuber by reviewing its major constituents, food processing, food products, and health‐promoting benefits. Sagittaria trifolia tuber comprises a series of nutritional and bioactive constituents, including dietary fibers, amino acids, minerals, starches, non‐starch polysaccharides, diterpenoids, colchicine, phenols, and organic acids. Food processing affects its flavor, biocomponents, and bioactivity. Numerous S. trifolia tuber‐based food products and nutraceuticals have been developed, but new categories of products and the anticipated functions still need to be explored. The non‐starch polysaccharides could be the central ingredients that contribute to the plant's antioxidant, hepatoprotective, hypoglycemic, lipid‐regulating, and immunostimulatory properties. Of these, antioxidant and hepatoprotective effects have been thoroughly investigated. Procedures for the extraction and purification of polysaccharides influence their health‐promoting actions. Overall, S. trifolia tuber is an underutilized aquatic vegetable species that is an emerging subject for nutraceutical research. © 2020 Society of Chemical Industry [ABSTRACT FROM AUTHOR]

Increasing evidence has suggested that microRNAs (miRNAs; miRs) are extensively involved in the progression of chondrosarcoma (CHS). However, few studies have investigated the functional role of miR-525 in CHS tissues and cells. In the present study, it was discovered that miR-525 levels were decreased in CHS tissues and cells. Dual luciferase assays indicated that F-spondin 1 (SPON1) is a target gene of microRNA (miR)-525. In addition, miR-525 overexpression suppressed SW1353 cell migration and invasion and enhanced SW1353 cell apoptosis. Increased SPON1 expression levels were identified in CHS tissues and cell lines. Furthermore, miR-525 overexpression significantly suppressed the activation of focal adhesion kinase (FAK)/Src/phosphatidylinositol-4,5-bisphosphate 3-kinase (PI3K)/protein kinase B (Akt) signaling in CHS cells; this suppression led to SPON1 silencing. In comparison, the SPON1 knockdown-mediated inactivation of FAK/Src/PI3K/Akt signaling was inhibited by inhibiting miR-525. In summary, the present study revealed that decreased miR-525 levels could enhance CHS malignancy as decreased miR-525 binding to the 3′ untranslated region of SPON1 activates FAK/Src/PI3K/Akt signaling. [ABSTRACT FROM AUTHOR]

The current study mainly aims to evaluate the expression pattern and underlying mechanism of upstream stimulating factor 1 (USF1) in the muscle tissues of knee osteoarthritis (KOA) patients. In accordance with previous findings, our data showed that muscle strength was significantly decreased in KOA patients compared with controls. Furthermore, several inflammatory factors, including tumor necrosis factor α (TNFα), IL-8, IL-6 and MCP-1, were associated with reduced muscle strength in KOA patients. Not surprisingly, NF-κB signaling was significantly activated in the muscle tissues of KOA patients compared with control individuals. Furthermore, we showed that USF1 was increased in the muscles of KOA patients compared with controls. More importantly, overexpression of USF1 in primary human skeletal muscle cells significantly increased the activation of NF-κB signaling as well as the levels of pro-inflammatory factors. In summary, we showed novel data that the upregulation of USF1 promoted NF-κB activation-induced inflammatory responses in muscle tissues of KOA patients. [ABSTRACT FROM AUTHOR]

GRAPH: Supporting Information ASPS Exhibits Anti-Rheumatic Effects by Reprogramming Gut Microbiota and Increasing Serumy-Glutamylcysteine Leve B 2022 b , I 9 i , 2205645 DOI: 10.1002/advs.202205645 Supporting Information file was replaced on May 5, 2023, after initial article online publication, to correct the description of the "immunofluorescence staining" method. [Extracted from the article]

Two new ceramides, (3S,4S,5R)-3-octadecanoylamino-4-hydroxy-5-dodecane-2,3,4,5-tetrahydrofuran (1) and (3S,4S,5R)-3-[(2R)-2-hydroxyhexacosanoylamino]-4-hydroxy-5-[(4E)-dodecane-4-ene]-2,3,4,5-tetrahydrofuran (2), together with eight known compounds, eleutheroside A (3), eleutheroside B (4), eleutheroside E (5), 7-hydroxy-6-methoxy-coumarin (6), 6,7-dimethoxycoumarin (7), 5α,8α-epidioxyergosta-6,22-dien-3-ol (8), stigmasterol (9) and rutin (10), were isolated from the fruit pulp ofAcanthopanax senticosus(Rupr. et Maxim) Harms. Their structures were elucidated by means of physicochemical properties and spectroscopic methods (1D, 2D NMR and MS). [ABSTRACT FROM PUBLISHER]

We consider the vulnerable option pricing problem when the stochastic interest rate is driven by a Hull-White model. Based on the firm value model, we suppose that the stock prices, assets and liabilities of a company follow the relevant O-U processes. We adopt the martingale approach to determine the equivalent martingale measure for pricing the vulnerable binary option, the analytical pricing formula of the vulnerable binary options is derived. [ABSTRACT FROM AUTHOR]

[Display omitted] Podophyllotoxin (PPT) has been reported to have many pharmacological activities, especially its anti-tumor effects. To improve the cytotoxicity and selective effect of PPT, in this study, we have designed and synthesized 20 ester derivatives by introducing Boc-amino acids or organic acids at the C-4 position of PPT. The cytotoxicity of these compounds was evaluated with PC-3M, HemECs, A549, MCF-7 and HepG2 cells. We observed that the proliferation of PC-3M cells was inhibited by all 20 ester derivatives in the largest degree, comparing to the other cell lines. Comparing to PPT (IC 50 = 234.90 ± 20.7 nM), eight derivatives had better performance in inhabiting proliferation of PC-3M cells, six of them belong to Boc-amino acid ester derivatives, and the derivative named V-05 (IC 50 = 1.28 ± 0.1 nM) had the strongest inhibitation effect. Changes in cell proliferation and apoptotic signaling pathways were studied by DAPI staining, colony formation assay, migration assay, flow cytometry and western blot analysis. We found that V-05 were able to inhibit PC-3M cells proliferation and migration, and induced apoptosis by downregualting p-PI3K, p-Akt and Bcl-2, and upregulating Cleaved caspase-3 and Bax. Our research provides the first insight for the application of PPT derivatives in PC-3M cells, which may offer information to the effective medicine development for human prostate cancer treatment. [ABSTRACT FROM AUTHOR]