Coptisine inhibits aggressive and proliferative actions of fibroblast like synoviocytes and exerts a therapeutic potential for rheumatoid arthritis.

OBJECTIVE: Coptisine, a natural bioactive small molecular compound extracted from traditional Chinese herb Coptis chinensis, has been shown to exhibit anti-tumor effect. However, its contribution to autoimmune diseases such as rheumatoid arthritis (RA) is unknown. Here, we evaluate the effect of coptisine in controlling fibroblast-like synoviocytes (FLS)-mediated synovial proliferation and aggression in RA and further explore its underlying mechanism(s). METHODS: FLS were separated from synovial tissues obtained from patients with RA. Protein expression was measured by Western blot or immunohistochemistry. Gene expression was detected by quantitative RT-PCR. The EdU incorporation was used to measure cell proliferation. Migration and invasion were determined by Boyden chamber assay. RNA sequencing analysis was used to seek for the target of coptisine. The in vivo effect of coptisine was evaluated in collagen-induced arthritis (CIA) model. RESULTS: Treatment with coptisine reduced the proliferation, migration, and invasion, but not apoptosis of RA FLS. Mechanistically, we identified PSAT1, an enzyme that catalyzes serine/one-carbon/glycine biosynthesis, as a novel targeting gene of coptisine in RA FLS. PSAT1 expression was increased in FLS and synovial tissues from patients with RA compared to healthy control subjects. Coptisine treatment or PSAT1 knockdown reduced the TNF-α-induced phosphorylation of p38, ERK1/2, and JNK MAPK pathway. Interestingly, coptisine administration improved the severity of arthritis and reduced synovial PSAT1 expression in mice with CIA. CONCLUSIONS: Our data demonstrate that coptisine treatment suppresses aggressive and proliferative actions of RA FLS by targeting PSAT1 and sequential inhibition of phosphorylated p38, ERK1/2, and JNK MAPK pathway. Our findings suggest that coptisine might control FLS-mediated rheumatoid synovial proliferation and aggression, and be a novel potential agent for RA treatment.

Untargeted metabolite profiling of serum in rats exposed to pyrraline.

Pyrraline, one of advanced glycation end-products, is formed in advanced Maillard reactions. It was reported that the presence of pyrraline was tested to be associated with nephropathy and diabetes. Pyrraline might result in potential health risks because many modern diets are heat processed. In the study, an integrated metabolomics by ultra-high-performance liquid chromatography with mass spectrometry was used to evaluate the effects of pyrraline on metabolism in rats. Thirty-two metabolites were identified as differential metabolites. Linolenic acid metabolism, phenylalanine, tyrosine and tryptophan biosynthesis, arachidonic acid metabolism, tyrosine metabolism and glycerophospholipid metabolism were the main perturbed networks in this pathological process. Differential metabolites and metabolic pathways we found give new insights into studying the toxic molecular mechanisms of pyrraline. Supplementary Information: The online version contains supplementary material available at 10.1007/s10068-023-01256-7.

Ecological and health risk assessment of heavy metals in soil and Chinese herbal medicines.

As medicinal plants can accumulate harmful metals from the native soil, people's consumption of these materials may cause the human body to accumulate toxic metal elements. This has given rise to people's concerns about the quality and safety of Chinese medicinal materials. This research aims to determine the levels of Cr, Ni, Cu, Zn, As, Cd, Hg and Pb in four medicinal plant species (Aster tataricus L.f., Salvia miltiorrhiza Bge, Radix Aucklandiae, Scutellaria baicalensis Georgi) and their native soil. All samples were collected from Qian'an city, beside Yanshan Mountain Range in Tangshan city, east Hebei Province, north China. The contents of heavy metals we detected in the soil conformed to the current limits. However, the Cd and Hg in the soil had a very high potential ecological risk because of their contents higher than the base level of local soil. The contents of Cu, Cd, Hg and Pb in some medicinal herbs exceeded the standards. The content of Cu in Radix Aucklandiae exceeded the standard by 3 times, and others exceeded the standard by less than one time. The comprehensive health risk assessment of heavy metals with chronic non-carcinogenic effects for human body showed that none of the four medicinal herbs can create a health risk. Thus, there is no strong positive correlation between heavy metal pollution in medicinal herbs and that in the native soil. Further research should be investigated to the connection between the heavy metal levels in the soil and plants, and the comprehensive effects of soil, air and irrigation water on heavy metal pollution of Chinese herbal medicines. We also recommend that Chinese herbal medicines should be cultivated and gathered only from controlled or uncontaminated areas.

Potential mechanisms underlying the ameliorative effect of Lactobacillus paracasei FZU103 on the lipid metabolism in hyperlipidemic mice fed a high-fat diet.

Lactobacillus paracasei FZU103, a probiotic previously isolated from the traditional brewing process of Hongqu rice wine, may have the beneficial effect of improving the disorder of lipid metabolism. This study aimed to determine the beneficial effects of L. paracasei FZU103 on improving hepatic lipid accumulation associated with hyperlipidemia. Results indicated that L. paracasei FZU103 intervention significantly inhibited the abnormal growth of body weight and epididymal white adipose tissue (eWAT), prevented the hypertrophy of epididymal adipocytes, ameliorated the biochemical parameters of serum and liver related to lipid metabolism in HFD-fed mice. Histological analysis also showed that the excessive accumulation oflipid dropletsin the livers induced by HFD-feeding was greatly alleviated by L. paracasei FZU103 intervention. In addition, L. paracasei FZU103 also promoted the excretion of bile acids (BAs) through feces. Metagenomic analysis revealed that oral supplementation with L. paracasei FZU103 significantly increased the relative abundance of Ruminococcus, Alistipes, Pseudoflavonifractor and Helicobacter, but decreased the levels of Blautia, Staphylococcos and Tannerella in HFD-fed mice. The relationships between lipid metabolic parameters and intestinal microbial phylotypes were also revealed by correlation heatmap and network. Furthermore, ultra-performance liquid chromatography-quadrupole time-of-flight mass spectrometry (UPLC-QTOF/MS)-based liver metabolomics demonstrated that L. paracasei FZU103 had a significant regulatory effect on the metabolic pathways of glycerophospholipid metabolism, fatty acid degradation, fatty acid elongation, unsaturated fatty acids biosynthesis, riboflavin metabolism, glycerolipid metabolism, primary bile acid biosynthesis, arachidonic acid metabolism, etc. Additionally, L. paracasei FZU103 intervention regulated expression of hepatic genes involved in lipid metabolism and bile acid homeostasis, and promoted fecal excretion of intestinal BAs. These findings present new evidence supporting that L. paracasei FZU103 has the potential to improve lipid metabolism, and could be used as a potential functional food for the prevention of hyperlipidemia.

Effect of alkylresorcinols on the formation of Nε-(carboxymethyl)lysine and sensory profile of wheat bread.

Alkylresorcinols (ARs) are important bioactive components in wheat bran which have been used as biomarkers for whole grain wheat consumption. In this study, the impact of ARs on the formation of Nε-(carboxymethyl)lysine (CML), the main component of dietary advanced glycation end products which could induce chronic disease was analyzed. Moreover, the influence of the addition of ARs on the sensory profiles of wheat bread was evaluated. ARs supplementation (0.03%, 0.1%, and 0.3% w/w) could significantly decrease the formation of CML by 21.70%, 35.11%, and 42.18%, respectively, compared with the control. Moreover, ARs-supplemented bread achieved a higher score in overall acceptability and buttery-like aroma through sensory evaluation. The volatile compounds in bread supplemented with ARs were characterized by headspace solid phase microextraction-gas chromatography-mass spectrometry (HS-SPME-GC-MS), among which acetoin, 2,3-butanedione, 3-methyl-1-butanol, 2-phenylethanol, and 2-methylbutanal were confirmed as the main volatile compounds through determination of odor activity value. In addition, ARs supplementation had no negative impact on the chewiness, hardness, and springiness of bread. These findings demonstrated that ARs could be applied as potential food additives to improve the quality and sensory profile of bread.

Enhancement of glucaric acid production in Saccharomyces cerevisiae by expressing Vitreoscilla hemoglobin.

OBJECTIVE: To enhance the glucaric acid (GA) production in Saccharomyces cerevisiae, the Vitreoscilla hemoglobin was employed to reinforce cellular oxygen supplement. Additionally, the pH-free fermentation strategy was engaged to lower the cost brought by base feeding during the acid-accumulated and long-period glucaric acid production. RESULTS: Recombinant yeast Bga-4 was constructed harboring Vitreoscilla hemoglobin on the basis of previous Bga-3. Higher glucose uptake rate, growth rate, and ethanol reuse rate were achieved in Bga-4 in shake-flask fermentation than those in Bga-3. Furthermore, the fed-batch fermentation in a 5-L bioreactor was performed without pH control, resulting in a final glucaric acid titer of 6.38 g/L. CONCLUSIONS: Both the GA titer and biomass were enhanced along with the efficiency of ethanol re-utilization in the presence of VHb. Moreover, the absence of base feeding for long-period fermentation reduced production cost, which is meaningful for industrial applications.

Untargeted Metabolite Profiling of Adipose Tissue in Hyperlipidemia Rats Exposed to Hawthorn Ethanol Extracts.

The study aimed to explore the metabolic changes of adipose tissue of hyperlipidemia rats with hawthorn ethanol extracts (HEE) consumption by a high-throughput metabolomics approach. HEE were mainly composed of chlorogenic acid, hyperoside, isoquercitrin, rutin, vitexin, quercetin, and apigenin by HPLC analysis. HEE administration significantly lowered levels of the total cholesterols, triglyceride and low-density lipoprotein cholesterol as compared to the high-fat diet model. Gas chromatography-mass spectrometry was used to identify adipose metabolite profiles. Numerous endogenous molecules were altered by high-fat diet and restored following intervention of HEE. Metabolites elevated in adipose, including l-threonine, aspartic acid, glutamine, mannose, inositol and oleic acid, were detected after HEE consumption. Fifteen metabolites were identified as potential biomarkers of hyperlipidemia. Pathway analysis showed that most of the discriminant metabolites were included in fatty acid biosynthesis, galactose metabolism, biosynthesis of unsaturated fatty acids, arginine and proline metabolism, alanine, aspartate and glutamate metabolism, glycerolipid metabolism and steroid biosynthesis. These metabolites and metabolic networks we found offer new insights into exploring the molecular mechanisms of lipid-lowering of hawthorn ethanol extracts on adipose tissue of rats. PRACTICAL APPLICATION: There was a very high proportion of hyperlipidemia in China. Hawthorn is attracting increasing attention owing to their health benefits, low toxicity, effectiveness and might be suitable for long-term use.

Glutinous rice amylopectin can adjust the plasma gut-regulated peptide levels in rhubarb-induced spleen deficiency rats.

The pharmacological effects of glutinous rice (GR) and GR amylopectin (GRA) on the gastrointestine were investigated in rhubarb-induced spleen deficiency rats by determining the levels of gastrointestinal hormones such as the peptides serum gastrin, amylase motilin, and somatostatin. GR and GRA were given by gavage at various doses of GR (7.5, 15, and 30 g per kg body weight) and GRA (3.8, 7.6, and 15 g per kg body weight) every day for 4 weeks, respectively. The results indicated that the final body weight of rats in the highest-dose GR (GRH) group and all the GRA groups significantly (P < 0.05) increased (7.2-12.1%) compared with the model control (MC) group. All the GR and GRA treated groups had significantly (P < 0.05) higher gastrin contents (32.8-51.2%), motilin levels (13.8-39.2%), and amylase contents (22.5-39.4%) and the GRH and highest-dose GRA (GRAH) groups had significantly (P < 0.05) lower somatostatin contents compared with the MC group. Meanwhile, the somatostatin contents were negatively correlated with the motilin levels (r = -0.964, P < 0.01) and amylase contents (r = -0.981, P < 0.01). The GRAH treatment group had the highest final body weight, gastrin contents, motilin levels, and amylase contents and the lowest somatostatin contents, which demonstrated that GRA might play the most important role in the spleen-regulating activities of GR.

Application of an optosensing chip based on molecularly imprinted polymer coated quantum dots for the highly selective and sensitive determination of sesamol in sesame oils.

A novel optosensing chip was constructed by anchoring the fluorescence sensing material layer based on molecularly imprinted polymer (MIP) coated CdSe/ZnS quantum dots (QDs) on a chip for highly selective and sensitive optosensing of sesamol in sesame oil. Many factors that affected the performance of the optosensing chip based on MIP-coated QDs are discussed. Under optimized conditions, the relative fluorescence intensity of the optosensing chip decreased linearly (r(2) > 0.99) with increasing sesamol concentration in the range from 2.4 × 10(-6) to 1.2 × 10(-3) mol L(-1) with a detection limit of 7.2 × 10(-8) mol L(-1). The relative standard deviation for five replicate detections of 4.8 × 10(-4) mol L(-1) sesamol was 2.2%. Recoveries of 94.8-102.3% were achieved by direct detection when the optosensing chip was used for the selective detection of sesamol in sesame oil. Practically, the optosensing approach showed high sensitivity, good selectivity, and excellent reproducibility for the detection of sesamol in real oil samples.

Effects of ellagic acid-rich extract of pomegranates peel on regulation of cholesterol metabolism and its molecular mechanism in hamsters.

The study investigated the effect of pomegranates ellagic acid (PEA) on blood cholesterol and investigated its effects on LXR/RXR/PPAR-ABCA1 nuclear receptors-signaling pathways of cholesterol metabolism on molecular level in hamsters. In this experiment, hamsters were randomly divided into two groups: the first group (NG, n = 9) was always fed the normal diet, whereas the other group (HFG, n = 45) was fed a high fat diet during the first 4 weeks and then fed the normal diet for the last 4 weeks. In HFG, which was divided into five groups (n = 9) during the last 4 weeks, three groups were treated with PEA at 44 mg per kg bw, 88 mg per kg bw and 177 mg per kg bw, one group was treated with simvastatin at 1.77 mg per kg bw, and one was given sterile double-distilled water. The data validated that PEA dose-dependently decreased plasma total cholesterol and triglyceride level accompanied by a greater excretion of fecal bile acid. The result of RT-PCR revealed that PEA up-regulated liver X receptor (LXRα), peroxisome proliferator-activated receptor α (PPARα), peroxisome proliferator-activated receptor γ (PPARγ) and their downstream gene ATP-binding cassette transporter A1 (ABCA1), with no effect on retinoid X receptor (RXRα). PEA promoted cholesterol removal by enhancing fecal bile acid and up-regulation of the two pathways, LXR/PPAR-ABCA1. Moreover, PEA was stronger than simvastatin in some aspects.

Hepatotoxicity and nephrotoxicity of organic contaminants in wastewater-irrigated soil.

The objective of this study is to investigate the hepatotoxicity and nephrotoxicity of organic contaminants in wastewater-irrigated soil using in vivo and in vitro experiments on mice and rat. Soil samples were collected from a wastewater-irrigated area and groundwater-irrigated area, i.e. clean water-irrigated area as control group. The organic contaminants were extracted using an ultrasonic oscillator. In vivo experiment was performed by contamination of hepatocytes of rat using the organic extract, and comet assay was used to analyse the DNA damage of hepatocytes. For in vitro experiment, mice were first gavaged with extracts, and then the indicators for kidney functions, liver functions and oxidative damage of tissues were investigated. The result shows, for in vitro experiments, compared with clean water-irrigated area groups, the average DNA tailing length for the wastewater-irrigated area group is larger, and for the wastewater-irrigated area groups with extract concentration 0.6 g/ml and 0.9 g/ml, the tailing rate increases significantly (P < 0.05). For in vivo experiments, the change of weight across each group shows no significant difference (P < 0.05). Compared with clean water-irrigated groups, the liver indices have decreased for all groups of the wastewater-irrigated area, while both kidney and liver indices decreased for wastewater-irrigated area high-dose group (P < 0.05 or P < 0.01). The total proteins for wastewater-irrigated low-dose group and Gamma-glutamyl transpeptidase, creatinine for high-dose group all increased (P < 0.01). Compared with the reagent control group, total superoxide dismutase activity of liver for wastewater-irrigated groups and glutathione peroxidase activity for high-dose group, malondialdehyde content all decreased (P < 0.05 or P < 0.01); glutathione peroxidase activity of kidney tissue for wastewater-irrigated high-dose group decreased (P < 0.01). The result shows that the joint toxicity in extracts of wastewater-irrigated soil is able to cause DNA damage of hepatocytes in rats, changes of liver functions in mice and lead to oxidative damage of liver and kidney.

Characterization of C-terminally engineered laccases.

Extremities of proteins are potent sites for functionalization. Carboxy terminus variants of the Trametes sp. strain C30 LAC3 laccase were generated and produced in Saccharomyces cerevisiae. A variant deleted of the last 13 residues (CΔ) and its 6 His tagged counterpart (CΔ6H) were found active enzymes. The production of CΔ6H resulted in the synthesis of a unusually high proportion of highly glycosylated forms of the enzyme therefore allowing the additional purification of a hyper-glycosylated form of CΔ6H noted CΔ6Hh. Properties of CΔ, CΔ6H and CΔ6Hh were compared. Globally, LAC3 catalytic efficiency was moderately affected by terminal modifications except in CΔ for which the kcat/KM ratio decreased 4 fold (with syringaldazine as substrate) and 10 fold (with ABTS as substrate) respectively. The catalytic parameters kcat and KM of CΔ6H and CΔ6Hh were found to be strictly comparable revealing that over glycosylation does not affect the enzyme catalytic efficiency. To the contrary, in vitro deglycosylation of laccase drastically reduced its activity. So, despite a complex glycosylated pattern observed for some of the variant enzymes, terminal sequences of laccases appear to be appropriate sites for the functionalization/immobilization of laccase.

Optimisation of ultrasound-assisted enzymatic extraction of arabinoxylan from wheat bran.

Arabinoxylan, the major dietary fibre component of wheat bran, is important from both technological and nutritional points of view. In this study, ultrasound-assisted enzymatic extraction technology was first employed to extract arabinoxylan from wheat bran. The process for extraction of arabinoxylan was optimised using response surface methodology, employing a five-level, five-variable central composite rotatable design. The optimum extraction conditions were as follows: raw material concentration, 50g/l, enzyme dose, 4.5g/l, extraction temperature, 50°C; extraction time, 70min; and ultrasonic power, 180W. Under the above mentioned conditions, the experimental yield was 142.6±0.17mg/g of wheat bran, which is well matched with the predictive yield. Ultrasound increased the efficiency of enzymatic treatment with higher extraction yield.

Total saponins of panax ginseng inhibiting human endothelium cells' damages induced by angiotensin II via AT1 receptor.

AIM OF THE STUDY: To investigate the effect and mechanism of total saponins of panax ginseng (TSPG) on the damages of endothelium cells induced by Angiotensin II (AngII). MATERIALS AND METHODS: Fifty SD rats were randomly divided into three groups: sham, AngII, and AngII+TSPG. The osmotic pumps with AngII were embedded in the backs of the animals in AngII and AngII+TSPG group, and TSPG was delivered through the gastric tube in AngII+TSPG group. The plasma tumor necrosis factor-α (TNF-α) and nitric oxide (NO) were measured by ELISA, and Human aortic endothelial cells (HAECs) were observed with scanning electron microscope (SEM). In addition, HAECs were treated with AngII and TSPG or Ang-(1-7), and the ECs were incubated with AngII for 30min, before with AT1 receptor antagonist (AT1RA) and TSPG. Tested were NAD(P)H oxidase subunit P22phox mRNA, intracellular reactive oxidative species (ROS), nuclear factor-κB (NF-κB) and vascular cell adhesion molecule-1(VCAM) expression. RESULTS: In the in vivo study, the plasma TNF-α increased significantly in AngII group when compared with the sham group, and decreased significantly in AngII+TSPG group. However, NO measurement produced opposite results. The surface of the thoracic aorta ECs desquamated in the AngII group, and most of them were restored in the AngII+TSPG group. In the in vitro study, TSPG reduced significantly the expressions of the NAD(P)H oxidize subunit P22phox, NF-κB and intracellular ROS production induced by AngII, and the inhibitory effects of TSPG were partially blocked by AT1 receptor antagonist. CONCLUSION: TSPG was found to be capable of preventing the damages of ECs induced by Ang II via AT1 receptor pathway.

[Effect of tea polypheonls and ascorbic acid on the activity of antioxidant enzymes in rats with experimental silicosis].

To explore the effect of tea polypheonls (TP) combined with ascorbic acid on the activity of antioxidant enzymes of rats induced by silica, the activities of nitric oxide synthase (NOS), glutathione peroxidase (GSH-PX) and superoxide dismutase (SOD) were determined. Compared with the normal saline control group, the activities of SOD and NOS of the silica-induced group increased (P < 0.05), but the activity of GSH-PX was gradually decreased. The activities of SOD and NOS decreased and GSH-PX increased in the intervention group. It is concluded that TP combined with ascorbic acid can alleviate the abnormal change of antioxidant enzymes in rats induced by silica.