In order to evaluate the application potential of rainbow trout (Oncorhynchus mykiss) heads and skipjack tuna (Katsuwonus pelamis) heads; proximate composition, amino acids, fatty acids, carnosine, and anserine contents were analyzed in this study. Rainbow trout heads showed significantly higher protein (29.31 g/100 g FW, FW is abbreviation of fresh weight) and lipid (6.03 g/100 g FW) contents than skipjack tuna heads (18.47 g/100 g FW protein and 4.83 g/100 g FW lipid) (p < 0.05). Rainbow trout heads and skipjack tuna heads exhibited similar amino acid composition. Essential amino acids constituted more than 40% of total amino acids in both rainbow trout head and skipjack tuna head. The fatty acid profile was different between rainbow trout heads and skipjack tuna heads. Rainbow trout heads mainly contained 38.64% polyunsaturated fatty acids (PUFAs) and 38.57% monounsaturated fatty acids (MUFAs), whereas skipjack tuna heads mainly contained 54.46% saturated fatty acids (SFAs). Skipjack tuna heads contained 4563 mg/kg FW anserine and 1761 mg/kg FW carnosine, which were both significantly higher than those of rainbow trout heads (p < 0.05). These results demonstrate that both rainbow trout heads and skipjack tuna heads may be used as materials for recycling high-quality protein. Meanwhile, rainbow trout heads can be used to extract oil with high contents of unsaturated fatty acids, while skipjack tuna heads may be a source for obtaining carnosine and anserine.

Protocatechuic acid (PCA) is a natural component with multiple biological activities. However, the underlying mechanisms of the effects of PCA on anti-ulcerative colitis (UC) are unclear. A UC mouse model was established by allowing the mice to freely drink a dextran sulfate sodium solution. The mice were administered PCA intragastrically for 7 days. Histological pathology, intestinal flora, and ferroptosis regulators were determined in vivo. Additionally, ferroptotic Caco-2 cells were modeled to investigate the role of PCA in ferroptosis. Our results showed that PCA reduced the levels of the disease activity index, inflammatory factors, and histological damage in UC mice. We also found that the regulation of intestinal flora, especially Bacteroidetes, was one of the potential mechanisms underlying the protective effects of PCA anti-UC. Moreover, PCA downregulated the level of ferroptosis in the colon tissue, as evidenced by a reduced iron overload, decreased glutathione depletion, and a lower level of malondialdehyde production compared with the model group. Similar effects of PCA on ferroptosis were observed in Erastin-treated Caco-2 cells. The results obtained using reactive oxygen species assays and the changes in mitochondrial structure observed via scanning electron microscopy also support these results. Our findings suggested that PCA protected against UC by regulating intestinal flora and ferroptosis.

It is known that the ATP-binding cassette transporter A1 (ABCA1) plays a major role in cholesterol homeostasis and high density lipoprotein (HDL) metabolism. Several laboratories have demonstrated that ABCA1 binding to lipid-poor apolipoprotein A-I (apoA-I) will mediate the assembly of nascent HDL and cellular cholesterol efflux, which suggests a possible receptor-ligand interaction between ABCA1 and apoA-I. In this study, a cell-based-ELISA-like high-throughput screening (HTS) method was developed to identify the synthetic and natural compounds that can regulate binding activity of ABCA1 to apoA-I. The cell-based-ELISA-like high-throughput screen was conducted in a 96-well format using Chinese hamster ovary (CHO) cells stably transfected with ABCA1 pIRE2-EGFP (Enhanced Green Fluorecence Protein) expression vector and the known ABCA1 inhibitor glibenclamide as the antagonist control. From 2,600 compounds, a xanthone compound (IMB 2026791) was selected using this HTS assay, and it was proved as an apoA-I binding agonist to ABCA1 by a flow cytometry assay and western blot analysis. The [3H] cholesterol efflux assay of IMB2026791 treated ABCA1-CHO cells and PMA induced THP-1 macrophages (human acute monocytic leukemia cell) further confirmed the compound as an accelerator of cholesterol efflux in a dose-dependent manner with an EC(50) of 25.23 μM.

In this study, the encapsulation mechanism of oxyresveratrol and β-cyclodextrin (β-CD) and hydroxypropyl-β-cyclodextrin (HP-β-CD) was studied. As this research shows, oxyresveratrol and two cyclodextrins (CDs) were able to form inclusion complexes in a 1:1 stoichiometry. However, the interaction with HP-β-CD was more efficient, showing up as higher encapsulation constant (KF) (35,864.72 ± 3415.89 M-1). The KF values exhibited a strong dependence on temperature and pH, which decreased as they increased. From the thermodynamic parameters (ΔH⁰, ΔS⁰, and ΔG⁰) of the oxyresveratrol loaded β-CD (oxyresveratrol-β-CD) and HP-β-CD (oxyresveratrol-HP-β-CD), it could be seen that the complexation process was spontaneous and exothermic, and the main driving forces between oxyrsveratrol and CDs were hydrogen bonding and van der waals force. Besides, molecular docking combined with ¹H-NMR were used to explain the most possible mode of interactions between oxyresveratrol and CDs.

Prenylated natural products have interesting pharmacological properties and prenylation reactions play crucial roles in controlling the activities of biomolecules. They are difficult to synthesize chemically, but enzymatic synthesis production is a desirable pathway. Cyclic dipeptide prenyltransferase catalyzes the regioselective Friedel-Crafts alkylation of tryptophan-containing cyclic dipeptides. This class of enzymes, which belongs to the dimethylallyl tryptophan synthase superfamily, is known to be flexible to aromatic prenyl receptors, while mostly retaining its typical regioselectivity. In this study, seven tryptophan-containing cyclic dipeptides 1a-7a were converted to their C7-regularly prenylated derivatives 1b-7b in the presence of dimethylallyl diphosphate (DMAPP) by using the purified 7-dimethylallyl tryptophan synthase (7-DMATS) as catalyst. The HPLC analysis of the incubation mixture and the NMR analysis of the separated products showed that the stereochemical structure of the substrate had a great influence on their acceptance by 7-DMATS. Determination of the kinetic parameters proved that cyclo-l-Trp-Gly (1a) consisting of a tryptophanyl and glycine was accepted as the best substrate with a KM value of 169.7 μM and a turnover number of 0.1307 s-1. Furthermore, docking studies simulated the prenyl transfer reaction of 7-DMATS and it could be concluded that the highest affinity between 7-DMATS and 1a. Preliminary results have been clearly shown that prenylation at C7 led to a significant increase of the anticancer and antimicrobial activities of the prenylated derivatives 1b-7b in all the activity test experiment, especially the prenylated product 4b.

Apolipoprotein A-I (Apo A-I) is the principal protein component of high density lipoprotein (HDL), which is generally considered as a potential therapeutic target against atherosclerosis. The understanding of the Apo A-I regulation mechanism has fuelled the development of novel HDL targeted therapeutic approaches. To identify novel agents that can upregulate Apo A-I expression, we performed a cell-based reporter assay to screen 25,600 small molecules. Based on the dataset obtained from screening, a series of novel analogs of substituted benzamides containing azaspiro rings were assessed for their ability to induce the transcription of the Apo A-I gene, and the structure-activity relationship (SAR) around these analogs was also proposed. The results indicated that the trifluoromethyl substituted benzamide containing an azaspiro ring is a promising backbone for designing Apo A-I transcriptional upregulator and could be viable leads for development of new drugs to prevent and treat atherosclerosis in the future.

A new abeo-abietane diterpenoid, 12-methoxy-6,11,14,16-tetrahydroxy-17(15→16)-abeo-5,8,11,13-abietatetraen-3,7-dione (8), was isolated from the hydroalcoholic extract of the herb of Clerodendrum kiangsiense along with seven known diterpenoids (1-7). Their structures were identified on the basis of spectroscopic analyses including two-dimensional NMR and comparison with literature data. All of these compounds were evaluated for their cytotoxic activities against the growth of human cancer cells lines HL-60, SMMC-7721, A-549 and MCF-7 by the MTT assay. The results showed that cryptojaponol (4), fortunin E (6) and 8 exhibited significant cytotoxicity against four human cancer cell lines.

Two new abietane diterpenoids (1,2), along with five known diterpenoids (3-7), were first isolated and purified from the stems of Clerodendrum bracteatum. The structures of the new compounds were established by extensive analysis of mass spectrometric and 1-D, 2-D NMR spectroscopic data. Their antioxidant activities were determined on DPPH radical scavenging and ABTS. The in vitro cytotoxic activities of the compounds were evaluated against the HL-60 and A549 cell lines by the MTT method.

The pollution of heavy metal ions can cause damage to the human body through food, so developing a new biocompatible material that can remove the damage of heavy metal ions has a good application prospect. In this study, we obtained a new homogeneous polysaccharide composed of seven monosaccharides from Zingiber strioatum by using the method of separation and purification of polysaccharide. The results of adsorption behavior showed that the concentration, temperature and pH value could affect the adsorption effect of Zingiber strioatum polysaccharide (ZSP). Through model fitting of the data of adsorption time and metal concentration, the pseudo second-order kinetic model can well describe the kinetics of the adsorption process, and the adsorption isotherm data fit well with the Langmuir model. In the preliminary research results of adsorption mechanism, SEM showed the appearance of ZSP as flake and porous surface; EDX analysis confirmed the metal adsorption capacity of ZSP. Meanwhile, XPS and FT-IR further clarified the adsorption based on functional groups composed of C and O. The cells preprotected by ZSP can resist heavy metal ions. The above results show that ZSP can be used as a new macromolecule to bind heavy metal ions, which can broaden the research scope of polysaccharides in contaminated food systems.

Diabetic nephropathy (DN) contributes to increased morbidity and mortality among patients with diabetes and presents a considerable global health challenge. However, reliable biomarkers of DN have not yet been established. Phosphorylated proteins are crucial for disease progression. However, their diagnostic potential remains unexplored. In this study, we used ultra-high-sensitivity quantitative phosphoproteomics to identify phosphoproteins in urinary extracellular vesicles (uEVs) as potential biomarkers of DN. We detected 233 phosphopeptides within the uEVs, with 47 phosphoproteins exhibiting significant alterations in patients with DN compared to those in patients with diabetes. From these phosphoproteins, we selected phosphorylated aquaporin-2 (p-AQP2[S256]) and phosphorylated glycogen synthase kinase-3β (p-GSK3β[Y216]) for validation, as they were significantly overrepresented in pathway analyses and previously implicated in DN pathogenesis. Both phosphoproteins were successfully confirmed through Phos-tag western blotting in uEVs and immunohistochemistry staining in kidney sections, suggesting that phosphoprotein alterations in uEVs reflect corresponding changes within the kidney and their potential as candidate biomarkers for DN. Our research proposes the utilization of phosphoproteins in uEVs as a liquid biopsy, presenting a highly feasible diagnostic tool for kidney disease.

Genipin has been the focus of research as a multifunctional compound for the treatment of pathogenic diseases. However, hepatotoxicity caused by oral genipin raises concerns about its safety. To obtain novel derivatives with low toxicity and efficacy, we synthesized methylgenipin (MG), a new compound, using structural modification, and investigated the safety of MG administration. The results showed that the LD50 of oral MG was higher than 1000 mg/kg, no mice died or were poisoned during the experiment in the treatment group, and there was no significant difference in biochemical parameters and liver pathological sections compared with the control. Importantly, MG (100 mg/kg/d) treatment for 7 days reduced alpha-naphthylisothiocyanate (ANIT)-induced increases in liver index, alanine aminotransferase (ALT), aspartate aminotransferase (AST), alkaline phosphatase (AKP), and total bilirubin (TBIL) levels. Histopathology demonstrated that MG could treat ANIT-induced cholestasis. In addition, using proteomics to investigate the molecular mechanism of MG in the treatment of a liver injury may be related to enhancing antioxidant function. Kit validation showed that ANIT induced an increase in malondialdehyde (MDA) and a decrease in superoxide dismutase (SOD) and glutathione (GSH) levels, while the MG pretreatments, both of which were significantly reversed to some extent, suggested that MG may alleviate ANIT-induced hepatotoxicity by enhancing endogenous antioxidant enzymes and inhibiting oxidative stress injury. In this study, we demonstrate that the treatment of mice with MG does not cause impaired liver function and provide an investigation of the efficacy of MG against ANIT-induced hepatotoxicity, laying the foundation for the safety evaluation and clinical application of MG.

Salvianolic acid B (Sal B) is the primary water-soluble bioactive constituent derived from the roots of Salvia miltiorrhiza Bunge. This research was designed to reveal the potential mechanism of Sal B anti-liver injury from the perspective of macrophages. In our lipopolysaccharide-induced M1 macrophage model, Sal B showed a clear dose-dependent gradient of inhibition of the macrophage trend of the M1 type. Moreover, Sal B downregulated the expression of lactate dehydrogenase A (LDHA), while the overexpression of LDHA impaired Sal B's effect of inhibiting the trend of macrophage M1 polarization. Additionally, this study revealed that Sal B exhibited inhibitory effects on the lactylation process of histone H3 lysine 18 (H3K18la). In a ChIP-qPCR analysis, Sal B was observed to drive a reduction in H3K18la levels in the promoter region of the LDHA, NLRP3, and IL-1β genes. Furthermore, our in vivo experiments showed that Sal B has a good effect on alleviating CCl4-induced liver injury. An examination of liver tissues and the Kupffer cells isolated from those tissues proved that Sal B affects the M1 polarization of macrophages and the level of histone lactylation. Together, our data reveal that Sal B has a potential mechanism of inhibiting the histone lactylation of macrophages by downregulating the level of LDHA in the treatment of liver injury.