Antioxidant properties and changes in vitro digestion of the fermented kiwifruit extract prepared by lactic acid bacteria and yeasts.

The health benefits of fermented fruits have attracted consumers' attention. High levels of antioxidant ability in the fermented kiwifruit extract were found at the early stage of fermentation. The co-fermention with Lactobacillus paracasei LG0260 and Kluyveromyces marxianus J2853 showed the highest ABTS radical scavenging ability (ABTS⋅+-SA) and superoxide dismutase (SOD) activity. Also, the typical antioxidant components of SOD activity, vitamin C concentration and total phenol content were highly correlated with ABTS⋅+-SA. Obviously, polyphenols in the fermented kiwifruit extract evolved into monophenols during fermentation. Compared to undigested samples, the activity of ABTS⋅+-SA and reducing power capacity (RP-CA) after the final intestinal digestion decreased and ranged 387.44-531.89 VCµg/mL, 650.95-981.63 VCµg/mL, respectively (P < 0.05). Meanwhile, SOD activity on the 10th day of fermentation were still remained 222.82 U/mL, 206.98 U/mL and 217.23 U/mL, respectively. These results suggested that the fermented kiwifruit extract could exhibit antioxidant activity through tolerance to the digestive environment.

Exogenous methionine contributes to reversing the resistance of Streptococcus suis to macrolides.

Streptococcus suis (S. suis) has been increasingly recognized as a porcine zoonotic pathogen that threatens the health of both pigs and humans. Multidrug-resistant Streptococcus suis is becoming increasingly prevalent, and novel strategies to treat bacterial infections caused by these organisms are desperately needed. In the present study, an untargeted metabolomics analysis showed that the significant decrease in methionine content and the methionine biosynthetic pathway were significantly affected by the Kyoto Encyclopedia of Genes and Genomes pathway enrichment analysis in drug-resistant S. suis. The addition of L-methionine restored the bactericidal activity of macrolides, doxycycline, and ciprofloxacin on S. suis in vivo and in vitro. Further studies showed that the exogenous addition of methionine affects methionine metabolism by reducing S-adenosylmethionine synthetase activity and the contents of S-adenosylmethionine, S-adenosyl homocysteine, and S-ribose homocysteine. Methionine can decrease the total methylation level and methylesterase activity in multidrug resistant S. suis. The drug transport proteins and efflux pump genes were significantly downregulated in S. suis by exogenous L-methionine. Moreover, the exogenous addition of methionine can reduce the survival of S. suis by affecting oxidative stress and metal starvation in bacteria. Thus, L-methionine may influence the development of resistance in S. suis through methyl metabolism and metal starvation. This study provides a new perspective on the mitigation of drug resistance in S. suis.IMPORTANCEBacterial antibiotic resistance has become a severe threat to human and animal health. Increasing the efficacy of existing antibiotics is a promising strategy against antibiotic resistance. Here, we report that L-methionine enhances the efficacy of macrolides, doxycycline, and ciprofloxacin antibiotics in killing Streptococcus suis, including multidrug-resistant pathogens. We investigated the mechanism of action of exogenous methionine supplementation in restoring macrolides in Streptococcus suis and the role of the methionine cycle pathway on methylation levels, efflux pump genes, oxidative stress, and metal starvation in Streptococcus suis. It provides a theoretical basis for the rational use of macrolides in clinical practice and also identifies a possible target for restoring drug resistance in Streptococcus suis.

Signaling pathways and targeted therapeutic strategies for polycystic ovary syndrome.

Polycystic ovary syndrome (PCOS) is the most common endocrine disorder among women of reproductive age. Although promising strides have been made in the field of PCOS over the past decades, the distinct etiologies of this syndrome are not fully elucidated. Prenatal factors, genetic variation, epigenetic mechanisms, unhealthy lifestyles, and environmental toxins all contribute to the development of this intricate and highly heterogeneous metabolic, endocrine, reproductive, and psychological disorder. Moreover, interactions between androgen excess, insulin resistance, disruption to the hypothalamic-pituitary-ovary (HPO) axis, and obesity only make for a more complex picture. In this review, we investigate and summarize the related molecular mechanisms underlying PCOS pathogenesis from the perspective of the level of signaling pathways, including PI3K/Akt, TGF-ß/Smads, Wnt/ß-catenin, and Hippo/YAP. Additionally, this review provides an overview of prospective therapies, such as exosome therapy, gene therapy, and drugs based on traditional Chinese medicine (TCM) and natural compounds. By targeting these aberrant pathways, these interventions primarily alleviate inflammation, insulin resistance, androgen excess, and ovarian fibrosis, which are typical symptoms of PCOS. Overall, we hope that this paper will pave the way for better understanding and management of PCOS in the future.

Natural antibacterial agent-based nanoparticles for effective treatment of intracellular MRSA infection.

Intracellular MRSA is extremely difficult to eradicate by traditional antibiotics, leading to infection dissemination and drug resistance. A general lack of facile and long-term strategies to effectively eliminate intracellular MRSA. In this study, glabridin (GLA)-loaded pH-responsive nanoparticles (NPs) were constructed using cinnamaldehyde (CA)-dextran conjugates as carriers. These NPs targeted infected macrophages/MRSA via dextran mediation and effectively accumulated at the MRSA infection site. The NPs were then destabilized in response to the low pH of the lysosomes, which triggered the release of CA and GLA. The released CA downregulated the expression of cytotoxic pore-forming toxins, thereby decreasing the damage of macrophage and risk of the intracellular bacterial dissemination. Meanwhile, GLA could rapidly kill intracellularly entrapped MRSA with a low possibility of developing resistance. Using a specific combination of the natural antibacterial agents CA and GLA, NPs effectively eradicated intracellular MRSA with low toxicity to normal tissues in a MRSA-induced peritonitis model. This strategy presents a potential alternative for enhancing intracellular MRSA therapy, particularly for repeated and long-term clinical applications. STATEMENT OF SIGNIFICANCE: Intracellular MRSA infections are a growing threat to public health, and there is a general lack of a facile strategy for efficiently eliminating intracellular MRSA while reducing the ever-increasing drug resistance. In this study, pH-responsive and macrophage/MRSA-targeting nanoparticles were prepared by conjugating the phytochemical cinnamaldehyde to dextran to encapsulate the natural antibacterial agent glabridin. Using a combination of traditional Chinese medicine, the NPs significantly increased drug accumulation in MRSA and showed superior intracellular and extracellular bactericidal activity. Importantly, the NPs can inhibit potential intracellular bacteria dissemination and reduce the development of drug resistance, thus allowing for repeated treatment. Natural antibacterial agent-based drug delivery systems are an attractive alternative for facilitating the clinical treatment of intracellular MRSA infections.

Gallic Acid Restores the Sulfonamide Sensitivity of Multidrug-Resistant Streptococcus suis via Polypharmaceology Mechanism.

Due to the large amount of antibiotics used for human therapy, agriculture, and even aquaculture, the emergence of multidrug-resistant Streptococcus suis (S. suis) led to serious public health threats. Antibiotic-assisted strategies have emerged as a promising approach to alleviate this crisis. Here, the polyphenolic compound gallic acid was found to enhance sulfonamides against multidrug-resistant S. suis. Mechanistic analysis revealed that gallic acid effectively disrupts the integrity and function of the cytoplasmic membrane by dissipating the proton motive force of bacteria. Moreover, we found that gallic acid regulates the expression of dihydrofolate reductase, which in turn inhibits tetrahydrofolate synthesis. As a result of polypharmacology, gallic acid can fully restore sulfadiazine sodium activity in the animal infection model without any drug resistances. Our findings provide an insightful view into the threats of antibiotic resistance. It could become a promising strategy to resolve this crisis.

Modifying the Expression of Cysteine Protease Gene PCP Affects Pollen Development, Germination and Plant Drought Tolerance in Maize.

Cysteine proteases (CPs) are vital proteolytic enzymes that play critical roles in various plant processes. However, the particular functions of CPs in maize remain largely unknown. We recently identified a pollen-specific CP (named PCP), which highly accumulated on the surface of maize pollen. Here, we reported that PCP played an important role in pollen germination and drought response in maize. Overexpression of PCP inhibited pollen germination, while mutation of PCP promoted pollen germination to some extent. Furthermore, we observed that germinal apertures of pollen grains in the PCP-overexpression transgenic lines were excessively covered, whereas this phenomenon was not observed in the wild type (WT), suggesting that PCP regulated pollen germination by affecting the germinal aperture structure. In addition, overexpression of PCP enhanced drought tolerance in maize plants, along with the increased activities of the antioxidant enzymes and the decreased numbers of the root cortical cells. Conversely, mutation of PCP significantly impaired drought tolerance. These results may aid in clarifying the precise functions of CPs in maize and contribute to the development of drought-tolerant maize materials.

Sustainable extraction of ligustilide and ferulic acid from Angelicae Sinensis Radix, for antioxidant and anti-inflammatory activities.

The 2030 Agenda for Sustainable Development envisions a rational use of energy and resources in all technological processes. However, in the extraction methods of compounds from medicinal plants and herbs, there is an urgent to reduce the use of organic solvents and increase the energy efficiency of these methods. Therefore, a sustainable extraction method (enzyme and ultrasonic co-assisted aqueous two-phase extraction, EUA-ATPE) of simultaneous extraction and separation of ferulic acid and ligustilide from Angelicae Sinensis Radix (ASR) was developed by integrating enzyme-assisted extraction (EAE) with ultrasonic-assisted aqueous two-phase extraction (UAE- ATPE). The effects of different enzymes, extraction temperature, pH, ultrasonic time, liquid-to-materials ratio, etc., were optimized by single-factor experiments and central composite design (CCD). Under the optimum conditions, the highest comprehensive evaluation value (CEV) and extraction yield were obtained by EUA-ATPE. Furthermore, recovery (R), partition coefficient (K), and scanning electron microscopy (SEM) analysis revealed that enzyme and ultrasonic treatment improved mass transfer diffusion and increased the degree of cell disruption. Besides, the EUA-ATPE extracts have shown great antioxidant and anti-inflammatory activity in vitro. Finally, compared to different extraction methods, EUA-ATPE achieved higher extraction efficiency and higher energy efficiency due to the synergistic effect between EAE and UAE-ATPE. Therefore, the EUA-ATPE provides a sustainable method for extracting bioactive compounds from medicinal plants and herbs, contributing to Sustainable Development Goals (SDG), including SDG-6, SDG-7, SDG-9, SDG-12, and SDG-15.

A Recombinant Genotype I Japanese Encephalitis Virus Expressing a Gaussia Luciferase Gene for Antiviral Drug Screening Assay and Neutralizing Antibodies Detection.

Japanese encephalitis virus (JEV) is the major cause of viral encephalitis in humans throughout Asia. In the past twenty years, the emergence of the genotype I (GI) JEV as the dominant genotype in Asian countries has raised a significant threat to public health security. However, no clinically approved drug is available for the specific treatment of JEV infection, and the commercial vaccines derived from the genotype III JEV strains merely provided partial protection against the GI JEV. Thus, an easy-to-perform platform in high-throughput is urgently needed for the antiviral drug screening and assessment of neutralizing antibodies specific against the GI JEV. In this study, we established a reverse genetics system for the GI JEV strain (YZ-1) using a homologous recombination strategy. Using this reverse genetic system, a gaussia luciferase (Gluc) expression cassette was inserted into the JEV genome to generate a reporter virus (rGI-Gluc). The reporter virus exhibited similar growth kinetics to the parental virus and remained genetically stable for at least ten passages in vitro. Of note, the bioluminescence signal strength of Gluc in the culture supernatants was well correlated with the viral progenies determined by viral titration. Taking advantage of this reporter virus, we established Gluc readout-based assays for antiviral drug screening and neutralizing antibody detection against the GI JEV. These Gluc readout-based assays exhibited comparable performance to the assays using an actual virus and are less time consuming and are applicable for a high-throughput format. Taken together, we generated a GI JEV reporter virus expressing a Gluc gene that could be a valuable tool for an antiviral drug screening assay and neutralization assay.

An active tumor-targeting organic photochemotherapy agent with naproxen for enhanced cancer therapy.

An active tumor-targeting organic photochemotherapy agent via the combination of a an organic photothermal material and a naproxen prodrug was developed to precisely kill cancer cells and suppress the inflammatory response induced by cell necrosis; in vitro, and in vivo experiments illustrated its low cytotoxicity and excellent tumor inhibitory effect.

Study on the validity of the theoretical paradigm of art therapy for vulnerable children.

PURPOSE: The vulnerable children refer to the special group of children with deviation in the process of children's psychological development and personality formation due to growth dilemmas. MATERIALS AND METHODS: This may incur a series of serious social and family problems. The vulnerable children mainly cover the children suffering from children's psychological problems, such as childhood autism, autism, social anxiety and hypersensitivity, fear, depression, and PTSD arising from other factors. At present, the research results at home and abroad mainly focus on the psychological dynamic correlation investigation and solution discussion of a certain kind of difficult factor in the children's psychological development based on statistical data by the experimental methods, such as scale and model, and there is a blind spot in the humanistic orientation theory construction of psychological treatment for vulnerable children, causing the social reflection on children's psychological predicament from the humanistic perspective cannot be performed in related researches and going against searching for universal and integral theoretical paradigm for solving related problems. RESULTS: Sophisticated technologies for the observations have emerged increasingly for enabling the psychological features of vulnerable children through developmental cognitive neuroscience experiments. CONCLUSION: This paper introduces humanistic art therapy theory, focuses on the construction of a theoretical paradigm, and verifies its effectiveness based on the experimental results on the psychological development of vulnerable children, with an efficient performance.IMPLICATIONS FOR REHABILITATIONThis study mainly refers to children with difficulty in social inclusion and psychological development.The results showed that two kinds of art therapy can obviously improve the psychological disorders of vulnerable children.The goal was to enhance self-cognition, strengthen emotional interaction, and implement positive motivation.

Ultrasound-assisted deep eutectic solvents extraction of glabridin and isoliquiritigenin from Glycyrrhiza glabra: Optimization, extraction mechanism and in vitro bioactivities.

Licorice (Glycyrrhiza glabra) is extensively used owing to the superior pharmacological effects. However, its maximum application potential has not been fully exploited due to the limitation of currently available extraction solvent and methods. In this study, an eco-friendly deep eutectic solvent (NADESs) based ultrasound-assisted extraction (DES-UAE) method was applied to prepare licorice extracts. The DES-UAE using choline chloride and lactic acid as solvent was optimized and modeled by using response surface methodology to maximize the extraction yields of glabridin (GLA) and isoliquiritigenin (ISL). The optimized extracts possessed higher contents of GLA and ISL than available extraction methods, and the enriched products showed superior pharmacological activities in vitro. Furthermore, scanning electron microscopy (SEM) and molecular dynamic simulation analyses were performed to deeply investigate the interaction between solvent and targeted compounds. This study not only provides an eco-friendly method for high-efficient extraction of GLA and ISL from licorice but also illustrates the mechanism of the increased extraction efficacy, which may contribute to the application of licorice and deep insight into extraction mechanism using DES.

An Active Fraction of Trillium tschonoskii Promotes the Regeneration of Intestinal Epithelial Cells After Irradiation.

Despite significant scientific advances toward the development of safe and effective radiation countermeasures, no drug has been approved for use in the clinic for prevention or treatment of radiation-induced acute gastrointestinal syndrome (AGS). Thus, there is an urgent need to develop potential drugs to accelerate the repair of injured intestinal tissue. In this study, we investigated that whether some fractions of Traditional Chinese Medicine (TCM) have the ability to regulate intestinal crypt cell proliferation and promotes crypt regeneration after radiation. By screening the different supplements from a TCM library, we found that an active fraction of the rhizomes of Trillium tschonoskii Maxim (TT), TT-2, strongly increased the colony-forming ability of irradiated rat intestinal epithelial cell line 6 (IEC-6) cells. TT-2 significantly promoted the proliferation and inhibited the apoptosis of irradiated IEC-6 cells. Furthermore, in a small intestinal organoid radiation model, TT-2 promoted irradiated intestinal organoid growth and increased Lgr5+ intestinal stem cell (ICS) numbers. More importantly, the oral administration of TT-2 remarkably enhanced intestinal crypt cell proliferation and promoted the repair of the intestinal epithelium of mice after abdominal irradiation (ABI). Mechanistically, TT-2 remarkably activated the expression of ICS-associated and proliferation-promoting genes and inhibited apoptosis-related gene expression. Our data indicate that active fraction of TT can be developed into a potential oral drug for improving the regeneration and repair of intestinal epithelia that have intestinal radiation damage.

Study on the Effective Material Basis and Mechanism of Traditional Chinese Medicine Prescription (QJC) Against Stress Diarrhea in Mice.

Stress diarrhea is a major challenge for weaned piglets and restricts pig production efficiency and incurs massive economic losses. A traditional Chinese medicine prescription (QJC) composed of Astragalus propinquus Schischkin (HQ), Zingiber officinale Roscoe (SJ), and Plantago asiatica L. (CQC) has been developed by our laboratory and shows marked anti-stress diarrhea effect. However, the active compounds, potential targets, and mechanism of this effect remain unclear and warrant further investigation. In our study, we verified the bioactive compounds of QJC and relevant mechanisms underlying the anti-stress diarrhea effect through network pharmacology and in vivo experimental studies. After establishing a successful stress-induced diarrhea model, histomorphology of intestinal mucosa was studied, and Quantitative real-time PCR (RT-qPCR) probe was used for the phosphoinositide 3-kinase (PI3K)-Akt signaling pathway to verify the therapeutic effect of QJC on diarrhea. First, using the network pharmacology approach, we identified 35 active components and 130 Kyoto Encyclopedia of Genes and Genomes (KEGG) pathways in QJC. From among these, we speculated that quercetin, luteolin, kaempferol, scutellarein, and stigmasterol were the main bioactive compounds and assumed that the anti-diarrhea effect of QJC was related to the PI3K-Akt signaling pathway. The RT-qPCR indicated that QJC and its bioactive components increased the expression levels of PI3K and Akt, inhibited the expression of phosphatase and tensin homolog (PTEN), and activated the PI3K-Akt signaling pathway to relieve stress-induced diarrhea. Furthermore, we found that QJC alleviated the pathological condition of small intestine tissue and improved the integrity of the intestinal barrier. Taken together, our study showed that the traditional Chinese medicine QJC, quercetin, luteolin, kaempferol, scutellarein, and stigmasterol alleviated the pathological condition of small intestine tissue and relieved stress-induced diarrhea by increasing the expression levels of PI3K and Akt and inhibiting the expression levels of PTEN.

Covalent organic framework based nanoagent for enhanced mild-temperature photothermal therapy.

Photothermal therapy effectively ablates tumors by hyperthermia (>50 °C) under laser irradiation. However, the hyperthermia may inevitably diffuse to the surrounding healthy tissues to induce additional damage. Thus, effective cancer therapy by mild photothermal therapy at low temperatures is greatly desirable. In this study, a nanoagent (COF-GA) was designed to inhibit HSP90 for enhanced photothermal therapy against cancer at low temperatures. The nanoscale covalent organic frameworks (COFs) were able to increase the temperature of the tumor tissue under laser irradiation, which can transfer the energy of laser into heat for cancer cell killing. Gambogic acid (GA), as an inhibitor of HSP90, was used to overcome the heat resistance of tumor, achieving efficient mild-temperature photothermal therapy. As an excellent candidate for the photothermal therapy agent, COF-GA can induce the temperature to elevate as the exposure time increased when irradiated with laser. In vivo tests further demonstrated that the tumor growth was able to be significantly suppressed after being treated with COF-GA. The mild-temperature photothermal therapy exhibits an excellent antitumor efficacy at a relatively low temperature and minimizes the nonspecific thermal damage to normal tissues. This COF-GA nanoagent also enriches our understanding towards the various applications of COFs, particularly in the biomedicine field.

Effect of Syringopicroside Extracted from Syringa oblata Lindl on the Biofilm Formation of Streptococcus suis.

Syringopicroside is a natural drug with antibacterial activity, which is the main ingredient of Syringa oblata Lindl (S. oblata). In order to further develop the application of S. oblata and evaluate the ability of syringopicroside against Streptococcus suis (S. suis), this investigation first applied an ultrasonic-assisted method to extract syringopicroside, and then response surface methodology (RSM) was performed to get the optimum condition. Based on RSM analysis, a second-order polynomial equation about the syringopicroside yield and four variables, including ultrasonic power, time, temperature, and liquid-to-solid ratio, was purposed. Through RSM prediction and model verification experiments, the optimum conditions were determined, as follows: ultrasonic time was 63 min, temperature was 60 °C, a liquid-to-solid ratio was set to 63 mL/g, and ultrasonic power was 835 W. Under this condition, a high syringopicroside yield was obtained (3.07 ± 0.13 mg/g), which was not significantly different with a predicated value. After separation and purification by HPD 500 microporous resin, then mass spectrum was applied to identify the main ingredient in aqueous extract. A minimal inhibitory concentration (MIC) assay revealed the value against S. suis of syringopicroside was 2.56 µg/µL and syringopicroside with sub-inhibitory concentrations that could effectively inhibit biofilm formation of S. suis. Besides, scanning electron microscopy analysis indicated syringopicroside could destroy the multi-layered aggregation structure of S. suis. Finally, molecular docking analysis confirmed that syringopicroside was combined with Orfy protein of S. suis through hydrogen bonds, hydrophobic interaction, and π-π stacking.

FLOURY ENDOSPERM19 encoding a class I glutamine amidotransferase affects grain quality in rice.

As a staple food for more than half of the world's population, the importance of rice is self-evident. Compared with ordinary rice, rice cultivars with superior eating quality and appearance quality are more popular with consumers due to their unique taste and ornamental value, even if their price is much higher. Appearance quality and CEQ (cooking and eating quality) are two very important aspects in the evaluation of rice quality. Here, we performed a genome-wide association study on floury endosperm in a diverse panel of 533 cultivated rice accessions. We identified a batch of potential floury genes and prioritize one (LOC_Os03g48060) for functional analyses. Two floury outer endosperm mutants (flo19-1 and flo19-2) were generated through editing LOC_Os03g48060 (named as FLO19 in this study), which encodes a class I glutamine amidotransferase. The different performances of the two mutants in various storage substances directly led to completely different changes in CEQ. The mutation of FLO19 gene caused the damage of carbon and nitrogen metabolism in rice, which affected the normal growth and development of rice, including decreased plant height and yield loss by decreased grain filling rate. Through haplotype analysis, we identified a haplotype of FLO19 that can improve both CEQ and appearance quality of rice, Hap2, which provides a selection target for rice quality improvement, especially for high-yield indica rice varieties. Supplementary Information: The online version contains supplementary material available at 10.1007/s11032-021-01226-z.

[Mechanism action of Chinese herbal compound and target network pharmacology of Yougui (YG) pill for the treatment of osteoporosis].

OBJECTIVE: To explore compounds, targets and mechanism of Yougui (YG) pill in treating osteoporosis based on systemic pharmacology of traditional Chinese medicine. METHODS: The known effective Chinese herbal compound of YG pill was searched from traditional Chinese medicine integrated database(TCMID). Bioinformatics analysis tool for molecular mechanism of traditional Chinese medicine (BATMAN-TCM) was used to predict target of components;DisGeNET and artificial literature reading were used to obtain targets of osteoporosis and bone remodeling;Cytoscape 3.7.1 software and its plug-ins BiN-GO and ClueGO were used to enrich the GO annotation and pathwaysof the related targets, and validation of the predicted target of YG pill were validated by 87 differentially expressed proteins in postmenopausal osteoporosis and postmenopausal osteoporosis disease models in postmenopausal patients with normal bone mass from the previous serum proteomics data. RESULTS: Totally 392 compounds were retrieved from YG pill, including 83 sovereign drugs (monkshood, cinnamon, deerhorn gelatin), 127 ministerial drugs (prepared rehmannia root, dogwood, wolfberry fruit and Chinese yam) and 182 supplementary drugs (cuscuta chinensis, eucommia ulmoides and Chinese angelica). Among them, there were 4 same compounds between sovereign drug and ministerial drug, 1 same compound between sovereign drug and supplementary drug, and 14 same compounds between ministerial drug and supplementary drug. Totally 2 112 trusted targets were identified, included 775 sovereign drugs, 1 483 ministerial drugs and 1 491 supplementary drugs;227 targets were selected from YG pill for treating osteoporosis, which participate in nearly 20 process of metabolic process, cell differentiation and biology, and data mining revealed that the process involved bone remodeling and bone mineralization. Acting site of cell mainly inclded 9 kinds of cell which had 13 molecular function. Results of KEGG metabolic pathway enrichment analysis showed 137 signal passages were obviously enriched. Among them, classical osteoclast differentiation signal passages and relative estrogen regulates signaling pathways of menopause were widely distributed in 27 signal passages. Sixtargets were screened by target validation, such as AGT, FGA, APOE, DKK3, P4HB and RAB7A. CONCLUSION: The characteristics of multi-targets and multi-pathways of YG pill for the treatment of osteoporosis were clarified, which provided a clear direction for the in-depth research. The pharmacodynamic components of YG pill include 36 compounds, and their main action targets include FGA, AGT, APOE, DKK3, P4HB and RAB7A.

Furostanol Saponins from Trillium tschonoskii Promote the Expansion of Human Cord Blood Hematopoietic Stem and Progenitor Cells.

Trillium tschonoskii is a medicinal plant known to biosynthesize steroidal saponins. A phytochemical investigation of the rhizomes of T. tschonoskii led to the isolation of nine new furostanol saponins (1-9) and 11 known analogues (10-20). Five of these new compounds were shown to have hydroxy groups at the C-5 and C-6 positions, while two possess a rare aglycone containing carbonyl groups at the C-16 and C-22 positions as well as a Δ17(20) double bond, and the others have conjugated double bonds in the E-ring or have different sugar chains at the C-3 position. All the isolates were tested for their effect on the expansion of human cord blood (CB) CD34+ hematopoietic stem and progenitor cells. It was found that CB CD34+ cells treated with compounds 6, 7, 9, 10, 14, 15, and 19 showed increased numbers of rigorously phenotype-defined hematopoietic stem cells. Notably, compounds 9, 10, 13, and 14 demonstrated an enhanced ability to increase the percentages and numbers of CB CD34+CD38- cells and multipotential progenitors. The present study is the first to report that furostanol saponins from T. tschonoskii rhizomes can promote hematopoietic stem/progenitor cell (HSPC) expansion.

Antiviral Strategies of Chinese Herbal Medicine Against PRRSV Infection.

Bioactive compounds from Traditional Chinese Medicines (TCMs) are gradually becoming an effective alternative in the control of porcine reproductive and respiratory syndrome virus (PRRSV) because most of the commercially available PRRSV vaccines cannot provide full protection against the genetically diverse strains isolated from farms. Besides, the incomplete attenuation procedure involved in the production of modified live vaccines (MLV) may cause them to revert to the more virulence forms. TCMs have shown some promising potentials in bridging this gap. Several investigations have revealed that herbal extracts from TCMs contain molecules with significant antiviral activities against the various stages of the life cycle of PRRSV, and they do this through different mechanisms. They either block PRRSV attachment and entry into cells or inhibits the replication of viral RNA or viral particles assembly and release or act as immunomodulators and pathogenic pathway inhibitors through cytokines regulations. Here, we summarized the various antiviral strategies employed by some TCMs against the different stages of the life cycle of PRRSV under two major classes, including direct-acting antivirals (DAAs) and indirect-acting antivirals (IAAs). We highlighted their mechanisms of action. In conclusion, we recommended that in making plans for the use of TCMs to control PRRSV, the pathway forward must be built on a real understanding of the mechanisms by which bioactive compounds exert their effects. This will provide a template that will guide the focus of collaborative studies among researchers in the areas of bioinformatics, chemistry, and proteomics. Furthermore, available data and procedures to support the efficacy, safety, and quality control levels of TCMs should be well documented without any breach of data integrity and good manufacturing practices.

Photothermal therapy-induced immunogenic cell death based on natural melanin nanoparticles against breast cancer.

A photothermal and immune co-therapy strategy based on natural melanin nanoparticles was developed for treating primary and abscopal breast cancers.