Polydatin from Polygoni Cuspidati Rhizoma et Radix regulates glucolipid metabolism in the liver of diabetic rats: Multiscale analysis of network pharmacology and multiomics.

BACKGROUND: Polygoni Cuspidati Rhizoma et Radix (Huzhang in Chinese), refers to the root and rhizome of Polygonum cuspidatum Sieb. et Zucc. Huzhang is commonly used in clinical practice for the prevention and treatment of diabetes and its complications, but its active components and regulatory mechanisms have not yet been thoroughly analyzed. PURPOSE: The network pharmacology combined with multi-omics analysis will be employed to dissect the substance basis and action mechanism of Huzhang in exerting its anti-diabetic activity. METHODS: This study employed phenotypic indicators for baseline assessment, followed by integrated analysis using network pharmacology, metabolomics, transcriptomics, and qPCR technology to elucidate the active components and pharmacological mechanisms of Huzhang. RESULTS: The analysis of network pharmacology revealed that polydatin is a potential active component responsible for the anti-T2DM pharmacological effects of Huzhang. In vivo experimental results demonstrated that polydatin significantly regulates blood glucose, lipid levels, liver function, and liver pathological damage in diabetic rats. Analysis results from transcriptomics, metabolomics, and qPCR validation showed that polydatin comprehensively regulates glucose and lipid metabolism in T2DM by modulating bile acid metabolism, fatty acid oxidation, and lipogenesis. CONCLUSION: Polydatin is a key component of Huzhang in treating T2DM, and its regulatory mechanisms are diverse, indicating significant development potential.

Quantitative predictive model for screening optimal processing methods of Polygonati rhizoma.

Polygonati rhizoma (Huangjing in Chinese) is a common clinical tonic with the traditional effects of tonifying Qi, nourishing Yin. However, the lack of precise control of processing parameters has led to the uneven quality of processed Huangjing. A prediction model using the CRITIC method optimizes processing by correlating method, component contents, and biological activity, ensuring consistent quality and efficacy.

Propylene glycol alginate sodium sulfate suppressed lung metastasis by blocking P-selectin to recruit CD4 regulatory T cells.

P-selectin has been shown to enhance growth and metastasis of mouse tumors by promoting regulatory T cell (Treg) infiltration into the tumors. Theoretically, a P-selectin antagonist could suppress the process. Popylene glycol alginate sodium sulfate (PSS) is a heparin-like marine drug, which was originally approved to treat cardiovascular disease in China. Previously, we reported that PSS was an effective P-selectin antagonist in vitro. However, it is unknown whether PSS can regulate Treg infiltration and its effect on lung metastasis in vivo. Our results showed that PSS at 30 mg/kg significantly suppressed lung metastasis and improved overall survival, with potency comparable to the positive control LMWH. Mechanistic study indicated that PSS blocked tumor cells adhesion and activated platelets by directly binding with activated platelet's P-selectin. Compared to the model group, PSS decreased the percent of Tregs by 63 % in lungs after treating for 21 days while increasing CD8+ T cells (1.59-fold) and Granzyme B+ CD8 T cells (2.08-fold)' percentage for generating an adaptive response for systemic tumor suppression. The study indicated that the P-selectin antagonist, PSS, suppressed lung metastasis by inhibiting the infiltration of regulatory T cells (Treg) into the tumors.

TFEB activator tanshinone IIA and derivatives derived from Salvia miltiorrhiza Bge. Attenuate hepatic steatosis and insulin resistance.

ETHNOPHARMACOLOGICAL RELEVANCE: Salvia miltiorrhiza Bge. (SMB) is an herbal medicine extensively used for improving metabolic disorders, including Nonalcoholic fatty liver disease (NAFLD). However, the potential material basis and working mechanism still remained to be elucidated. AIM OF THE STUDY: To find potential ingredients for therapy of NAFLD by high content screening and further verify the efficacy on restoring hepatic steatosis and insulin resistance, and clarify the potential working mechanism. MATERIALS AND METHODS: The mouse transcription factor EB (Tfeb) in preadipocytes was knocked out by CRISPR-Cas9 gene editing. High content screening of TFEB nuclear translocation was performed to identify TFEB activators. The effect of candidate compounds on reducing lipid accumulation was evaluated using Caenorhabditis elegans (C. elegans). Then the role of Salvia miltiorrhiza extract (SMB) containing Tanshinone IIA and the derivatives were further investigated on high-fat diet (HFD) fed mice. RNA-seq was performed to explore potential molecular mechanism of SMB. Finally, the gut microbiota diversity was evaluated using 16S rRNA sequencing to investigate the protective role of SMB on regulating gut microbiota homeostasis. RESULTS: Knockout of Tfeb led to excessive lipid accumulation in adipocytes while expression of TFEB homolog HLH-30 in C. elegans (MAH240) attenuated lipid deposition. Screening of TFEB activators identified multiple candidates from Salvia miltiorrhiza, all of them markedly induced lysosome biogenesis in HepG2 cells. One of the candidate compounds Tanshinone IIA significantly decreased lipid droplet deposition in HFD fed C. elegans. Administration of SMB on C57BL/6J mice via gastric irrigation at the dose of 15 g/kg/d markedly alleviated hepatic steatosis, restored serum lipid profile, and glucose tolerance. RNA-seq showed that gene expression profile was altered and the genes related to lipid metabolism were restored. The disordered microbiome was remodeled by SMB, Firmicutes and Actinobacteriotawere notably reduced, Bacteroidota and Verrucomicrobiota were significantly increased. CONCLUSION: Taken together, the observations presented here help address the question concerning what were the main active ingredients in SMB for alleviating NAFLD, and established that targeting TFEB was key molecular basis for the efficacy of SMB.

[Critical Review on Heavy Metal Contamination in Urban Soil and Surface Dust].

With the rapid urbanization and industrialization, heavy metal contamination in urban soil and surface dust has received particular attention due to its negative effects on the eco-environment and human health. Contamination and spatio-temporal characteristics, contamination sources, and source apportionment methods, as well as the ecological and health risks of heavy metals in urban soil and surface dust were reviewed. The knowledge gaps in current research and prospects of future works were proposed. Four key points were presented, including improving the research on the interaction mechanism of heavy metals in urban soil and surface dust under complex conditions, enriching verification methods to improve the source apportionment reliability of anthropogenic metals by receptor models, strengthening the research on chemical forms of heavy metals from different sources and their short-term accumulation processes in surface dust, and raising the credibility of ecological and health risk forecast of heavy metals by integrating the improved exposure parameters and chemical forms.

Unlocking the Potential of Microwave Sterilization Technology in Ready-to-Eat Imitation Crab Meat Production.

Microwave sterilization is a novel potential sterilization technology to improve food quality. An industrial microwave sterilization system was used to sterilize imitation crab meat under thermal processing intensity F0 = 1, 2, 3. The characteristics of the microwave process, such as heating rate, processing time, and C100, were calculated. In addition, the quality of processed imitation crab meat was investigated. Compared with the conventional retort method, microwave sterilization significantly shortened the processing time of imitation crab meat by 63.71% to 72.45%. Under the same thermal processing intensity, microwave sterilization has demonstrated better results than retort sterilization in terms of water-holding capacity, color, and texture. Furthermore, microwave-treated imitation crab meat ingredients had a greater capacity to bind water molecules and obtained a more appropriate secondary protein structure. In addition, microwave technology can better preserve the unsaturated fatty acids (UFA) of imitation crab meat, which are 9.14%, 1.19%, and 0.32% higher than the traditional method at F0 = 1, 2, 3. The results would provide useful data for the subsequent research and development of ready-to-eat surimi products.

The serum lipidomics reveal the action mechanism of Danggui-Yimucao herbal pair in abortion mice.

Medical abortion is a common medical procedure that women choose to terminate an unwanted pregnancy, but it often brings post-abortion complications. Danggui (Angelica sinensis Radix)-Yimucao (Leonuri Herba), as a herbal pair (DY) in clinical prescriptions of traditional Chinese medicine, is often used in the treatment of gynecological diseases and has the traditional functions of tonifying the blood, promoting blood circulation, removing blood stasis and regulating menstruation. In this study, serum lipidomics were adopted to dissect the mechanism of DY in promoting recovery after medical abortion. A total of 152 differential metabolites were screened by lipidomics. All metabolites were imported into MetaboAnalyst for analysis, and finally key metabolic pathways such as glycerophospholipid metabolism, linoleic acid metabolism and pentose and glucuronate interconversions were enriched. Our results indicated that metabolic disorders in abortion mice were alleviated by DY through glycerophospholipid metabolism, while prostaglandin and leukotriene metabolites might be the key targets of DY to promote post-abortion recovery.

Design, synthesis and anti-tumor evaluation of plinabulin derivatives as potential agents targeting ß-tubulin.

Plinabulin is a promising microtubule destabilizing agent in phase 3 clinical stage for treating non-small cell lung cancer. However, the high toxicity and the poor water solubility of plinabulin limited its use and more plinabulin derivatives need to be explored. Here, two series of 29 plinabulin derivatives were designed, synthesized and evaluated for their anti-tumor effect against three types of cancer cell lines. Most of derivatives exerted obvious inhibition to the proliferation of the cell lines tested. Among them, compound 11c exerted stronger efficiency than plinabulin, and the reason might be the additional hydrogen bond between the nitrogen atom of the indole ring in compound 11c and Gln134 of ß-tubulin. Immunofluorescence assay showed that compound 11c at 10 nM significantly disrupted tubulin structure. Compound 11c also significantly induced G2/M cell cycle arrest and apoptosis in dose dependent manner. These results suggest that compound 11c might be a potential candidate for cancer treatment as antimicrotubule agent.

Preliminary exploration of method for screening efficacy markers compatibility in TCM prescriptions based on Q-markers: Anti-inflammatory activity of Dachaihu decoction as an example.

ETHNOPHARMACOLOGICAL RELEVANCE: Dachaihu Decoction (DD), a classic Chinese herbal prescription, is composed of radix of Bupleurum chinense DC. (Chaihu), radix of Scutellaria baicalensis Georgi (Huangqin), radix of Paeonia lactiflora Pall. (Baishao), rhizoma of Pinellia ternata (Thunb.) Breit. (Banxia), fructus of Citrus aurantium L. (Zhishi), rhizoma of Zingiber officinale Rosc. (Shengjiang), fructus of Ziziphus jujuba Mill. (Dazao) and rhizoma of Rheum officinale Baill. (Dahuang). DD has the traditional effects of soothing the liver, relieving depression and clearing heat from the stomach, and is mainly used to treat heat stagnation in the liver and stomach. AIM OF THE STUDY: Dachaihu decoction (DD), a classic prescription commonly used in clinical practice for the treatment of pancreatitis and cholecystitis. Although its pharmacological effects are clear, the efficacy components and mechanism of action remain intricate and difficult to clarify. MATERIALS AND METHODS: The action targets and components of the anti-inflammatory activity of DD were predicted by network pharmacology; the effective components and targets were verified by HPLC and qPCR; the efficacy markers of DD were further screened by in vitro experiments; the pharmacological value of DD and its components compatibility were evaluated by in vitro experiments. RESULTS: The key targets MMP9, JAK2, MAP2K1 and NR3C1 were screened by network pharmacology; HPLC analysis showed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were identified as potential efficacy markers of DD; molecular docking combined with qPCR verification suggested that baicalin, naringin, neohesperidin, hesperidin and baicalein and wogonoside had certain ability to regulate above targets; in vitro studies revealed that paeoniflorin, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 could inhibit the release of NO, pancreatic lipase and α-glucosidase; after comprehensive comparison and analysis, naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 were selected as the efficacy markers of DD; in vivo studies indicated that DD and its efficacy markers (components compatibility) had definite therapeutic effects on guinea pigs with cholecystitis. CONCLUSIONS: The efficacy markers of DD including naringin, hesperidin, neohesperidin, baicalin, wogonoside, baicalein and saikosaponin B2 can be used as components compatibility to exert anti-inflammatory activity. In addition, a method for obtaining the compatibility of efficacy markers by simplifying the prescription is initially established.

Effects of cooling rates during depuration on the quality of Pacific oysters (Crassostrea gigas) at anhydrous preservation stage.

The Pacific oyster could be affected by several pressure sources during cold chain logistics, which reduce the quality of oyster, and even improve its mortality. For improving the quality of oyster, the effects of depuration process at different cooling rates (1, 3, 7, 11 and 16 °C/h) on selected Pacific oyster were studied. The results indicated that extreme fluctuations in the depuration temperatures could affect the survival rates and qualities of oysters. The oysters exhibited low survival rates, glycogen contents and pH values at an increased cooling rate. Their contents in the 1 °C/h group after 3 d preservation were 100 %, 16.30 ± 1.64 mg/100 g and 6.72 ± 0.01, respectively, while there were 71 %, 7.72 ± 0.88 mg/100 g and 6.53 ± 0.01 in the 16 °C/h group after 3 d preservation, respectively. Furthermore, the ATP-related compounds were affected by the different cooling rates. AMP and IMP were the main ATP-related compounds, and their contents in the 1 °C/h group after 3 d preservation were 37.21 ± 1.10 mg/100 g and 29.47 ± 1.10 mg/100 g, respectively, while there were 32.07 ± 1.10 mg/100 g and 13.16 ± 1.60 mg/100 g in the 16 °C/h group after 3 d preservation, respectively. The proportions of the total umami, as well as the sweet amino acids also decreased, the proportions of the umami amino acids and sweet amino acids in the total amino acids, were 31.37%-38.80%, and their proportions in 1 °C/h group were higher than that in 16 °C/h group. Conversely, the fatty acid content of each group exhibited significant differences. Combined with the above results, the oyster maintained a high survival rate and higher quality at a cooling rate of 1 °C/h during depuration.

A chemometric study on the identification of 5-methylfurfural and 2-acetylfuran as particular volatile compounds of oxidized fish oil based on SHS-GC-IMS.

Fish oil develops particular off-odors, mainly fishy odor, from the oxidation of its characteristic fatty acids, docosahexaenoic (DHA) and eicosapentaenoic (EPA). Anchovy oil (AO) was taken as representative of fish oils. This was compared to three vegetable oils with different fatty acid compositions, i.e. camellia, sunflower and linseed oil, and differential volatile compounds were identified by static-headspace gas-chromatography ion-mobility-spectrometry (SHS-GC-IMS) and orthogonal partial-least-squares discriminant analysis (OPLS-DA) during oxidation at 60 °C. Three groups of differential volatile compounds detected at higher concentrations in the AO were screened out and two compounds, identified as 5-methylfurfural and 2-acetylfuran, were characteristic to the AO and not found in the vegetable oils. They were formed from both EPA and DHA, only present in the AO, and their formation mechanisms were proposed. The contents of 5-methylfurfural and 2-acetylfuran increased linearly with the oxidation time and consequently they could be used as oxidative markers of fish oils.

Concomitant oxidation of fatty acids other than DHA and EPA plays a role in the characteristic off-odor of fish oil.

The aim of the present research was to explore the development of off-odors in fish oil from the perspective of fatty acid oxidation. It was found that the off-odors elicited by the two major ω-3 PUFAs in fish oil, i.e. DHA and EPA, were different from those by fish oil. Results showed that simultaneous oxidation of fatty acids other than DHA and EPA can be involved. The off-odors of fish oil was successfully simulated by combining oxidized samples of DHA, EPA and sunflower oil. Therefore, oxidation of oleic and linoleic acids also contributed to the off-odors in fish oil. A novel analytical approach that consisted in the combination of gas chromatography-ion mobility spectrometry (GC-IMS) and orthogonal partial least squares discriminant analysis (OPLS-DA) was applied to identify differences in the volatile components between the recombinant oil and the fish oil.

Cytotoxic and Antibacterial Isomalabaricane Terpenoids from the Sponge Rhabdastrella globostellata.

Nine new isomalabaricane terpenoids (1-9) were isolated from the sponge Rhabdastrella globostellata of Ximao Island, together with 13 known ones (10-22). The structures were established by spectroscopic data interpretation and chemical calculations, as well as by comparison with spectroscopic data of known compounds. Notably, of the new isolates, hainanstelletin A (5) is the first representative of a nitrogenous isomalabaricane. The isolated compounds were evaluated against several cancer cell lines and two bacterial pathogens. In addition, moderate to strong antibacterial activities against Streptococcus pyogenes were also detected among geometric isomers 1, 2, and 10-12, with minimum inhibitory concentrations of 0.1-1.8 µg/mL.

Network pharmacology-based study on immunomodulatory mechanism of danggui-yimucao herb pair for the treatment of RU486-induced abortion.

ETHNOPHARMACOLOGICAL RELEVANCE: The Danggui-Yimucao herb pair (DY) is a classic combination in Chinese herbal formulas, consisting of the root of Angelica sinensis (Oliv.) Diels and the aerial parts of Leonurus japonicus Houtt. DY first appeared in "Zhulinsi fuke mifang" in the Jin Dynasty, and it has a long history as a drug for the treatment of abortion. However, its underlying immunomodulatory mechanisms involved are still unclear. AIM OF THE STUDY: In this study, network pharmacology and pharmacological experiments were used to explore the role and mechanism of DY in the treatment of medical abortion. MATERIALS AND METHODS: Network pharmacology was used to establish the relationship between the components of DY and abortion-related targets, and to enrich important pathways and biological process for verification. ELISA was used to assess progesterone levels. Flow cytometry was used to detect the degree of differentiation of Th1/Th2 cells. Immunohistochemical methods and qPCR were used to measure the expression levels of T-bet, GATA-3 and IL-4. RESULTS: Through the prediction analysis of network pharmacology, we found that key pathway for DY treatment of abortion, such as anemia, pelvic infection, immune disorders, and coagulation disorders, was Th1/Th2 cell differentiation pathway. The pharmacological results revealed that DY greatly corrected the imbalance of Th cell subsets in abortion mice, significantly inhibited the differentiation of Th2 cells, and resulted in an increase in the Th1/Th2 ratio. In addition, the concentration of progesterone in the serum of mice after abortion was significantly reduced. We also found that DY upregulated spleen T-bet and downregulated IL-4 gene expression in mice. Besides, immunohistochemical results showed that DYE could up-regulate T-bet but inhibit GATA-3 expression. CONCLUSIONS: Our results showed that after RU486-induced abortion, progesterone and Th1/Th2 paradigm were disordered in mice, but DY could make mice recover more quickly, which indicated that DY had great development value in immunoregulation.

Danggui-Yimucao Herb Pair Can Protect Mice From the Immune Imbalance Caused by Medical Abortion and Stabilize the Level of Serum Metabolites.

Unintended pregnancy is a situation that every woman may encounter, and medical abortion is the first choice for women, but abortion often brings many sequelae. Angelica sinensis Radix (Danggui) and Leonuri Herba (Yimucao) are widely used in the treatment of gynecological diseases, which can regulate menstrual disorders, amenorrhea, dysmenorrhea, and promote blood circulation and remove blood stasis, but the mechanism for the treatment of abortion is not clear. We determined the ability of Danggui and Yimucao herb pair (DY) to regulate the Th1/Th2 paradigm by detecting the level of progesterone in the serum and the expression of T-bet and GATA-3 in the spleen and uterus. Then, we detected the level of metabolites in the serum and enriched multiple metabolic pathways. The arachidonic acid pathway can directly regulate the differentiation of Th1/Th2 cells. This may be one of the potential mechanisms of DY in the treatment of abortion.

Application of Plackett-Burman Design in Screening of Natural Antioxidants Suitable for Anchovy Oil.

Considering the safety of synthetic antioxidants, more and more natural antioxidants have been developed and utilized in foods. This study aimed to screen out a natural antioxidant combination from many antioxidants, which could significantly affect the oxidation stability of anchovy oil, while Plackett-Burman design (PBD) methodology was employed in this screening. According to the statistical results of this design, sesamol, dihydromyricetin, teapolyphenol, and rosemary acid were four significant parameters on the oxidation stability of anchovy oil. Moreover, dihydromyricetin presented the best antioxidant effect among nine kinds of selected antioxidants when they were used alone in anchovy oil. Meanwhile, a combination including sesamol (0.02%), teapolyphenol (0.02%). and rosemary acid (0.02%) was adopted, and its antioxidant ability was similar to that of tert-butylhydroquinone (TBHQ). Additionally, phytic acid as a synergist was used and combined with sesamol, and the antioxidant ability of this combination was better than that of TBHQ. This study presented a reference for the industrial applications of natural antioxidants and synergists in anchovy oil.

ERK/CANP rapid signaling mediates 17ß-estradiol-induced proliferation of human breast cancer cell line MCF-7 cells.

OBJECTIVE: 17ß-estradiol (E2) exerts its functions through both genomic and non-genomic signaling pathways. Because E2 is important in breast cancer development, we investigated whether its actions in promoting breast cancer cell proliferation occur through the non-genomic signaling pathway via extracellular signal-regulated kinase 1/2 (ERK1/2)/calcium-activated neutral protease (CANP). METHODS: MCF-7 breast cancer cells were treated with ERKl/2 inhibitor (PD98059) or CANP inhibitor (calpeptin) before exposure to 1×10(-8) M E2. MTT colorimetry and flow cytometry were used to analyze effects on cell proliferation and cell cycle progression, respectively. Expression of phosphorylated-ERK (p-ERK), total ERK, and Capn4 proteins were assessed by Western blotting. RESULTS: Cell proliferation increased in cells treated with E2 for 24 h (P<0.05), and the proportion of cells in G0/G1 was decreased, accompanied by accelerated G1/S. Calpeptin pre-treatment significantly inhibited the E2-induced proliferation of MCF-7 cells (P<0.05), while also ameliorating the effects of E2 on cell cycle progression. Further, expression of p-ERK was rapidly up-regulated (after 10 min) by E2 (P<0.05), an effect that persisted 16 h after E2 exposure but which was significantly inhibited by PD98059 (P<0.05). CONCLUSIONS: Finally, expression of Capn4 protein was rapidly up-regulated in E2-exposed cells (P<0.05), but this change was significantly inhibited by PD98059 or calpeptin (P<0.05) pre-treatment. Thus, the rapid, non-genomic ERK/CANP signaling pathway mediates E2-induced proliferation of human breast cancer cells.

Pathological features and prognosis of different molecular subtypes of breast cancer.

To examine the pathological features and prognosis of different molecular subtypes of breast cancer, the clinical data of 892 breast cancer patients were retrospectively analyzed and divided into four subtypes according to hormone receptor expression in breast cancer tissue: Her-2 overexpression, luminal A, luminal B and basal-like subtypes. The pathological data and prognosis of these subtypes were compared. Of the 892 breast cancer patients, there were 46 cases (5.2%) with Her-2 overexpression-type, 698 cases (78.3%) with luminal A-type, 38 cases (4.3%) with luminal B-type and 110 patients (12.2%) with basal-like-type. Immunohistochemistry was used to identify the progesterone and estrogen receptors in the tumor tissues. The χ2 test was used to verify the measurement data. The Cox proportional hazard regression model was used for the univariate and multivariate analyses. Results showed there was no statistical difference for lymphatic metastasis among the various molecular subtypes of breast cancer (P>0.05). The distant metastatic rate of patients with Her-2-type breast cancer was significantly higher compared to patients with the other three subtypes (P<0.05). The difference in local recurrence among molecular subtypes was not significantly significant (P>0.05). Lymph node metastasis, age and different molecular subtypes were found to have an impact on patient overall survival (OS) and disease-free survival (DFS). Her-2 overexpression-type breast cancer patients had the lowest 9-year DFS and 7-year OS compared to the other subtypes (P<0.05). Thus, Her-2-type was associated with the worst prognosis. In conlusion, the molecular typing of breast cancer has important clinical value in prognosis estimation and is expected to affect breast cancer treatment approaches.