Hypolipidemic effect and gut microbiota regulation of Gypenoside aglycones in rats fed a high-fat diet.

ETHNOPHARMACOLOGICAL RELEVANCE: Gynostemma pentaphyllum (Thunb.) Makino has traditional applications in Chinese medicine to treat lipid abnormalities. Gypenosides (GPs), the main bioactive components of Gynostemma pentaphyllum, have been reported to exert hypolipidemic effects through multiple mechanisms. The lipid-lowering effects of GPs may be attributed to the aglycone portion resulting from hydrolysis of GPs by the gut microbiota. However, to date, there have been no reports on whether gypenoside aglycones (Agl), the primary bioactive constituents, can ameliorate hyperlipidemia by modulating the gut microbiota. AIM OF THE STUDY: This study explored the potential therapeutic effects of gypenoside aglycone (Agl) in a rat model of high-fat diet (HFD)-induced hyperlipidemia. METHODS: A hyperlipidemic rat model was established by feeding rats with a high-fat diet. Agl was administered orally, and serum lipid levels were analyzed. Molecular techniques, including RT-polymerase chain reaction (PCR) and fecal microbiota sequencing, were used to investigate the effects of Agl on lipid metabolism and gut microbiota composition. RESULTS: Agl administration significantly reduced serum levels of total cholesterol (TC), triglycerides (TG), and low-density lipoprotein cholesterol (LDL-C) and mitigated hepatic damage induced by HFD. Molecular investigations have revealed the modulation of key lipid metabolism genes and proteins by Agl. Notably, Agl treatment enriched the gut microbiota with beneficial genera, including Lactobacillus, Akkermansia, and Blautia and promoted specific shifts in Lactobacillus murinus, Firmicutes bacterium CAG:424, and Allobaculum stercoricanis. CONCLUSION: This comprehensive study established Agl as a promising candidate for the treatment of hyperlipidemia. It also exhibits remarkable hypolipidemic and hepatoprotective properties. The modulation of lipid metabolism-related genes, along with the restoration of gut microbiota balance, provides mechanistic insights. Thus, Agl has great potential for clinical applications in hyperlipidemia management.

Garlic-derived compounds: Epigenetic modulators and their antitumor effects.

Cancer is a highly heterogeneous disease that poses a serious threat to human health worldwide. Despite significant advances in the diagnosis and treatment of cancer, the prognosis and survival rate of cancer remain poor due to late diagnosis, drug resistance, and adverse reactions. Therefore, it is very necessary to study the development mechanism of cancer and formulate effective therapeutic interventions. As widely available bioactive substances, natural products have shown obvious anticancer potential, especially by targeting abnormal epigenetic changes. The main active part of garlic is organic sulfur compounds, of which diallyl trisulfide (DATS) content is the highest, accounting for more than 40% of the total composition. The garlic-derived compounds have been recognized as an antioxidant for cancer prevention and treatment. However, the molecular mechanism of the antitumor effect of garlic-derived compounds remains unclear. Recent studies have identified garlic-derived compound DATS that plays critical roles in enhancing CpG demethylation or promoting histone acetylation as an epigenetic inhibitor. Here, we review the therapeutic progress of garlic-derived compounds against cancer through epigenetic pathways.

Multi­omics­based analysis of the regulatory mechanism of gypenosides on bile acids in hypercholesterolemic mice.

Gynostemma pentaphyllum is a traditional medicine used by ethnic minorities in southwest China and gypenosides are currently recognized as essential components of the pharmacological substances of Gynostemma pentaphyllum, which are effective in regulating metabolic syndrome, especially in improving hepatic metabolic disorders. The present study randomly divided C57BL/6J male mice into the normal diet control group (ND), high-fat diet modeling group (HFD) and gypenosides group (GP). Liquid chromatography-mass spectrometry (UPLC-MS) was applied to quantify bile acids in the liver, bile and serum of mice in ND, HFD and GP groups. Liver proteins were extracted for trypsin hydrolysis and analyzed quantitatively using UPLC-MS + MS/MS (timsTOF Pro 2). Total mouse liver RNA was extracted from ND, HFD and GP groups respectively, cDNA sequencing libraries constructed and sequenced using BGISEQ-500 sequencing platform. The expression of key genes Fxr, Shp, Cyp7a1, Cyp8b1, and Abab11 was detected by RT-qPCR. The results showed that gypenosides accelerated free bile acid synthesis by promoting the expression of bile acid synthase CYP7A1 and CYP8B1 genes and proteins and accelerating the secretion of conjugated bile acids from the liver to the bile ducts. GP inhibited the bile acid transporters solute carrier organic anion transporter family member (SLCO) 1A1 and SLCO1A4, reducing the reabsorption of free bile acids and accelerating the excretion of free bile acids from the blood to the kidneys. It also promoted the metabolic enzyme CYP3A11, which accelerated the metabolism and clearance of bile acids, thus maintaining the balance of the bile acid internal environment.

Mulberry leaf extract reduces abdominal fat deposition via adenosine-activated protein kinase/sterol regulatory element binding protein-1c/acetyl-CoA carboxylase signaling pathway in female Arbor Acre broilers.

This experiment was carried out to investigate the mechanism of action of mulberry leaf extract (MLE) in reducing abdominal fat accumulation in female broilers. A total of 192 one-day-old female Arbor Acres (AA) broilers were divided into 4 diet groups, with each group consisting of 8 replicates with 6 birds per replicate. The diets contained a basal diet and 3 test diets with supplementation of 400, 800, or 1,200 MLE mg/kg, respectively. The trial had 2 phases that lasted from 1 to 21 d and from 22 to 56 d, respectively. The growth performance, abdominal fat deposition, fatty acid composition, serum biochemistry and mRNA expression of genes related to fat metabolism in liver were determined. The results showed that, 1) dietary supplementation with MLE had no significant impact on broilers final body weight, average daily gain (ADG), or feed to gain ration (F/G) (P > 0.05), but linearly reduced abdominal fat accumulation in both experimental phases (P < 0.05); 2) the total contents of monounsaturated fatty acids (MUFA) and polyunsaturated fatty acids (PUFA), such as palmitoleic acid, oleic acid, and eicosadienoic acid, were increased quadratically as a result of dietary supplements of 400, 800, and 1,200 mg/kg MLE (P < 0.01), while the total contents of saturated fatty acids (SFA), such as teracosanoic acid were decreased (P < 0.01); 3) the addition of 800 or 1,200 MLE mg/kg to the diet linearly reduced total cholesterol (TC) in the serum and liver (P < 0.05). Adenosine-activated protein kinase (AMPK) mRNA expression in the liver was quadratically increased by the addition of 800 or 1,200 MLE mg/kg to the diet (P < 0.05), and the mRNA expression of sterol regulatory element binding protein-1c (SREBP-1c), acetyl-CoA carboxylase (ACC), and acetyl-CoA carboxylate), fatty acid synthase (FAS) were linearly decreased (P < 0.05). In conclusion, MLE can be employed as a viable fat loss feed supplement in fast-growing broiler diets since it reduces abdominal fat deposition in female AA broilers via the AMPK/SREBP-1c/ACC signaling pathway. MLE can also be utilized to modify the fatty acid profile in female broilers (AA) at varied inclusion levels.

An UPLC-Q-TOF/MS-Based Analysis of the Differential Composition of Dendrobium officinale in Different Regions.

Dendrobium officinale (D. officinale) is a valuable traditional Chinese herbal medicine with high commercial value. In Chinese Pharmacopoeia (Ch.P., 2020 edition), the quality of D. officinale is mainly evaluated by its polysaccharide content. However, varying growth and production conditions, such as cultivation environment, origin, harvesting process, or processing methods, resulting in highly variable yields, quality, and composition. The aim of this study was to investigate whether the content of secondary metabolites in D. officinale from different origins is consistent with the polysaccharide content. The results showed that the polysaccharide content and pass rate were ranked as GX > AH > GZ > YN. Based on the nontargeted metabolomics approach, we searched for differential components in 22 different regions of D. officinale, including amides, bibenzyls, disaccharide, flavonoids, organic nitrogenous compounds, and phenolic glycosides. The overall expression was opposite to the polysaccharide, and the most expressed was YN, followed by GZ, AH, and GX. These results indicated that the current quality standard for evaluating the quality of D. officinale by polysaccharide content alone is imperfect, and small molecule compounds need to be included as quality markers.

Opposite trends of glycosides and alkaloids in Dendrobium nobile of different age based on UPLC-Q/TOF-MS combined with multivariate statistical analyses.

INTRODUCTION: Alkaloids and glycosides are the active ingredients of the herb Dendrobium nobile, which is used in traditional Chinese medicine. The pharmacological effects of alkaloids include neuroprotective effects and regulatory effects on glucose and lipid metabolism, while glycosides improve the immune system. The pharmacological activities of the above chemical components are significantly different. In practice, the stems of 3-year-old D. nobile are usually used as the main source of Dendrobii Caulis. However, it has not been reported whether this harvesting time is appropriate. OBJECTIVE: The aim of this study was to compare the chemical characteristics of D. nobile in different growth years (1-3 years). METHODS: In this study, ultra-high-performance liquid chromatography coupled with quadrupole time-of-flight tandem mass spectrometry (UPLC-Q/TOF-MS) was employed to analyze the constituents of D. nobile. The relative abundance of each constituent was analyzed with multivariate statistical analyses to screen the characteristic constituents that contributed to the characterization and classification of D. nobile. Dendrobine, a component of D. nobile that is used for quality control according to the Chinese Pharmacopoeia, was assayed by gas chromatography. RESULTS: As a result, 34 characteristic constituents (VIP > 2) were identified or tentatively identified as alkaloids and glycosides based on MS/MS data. Moreover, the content of alkaloids decreased over time, whereas the content of glycosides showed the opposite trend. The absolute quantification of dendrobine was consistent with the metabolomics results. CONCLUSION: Our findings provide valuable information to optimize the harvest period and a reference for the clinical application of D. nobile.

Effect of oral iodized oil pills on thyroid function of pregnant women / 中华地方病学杂志

Objective:To evaluate the effect of oral iodized oil pills on iodine nutrition and thyroid function of pregnant women in Xinjiang Uygur Autonomous Region (Xinjiang).Methods:From May to July 2017, one county was selected from Ili Prefecture without taking iodized oil pills, Aksu Prefecture taking iodized oil pills once a year, and Kashgar Prefecture taking iodized oil pills twice a year in Xinjiang as survey sites, respectively; 100 pregnant women (evenly distributed in early, middle and late pregnancy) were selected from each survey county, the general data, urine and blood samples were collected, and urinary iodine and thyroid function indicators [free triiodothyronine (FT 3), free thyroxine (FT 4), thyrotropin (TSH), anti thyroglobulin antibody (TgAb), and anti thyroid peroxidase antibody (TPOAb)] were tested. Results:A total of 308 pregnant women were investigated, and 289 were finally included in the analysis, with an average age of 25 years; the body mass index (BMI) was (22.69 ± 3.07) kg/m 2. The occupation distribution was mainly farmer, accounting for 93.77% (271/289); most of them had junior high school education or below, accounting for 71.97% (208/289). The median urinary iodine of early, middle and late pregnant women in Kashgar Prefecture was 712.87, 604.50 and 656.23 μg/L, respectively, which were in iodine excess state. The iodine nutrition level of early pregnant women in Ili Prefecture and Aksu Prefecture was in iodine super suitability state, and the iodine nutrition level of middle and late pregnant women was in the iodine suitability state. The difference of median urinary iodine in early, middle and late pregnancy women between different regions was statistically significant ( Z = 53.02, 49.60, 44.66, P < 0.001). In addition, the urinary iodine of women in Kashgar Prefecture during each pregnancy period was significantly higher than that in Ili Prefecture and Aksu Prefecture ( P < 0.05). There were statistically significant differences in the levels of FT 3 among women in early pregnancy, FT 4 and TSH among women in middle pregnancy between different regions ( F = 4.59, 10.92, Z = 8.61, P < 0.05 or < 0.001). Among them, the level of FT 3 in early pregnancy in Kashgar Prefecture was lower than that in Ili Prefecture ( P < 0.05); the level of FT 4 in Kashgar Prefecture during middle pregnancy was higher than that in Ili Prefecture, and the level of TSH was lower than that in Ili Prefecture ( P < 0.05). There was no significant difference in TgAb positive rate, TPOAb positive rate and double antibody positive rate of early, middle and late pregnant women between different regions ( P > 0.05). The detection rates of hypothyroxinemia in early pregnant women in Ili Prefecture, Aksu Prefecture and Kashgar Prefecture were 13.9% (5/36), 3.2% (1/31) and 0 (0/33), respectively, and there was a statistically significant difference between different regions ( P = 0.036). The detection rates of subclinical hyperthyroidism in middle pregnant women were 0 (0/35), 0 (0/40), 17.6% (6/34), respectively, and there was a statistically significant difference between different regions ( P = 0.001). Conclusions:The results of urinary iodine in the three regions are in line with the iodine nutrition distribution under their respective iodine supplement strategies. Pregnant women in Kashgar Prefecture present iodine excess status after taking iodized oil pills; at the same time, the serum FT 3, FT 4 and TSH levels of pregnant women in Kashgar Prefecture are affected by iodine nutrition levels. Although it is scientific and effective to implement the intensified iodine supplement measures for pregnant women, it is still necessary to further study the suitability of oral iodine oil pills to ensure that pregnant women are at an suitability iodine nutrition level.

Identification and Simultaneous Determination of the Main Toxical Pyrrolizidine Alkaloids in a Compound Prescription of Traditional Chinese Medicine: Qianbai Biyan Tablet.

Qianbai biyan tablet (QT) is a compound prescription of traditional Chinese medicine which is used to treat nasal congestion, rhinitis, and nasosinusitis, with Senecio scandens as its main plant material. Several pyrrolizidine alkaloids (PAs) were reported in Senecio scandens and others of Senecio species. Although Senecio scandens is assigned as the legal plant material of QT, whether replaced use of it by other Senecio plants can bring toxicity is unknown because of the lack of quantitative data about toxic PAs between different Senecio species. In the present study, adonifoline, senkirkine, and another PA presumed as emiline have been identified in QT; however, there was no senecionine detected in all tablets. PA contents in QTs varied in different companies and different batches. Adonifoline existed only in Senecio scandens, and senecionine was detected in all eight Senecio plants investigated in the present study. Data showed that replaced use of Senecio scandens with a low level of senecionine by other Senecio plants such as Senecio vulgaris containing a high level of senecionine is advertised to be forbidden. Data of the present study may be used as a reference to make new drug quality regularity and recommendation guideline for the safety of QT.

A dye combination for the staining of pollen coat and pollen wall.

The pollen coat, which forms on the pollen surface, consists of a lipid-protein matrix. It protects pollen from desiccation and is involved in adhesion, pollen-stigma recognition, and pollen hydration during interactions with the stigma. The classical methods used for pollen coat observation are scanning and transmission electron microscopy. In this work, we screened a collection of fluorescence dyes and identified two fluorescent brighteners FB-52 and FB-184. When they were used together with the exine-specific dye, Basic fuchsin, the pollen coat and the exine structures could be clearly visualized in the pollen of Brassica napus. This co-staining method was applied successfully in staining pollen from Fraxinus chinensis, Calystegia hederacea, and Petunia hybrida. Using this method, small pollen coat-containing cavities were detected in the outer pollen wall layer of Oryza sativa and Zea mays. We further showed these dyes are compatible with fluorescent protein markers. In the Arabidopsis thaliana transgenic line of GFP-tagged pollen coat protein GRP19, GRP19-GFP was observed to form particles at the periphery of pollen coat. This simple staining method is expected to be widely used for the studies of the palynology as well as the pollen-stigma interaction.

Quantity of supplementary LED lightings regulates photosynthetic apparatus, improves photosynthetic capacity and enhances productivity of Cos lettuce grown in a tropical greenhouse.

Although cooling their rootzone allows year-round (temperate) vegetable production in Singapore's warm climate, these crops have frequently experienced increasingly unpredictable cloudy and hazy weather. Supplementary lighting with light-emitting diodes (LEDs) could be used to reduce the impacts of low light intensity. This study investigated the responses of temperate Cos lettuce (Lactuca sativa L.) to different quantities (photosynthetic photon flux density, PPFD of 0, 150, 300 µmol m-2 s-1) of supplementary LED lightings in the tropical greenhouse. Increasing light intensity significantly increased total leaf area, shoot and root fresh weight (FW) and dry weight (DW), total chlorophyll (Chl) and carotenoids (Car) contents, light-saturated photosynthetic CO2 assimilation rate (Asat) and transpiration rate (Tr). There were no significant differences in Fv/Fm ratio, total reduced nitrogen, specific leaf area (SLA) and PSII concentration among the three light treatments. However, there was an increasing trend with increasing light intensity for Chl a/b ratio, net photosynthetic O2 evolution rate (PN), cytochrome b6f (Cyt b6f), leaf total soluble protein and Rubisco concentrations. This study provides the basic understanding of photosynthetic apparatus and capacity of temperate crops grown under different supplementary LED lightings in the tropical greenhouse.

Effects of different iodine levels on thyroid function in rats after pregnancy / 中华地方病学杂志

Objective:To investigate the effects of different levels of iodine intake on thyroid function in Wistar rats after pregnancy, and to provide experimental basis for scientific supplementation of iodine and thyroid function screening during pregnancy.Methods:One hundred and fifty female SPF Wistar rats weaned for 2 weeks were selected. Female Wistar rats were intervened with iodine nutrition by drinking deionized water containing potassium iodide (KI). According to the random number table, female Wistar rats were divided into 5 groups [severe iodine deficiency (SID) group, mild iodine deficiency (MID) group, control group (NI), mild iodine excess (MIE) group, and severe iodine excess (SIE) group, 30 rats per group]. The iodine doses of the five groups were 0.0, 1.5, 5.5, 70.0 and 350.0 μg/d, respectively. The animal model was established and intervened for 3 months to detect the 24 h urinary iodine content of rats, and compared with the NI group to determine the success of the model or not. After successful modeling, the tested female Wistar rats were mated with male Wistar rats (female : male=2-3 : 1). There were about 15 pregnant rats in each group, and continued to intervene the pregnant rats for 21 d with the same doses as the modeling conditions. The abdominal aortic blood of non-pregnant and pregnant rats was taken. After serum separation, 5 items [free thyroxine (FT 4), free triiodothyronine (FT 3), thyroid stimulating hormone (TSH), anti-thyroglobulin antibodies (TgAb), thyroid peroxidase antibody (TPOAb)] of serum thyroid function were detected in each group. Results:There was significant difference in urinary iodine content between the five groups (the medians urinary iodine were 3.540, 51.410, 286.801, 644.192 and 2 368.701, respectively, H = 94.791, P < 0.01). Rats with different iodine nutrition levels were successfully established. There were no significant differences in TSH level, TPOAb and double antibodies positive rates of non-pregnant rats among groups ( P > 0.05). There were statistically significant differences in the levels of FT 4, FT 3 and the positive rate of TgAb among groups ( P < 0.05). The level of FT 4 in SID group was lower than that in NI group ( P < 0.05). The level of FT 3 in SID group was higher than that in NI group ( P < 0.05). The positive rate of TgAb in SIE group was higher than that in NI group ( P < 0.05). There were no significant differences in TSH, FT 4 and FT 3 levels of pregnant rats among groups ( P > 0.05). There were significant differences in the positive rates of TgAb, TPOAb and double antibodies among the groups ( P < 0.05). The positive rates of TgAb, TPOAb and double antibodies in MIE and SIE groups were higher than those in NI group ( P < 0.05). The positive rate of TPOAb in MIE group was higher than that in NI group ( P < 0.05), and the positive rates of double antibodies in MID and MIE groups were higher than that in NI group ( P < 0.05). Conclusions:Iodine deficiency can lead to the change of thyroid hormone level in non pregnant rats, while iodine excess can increase the positive rate of related antibodies in non pregnant and pregnant rats.

A tumor-to-lymph procedure navigated versatile gel system for combinatorial therapy against tumor recurrence and metastasis.

Application of cancer vaccines is limited due to their systemic immunotoxicity and inability to satisfy all the steps, including loading of tumor antigens, draining of antigens to lymph nodes (LNs), internalization of antigens by dendritic cells (DCs), DC maturation, and cross-presentation of antigens for T cell activation. Here, we present a combinatorial therapy, based on a α-cyclodextrin (CD)-based gel system, DOX/ICG/CpG-P-ss-M/CD, fabricated by encapsulating doxorubicin (DOX) and the photothermal agent indocyanine green (ICG). Upon irradiation, the gel system exhibited heat-responsive release of DOX and vaccine-like nanoparticles, CpG-P-ss-M, along with chemotherapy- and phototherapy-generated abundant tumor-specific antigen storage in situ. The released CpG-P-ss-M acted as a carrier adsorbed and delivered antigens to LNs, promoting the uptake of antigens by DCs and DC maturation. Notably, combined with PD-L1 blocking, the therapy effectively inhibited primary tumor growth and induced tumor-specific immune response against tumor recurrence and metastasis.

Growth and photosynthetic characteristics of sweet potato (Ipomoea batatas) leaves grown under natural sunlight with supplemental LED lighting in a tropical greenhouse.

Leaf growth and photosynthetic characteristics of sweet potato (Ipomoea batatas var. Biru Putih) grown under different light quantities were studied in a tropical greenhouse. The stem cuttings of I. batataswith adventitious roots were grown hydroponically under (1) only natural sunlight (SL); (2) SL with supplemental LED at a PPFD of 150 µmol m-2 s-1 (SL + L-LED); and (3) SL with supplemental LED at a PPFD of 300 µmol m-2 s-1 (SL + H-LED). One week after emergence, all leaves had similar area and water content. However, leaf fresh weight and dry weight were significantly higher in plants grown under SL+L-LED and SL + H-LED than under SL due to their thicker leaves reflected by the lower specific leaf area. Plants grown under SL had significantly lower concentrations of total chlorophyll (Chl) and total carotenoids (Car) but higher Chl a/b ratio than under SL + L-LED and SL + H-LED. However, all plants had similar Chl/Car ratios. Although midday Fv/Fm ratio was the lowest in leaves grown under SL+ H-LED followed by SL + L-LED and SL, predawn Fv/Fm ratios of all leaves were higher than 0.8. Increasing growth irradiance with supplemental LED resulted in higher electron transport rate and photochemical quenching but lower non-photochemical quenching compared to those of plants grown under SL. Measured under their respective growth irradiance in the greenhouse, attached leaves grown under SL + L-LED and SL+H-LED had significantly higher photosynthetic CO2 assimilation rate and stomatal conductance than under SL. However, measuring the detached leaves at 25 °C in the laboratory, there were no significant differences in PS II and Cyt b6f concentrations although light- and CO2-statured photosynthetic O2 evolution rates were slightly higher in leaves grown under SL+ H-LED than under SL. Impacts of supplemental LED on leaf growth and photosynthetic characteristics were discussed.

Emerging senolytic agents derived from natural products.

Cellular senescence is a hallmark of aging, it is a permanent state of cell cycle arrest induced by cellular stresses. During the aging process, senescent cells (SCs) increasingly accumulate in tissues, causing a loss of tissue-repair capacity because of cell cycle arrest in progenitor cells and produce proinflammatory and matrix-degrading molecules which are known as the senescence-associated secretory phenotype (SASP), and thereby contribute to the development of various age-related diseases. Genetic evidence has demonstrated that clearance of SCs can delay aging and extend healthspan. Senolytics, small molecules that can selectively kill SCs, have been developed to treat various age-related diseases. In recent years, emerging natural compounds have been discovered to be effective senolytic agents, such as quercetin, fisetin, piperlongumine and the curcumin analog. Some of the compounds have been validated in animal models and have great potential to be pushed to clinical applications. In this review, we will discuss cellular senescence and its potential as a target for treating age-related diseases, and summarize the known natural compounds as senolytic agents and their applications.

Method to Calculate the Retention Index in Hydrophilic Interaction Liquid Chromatography Using Normal Fatty Acid Derivatives as Calibrants.

Hydrophilic interaction liquid chromatography-mass spectrometry (HILIC-MS) is a complementary technique to reversed-phase liquid chromatography-mass spectrometry (RPLC-MS) and has been widely used to expand the coverage of the metabolome in MS-based metabolomics. However, the use of HILIC retention time (HILIC RT) in metabolites annotation is quite limited because of its poor reproducibility. Here, we developed a method to calculate the retention index in HILIC (HILIC RI) for calibration of HILIC RT. In this method, a mixture of 2-dimethylaminoethylamine (DMED)-labeled fatty acid standards with carbon chain length from C2 to C22 were selected as calibrants to establish a linear calibration equation between HILIC RT and carbon number for the calculation of HILIC RI. The calculated HILIC RIs based on a regression equation could efficiently calibrate the retention time shifts for 28 DMED-labeled carboxyl standards and DMED-labeled carboxyl metabolites in rat urine, serum and feces on a HILIC column with different gradient elution conditions. Furthermore, the developed HILIC RI strategy was applied to RT calibration of screened metabolites, the annotation of isomers in HILIC-MS-based metabolomics analysis for real samples, and the correction of isotope effects in chemical isotope labeling HILIC-MS analysis. Taken together, the resulting HILIC RI strategy is a promising analytical technique to improve the accuracy of metabolite annotation; it would be widely used in HILIC-MS-based metabolome analysis.

Study on Mechanism of Dahuang Huanglian Xiexintang in Treatment of Type 2 Diabetes Mellitus Based on Network Pharmacology / 中国实验方剂学杂志

Objective: To explore the mechanism of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mellitus based on network pharmacology. Method: Major chemical constituents, corresponding targets and target genes of Dahuang Huanglian Xiexintang were obtained by Traditional Chinese Medicine Systems Pharmacology(TCMSP), and target genes of type 2 diabetes mellitus were obtained by GeneCards. The target genes of drug and disease were mapped to predict target genes of Dahuang Huanglian Xiexintang for type 2 diabetes mellitus. Cytoscape3.7.1 software was used to construct the compound-target network and protein-protein interaction network (PPI) of traditional Chinese medicine. Gene ontology (GO) analysis of potential genes and enrichment analysis of gene encyclopedia kyoto encyclopedia of genes and genomes (KEGG) pathway were carried out using DAVID 6.8 online tool. Result: There were 17 active ingredients, 94 related targets, 17 key active ingredients and 16 key targets in Dahuang Huanglian Xiexintang on type 2 diabetes mellitus. GO analysis showed that the biological functions of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes were mainly related to oxidative stress, apoptosis, protein binding, inflammatory reaction, et al. KEGG pathway enrichment results showed that the pathways of potential genes of Dahuang Huanglian Xiexintang in the treatment of type 2 diabetes mainly involved hypoxia inducible factor(HIF), tumor necrosis factor(TNF), phosphatidylinositol 3 kinase/protein kinase B(PI3K/Akt), nuclear transcription factor-кB(NF-кB), and vascular endothelial growth factor(VEGF) signaling pathways. Conclusion: Dahuang Huanglian Xiexintang is a complex process of multi-component, multi-target and multi-pathway in the treatment of type 2 diabetes mellitus. It plays an important role in the treatment of type 2 diabetes mellitus by participating in oxidative stress, apoptosis, protein binding and inflammatory reaction.

Clinical observation of warm moxibustion therapy to improve quadriceps weakness after total knee arthroplasty / 中国针灸

OBJECTIVE@#To evaluate the clinical efficacy of warm moxibustion therapy in the recovery of quadriceps muscle strength in patients undergoing total knee arthroplasty (TKA) with analgesia of the femoral nerve block (FNB).@*METHODS@#A total of 174 patients with KOA were randomized into a warm moxibustion group and a rehabilitation group, 87 cases in each group. In the warm moxibustion group, warm moxibustion combined with conventional quadriceps strength training were used. In the rehabilitation group, conventional quadriceps strength training was given. The warm moxibustion was applied at Liangqiu (ST 34) and Zusanli (ST 36), the treatment was given twice a day, 7 days for one course, with a total of 2 courses.The quadriceps muscle strength of the two groups was recorded and compared at 24 h before FNB, 24, 48, 72 and 96 h after surgery, and the resting and exercise VAS pain scores were also recorded at the same time point. And the first time for standing up and the first straight raising time in the two groups were compared, and the occurrence of adverse reactions in the two groups were observed.@*RESULTS@#At 24, 48, 72 and 96 h after FNB, the quadriceps muscle strength in the warm moxibustion group was better than that in the rehabilitation group (<0.05, <0.01). At 72 h and 96 h after FNB, the resting and exercise VAS scores of the warm moxibustion group were lower than those of the rehabilitation group (both <0.001). The average first straight leg raising time in the warm moxibustion group was postoperative (31.03±10.78) h, and the time in the rehabilitation group was postoperative (47.23±15.78) h. The difference was statistically significant (<0.001). The average time of the first time for standing up in the warm moxibustion group was postoperative (25.76±7.00) h, and postoperative (33.12±11.18) h in the rehabilitation group. The difference was also statistically significant (<0.001). No adverse reactions occurred in both groups.@*CONCLUSION@#Warm moxibustion combined with conventional quadriceps strength training can improve the symptoms of quadriceps weakness in patients with femoral nerve block after total knee arthroplasty, and accelerate the recovery of joint function, which is superior to conventional quadriceps strength training.

Gypenosides Altered Hepatic Bile Acids Homeostasis in Mice Treated with High Fat Diet.

Gypenosides extracted from Gynostemma pentaphyllum (Thunb.) Makino have significant role in reducing serum lipid level and treating fatty liver diseases, however, without clear mechanism. As gypenosides share the similar core structures with bile acids (the endogenous ligands of nuclear receptor FXR), we hypothesize that gypenosides may improve hypercholesterolemia via FXR-mediated bile acids signaling. The present study was designed to validate the role of gypenosides in reducing levels of serum total cholesterol (TC) and low density lipoprotein cholesterol (LDL-C), as well as in regulating bile acids homeostasis and related gene expression levels. The C57BL/6 male mice were divided into four groups. Mice in groups ND and HFD were fed with normal diet and high fat diet for 38 weeks, respectively. In groups HFD+GP and HFD+ST, mice were fed with high fat diet for 38 weeks and treated with gypenosides and simvastatin (positive control) from weeks 16 to 38, respectively. Serum TC and LDL-C levels were assayed by commercially available kits. Expression levels of genes were tested by the quantitative real-time PCR. The LC-MS/MS was applied to quantify major bile acids in mice livers. Our results showed that gypenosides significantly decreased serum TC and LDL-C levels. The gene expression level of Shp was downregulated while the levels of Cyp7a1, Cyp8b1, Fxr, Lrh1, Jnk1/2, and Erk1/2 were upregulated by gypenosides. Indicated by LC-MS/MS technology, gypenosides increased the hepatic levels of several free bile acids and most taurine-conjugated bile acids while decreasing glycine-conjugated bile acids levels. In addition, gypenosides decreased the CA/CDCA ratio. Gypenosides may improve the abnormal lipid profile of HFD-fed mice via two pathways: (1) enhancing the bile acids biosynthesis from cholesterol; (2) decreasing the CA/CDCA ratio which is positively related to cholesterol absorption.

Coagulation pretreatment of highly concentrated acrylonitrile wastewater from petrochemical plants.

Acrylonitrile (AN) wastewater is a heavily polluted and a likely hazardous liquid that is generated during the production of AN. Several chemical methods for the pretreatment of AN wastewater are available in laboratory scale. However, the harsh reaction conditions and high operational cost make these methods undesirable. Until now, four-effect evaporation is the only pretreatment method used for AN wastewater in industry despite its huge energy consumption and high cost. It is difficult to find an energy-saving pretreatment technique from the perspective of industrial application. In this study, a safe and low-cost coagulation technique was developed for the pretreatment of AN wastewater. Three types of inorganic coagulant and three types of polymer coagulant were investigated for the coagulation treatment of highly concentrated AN wastewater from petrochemical plants. The effects of coagulant type, dosage, and coagulation conditions on the pretreatment efficiency of AN wastewater were investigated. The results show that a combination of inorganic and polymer coagulants is effective for the pretreatment of AN wastewater.

Icariin prevents ovariectomy-induced bone loss and lowers marrow adipogenesis.

OBJECTIVE: Icariin prevents bone loss by stimulating new bone formation and by inhibiting bone resorption. However, less is known about how icariin affects marrow adiposity. This lack of information is a vital problem, as the degree of marrow adipogenesis may be an alternative indicator of the severity of osteoporosis in relation to the degree of osteogenesis and osteoblastogenesis. To explore this question, we tested the effects of icariin on bone mineral density (BMD) and marrow fat content in a rat model of postmenopausal osteoporosis. METHODS: Thirty-six 3-month-old female Sprague-Dawley rats were randomly assigned to one of the following treatment groups: sham operation, ovariectomized controls, and ovariectomized rats treated orally with either 17ß-estradiol or icariin for 12 weeks. BMD and marrow fat fraction were dynamically measured on weeks 0, 6, and 12. After 12 weeks of treatment, serum 17ß-estradiol and bone biomarker levels were measured, and marrow adipocytes were quantitatively evaluated by histopathology. RESULTS: Ovariectomized controls experienced a marked increase in fat fraction over time, with increases of 40% between weeks 0 and 6 and 69.4% between weeks 6 and 12 (P < 0.001). Marrow adiposity in ovariectomized controls was dramatically higher than that in sham rats on week 6; however, a reduction in BMD was detected in ovariectomized rats on week 12 (P < 0.001). Ovariectomized rats had levels of serum alkaline phosphatase and serum C-terminal telopeptide of type I collagen that were 49.4% and 67.2% higher, respectively, than those of sham rats (P < 0.001). The density, size, and volume of marrow adipocytes in ovariectomized controls were 57.3%, 29.5%, and 163% higher, respectively, than those in sham rats. Early icariin treatment decreased bone biomarker levels, inhibited bone degeneration, and restored marrow fat infiltration and adipocyte parameters to the levels observed in sham rats. Overall, the osteoprotective effect of icariin was comparable with that of 17ß-estradiol; however, icariin did not produce uterine estrogenicity. CONCLUSIONS: Early icariin treatment restores marrow adiposity in the estrogen-deficient rat model.