Extracts of Periplaneta americana alleviate hepatic fibrosis by affecting hepatic TGF-ß and NF-κB expression in rats with pig serum-induced liver fibrosis.

INTRODUCTION: Liver fibrosis is caused by continuous wound healing responses to various harmful stimuli, including viral infection, drugs, alcohol, and autoimmune liver disease. The purpose of this study was to examine the effects of extracts of Periplaneta americana (EPA) in rats with pig serum-induced liver fibrosis to preliminarily assess the antifibrotic effect of EPA. MATERIAL AND METHODS: Seventy rats were randomly divided into 7 groups (10 rats in each group): HC, the healthy control group; FC, the fibrotic control group; TL, low-dose EPA treatment group group; TM, medium-dose EPA group; TH, high-dose EPA treatment group; TC1, Panax notoginseng/Salvia mitiorrhiza treatment control group 1; TC2, colchicine treatment control group 2. TC1 and TC2 were used as the positive control to demonstrate the difference between EPA and the effects of other compounds. The liver fibrosis model was induced by intraperitoneal injection of 0.5 mL pig serum twice a week for 13 weeks in all groups except for the HC group. The hepatic fibrosis model was established at the 7th week, and followingly, the corresponding compounds were administered once a day in all groups for 6 weeks. Alanine aminotransferase (ALT) and aspartate aminotransferase (AST) activity was determined in rat blood serum. We also measured liver fibrosis-related serum markers, including hyaluronic acid (HA), mucin layer (LN), type III pre-collagen (PC-III) and type IV collagen (IV-C). Hematoxylin and eosin (H&E) and Masson stainings were used to assess liver morphology and determine the stage of fibrosis. Immunohistochemistry was used to detect the protein expression of NF-κB, α-smooth muscle actin (α-SMA), transforming growth factor-ß1 (TGF-ß1) and tissue inhibitor of metalloproteinase-1 (TIMP-1) in rat liver tissue. RESULTS: Compared with that of the HC group, the liver tissue of the FC group presented obvious liver damage and collagen deposition. The serum levels of ALT, AST, HA, LN, PC-III and IV-C and the expression of NF-κB, α-SMA, TGF-ß1 and TIMP-1 in the FC group were significantly higher than those in the HC group, the EPA treatment groups, the TC1 group and the TC2 group (P < 0.01). The levels of serum ALT, AST, HA, LN, PC-III and IV-C and the expression of α-SMA, NF-κB, TGF-ß1 and TIMP-1 in the TL, TC1 and TC2 groups were significantly higher than those TM and TH groups (P < 0.05). EPA treatment significantly improved liver function, decreased collagen deposition and reversed the pathological changes related to liver fibrosis. CONCLUSIONS: We found that EPA could reduce liver inflammation, suppress liver cell degeneration and necrosis, and reduce the formation of liver fibrous tissue. Its mechanism might be associated with inhibiting the expression of TGF-ß1, TIMP-1, NF-κB and α-SMA to block signal transduction pathways in the hepatic fibrosis process. Therefore, EPA, as a traditional Chinese medicine, might be potentially used to prevent and treat hepatic fibrosis in the future. However, further more experiments are necessary to verify its effectiveness and possible signaling pathways.

Effect of different levels of pomegranate peel powder and probiotic supplementation on growth, carcass traits, blood serum metabolites, antioxidant status and meat quality of broilers.

The present study aimed to investigate the effect of dietary pomegranate peel powder (PPP) and probiotic bacteria (PB) on the growth rate, carcass traits, blood serum metabolites, and meat quality of Ross broiler chickens during 1-5 weeks of age. A total of 480 unsexed Ross broiler chicks 7-days old with the beginning bodyweight of 110.58 ± 0.17 g were employed in a complete randomized purpose trail with eight groups; 60 chicks in six replicates (8 × 6 × 10). The dietary treatments were as follows: NC: negative group (without additives) group one; PC: positive control (main diet + 0.5 g Colostin antibiotic/kg feed); PPP 3-5: basal diet + 2, 3, 4 g pomegranate peel powder/kg diet and PPP 6-8: basal diet + 2, 3, 4 g pomegranate peel powder + 1 cm3 probiotic (Bacillus toyonensis (BT)/kg diet, respectively. The results showed that live body weight (LBW) at five weeks and body weight gain (BWG) during 1-5 weeks of age were affected by adding PPP in the ration and the good grads of PPP were 2 and 4 g PPP without PB/kg diet compared to NC and PC, respectively. Otherwise, daily feed conception (DFC) and feed conversion ratio (FCR) were not affected by adding the different grads of PPP with or without PB, except the first period of DFC (1-3 weeks of old) were affected. Results showed a significant effect on all carcass characteristics studied, except gizzard and abdominal fat ratio were not influenced by the treatment used. Likewise, the addition of PPP to broiler chicken diets has a good effect on almost the blood serum metabolites, immunological parameters and quality of meat studied. In the end, the outcome of this study concluded that the addition of PPP to broiler diets has a good effect on the growth rate, blood serum metabolites, immunological parameters and the quality of meat as well as the health aspects.

Mood Disorder in Systemic Lupus Erythematosus Induced by Antiribosomal P Protein Antibodies Associated with Decreased Serum and Brain Tryptophan.

Antiribosomal P protein (anti-P) autoantibodies commonly develop in patients with systemic lupus erythematosus. We have previously established hybridoma clones producing anti-P mAbs. In this study, we explored the pathogenesis of behavioral disorders induced by anti-P Abs using these mAbs. New Zealand Black × New Zealand White F1, New Zealand White, C57BL/6, and BALB/c mice were treated with 1 mg of anti-P Abs once every 2 wk. The behavioral disorder was evaluated by the tail suspension test, forced swim test, and open field test. Following administration of anti-P Abs, New Zealand Black × New Zealand White F1 and C57BL/6 mice developed depressive behavior and showed increased anxiety with elevated serum TNF-α and IL-6 levels. Anti-P Abs were not deposited in the affected brain tissue; instead, this mood disorder was associated with lower serum and brain tryptophan concentrations. Tryptophan supplementation recovered serum tryptophan levels and prevented the behavioral disorder. TNF-α and IL-6 were essential for the decreased serum tryptophan and disease development, which were ameliorated by treatment with anti-TNF-α neutralizing Abs or dexamethasone. Peritoneal macrophages from C57BL/6 mice produced TNF-α, IL-6, and IDO-1 via interaction with anti-P Abs through activating FcγRs, which were required for disease development. IVIg, which has an immunosuppressive effect partly through the regulation of FcγR expression, also prevented the decrease in serum tryptophan and disease development. Furthermore, serum tryptophan concentrations were decreased in the sera of systemic lupus erythematosus patients with anti-P Abs, and lower tryptophan levels correlated with disease activity. Our study revealed some of the molecular mechanisms of mood disorder induced by anti-P Abs.

Copper concentration in erythrocytes, platelets, plasma, serum and urine: influence of physical training.

BACKGROUND: Physical training produces changes in the extracellular and intracellular concentrations of trace minerals elements. To our knowledge, only three compartments have been studied simultaneously. The aim of the present study was to analyze the influence of physical training on extracellular (serum, plasma and urine) and intracellular (erythrocytes and platelets) concentrations of Copper (Cu). METHODS: Forty young men participated in this study. The participants were divided into a training group (TG; n = 20; 18.15 ± 0.27 years; 68.59 ± 4.18 kg; 1.76 ± 0.04 m) and a control group (CG; n = 20; 19.25 ± 0.39 years; 73.45 ± 9.04 kg; 1.79 ± 0.06 m). The TG was formed by semi-professional soccer players from a youth category with a regular training plan of 10 h/week. All of them had been participating in high level competitions and had trained for at least 5 years. Plasma, serum, urine, erythrocyte and platelet samples of Cu were obtained and analyzed by inductively coupled plasma mass spectrometry (ICP-MS). RESULTS: The TG showed lower concentrations of Cu in erythrocytes (p < 0.05) despite similar intakes. There were no significant differences in Cu concentrations in plasma, serum, urine and platelets although the trend was similar to that observed in erythrocytes. CONCLUSIONS: The assessment of trace element concentrations should be carried out in both extracellular and intracellular compartments to obtain a proper evaluation and to identify possible deficiencies of the element. We believe that additional Cu supplementation is needed in athletes who perform physical training regularly.

Molecular classification and clinical diagnosis of acute-on-chronic liver failure patients by serum metabolomics.

Prevalence of acute-on-chronic liver failure (ACLF) patients is growing worldwide, associating with multi-organ failure and high short-term mortality rates. ACLF can be of varying entity manifestation, whereas it remains poorly defined. Traditional Chinese medicine (TCM) stratifies ACLF into two types, damp hot (DH) and cold damp (CD), by seasoned TCM practitioners, for specific treatment with different TCMs. The biggest challenge for the outcome of TCM therapy is the accuracy of diagnosis. However, it is difficult to guarantee it due to lack of the molecule classification of ACLF. Herein, we recruited 58 subjects including 34 ACLF patients (18 DH and 16 CD) and 24 healthy controls, and analyzed serum metabolic profiles using untargeted ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-Q-TOF/MS) metabolomics approach. A total of 10 serum metabolites were found as potential biomarkers for diagnosis of ACLF. Among them, taurochenodesoxycholic acid (N3), glycyldeoxycholic acid (N5) and 12-HETE-GABA (N7), varied between two types of ACLF and can be merged as a combination marker to differentiate CD from DH patients with area under the receiver operating curve (AUC) of 0.928 (95 % CI 0.8-1). CD patients possessed comparatively higher bile acid metabolism and lower arachidonic acid metabolism compared with DH patients. The results provide not only serum molecules for early accurate diagnosis of ACLF patients, but also potential clinical biomarkers for classification of CD and DH types. The findings clarify that molecular markers will be objective criteria for diagnosis of clinical types in TCM practice.

Can Serum Nitrosoproteome Predict Longevity of Aged Women?

Aging is characterized by increase in reactive oxygen (ROS) and nitrogen (RNS) species, key factors of cardiac failure and disuse-induced muscle atrophy. This study focused on serum nitroproteome as a trait of longevity by adopting two complementary gel-based techniques: two-dimensional differential in gel electrophoresis (2-D DIGE) and Nitro-DIGE coupled with mass spectrometry of albumin-depleted serum of aged (A, n = 15) and centenarian (C, n = 15) versus young females (Y, n = 15). Results indicate spots differently expressed in A and C compared to Y and spots changed in A vs. C. Nitro-DIGE revealed nitrosated protein spots in A and C compared to Y and spots changed in A vs. C only (p-value < 0.01). Nitro-proteoforms of alpha-1-antitripsin (SERPINA1), alpha-1-antichimotripsin (SERPINA3), ceruloplasmin (CP), 13 proteoforms of haptoglobin (HP), and inactive glycosyltransferase 25 family member 3 (CERCAM) increased in A vs. Y and C. Conversely, nitrosation levels decreased in C vs. Y and A, for immunoglobulin light chain 1 (IGLC1), serotransferrin (TF), transthyretin (TTR), and vitamin D-binding protein (VDBP). Immunoblottings of alcohol dehydrogenase 5/S-nitrosoglutathione reductase (ADH5/GSNOR) and thioredoxin reductase 1 (TRXR1) indicated lower levels of ADH5 in A vs. Y and C, whereas TRXR1 decreased in A and C in comparison to Y. In conclusion, the study identified putative markers in C of healthy aging and high levels of ADH5/GSNOR that can sustain the denitrosylase activity, promoting longevity.

Rumen and Serum Metabolomes in Response to Endophyte-Infected Tall Fescue Seed and Isoflavone Supplementation in Beef Steers.

Fescue toxicosis impacts beef cattle production via reductions in weight gain and muscle development. Isoflavone supplementation has displayed potential for mitigating these effects. The objective of the current study was to evaluate isoflavone supplementation with fescue seed consumption on rumen and serum metabolomes. Angus steers (n = 36) were allocated randomly in a 2 × 2 factorial arrangement of treatments including endophyte-infected (E+) or endophyte-free (E-) tall fescue seed, with (P+) or without (P-) isoflavones. Steers were provided a basal diet with fescue seed for 21 days, while isoflavones were orally administered daily. Following the trial, blood and rumen fluid were collected for metabolite analysis. Metabolites were extracted and then analyzed by UPLC-MS. The MAVEN program was implemented to identify metabolites for MetaboAnalyst 4.0 and SAS 9.4 statistical analysis. Seven differentially abundant metabolites were identified in serum by isoflavone treatment, and eleven metabolites in the rumen due to seed type (p < 0.05). Pathways affected by treatments were related to amino acid and nucleic acid metabolism in both rumen fluid and serum (p < 0.05). Therefore, metabolism was altered by fescue seed in the rumen; however, isoflavones altered metabolism systemically to potentially mitigate detrimental effects of seed and improve animal performance.

Determination and Comparison of Short-Chain Fatty Acids in Serum and Colon Content Samples: Alzheimer's Disease Rat as a Case Study.

Short-chain fatty acids (SCFAs) are the main microbial fermentation products from dietary fibers in the colon, and it has been speculated that they play a key role in keeping healthy in the whole-body. However, differences in SCFAs concentration in the serum and colon samples had attracted little attention. In this study, we have optimized the extract and analysis methods for the determination of ten SCFAs in both serum and colon content samples. Methanol and acetonitrile were chosen for extraction of SCFAs from serum and colon content samples, respectively. Biological samples were collected from Alzheimer's disease rats treated by extract of Schisandra chinensis (Turcz.) Baill (SC-extract) were taken as research objects. The results showed that, the relative peak intensities of SCFAs in the colon content from all groups were quite similar, and the trend was identical in the serum samples. Compared with the values in humans, the ratio of ten SCFAs in rat's colon was similar, while the percent of acetate in rat's serum was significantly higher. For therapy of Alzheimer's disease (AD), SC-extract decreased the concentration of butyrate, 3-Methyvalerate, and caproate in the serum samples towards the trend of normal rats. This study may help our understanding of how SCFAs are transported across colonic epithelium in healthy and diseased organisms.

Reduced serum methods for contact-based coculture of human dermal fibroblasts and epidermal keratinocytes.

Direct contact-based coculture of human dermal fibroblasts and epidermal keratinocytes has been a long-standing and challenging issue owing to different serum and growth factor requirements of the two cell types. Existing protocols employ high serum concentrations (up to 10% fetal bovine serum), complex feeder systems and a range of supplemental factors. These approaches are technically demanding and labor intensive, and pose scientific and ethical limitations associated with the high concentrations of animal serum. On the other hand, serum-free conditions often fail to support the proliferation of one or both cell types when they are cultured together. We have developed two reduced serum approaches (1-2% serum) that support the contact-based coculture of human dermal fibroblasts and immortalized keratinocytes and enable the study of cell migration and wound closure.

[Establishment of rat heart-kidney insomnia model consistent with traditional Chinese medicine syndrome and its serum metabolomics].

Enzyme-linked immunosorbent assay(ELISA) and metabolomics were used to analyze and compare two animal models of heart-kidney insomnia, in order to explore a more ideal animal model and preliminarily explore the essence of heart-kidney insomnia. Based on the clinical symptoms and disease characteristics of heart-kidney insomnia, the animal model of heart-kidney insomnia was reproduced through intraperitoneal injection with p-chlorophenylalanine(PCPA) and multi-factor interaction. The animal model of disease-syndrome combination was evaluated by behavioral observation, ELISA and metabolomics. Wistar rats were randomly divided into normal group, PCPA group and compound model group(FH). The rats' behavior, body weight, adrenal index and spleen index were recorded. The levels of corticotropin releasing hormone(CRH) and adrenocorticotropin(ACTH) in serum were detected by ELISA, and the differential metabolites in serum were detected by UPLC-QE-MS. The body weight and adrenal index in FH group were significantly lower than those in PCPA group(P<0.05); whereas ACTH and CRH in FH group were significantly higher than those in PCPA group by ELISA; nine potential biomarkers were identified by serum sample statistics. There were four main metabolic pathways in cardiorenal insomnia: pentose phosphate metabolism, alanine, aspartic acid and glutamic acid metabolism, histidine metabolism, and taurine and subtaurine metabolism. PCPA and multi-factor interaction method can successfully replicate the insomnia model, but multi-factor modeling method is more similar to clinical traditional Chinese medicine syndrome. Animal behavior, ELISA and metabolomics were used to evaluate the rat model of cardiorenal insomnia from in vitro to in vivo, from macro to micro, and from individual to the whole.

Microbiota and metabolome responses in the cecum and serum of broiler chickens fed with plant essential oils or virginiamycin.

This study investigated the cecal microbiota and serum metabolite profile of chickens fed with plant essential oils (PEO) or virginiamycin (VIRG) using high-throughput 16S rRNA gene sequencing and untargeted metabolomics approach. The main aim of this work was to explore the biochemical mechanisms involved in the improved growth performance of antibiotics and their alternatives in animal production. The results showed that both PEO and VIRG treatment significantly increased the relative abundance of phyla Bacteroidetes and decreased the abundance of phyla Firmicutes and genus of Lactobacillus in cecal microbiota of chickens. Compared to the control group (CT group), the relative abundance of genus of Alistipes, unclassified Rikenellaceae, Roseburia, and Anaeroplasma was enriched in the PEO group; that of genus Bacteroides, Lachnospiraceae, and unclassified Enterobacteriaceae was enriched in the cecal microbiota of the VIRG group. Untargeted metabolomics analyses revealed that the PEO treatment modified 102 metabolites and 3 KEGG pathways (primary bile acid biosynthesis and phenylalanine metabolism) in the cecal microbiota, and 81 metabolites and relevant KEGG pathways (fructose and mannose metabolism, biosynthesis of unsaturated fatty acids, and linoleic acid.) in the serum of the chicken. Compared to the CT group, VIRG treatment group differed 217 metabolites and 10 KEGG pathways in cecal contents and 142 metabolites and 7 KEGG pathways in serum of chickens. Pearson's correlation analysis showed that phyla Bacteroidetes and genus of Bacteroides, Alistipes, and unclassified Rikenellaceae (in the VIRG and PE group) were positively correlated with many lipid metabolites. However, phyla Firmicutes and genera Lactobacillus (higher in the CT group) were negatively correlated with the lipid and thymine metabolism, and positively correlated with hydroxyisocaproic acid, cytosine, and taurine. This study shows that dietary supplementation with PEO and VIRG altered the composition and metabolism profile of the cecal microbiota, modified the serum metabolism profile.

Nitroprusside induces melanoma ferroptosis with serum supplementation and prolongs survival under serum depletion or hypoxia.

BACKGROUND: When proliferating tumor cells expand to areas distant from vascular sites, poor diffusion of oxygen and nutrients occur, generating a restrictive hypoxic gradient in which susceptible tumor cells die. The heterogeneous population surviving hypoxia and metabolic starvation include de-differentiated cancer stem cells (CSC), capable of self-renewing tumor-initiating cells (TICs), or those that divide asymmetrically to produce non-tumor-initiating differentiated (NTI-D) cell progeny. Under such restrictive conditions, both populations slowly proliferate, entering quiescence or senescence, when exiting from cell cycle progression. This may drive chemoresistance and tumor recurrence, since most anti-cancer treatments target rapidly proliferating cells. PURPOSE: Since persistent or additional stress may increase NTI-D cells conversion to TICs, we investigated whether nutrient depletion or hypoxia influence expression of tyrosinase, a crucial enzyme for melanin synthesis, and B16 melanoma survival, when exposed to iron-dependent cell death oxidative stress produced by the Fenton reaction, resembling ferroptosis. RESULTS: -a) proliferating B16 melanoma with 10% serum-supplementation (10%S) normoxically express hypoxia inducible factor 1α (HIF1α) but lose tyrosinase, in contrast to those transiently exposed to (SF) serum-free medium, in which both HIF1α and tyrosinase are co-expressed; b) in contrast to the resistance to SNP toxicity in (SF) cells with higher tyrosinase expression, those in (10%S) are killed by iron from nitroprusside/ferricyanide (SNP) irrespective of exogenous H2O2, in a reaction antagonized by the anti-oxidant and MEK inhibitor UO126; c) Moreover, under transient serum depletion, SNP cooperates with hypoxia (1.5% oxygen), prolonging B16 melanoma (SF) survival; d) the hypoxia mimetic CoCl2 inhibits proliferation-associated cyclin A, irrespective of SNP, in (10%S) cells or in transiently serum-depleted (SF) cells. However, only in the latter cells, CoCl2 but not SNP, induce loss of HIF1α and apoptosis-associated PARP cleavage; e) longer term adaptation to survive serum depletion, generates (SS) cells resistant to SNP toxicity, which aerobically co-express HIF1α and tyrosinase. In SS B16 melanoma, exogenous non-toxic 100 µM H2O2 super-induces the ratio of tyrosinase to HIF1α. However, co-treatment of SS-B16 cells with SNP plus exogenous H2O2, partly increases PARP cleavage by reciprocally decreasing tyrosinase expression. SIGNIFICANCE: - These results suggest that a phenotypic plasticity in response to depletion of nutrients and/or oxygen, helps decide whether melanoma cells undergo either death by ferroptosis, or resistance to it, when challenged by the same exogenous oxidative stress (iron ± H2O2).

The Evaluation of the Antioxidant and Intestinal Protective Effects of Baicalin-Copper in Deoxynivalenol-Challenged Piglets.

The present study was performed to evaluate the antioxidant and intestinal protective effects of baicalin-copper on deoxynivalenol-challenged piglets. Forty weaned piglets were randomly divided into four groups and assigned to different diets: (1) basal diet (Con), (2) 4 mg/kg deoxynivalenol of basal diet (DON), (3) 5 g/kg baicalin-copper of basal diet (BCU); and (4) 4 mg/kg deoxynivalenol + 5 g/kg baicalin-copper of basal diet (DBCU). The results showed that the ADFI and ADG of piglets in the DON group were markedly lower than those in the Con group, but the ADFI and ADG of the DBCU group were not significantly different from those of the Con group. In piglets fed a DON-contaminated diet, dietary supplementation with BCU significantly decreased the mRNA levels of P70S6K, 4E-BP1, and HSP70 in the liver, the protein expression of HO-1 in the jejunum, and the expression of p-Nrf2 and p-NF-κB in the ileum but increased Mn-SOD activity in serum. Dietary supplementation with BCU increased jejunal maltase, ZIP4 and MT mRNA levels, and serum concentrations of Arg, Val, Ile, Leu, Lys, and Tyr in DON-contaminated piglets. In summary, BCU can alleviate the growth impairment induced by DON and enhance antioxidant capacity and nutrition absorption in piglets fed DON-contaminated diets.

Integrated network pharmacology analysis and serum metabolomics to reveal the cognitive improvement effect of Bushen Tiansui formula on Alzheimer's disease.

ETHNOPHARMACOLOGICAL RELEVANCE: Bushen Tiansui Formula (BSTSF) is a traditional Chinese medicine formula used clinically to treat Alzheimer's disease (AD) for many years. Previously, we have partially elucidated the mechanisms involved in the therapeutic effects of BSTSF on AD. However, the underlying mechanisms remain largely unclear. AIM OF THE STUDY: The aim of this study was to further investigate the therapeutic effects of BSTSF on AD using an integrated strategy of network pharmacology and serum metabolomics. MATERIALS AND METHODS: The rat models of AD were established using Aß 1-42 injection, and morris water maze test was used to evaluate the efficacy of BSTSF on AD. Next, network pharmacology analysis was applied to identify the active compounds and target genes, which might be responsible for the effect of BSTSF. Then, a metabolomics strategy has been developed to find the possible significant serum metabolites and metabolic pathway induced by BSTSF. Additionally, two parts of the results were integrated to confirm each other. RESULTS: The results of the network pharmacology analysis showed 37 compounds and 64 potential target genes related to the treatment of AD with BSTSF. The functional enrichment analysis indicated that the potential mechanism was mainly associated with the tumor necrosis factor signaling pathway and phosphatidylinositol 3 kinase/protein kinase B signaling pathway. Based on metabolomics, 78 differential endogenous metabolites were identified as potential biomarkers related to the BSTSF for treating AD. These metabolites were mainly involved in the relevant pathways of linoleic acid metabolism, α-linolenic acid metabolism, glycerophospholipid metabolism, tryptophan metabolism, and arginine and proline metabolism. These findings were partly consistent with the findings of the network pharmacology analysis. CONCLUSIONS: In conclusion, our results solidly supported and enhanced out current understanding of the therapeutic effects of BSTSF on AD. Meanwhile, our work revealed that the proposed network pharmacology-integrated metabolomics strategy was a powerful means for identifying active components and mechanisms contributing to the pharmacological effects of traditional Chinese medicine.

A Serum Metabolomic Study on Rats Induced by Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata by Pattern Recognition and Pathways Analysis.

This study focused on the differential metabolomic effects between water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata in rats. The extracts were subsequently administered for 28 d. Serum biochemical indicators were tested, hematoxylin-eosin staining and immunohistochemistry staining were used to detect histopathological changes in the livers. Ultra-performance LC/quadrupole time-of-flight mass spectrometry was used to detect the changes in endogenous metabolites. Finally, we performed detailed analysis of the changes in metabolic pathways. Hematoxylin-eosin staining and immunohistochemistry staining results indicated that the water extracts of Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata had mild liver injury effect. Fifty-two differential endogenous biomarkers were confirmed as potential biomarkers between Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups. In the positive ion mode, the biomarkers included 31 Phosphatidyl cholines (PCs), six lysoPCs, and ceramide. In the negative ion mode, 12 biomarkers were confirmed, including glycodeoxycholic acid, chenodeoxycholic acid, and deoxycholic acid, etc. In Hydrophilic Interaction Liquid Chromatography (HILIC) mode, nine biomarkers were confirmed, including niacinamide, L-palmitoylcarnitine, and butyrylcarnitine, etc. Using MetaboAnalyst 4.0, six related metabolic pathways, including taurine and hypotaurine metabolism, sphingolipid metabolism, glycerophospholipid metabolism, nicotinate and nicotinamide metabolism, arginine and proline metabolism, and tryptophan metabolism and primary bile synthesis, were confirmed as the most differential pathways between the Polygoni Multiflori Radix and Polygoni Multiflori Radix Preparata groups.

The antioxidant activities in vivo of bitter gourd polysaccharide.

The antioxidant activities of polysaccharide from bitter gourd were studied. It was found that bitter gourd polysaccharide could significantly increase SOD and CAT contents in serum, liver and brain of mice, and reduce MDA levels in serum, liver and brain to a certain extent in vivo. So, bitter gourd polysaccharide should be a potential antioxidant.

Functional design of pH-responsive folate-targeted polymer-coated gold nanoparticles for drug delivery and in vivo therapy in breast cancer.

BACKGROUND: Curcumin has been widely used owing to its various medicinal properties including antitumor effects. However, its clinical application is limited by its instability, poor solubility and low bioavailability. Folic acid (FA)-functionalized nanoformulations may enhance the sustained release of an anticancer drug (curcumin) by tumor-specific targeting to improve therapeutic benefit. This study aims to design a nanoconjugate (NC) comprised of folate-curcumin-loaded gold-polyvinylpyrrolidone nanoparticles (FA-CurAu-PVP NPs) for targeted delivery in breast cancer model systems. METHODS: We developed curcumin-loaded FA-functionalized Au-PVP NCs by layer-by-layer assembly. The folic acid-curcumin Au-PVP NCs (FA-CurAu-PVP NCs) were characterized by ultraviolet-visible spectra, Fourier transform infrared spectroscopy, X-ray powder diffraction and thermogravimetric analysis. In vitro anticancer and antimigratory effects of NCs were examined by performing MTT and wound migration assays. The in vivo antitumor efficacy of NCs was investigated using a preclinical breast cancer orthotopic mouse model. RESULTS: Curcumin (40 µg/mL) was loaded along with conjugation of folate onto Au-PVP NPs to form FA-CurAu-PVP NCs. The size and charge of the NCs were increased gradually through layer-by-layer assembly and showed 80% release of curcumin at acidic pH. The NC did not show aggregation when incubated with human serum and mimicked an intrinsic peroxidase-like property in the presence of 3,3',5,5'-tetramethylbenzidine substrate. The MTT data using these NCs showed efficient anticancer activity at lower doses in estrogen/progesterone receptor (ER/PR)-negative cells compared with ER/PR-positive cells. Furthermore, the NCs did not show cytotoxicity at the investigated concentration in human breast epithelial and mouse fibroblast cell lines. They showed inhibitory effects on cell migration and high antitumor efficacy in in vivo analysis. CONCLUSION: These results suggest that folate-based tumor targeting using CurAu-PVP NCs is a promising approach for tumor-specific therapy of breast cancer without harming normal cells.

Effects of in-feed clinoptilolite treatment on serum metabolic and antioxidative biomarkers and acute phase response in dairy cows during pregnancy and early lactation.

The objective of this study was to evaluate the effects of in-feed clinoptilolite (CPL) on serum metabolic and antioxidative biomarkers, acute phase proteins and reproductive performance in cows during pregnancy and lactation. A total of 78 Holstein-Friesian cows were randomly assigned into two groups: the treatment group, cows fed CPL (n = 38) which received 50 g of powdered CPL twice a day from day 180 before parturition to day 60 postpartum; and the control group (n = 40). Blood samples were taken on days 180, 90, 60, 30 and 10 before parturition, on day of calving and on days 5, 12, 19, 26, 33, 40 and 60 postpartum, and were analysed for metabolic biomarkers: glucose, triglycerides, total cholesterol, high density lipoprotein cholesterol, non-esterified fatty acids, beta-hydroxybutyrate (BHB), antioxidative biomarkers and acute phase proteins: paraoxonase-1 (PON1), apolipoprotein A-I, haptoglobin (Hp) and serum amyloid A (SAA). CPL supplementation increased concentration of glucose and significantly decreased (P < .05) level of BHB during puerperium. The SAA concentration in CPL-fed cows was significantly decreased (P < .05) on days 33, 40 and 60 postpartum as well as Hp concentration on days 0 and 12 postpartum. The results of this study suggest that the CPL-fed cows may have improved metabolic status due to the tendency of greater glucose levels and decreased BHB values during early lactation. In addition, acute phase response was lower (P < .05) in CPL-fed cows. Such an outcome might be attributed to the effect of dietary CPL on intensity and severity of the negative energy balance and inflammatory response in dairy cows.

Identifying mechanisms underlying the amelioration effect of Chrysanthemum morifolium Ramat. 'Boju' extract on hyperuricemia using biochemical characterization and UPLC-ESI-QTOF/MS-based metabolomics.

This study was aimed at evaluating the prospect of edible chrysanthemum extract as a potential substance for the prevention and treatment of hyperuricemia. Chrysanthemum morifolium Ramat. 'Boju' extract (CBE), which had the strongest xanthine oxidase inhibitory activity, showed a significant hypouricemic effect on potassium oxonate-induced hyperuricemic rats through inhibiting serum xanthine oxidase activity, regulating renal uric acid transport-related protein (ABCG2, URAT1 and GLUT9) expression and blood lipid levels, and protecting renal function. Serum metabolomics based on UPLC-ESI-QTOF/MS was used to illustrate mechanisms underlying the amelioration effect of CBE on hyperuricemia. A total of 35 potential biomarkers were identified. CBE prevented the pathological process of hyperuricemia by regulating 16/17 biomarkers associated with tryptophan, sphingolipid, glycerophospholipid and arachidonic acid metabolisms. CBE could alleviate hyperuricemia-related diseases including chronic kidney disease, hyperlipidemia and inflammation via reducing indoxyl sulfate, lysophosphatidylcholines and arachidonic acid levels, exhibiting its applicability and superiority in the treatment of hyperuricemia.