Exploring the mechanism of action of herbal compounding in the treatment of myasthenia gravis based on network pharmacology.

Myasthenia gravis is a major disease in the context of an ageing society, and the discovery of effective herbal compound and herbal active ingredients is a highly promising direction for the treatment of myasthenia gravis. In this study, we selected shujiao, dried ginger and ginseng from the compound ingredients through a network pathology approach. The three ingredients were used to obtain drug targets in Traditional Chinese Medicine Systems Pharmacology (TCMSP), HERB and BATMAN-TCM data and intersected with the disease targets of myasthenia gravis. The resulting regulatory network maps were then used to identify core genes through the String database, and finally the core genes were molecularly aligned with the corresponding active ingredients using Autodock vina software. The 'herbal-component-target' regulatory network of the Chinese herbal formulae was constructed, which is important for finding the potential molecular mechanism for the treatment of myasthenia gravis. It will provide a theoretical basis for the therapeutic and clinical research of myasthenia gravis.

A highly selective and sensitive europium-organic framework sensor for the fluorescence detection of fipronil in tea.

A europium-based metal organic framework (Eu-TFPA-MOF) was used for the fluorescence detection of fipronil in green tea and oolong tea for the first time. The red fluorescence of Eu-TFPA-MOF could be quenched significantly by low concentration (0.24 mM) of fipronil, and the "turn off" process exhibited quick response time (2 min), high sensitivity and selectivity, low detection limits (4.4 nM) and wide linear range (0-0.15 mM). The mechanism of fluorescence quenching was mainly attributed to static quenching process and the competitive absorption of excitation energy. Besides, the spiked and recovery test indicated that Eu-TFPA-MOF could be used in the fluorescence detection of fipronil in real green tea and oolong tea sample and the process had the advantages of simple pretreatment and satisfactory recoveries (98.33-106.17 %). More importantly, a simple, portable and low-cost smartphone-assisted test strip were designed for the visual detection of fipronil in real tea samples. The detection platform will be beneficial for tea quality safety and human heath, and is expected to be applied in other agricultural product safety field.

Multidimensional analysis of the essential elements in pregnant women's whole blood and characterization of maternal status by elemental pattern.

BACKGROUND: During pregnancy, the fetus needs to obtain a lot of nutrients from the mother, but the micronutrient deficiencies in pregnancy are not clear at present, and there is no reliable basis for nutrient intake and supplement. The purpose of this study was to understand the levels of essential elements in whole blood of pregnant women during various pregnancy stages at different ages and in different regions, to evaluate the deficiency of essential elements in Chinese pregnant women, and to explore the feasibility of using the elemental pattern to characterize maternal status. METHODS: Whole blood samples of 11222 healthy pregnant women enrolled in different areas of China from Jan-Dec 2019, were analyzed for concentrations of six essential elements including Mn, Cu, Zn, Ca, Mg, and Fe, using the inductively coupled plasma mass spectrometer. A retrospective comparative study during different pregnancy periods at different ages and in different regions in whole blood essential elements content from non-pregnant normal women and pregnant normal women was developed using multivariate statistical analysis. Principal component analysis evaluation elemental pattern was used to characterize pregnancy status of pregnant women. RESULTS: In general, the levels of six essential elements in whole blood of pregnant women can satisfy the needs of normal physiological activities. With the development of pregnancy, the contents of Cu and Mn increased, while the contents of Fe and Mg decreased, and the contents of Zn and Ca have no noteworthy change. At the same gestation stage, the Cu content in whole blood of elderly pregnant women was higher. There were some differences in whole blood essential elements content of pregnant women in different regions. Principal component analysis and heat map analysis showed the feasibility of using bioinformatics research strategies to identify different pregnancies. CONCLUSIONS: There are differences in the content of whole blood essential elements of women at different stages of pregnancy in different regions. It was found that there was no obvious deficiency in whole blood essential elements levels of pregnant women in recent years. The pattern of essential elements has a certain application potential in the evaluation of pregnancy and pregnant women's health status.

Chemical Characterization of Chinese Perilla Seed Oil.

Physicochemical properties and chemical composition of Chinese perilla seed oil has been characterized in this study. The result showed that both the cold press oil and the solvent extracted oil possessed low acid value and peroxide value. The fatty acid composition result showed that the oil has high content of linolenic acid (C18:3) up to 66.4 g/100 g, followed by linoleic acid (C18:2) of 15.3 g/100 g. The total triacylglycerol (TAG) profiles results showed that the oil contained 20 TAGs including 17 regioisomers, including LnLnLn (35.8 g/100 g), LLnLn (20.2 g/100 g), LLLn (17.7 g/100 g) and PLnLn (14.9 g/100 g) (Ln, linolenic acid; L, linoleic acid; P, palmitic acid). With content of only 0.57 g/100 g oil, the unsaponifiable matters were mainly composed of phytosterols, squalene, tocopherol, alcohols and hydrocarbons. The total phytosterols content was 0.39 g/100 g oil, in which ß-sitosterol has high content of 0.31 g/100 g oil.

Physicochemical properties and structure of modified potato starch granules and their complex with tea polyphenols.

The physicochemical, rheological properties and structure of potato starch and starch-tea polyphenols (TPs) complex modified by enzyme and alcohol was investigated in this study. Cavities on the modified starch granules and morphology change could be investigated by SEM, while significant birefringence observed in complete granules by polarizing light microscope, but disappeared in crashed starch. TPs inhibited the aggregation of amylose and retrogradation of starch-TPs complex, resulting in the decrease of gel strength, and the increase of viscosity and gelatinization stability of starch granules. Fourier transform infrared (FT-IR) spectra showed that intramolecular hydrogen bond could be formed between TPs with modified starch, and the hydrogen bond force formed by starch and TPs was stronger than that between starch molecules. X-ray diffraction (XRD) analysis revealed that three modification methods did not change the crystalline structure of starch, but new diffraction peaks appeared in the four starch-TPs complex, suggesting that the hydrogen bond was incurred by interaction between TPs and amylose to form V-type crystalline. These results demonstrated that the complex formed by TPs and native/modified potato starch could be used in food industrial applications due to the inhibition of starch retrogradation.

Nutritional Component and Chemical Characterization of Chinese Highland Barley Bran Oil.

The nutritional composition and chemical properties of the Chinese highland barley bran oil were characterized in this study. The barley bran oil extracted with solvent possessed relatively high acid value and peroxide value, indicating that the oil should be further refined before using. The fatty acid composition of the oil showed that the content of unsaturated fatty acids was 80.12 g/100 g, in which the content of polyunsaturated fatty acids was as high as 60.41 g/100 g. The overall triacylglycerol profile showed that the oil contained 27 TAGs including 21 regioisomers. Major TAGs included LLL (21.08 g/100 g), PLL (19.27 g/100 g), LLO (12.24 g/100 g), and LLLn (12.17 g/100 g). The total unsaponifiable matter of the oil reached up to 10.74 g/100 g oil. The total phytosterol content reached 7.90 g/100 g oil, in which ß-sitosterol was the most predominant, with the content of 5.69 g/100 g oil. Other important sterols included campesterol (1.32 g/100 g oil), lanosterol (0.70 g/100 g oil) and stigmasterol (0.19 g/100 g oil).

Liquid profiling in plants: identification and analysis of extracellular metabolites and miRNAs in pollination drops of Ginkgo biloba.

The pollination drop (PD), also known as an ovular secretion, is a critical feature of most wind-pollinated gymnosperms and function as an essential component of pollination systems. However, the metabolome and small RNAs of gymnosperm PDs are largely unknown. We employed gas chromatography-mass spectrometry to identify a total of 101 metabolites in Ginkgo biloba L. PDs. The most abundant metabolites were sugars (45.70%), followed by organic acids (15.94%) and alcohols (15.39%) involved in carbohydrate metabolism, glycine, serine and threonine metabolism. Through pollen culture of the PDs, we further demonstrated that the metabolic components of PDs are indispensable for pollen germination and growth; in particular, organic acids and fatty acids play defensive roles against microbial activity. In addition, we successfully constructed a small RNA library and detected 45 known and 550 novel miRNAs in G. biloba PDs. Interestingly, in a comparative analysis of miRNA expression between PDs and ovules, we found that most of the known miRNAs identified in PDs were also expressed in the ovules, implying that miRNAs in PDs may originate from ovules. Further, combining with potential target prediction, degradome validation and transcriptome sequencing, we identified that the interactions of several known miRNAs and their targets in PDs are involved in carbohydrate metabolism, hormone signaling and defense response pathways, consistent with the metabolomics results. Our results broaden the knowledge of metabolite profiling and potential functional roles in gymnosperm PDs and provide the first evidence of extracellular miRNA functions in ovular secretions from gymnosperms.

Amplified Cancer Immunotherapy of a Surface-Engineered Antigenic Microparticle Vaccine by Synergistically Modulating Tumor Microenvironment.

Efficient cancer vaccines not only require the co-delivery of potent antigens and highly immunostimulatory adjuvants to initiate robust tumor-specific host immune response but also solve the spatiotemporal consistency of host immunity and tumor microenvironment (TME) immunomodulation. Here, we designed a biomaterials-based strategy for converting tumor-derived antigenic microparticles (T-MPs) into a cancer vaccine to meet this conundrum and demonstrated its therapeutic potential in multiple murine tumor models. The internal cavity of T-MPs was employed to store nano-Fe3O4 (Fe3O4/T-MPs), and then dense adjuvant CpG-loaded liposome arrays (CpG/Lipo) were tethered on the surface of Fe3O4/T-MP through mild surface engineering to get a vaccine (Fe3O4/T-MPs-CpG/Lipo), demonstrating that co-delivery of Fe3O4/T-MPs and CpG/Lipo to antigen presenting cells (APCs) could elicit strong tumor antigen-specific host immune response. Meanwhile, vaccines distributed in the TME could reverse infiltrated tumor-associated macrophages into a tumor-suppressive M1 phenotype by nano-Fe3O4, amazingly induce abundant infiltration of cytotoxic T lymphocytes, and transform a "cold" tumor into a "hot" tumor. Furthermore, amplified antitumor immunity was realized by the combination of an Fe3O4/T-MPs-CpG/Lipo vaccine and immune checkpoint PD-L1 blockade, specifically inhibiting ∼83% of the progression of B16F10-bearing mice and extending the median survival time to 3 months. Overall, this study synergistically modulates the tumor immunosuppressive network and host antitumor immunity in a spatiotemporal manner, which suggests a general cell-engineering strategy tailored to a personalized vaccine from autologous cancer cell materials of each individual patient.

Enhancement of anticancer activity of docetaxel by combination with Fuzheng Yiliu decoction in a mouse model of castration-resistant prostate cancer.

Docetaxel (Doc) is the gold standard of care for castration-resistant prostate cancer (CRPC) patients, although the therapeutic effects are modest. Fuzheng Yiliu decoction (FZYL) comprises multiple herbs, and has been used for >10 years to treat various cancers, including hepatocellular tumors, malignant gastrointestinal tumors, and prostate cancer. In the study reported, we evaluated the anticancer effects of FZYL and of a combination of Doc and FZYL in CRPC tumor-bearing mice, and explored the underlying mechanisms. PC-3 tumor-bearing mice were treated with FZYL, Doc, Doc + FZYL or vehicle solution. Tumor volume was monitored, and tumor weight, proliferation and apoptosis of tumor tissues were measured. Deep sequencing was used to profile the miRNA expression patterns in tumor tissues. Our results suggested that FZYL alone could depress tumor growth, and the combination of Doc and FZYL treatment exhibited enhanced anticancer effects. Doc + FZYL regulated the expression of 10 miRNAs: miR-34b-5p, miR-674-3p, miR-140-3p, miR-342-3p, miR-214-3p, miR-149-5p, miR-378c, miR-29b-3p, miR-218-5p, and miR-378a-3p, involving in the PI3K-Akt pathway in the treatment of CRPC.

Fatty Acid, Triacylglycerol and Unsaponifiable Matters Profiles and Physicochemical Properties of Chinese Evening Primrose Oil.

This work focused on physicochemical property assaying, fatty acid composition, triacylglycerol (TAG) profiles, and unsaponifiable matters composition of the Chinese evening primrose oil. The cold press oil possessed very low acid value and peroxide value, and relatively high iodine value. Fatty acid composition results indicated that this oil was especially high in linoleic acid and linolenic acid. Characterization of TAG composition was achieved by a two-dimensional HPLC coupling of nonaqueous reverse-phase and silver ion HPLC with atmospheric pressure chemical ionization MS method. There was a total of 38 TAGs including 27 regioisomers which had been determined. Unsaponifiable matters composition results revealed that this oil possessed a number of phytosterols, in which ß-sitosterol and stigmasterol were most predominant.

Insight into the characterization and digestion of lotus seed starch-tea polyphenol complexes prepared under high hydrostatic pressure.

Complex starch is gaining research attention due to its unique physicochemical and functional properties. In this study, the effects of green tea polyphenols on the properties and digestion of lotus seed starch under high hydrostatic pressure were investigated. The particle size, swelling power, solubility, crystallization, morphology and thermal properties of lotus seed starch were affected by green tea polyphenols. These may be due to the formation of non-inclusive complexes between lotus seed starch and green tea polyphenols. The morphology and green tea polyphenols distribution of the complexes were determined by scanning electron microscopy and confocal laser scanning microscopy. In addition, slow digestion properties of starch were realized under a dynamic in vitro rat stomach-duodenum model and the erosion of granules by amylase gradually decreased by scanning electron microscopy. Furthermore, green tea polyphenols were shown to be able to form V-type inclusion complex with amylose via high hydrostatic pressure.

Preparation of High-Purity Trilinolein and Triolein by Enzymatic Esterification Reaction Combined with Column Chromatography.

High-purity trilinolein and triolein were prepared by Novozym 435-catalyzed esterification reaction combined with column chromatography purification in this study. Firstly, linoleic acid and oleic acid were respectively extracted from safflower seed oil and camellia seed oil by urea adduct method. Secondly, trilinolein and triolein were synthesized through Novozym 435 catalyzed esterification of glycerol and fatty acids. The best synthesis conditions were obtained as follows: reaction temperature 100°C, residual pressure 0.9 kPa, enzyme dosage 6%, molar ratio of glycerol to linoleic acid 1:3 and reaction time 8 h. Crude trilinolein and triolein were further purified by silica gel column chromatography. Finally, highpurity trilinolein (95.43±0.97%) and triolein (93.07±1.05%) were obtained.

Physicochemical properties and digestion of the lotus seed starch-green tea polyphenol complex under ultrasound-microwave synergistic interaction.

Complex starch is gaining research attention due to its unique physicochemical and functional properties. Lotus seed starch (LS) suspensions (6.7%, w/v) with added green tea polyphenols (GTPs) (10%, w/w) were subjected to ultrasound (200-1000 W)-microwave (150-225 W) (UM) treatment for 15 min. The effects of UM treatment on the physicochemical properties of the LS-GTP system were investigated and exceeded that of microwave or ultrasound alone. The properties (morphology, X-ray diffraction pattern and so on) were affected by GTPs to various extents, depending on ultrasonic power. These influences may be explained by the non-covalent interactions between GTPs and LS. V-type LS-GTP inclusion complex and non-inclusive complex formation were observed. Their morphology and the distribution of GTPs molecules within them were estimated using scanning electron microscopy and confocal laser scanning microscopy. Furthermore, the digestion of LS-GTP complex was investigated by a dynamic in vitro rat stomach-duodenum (DIVRSD) model, lower digestion efficiency of LS has been achieved and the residues showed gradual improvement in morphology. These all experimental results do provide new insight into the complex starch production.

C-type starches and their derivatives: structure and function.

The C-type starches are widely distributed in seeds or rhizomes of various legumes, medicinal plants, and crops. These carbohydrate polymers directly affect the application of starchy plant resources. The structural and crystal properties of starches are crucial parameters of starch granules, which significantly influence their physicochemical and mechanical properties. The unique crystal structure consisting of both A- and B-type polymorphs endows C-type starches with specific crystal adjustability. Furthermore, large proportions of resistant starches and slowly digestible starches are C-type starches, which contribute to benign glycemic response and proliferation of gut microflora. Here, we review the distribution of C-type starches in various plant sources, the structural models and crystal properties of C-type starches, and the behavior and functionality relevant to modified C-type starches. We outline recent advances, potential applications, and limitations of C-type starches in industry, aiming to provide a theoretical basis for further research and to broaden the prospects of its applications.

Glutathione peroxidase 4 inhibits Wnt/ß-catenin signaling and regulates dorsal organizer formation in zebrafish embryos.

The Wnt/ß-catenin signaling pathway plays pivotal roles in axis formation during embryogenesis and in adult tissue homeostasis. Glutathione peroxidase 4 (GPX4) is a selenoenzyme and participates in the reduction of peroxides. Its synthesis depends on the availability of the element selenium. However, the roles of GPX4 in vertebrate embryonic development and underlying mechanisms are largely unknown. Here, we show that maternal loss of zebrafish gpx4b promotes embryonic dorsal organizer formation, whereas overexpression of gpx4b inhibits the development of the dorsal organizer. Depletion of human GPX4 and zebrafish gpx4b (GPX4/gpx4b) increases, while GPX4/gpx4b overexpression decreases, Wnt/ß-catenin signaling in vivo and in vitro Functional and epistatic studies showed that GPX4 functions at the Tcf/Lef level, independently of selenocysteine activation. Mechanistically, GPX4 interacts with Tcf/Lefs and inhibits Wnt activity by preventing the binding of Tcf/Lefs to the promoters of Wnt target genes, resulting in inhibitory action in the presence of Wnt/ß-catenin signaling. Our findings unravel GPX4 as a suppressor of Wnt/ß-catenin signals, suggesting a possible relationship between the Wnt/ß-catenin pathway and selenium via the association of Tcf/Lef family proteins with GPX4.