Safflower Yellow Inhibits Progression of Hepatocellular Carcinoma by Modulating Immunological Tolerance via FAK Pathway.

OBJECTIVE: To explore the anti-tumor effect of safflower yellow (SY) against hepatocellular carcinoma (HCC) and the underlying potential mechanism. METHODS: An in vitro model was established by mixing Luc-Hepa1-6 cells and CD3+CD8+ T cells, followed by adding programmed cell death protein 1 (PD-1) antibody (Anti-mPD-1) with or without SY. The apoptosis was detected by flow cytometry and the level of inflammatory cytokines was determined by enzyme-linked immunosorbent assay. The protein levels of programmed cell death 1 ligand 1 (PD-L1), chemokine ligand (CCL5), C-X-C motif chemokine ligand 10 (CXCL10) were measured by Western blot. An in situ animal model was established in mice followed by treatment with anti-mPD-1 with or without SY. Bioluminescence imaging was monitored with an AniView 100 imaging system. To establish the FAK-overexpressed Luc-Hepa1-6 cells, cells were transfected with adenovirus containing pcDNA3.1-FAK for 48 h. RESULTS: The fluorescence intensity, apoptotic rate, release of inflammatory cytokines, and CCL5/CXCL10 secretion were dramatically facilitated by anti-mPD-1 (P<0.01), accompanied by an inactivation of PD-1/PD-L1 axis, which were extremely further enhanced by SY (P<0.05 or P<0.01). Increased fluorescence intensity, elevated percentage of CD3+CD8+ T cells, facilitated release of inflammatory cytokines, inactivated PD-1/PD-L1 axis, and increased CCL5/CXCL10 secretion were observed in Anti-mPD-1 treated mice (P<0.01), which were markedly enhanced by SY (P<0.05 or P<0.01). Furthermore, the enhanced effects of SY on inhibiting tumor cell growth, facilitating apoptosis and inflammatory cytokine releasing, suppressing the PD-1/PD-L1 axis, and inducing the CCL5/CXCL10 secretion in Anti-mPD-1 treated mixture of Luc-Hepa1-6 cells and CD3+CD8+ T cells were abolished by FAK overexpression (P<0.01). CONCLUSION: SY inhibited the progression of HCC by mediating immunological tolerance through inhibiting FAK.

Relationship between 25-hydroxy vitamin D and knee osteoarthritis: a systematic review and meta-analysis of randomized controlled trials.

Objective: In order to examine the relationship between 25-hydroxyl vitamin D and knee osteoarthritis (KOA), a meta-analysis of 8 randomized controlled trials (RCTs) publications was hereby performed. Methods: For the purpose of finding pertinent research, the databases of PubMed, Embase and the Cochrane Library were searched. Factors including tibial cartilage volume, joint space width (JSW), synovial fluid volume, and Western Ontario and McMaster Universities Arthritis Index (WOMAC) were correspondingly evaluated, and the results were expressed using SMD and 95% confidence intervals (CI). Results: The present meta-analysis evaluated the effects of vitamin D supplementation in patients with knee osteoarthritis, with 3,077 patients included. The results showed that vitamin D administration had a statistically significant impact on the amount of synovial fluid, Visual Analog Scale (VAS) and tibial cartilage. The pain and function scales of the WOMAC scale presented a statistically significant difference, and there was no discernible difference between the vitamin D and placebo groups in the stiffness scale. Additionally, bone marrow lesions and alterations in the diameter of the joint space were not influenced by the administration of vitamin D, and according to a subgroup study, a daily vitamin D supplement containing more than 2,000 IU significantly slowed the development of synovial tissue. Conclusion: Vitamin D supplementation did benefit those suffering from knee discomfort and knee dysfunction. Systematic review registration: https://www.crd.york.ac.uk/prospero/display_record.php?ID=CRD42022332033, identifier: CRD42022332033.

Chitosan@Puerarin hydrogel for accelerated wound healing in diabetic subjects by miR-29ab1 mediated inflammatory axis suppression.

Wound healing is one of the major global health concerns in patients with diabetes. Overactivation of pro-inflammatory M1 macrophages is associated with delayed wound healing in diabetes. miR-29ab1 plays a critical role in diabetes-related macrophage inflammation. Hence, inhibition of inflammation and regulation of miR-29 expression have been implicated as new points for skin wound healing. In this study, the traditional Chinese medicine, puerarin, was introduced to construct an injectable and self-healing chitosan@puerarin (C@P) hydrogel. The C@P hydrogel promoted diabetic wound healing and accelerated angiogenesis, which were related to the inhibition of the miR-29 mediated inflammation response. Compared to healthy subjects, miR-29a and miR-29b1 were ectopically increased in the skin wound of the diabetic model, accompanied by upregulated M1-polarization, and elevated levels of IL-1ß and TNF-α. Further evaluations by miR-29ab1 knockout mice exhibited superior wound healing and attenuated inflammation. The present results suggested that miR-29ab1 is essential for diabetic wound healing by regulating the inflammatory response. Suppression of miR-29ab1 by the C@P hydrogel has the potential for improving medical approaches for wound repair.

Efficacy and Safety of Traditional Chinese Medicine Based on the Method of "Nourishing Kidney and Clearing Heat" as Adjuvant in the Treatment of Diabetes Mellitus Patients with Periodontitis: A Systematic Review and Meta-Analysis.

Objective: The aim of this systematic review and meta-analysis was to assess the efficacy and safety of traditional Chinese medicine based on the method of "nourishing kidney and clearing heat" as an adjuvant in the treatment of diabetes mellitus patients with periodontitis. Methods: An electronic literature search was conducted in the China National Knowledge Infrastructure (CNKI), Wanfang Data, Chinese Scientific Journals Database (VIP), Chinese Biomedical Literature Database (CBM), PubMed, EMBASE, Web of Science, and Cochrane Library databases for articles published until October 2021. The primary outcomes were probing pocket depth (PPD), clinical attachment loss (CAL), plaque index (PLI), and sulcular bleeding index (SBI), while the secondary outcomes were tooth mobility (TM), glycosylated hemoglobin (HbA1c), fasting blood glucose (FBG), total effective rate, and adverse effects. Results: Eleven randomized controlled trials (RCT) were included in the meta-analysis. The pooled results showed PPD (WMD = 1.07, 95%CI: (0.82, 1.33), P < 0.00001, I 2 = 89%), CAL (WMD = 0.78, 95%CI: (0.62, 0.93), P < 0.00001, I 2 = 58%), PLI (WMD = 0.44, 95%CI: (0.09, 0.79), P=0.01, I2 = 97%), SBI (WMD = 0.87, 95%CI: (0.79, 0.95), P < 0.00001, I 2 = 37%), TM (WMD = 0.26, 95%CI: (0.21, 0.30), P < 0.00001, I 2 = 31%), HbA1c (WMD = 0.48, 95%CI: (0.28, 0.67), P < 0.00001, I2 = 26%), FBG (WMD = 1.34, 95%CI: (0.96, 1.72), P < 0.00001, I 2 = 52%), total effective rate (RR = 1.24, 95%CI: (1.14, 1.34), P < 0.00001, I 2 = 0%), and adverse effects (RR = 0.78, 95%CI: (0.20, 3.03), P=0.72, I 2 = 0%) in the traditional Chinese medicine based on the method of "nourishing kidney and clearing heat" + routine western medicine treatment (periodontal basic treatment, PBT, with or without antibiotic) group were significantly improved compared to control group, but no significant difference was observed for PLI at 2-3 months and 6 months. Conclusions: This review supports traditional Chinese medicine based on the method of "nourishing kidney and clearing heat" as an adjuvant to routine western medicine treatment in the management of diabetes mellitus patients with periodontitis. Within the limits of the evidence, the well-designed, long-term efficacy, and high-quality multicenter RCTs need to be further confirmed.

Glycyrrhetinic acid: A potential drug for the treatment of COVID-19 cytokine storm.

BACKGROUND: The cytokine storm (CS) triggered by coronavirus disease 2019 (COVID-19) has caused serious harm to health of humanity and huge economic burden to the world, and there is a lack of effective methods to treat this complication. PURPOSE: In this research, we used network pharmacology and molecular docking to reveal the interaction mechanism in the glycyrrhetinic acid (GA) for the treatment of CS, and validated the effect of GA intervention CS by experiments. STUDY DESIGN: First, we screened corresponding target of GA and CS from online databases, and obtained the action target genes through the Venn diagram. Then, protein-protein interaction (PPI) network, Gene ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment of the action target genes were acquired by R language to predict its mechanism. Next, molecular docking was performed on core targets. Finally, experiments in which GA intervened in lipopolysaccharide (LPS)-induced CS were implemented. RESULTS: 84 action target genes were obtained from online database. The PPI network of target genes showed that TNF, IL6, MAPK3, PTGS2, ESR1 and PPARG were considered as the core genes. The results of GO and KEGG showed that action target genes were closely related to inflammatory and immune related signaling pathways, such as TNF signaling pathway, IL-17 signaling pathway, Human cytomegalovirus infection, PPAR signaling pathway and so on. Molecule docking results prompted that GA had fine affinity with IL6 and TNF proteins. Finally, in vivo and in vitro experimental results showed that GA could significantly inhibit LPS-induced CS. CONCLUSION: GA has a potential inhibitory effect on CS, which is worthy of further exploration.

Integrating network pharmacology and experimental models to investigate the mechanisms of dihydroartemisinin in preventing NSCLC progression via mTOR/HIF-1α signaling.

Advanced Non-small cell lung cancer (NSCLC) is the most common type of lung cancer with a poor prognosis. The anti-malaria compounds dihydroartemisinin (DHA) have shown to regulate multiple targets and signaling pathways in cancers, but a global view of its mechanism of action remains elusive. In present study, we integrated network pharmacology and in vitro and in vivo experimental models to investigate the mechanisms of DHA in preventing NSCLC proliferation. We first proved that DHA inhibits the growth of lung cancer via inducing cell apoptosis and cell cycle arrest, then we integrated information from publicly available databases to predict interactions between DHA and its potential targets in NSCLC, as well as the signaling pathways involved. In this way we identified 118 common targets of DHA and NSCLC, and further analyzed with the correlation between these targets by KEGG and GO analysis. Our data indicate that mTOR/HIF-1α signaling is one of potential critical pathways involved in DHA-induced tumor inhibition in NSCLC. Finally, the data from human and mouse lung cancer cell lines and in mouse Lewis lung cancer models showed that DHA does decrease the expression level of mTOR and HIF-1α which supported the potential roles of mTOR/HIF-1α Signaling in NSCLC and deserves further investigation.

Effects of dehydroepiandrosterone (DHEA) supplementation on cortisol, leptin, adiponectin, and liver enzyme levels: A systematic review and meta-analysis of randomised clinical trials.

BACKGROUND AND AIMS: Dehydroepiandrosterone (DHEA) supplementation has been investigated in patients with altered cortisol levels and is proposed to ameliorate the metabolic profile related to adipose tissue. However, further research is warranted and evidence is no compelling for liver safety. Hence, we aimed to meta-analyse the effects of DHEA supplementation on circulating levels of cortisol, liver enzymes, and adipokines. METHODS: We searched literature published in PubMed, Web of Science, Embase and Scopus, until December 2020. We obtained overall results using the generic inverse of variance method with a random-effects model. RESULTS: Through 10 arms, serum cortisol levels decreased significantly after DHEA supplementation [weighted mean difference (WMD): -53.581 nmol/L, 95% confidence interval (CI): -88.2, -18.9, P = .002], without significant heterogeneity (I2  = 36%, P = .117). In contrast, any significance was noted for adiponectin (WMD: -0.045 µg/mL, 95% CI: -0.56, 0.47; P = .865), leptin (WMD: -2.55 µg/mL, 95% CI: -6.2, 1.06; P = .166), aspartate transaminase (AST) (WMD: -3.7 U/L, 95% CI: -10.35, 2.95; P = .276), and alanine aminotransferase (ALT) (WMD: -1.7 U/L, 95% CI: -3.45, 0.06; P = .058). CONCLUSION: DHEA supplementation decreased circulating cortisol but did not alter adiponectin, leptin, AST, and ALT levels. Hence, DHEA supplementation could be considered as an adjunct in the management of hypercortisolaemia and is safe for the liver.

Radiotheranostic Agent 64Cu-cyclam-RAFT-c(-RGDfK-)4 for Management of Peritoneal Metastasis in Ovarian Cancer.

PURPOSE: Ovarian cancer peritoneal metastases (OCPMs) are a pathophysiologically heterogeneous group of tumors that are rarely curable. αVß3 integrin (αVß3) is overexpressed on tumoral neovessels and frequently on ovarian cancer cells. Here, using two clinically relevant αVß3-positive OCPM mouse models, we studied the theranostic potential of an αVß3-specific radiopeptide, 64Cu-cyclam-RAFT-c(-RGDfK-)4 (64Cu-RaftRGD), and its intra- and intertumoral distribution in relation to the tumor microenvironment. EXPERIMENTAL DESIGN: αVß3-expressing peritoneal and subcutaneous models of ovarian carcinoma (IGR-OV1 and NIH:OVCAR-3) were established in nude mice. 64Cu-RaftRGD was administered either intravenously or intraperitoneally. We performed intratumoral distribution (ITD) studies, PET/CT imaging and quantification, biodistribution assay and radiation dosimetry, and therapeutic efficacy and toxicity studies. RESULTS: Intraperitoneal administration was an efficient route for targeting 64Cu-RaftRGD to OCPMs with excellent tumor penetration. Using the fluorescence surrogate, Cy5.5-RaftRGD, in our unique high-resolution multifluorescence analysis, we found that the ITD of 64Cu-RaftRGD was spatially distinct from, but complementary to, that of hypoxia. 64Cu-RaftRGD-based PET enabled clear visualization of multiple OCPM deposits and ascites and biodistribution analysis demonstrated an inverse correlation between tumor uptake and tumor size (1.2-17.2 mm). 64Cu-RaftRGD at a radiotherapeutic dose (148 MBq/0.357 nmol) showed antitumor activities by inhibiting tumor cell proliferation and inducing apoptosis, with negligible toxicity. CONCLUSIONS: Collectively, these results demonstrate the all-in-one potential of 64Cu-RaftRGD for imaging guided radiotherapy of OCPM by targeting both tumoral neovessels and cancerous cells. On the basis of the ITD finding, we propose that pairing αVß3- and hypoxia-targeted radiotherapies could improve therapeutic efficacy by overcoming the heterogeneity of ITD encountered with single-agent treatments.

A systematic review and meta-analysis of acupuncture treatment for oral ulcer.

BACKGROUND: Oral ulcers (OU) is a common oral mucosal disease manifested with obvious pain; in some studies, the efficacy of acupuncture in OU has been confirmed, but the systematic reviews and meta-analyses for them are lacking. Our aim is to evaluate the efficacy and safety of acupuncture in the treatment of OU. METHODS: Relevant randomized controlled trials (RCTs), quasi RCTs and non-RCTs will be identified by systematic searching from the following electronic databases: PubMed, Embase, the Cochrane Library, Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data (since inception of the databases to present). In addition, ongoing trials will be retrieved from the Chinese Clinical Trial Register, World Health Organization International Clinical Trials Registry Platform, Clinical Trials, and The Clinical Trials Register. Grey literature will be also taken into consideration, including academic dissertation, minutes of the meeting from Chinese Biomedical Literature Database, China National Knowledge Infrastructure, China Science and Technology Journal database, and Wanfang Data. There are no language restrictions. RESULTS: Ethical approval is not required because this study is based on published papers. After peer-review, the study will be disseminated in scientific journals and conferences. CONCLUSION: This systematic review will provide evidence for the efficacy and safety of acupuncture for Oral ulcers. TRIAL REGISTRATION NUMBER: CRD42020144911.

Short and long-term efficacy of massage for functional constipation: A protocol for systematic review and meta analysis.

BACKGROUND: Functional constipation (FC) is one of the most common diseases throughout the world, which brings a bad influence on life quality as well as mental health. Massage has been widely used in the treatment of functional constipation in china. In several randomized controlled trials indicate that massage has a positive effect on FC. However, there remain exist controversy towards its effectiveness and safety. What's more, how about the short and long-term efficacy? We, therefore, design this systematic review to assess the short and long-term effects of massage for FC. METHODS: The following electronic databases will be searched from their inception to May 2020, including PubMed, Cochrane Library, EMBASE, Web of Science, WHO International Clinical Trials Registry Platform, Chinese National Knowledge Infrastructure (CNKI), WanFang Database, Chinese Biomedical Literature Database (CBM), the Chongqing VIP Chinese Science, and Technology Periodical Database (VIP). RESULTS: This systematic review will assess the short and long-term effects of massage in the treatment of FC. CONCLUSION: This study will provide high-quality current evidence of short and long-term effects of massage for FC. ETHICS AND DISSEMINATION: Ethical approval is not required, for this review will not involve individuals' information. The results will be published in a peer-reviewed publication or disseminated in relevant conferences.INPLASY Registration number: INPLASY202050001.

Lianhuaqingwen exerts anti-viral and anti-inflammatory activity against novel coronavirus (SARS-CoV-2).

PURPOSE: Lianhuaqingwen (LH) as traditional Chinese medicine (TCM) formula has been used to treat influenza and exerted broad-spectrum antiviral effects on a series of influenza viruses and immune regulatory effects Ding et al. (2017). The goal of this study is to demonstrate the antiviral activity of LH against the novel SARS-CoV-2 virus and its potential effect in regulating host immune response. METHODS: The antiviral activity of LH against SARS-CoV-2 was assessed in Vero E6 cells using CPE and plaque reduction assay. The effect of LH on virion morphology was visualized under transmission electron microscope. Pro-inflammatory cytokine expression levels upon SARS-CoV-2 infection in Huh-7 cells were measured by real-time quantitative PCR assays. RESULTS: LH significantly inhibited SARS-CoV-2 replication in Vero E6 cells and markedly reduced pro-inflammatory cytokines (TNF-α, IL-6, CCL-2/MCP-1 and CXCL-10/IP-10) production at the mRNA levels. Furthermore, LH treatment resulted in abnormal particle morphology of virion in cells. CONCLUSIONS: LH significantly inhibits the SARS-COV-2 replication, affects virus morphology and exerts anti-inflammatory activity in vitro. These findings indicate that LH protects against the virus attack, making its use a novel strategy for controlling the COVID-19 disease.

Clove oil-in-water nanoemulsion: Mitigates growth of Fusarium graminearum and trichothecene mycotoxin production during the malting of Fusarium infected barley.

Fusarium mycotoxin contamination in malting barley is of great concerns in malting industry. Our recent study found that clove oil nanoemulsions can act as highly efficient antifungal agents in vitro. Therefore, we explored the efficacy of clove oil nanoemulsions on Fusarium growth and mycotoxin during malting process. The impact of emulsifier types (Tween 80, BSA and quillaja saponins) on the formation of clove oil nanoemulsion, the mitigation effects on mycotoxin levels and fungal biomass, and the clove oil flavor residues on malts were measured. We observed that 1.5 mg clove oil/g nanoemulsion showed a negligible influence on germinative energy of barley, while still efficiently eliminated the DON levels and toxicogenic fungal biomass as quantified by Tri5 DNA content. Tween 80-stablized clove oil nanoemulsion displayed higher mycotoxin inhibitory activity and less flavor impact on the final malt. The results indicated the potential application of essential oil nanoemulsion during the malting process.

Cultivation and Medicinal Value of the Red Belt Conk Mushroom Fomitopsis pinicola (Agaricomycetes).

This study examined biological characteristics, liquid fermentation, and cultivation of Fomitopsis pinicola. A single-factor test concluded that the optimal carbon and nitrogen sources for mycelial growth were soluble starch and yeast paste; the optimal culture temperature was 31°C, and the optimal pH was 6.0. The orthogonal experiment indicated that the optimal formula for mycelial culture was 25 g soluble starch, 2 g yeast extract, 1 g KH2PO4, and 1.5 g MgSO4 added to 1 L water. The optimal conditions for liquid fermentation culture consisted of the following: a loading volume 90 mL, inoculation volume 30 mL, and rotation speed 160 rpm. The optimal substrate formula for domestic culture was 20% corn cob, 30% sawdust, 20% wheat bran, 25% cotton seed shell, 3% corn meal, 1% gypsum, and 1% lime, which produced the highest yield of fruiting bodies. The results provided basic data for deep liquid fermentation culture and recommendations for the further development and utilization of F. pinicola.

Composition of Ophiopogon Polysaccharide, Notoginseng Total Saponins and Rhizoma Coptidis Alkaloids Inhibits the Myocardial Apoptosis on Diabetic Atherosclerosis Rabbit.

OBJECTIVE: To investigate the effects of Composition of Ophiopogon polysaccharide, Notoginseng total saponins and Rhizoma Coptidis alkaloids (CONR) on myocardial apoptosis of diabetic atherosclerosis (DA) rabbits METHODS: Sixty male New Zealand white rabbits were randomly divided into 6 groups [control group, model group, CONR high-dose group (450 mg/kg), CONR medium-dose group (150 mg/kg), CONR low-dose group (50 mg/kg), and simvastatin group] by using a completely random method, 10 in each group. DA model was established by intravenously injected alloxan combined with high-fat diet and abdominal aortic balloon injury. After mediation for 10 weeks, fasting blood glucose (FBG), glycosylated hemoglobin (GHB), glycosylated serum protein (GSP), fructoseamine (FRA), aldose reductase (AR), advanced glycation end products (AGEs) in serum were measured by enzyme linked immunosorbent assay (ELISA) method; the expression of receptor of AGEs (RAGE) in myocardial tissue were observed by immunohistochemical method; and p-Jun N-terminal kinase (p-JNK), caspase-3, B-cell lymphoma-2 (bcl-2) protein expression in myocardial tissue were measured by Western blotting. The myocardial apoptosis was detected by TdT-mediated dUTPnick-end labeling (TUNEL) method, and apoptosis index (AI) was calculated. RESULTS: Compared with the control group, serum FBG, GHB, GSP, FRA, AR, AGEs and the expression of myocardium RAGE, p-JNK, caspase-3 proteins, as well as apoptosis index (AI) were significantly increased and bcl-2 protein was significantly decreased in the model group (P<0.01). Compared with the model group, the levels of serum FBG, GHB, GSP, FRA and AR showed a significant decline in CONR high- and medium-dose groups (P<0.01). FBG and GHB showed a significant decline in CONR low-dose group (P<0.01). Compared with the model group, the expression of serum AGEs and myocardium RAGE, p-JNK and caspase-3 protein as well as AI were significantly decreased and bcl-2 protein was significantly up-regulated in all treatment groups (P<0.01); high-dose CONR had the most significant effect on abovementioned indices compared with other treatment groups (P<0.01). Middle-dose CONR had better effect on serum AGEs compared with the low-dose group (P<0.01); middle-dose CONR and simvastatin groups had better effect on the expression of caspase-3, bcl-2 protein, myocardium apoptosis compared with the CONR low-dose group (P<0.01). CONCLUSION: CONR may effectively inhibit myocardial apoptosis on DA rabbits by intervening AGEs-RAGE and JNK, caspase-3, and bcl-2 protein expressions.

Optimization and validation of in-situ derivatization and headspace solid-phase microextraction for gas chromatography-mass spectrometry analysis of 3-MCPD esters, 2-MCPD esters and glycidyl esters in edible oils via central composite design.

This study aimed to develop a headspace solid-phase microextraction gas chromatography-mass spectrometry (HS-SPME-GC-MS) method for the quantification of 3-monochloropropane-1,2-diol fatty acid esters (3-MCPDEs) and 2-monochloropropane-1,3-diol fatty acid esters (2-MCPDEs), and semi-quantification of glycidyl fatty acid esters (GEs) in edible oils. A central composite design was implemented to optimize the derivatization temperature and extraction time, which were 100 °C and 80 min, respectively. HS-SPME coupled with in-situ derivatization was more straightforward (three steps) and sensitive, with a limit of detection of 16% (3.9 µg/L) and 11% (5.3 µg/L) higher than that of liquid injection method, for 3-MCPD and 2-MCPD, respectively. The recoveries of 3-MCPD and 2-MCPD were in the range of 91.1% to 102.1%, with a relative standard deviation ranging from 0.08 to 9.29%. The validated methodology was successfully applied to oil samples. Further efforts will focus on shortening the extraction time, as 80 min is relatively long.

The preventable efficacy of ß-glucan against leptospirosis.

Leptospirosis, caused by pathogenic Leptospira species, has emerged as an important neglected zoonotic disease. Few studies have reported the preventable effects of immunoregulators, except for antibiotics, against leptospirosis. Generally, immunostimulatory agents are considered effective for enhancing innate immune responses. Many studies have found that beta-glucan (ß-glucan) could be a potent and valuable immunostimulant for improving immune responses and controlling diseases. In this study, we investigated the preventable role of ß-glucan against Leptospira infection in hamsters. First, ß-glucan was administered 24 h prior to, during and after infection. The results showed that ß-glucan increased the survival rate to 100%, alleviated tissue injury, and decreased leptospire loads in target organs. Additionally, we found using quantitative real-time PCR that application of ß-glucan significantly enhanced the expression of Toll-like receptor (TLR) 2, interleukin (IL)-1ß and iNOS at 2 dpi (days post infection) and reduced the increase of TLR2, IL-1ß and iNOS induced by Leptospira at 5 dpi. Furthermore, to induce memory immunity, ß-glucan was administered 5 days prior to infection. ß-Glucan also significantly increased the survival rates and ameliorated pathological damage to organs. Moreover, we demonstrated that ß-glucan-trained macrophages exhibited elevated expression of proinflammatory cytokines (IL-1ß and IL-6) in vitro, indicating that ß-glucan induces an enhanced inflammatory response against Leptospira infection. These results indicate that administration of ß-glucan and other immunostimulants could be potential valuable options for the control of Leptospira infection.

Effect of germination time on antioxidative activity and composition of yellow pea soluble free and polar soluble bound phenolic compounds.

This research aims to study antioxidative activities of polar solvent extractable phenolic compounds from yellow peas with different germination times against oil-in-water emulsion oxidation. After germination (0, 2, 4, and 6 days), soluble free and polar soluble bound phenolic compounds were extracted and their antioxidative activity was evaluated using stripped soybean oil (SSO)-in-water emulsions. Liquid chromatography coupled with electrospray ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS) and size-exclusion chromatography with multiangle-light-scattering and refractive-index detection (SEC-MALS-RI) were employed to analyze the phenolic composition and molar mass, respectively. Antioxidative activities of soluble free phenolic compounds increased in the SSO-in-water emulsion system, while those of polar soluble bound phenolic compounds decreased with germination. On the basis of chemometric analysis, pratensein (2), phloridzin (4), quercetin (9), sayanedine (12), hesperetin (13), glyzaglabrin (14), and pinocembrin (15) were speculated as the pivotal phenolic compounds responsible for the hydrogen donating capacity. Additionally, decreased molecular weight of soluble bound phenolic compounds was accompanied by the reduction of antioxidative activity in SSO-in-water emulsions indicating that the moieties of polar soluble bound phenolic compounds also have an important impact on the antioxidative activity of phenolic compounds.

Improvement of the Antioxidative Activity of Soluble Phenolic Compounds in Chickpea by Germination.

Our recent study found that antioxidative activity of phenolic compounds extracted from germinated chickpea was boosted in both in vitro assays and oil-in-water emulsions [ Xu et al. Food Chem. 2018 , 250 , 140 ]. The purpose of this study was to elucidate the mechanism by which germination enhances the antioxidative activity of the phenolic compounds extracted from chickpea. Liquid chromatography coupled with electrospray-ionization quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS) and size-exclusion chromatography with multiangle-light-scattering and refractive-index detection (SEC-MALS-RI) were employed to evaluate the phenolic composition of soluble phenolic compounds (free and bound) and molar masses of soluble bound phenolic compounds, respectively, over 6 days of germination. According to principal-component analysis of the interrelationship between germination time and phenolic composition, it is revealed that protocatechuic acid 4- O-glucoside and 6-hydroxydaidzein played a pivotal role in the soluble free phenolic compounds, whereas gentisic acid and 7,3',4'-trihydroxyflavone were important in the soluble bound phenolic compounds. Molar masses of soluble bound phenolic compounds were increased after 6 days of germination. Protective and dual antioxidative effects were proposed to explicate how the antioxidative activity of soluble bound phenolic compounds in oil-in-water emulsions was improved with germination.

Pulse seed germination improves antioxidative activity of phenolic compounds in stripped soybean oil-in-water emulsions.

The purpose of this study was to investigate antioxidative activity of phenolic compounds extracted from germinated pulse seed including chickpeas, lentils and yellow peas. Phenolic compounds were extracted at different germination time and total phenolic content was examined by Folin Ciocalteu's reaction. Antioxidative activity of extracts was characterized by in vitro assay including 2, 2-diphenyl-1-picrylhydrazyl radical scavenging capacity (DPPH), oxygen radical absorbance capacity (ORAC), iron-binding assay, and in stripped soybean oil-in-water emulsions. The results suggested that germination time is critical for phenolic compounds production. The form variation of phenolic compounds influenced the antioxidative activity of phenolic compounds both in vitro assay and in emulsion systems. Soluble bound phenolic compounds showed higher antioxidative ability in emulsion system with the order of chickpea > yellow pea > lentil. On the basis of these results, soluble bound phenolic compounds may be considered as a promising natural antioxidant to prevent lipid oxidation in foods.

Enhancement of oral bioavailability and immune response of Ginsenoside Rh2 by co-administration with piperine.

Ginsenoside Rh2 (Rh2) is one of the major bioactive ginsenosides in Panax ginseng. However, the oral bioavailability of Rh2 is low, with P-glycoprotein (P-gp) and CYP3A4 being reported to be the main factors. The purpose of the present study was to determine the enhancing effect of piperine on the oral bioavailability as well as bioactivity of Rh2. The inhibitory effect of piperine on P-gp and CYP3A4 was determined using a Caco-2 monolayer model and a recombinant CYP3A4 metabolic system, respectively. The pharmacokinetics of oral Rh2 (10 mg·kg-1) administered alone or in combination with piperine (10 and 20 mg·kg-1) was performed in rats. The immune boosting effect of Rh2 was assessed in rats by measuring IL-12 level after treated by Rh2 alone or co-administered with piperine. The results indicated that piperine significantly increased the permeability of Rh2 and inhibited the metabolism of Rh2. The pharmacokinetic study results showed that the AUC of Rh2 was significantly increased in combination with piperine at high dose (20 mg·kg-1) when compared to the control group, with relative bioavailability of 196.8%. The increase of Rh2 exposure led to increased serum levels of IL-12. In conclusion, piperine may be used as a bioenhancer to improve pharmacological effect of Rh2 when given orally.