Correlation of Homocysteine, AHSG, CRP with Insulin Resistance, 25-(OH)2-VitD, Blood Lipids in Gestational Diabetes Patients.

BACKGROUND: To investigate the correlations of serum homocysteine (Hcy), α2-Heremans-Schmid glycoprotein (AHSG), and C-reactive protein (CRP) with insulin resistance (IR), 25-hydroxyvitamin D (25-OH-VD), and blood lipids in patients with gestational diabetes mellitus (GDM) by detecting their levels. METHODS: A total of 72 GDM patients (GDM group) and 72 healthy pregnant women (control group) delivered in our hospital from February 2017 to January 2019 were randomly selected. The basic data, somatological parameters [height, weight, body mass index (BMI), waist circumference, hip circumference, waist-to-hip ratio (WHR), blood pressure, and body fat content], and biochemical indexes (glucose metabolism indexes, lipid metabolism indexes, Hcy, AHSG, CRP, and 25-OH-VD) were compared between the two groups. Additionally, Pearson's correlation analysis was employed to analyze the correlations among indicators. RESULTS: In comparison with the control group, the GDM group had a higher average rate of family history of DM (p < 0.05), larger waist circumference and WHR, and higher body fat content (p < 0.05). Besides, the fasting plasma glucose (FPG), 1-hour plasma glucose (1hPG) and 2-hour plasma glucose (2hPG), glycosylated hemoglobin (HbA1c), fasting insulin (FINS), homeostasis model assessment (HOMA)-IR, triglyceride (TG), total cholesterol (TC), and low density lipoprotein cholesterol (LDL-C) were higher in the GDM group than those in the control group (p < 0.05), while the high density lipoprotein cholesterol (HDL-C) was lower in the GDM group than that in the control group (p < 0.05). Compared with those in the control group, the serum Hcy, AHSG, and CRP levels rose, while the serum 25-OH-VD level declined in the GDM group (p < 0.05). The results of Pearson's correlation analysis revealed that HOMA-IR had positive correlations with FPG, FINS, TC, TG, Hcy, AHSG, and CRP (r = 0.591, 0.825, 0.312, 0.234, 0.458, 0.647, 0.487, p < 0.05) and negative correlation with 25-OH-VD (r = -0.323, p < 0.05). CRP was positively correlated with HOMA-IR, TC, and AHSG (r = 0.485, 0.331, 0.226, p < 0.05), negatively associated with 25-OH-VD (r = -0.443, p < 0.05), and had no correlation to TG and Hcy (r = 0.019, 0.058, p > 0.05). AHSG displayed positive correlations with HOMA-IR, TC, TG, and CRP (r = 0.647, 0.321, 0.314, 0.226, p < 0.05) and no association with Hcy and 25-OH-VD (r = 0.058, -0.034, p > 0.05). CONCLUSIONS: GDM patients have increased serum Hcy, AHSG, and CRP levels and a decreased serum 25-OH-VD level, indicating that serum Hcy, AHSG, CRP, and 25-OH-VD are correlated with glucose and lipid metabolism disorders in GDM patients.

Metabolic profiling of RB-2 and RB-4, two analogs of polyacetylene from Bupleurum.

RB-2 and RB-4 are two structural analogs of polyacetylene from Radix Bupleuri that show antidepressant effects. However, no metabolic data are available to elucidate their systemic homeostasis. Mass spectrometry combined with liver microsomes and recombinant drug-metabolizing enzymes were performed to profile the biotransformations of RB-2/RB-4 in vitro and in vivo. Oxidation should be the major metabolic pathways for them in phase I, while CYP2C9 and CYP2E1 was the major contributor. In phase II, conjugational groups usually combined with the metabolites from phase I. This study provides an important reference basis for the safety evaluation and rational application of RB-2/RB-4.

Evaluation of Injury Degree of Adriamycin-Induced Nephropathy in Rats Based on Serum Metabolomics Combined with Proline Marker.

Nephrotic syndrome (NS) is one of the leading causes of end-stage renal failure. Unfortunately, reliable surrogate markers for early diagnosing and monitoring the entire progression of NS are as yet absent. A method using UPLC-Q exactive HR-MS was established for the serum metabolomic study of adriamycin-induced nephropathy in rats. Two rat nephropathy models induced by adriamycin were adopted to reflect different degrees of renal damage of early and advanced stages. Then two MPC5 cell models were used to verify the role of proline in the progression of kidney injury. The results showed that seven metabolites such as 14S-HDHA, DPA, and DHA were associated with early renal injury, while 12 metabolites such as tryptophan, linoleyl carnitine, and LysoPC (18:3) reflected the advanced renal disease. At the same time, metabolites including LPE (22:6), LysoPC (22:5), and proline that changed during the whole process of NS were defined as progressive markers. Pathway analysis results showed that fatty acid metabolism, glycerophospholipid metabolism, and amino acids metabolism participated in the occurrence and development of NS. In addition, the change trend of intracellular proline content was consistent with that in serum, and the results were further supported by the detection of the crucial gene PYCRL. This study provides an important basis for searching for diagnostic markers of NS and also provides a methodological reference for early diagnosing and monitoring the pathogenesis of other progressive diseases.

A novel insight into the underlying mechanism of Baihe Dihuang Tang improving the state of psychological suboptimal health subjects obtained from plasma metabolic profiles and network analysis.

Psychological suboptimal health state (PSHS), a subtype of suboptimal health status (SHS), seriously threatens the physical and mental health of human beings. Baihe Dihuang Tang (BDT), a traditional Chinese medicine prescription, has been used to improve PSHS in clinical and achieve significant efficacy for a long time. Exploring of the underlying mechanism of BDT improving the state of PSHS is of significant importance. In the present work, all subjects were screened in strict accordance with inclusion and exclusion criteria. the UHPLC-Q Exactive Orbitrap-MS and Trace GC-PolarisQ Mass were performed to analyze the metabolic features of BDT improving the state of PSHS. Combined with the experimental results of metabolomics and the predicted results of network pharmacology, the metabolic biological network was constructed to find the potential targets of BDT intervention on PSHS. Finally, A total of 22 differential metabolites have been identified in PSHS group. 15 plasma biomarkers were significantly regulated by BDT. The results indicated that the BDT decoction is of a significant therapeutic effect on the improvement of PSHS primarily through regulating pyruvate metabolism and phenylalanine metabolism. Moreover, it is possible for BDT to improve PSHS through the functional targets including GLO1, MAOA and MAOB, which are closely related to monoamine neurotransmitters. Here, these approaches provide a tractable, powerful tool for understanding the underlying mechanism elucidating of BDT for PSHS management.

Integrative hepatoprotective efficacy comparison of raw and vinegar-baked Radix Bupleuri using nuclear magnetic resonance-based metabolomics.

Radix Bupleuri (RB), with a Chinese name Chaihu, is one of the most popular Traditional Chinese herbal drug. It can be baked with vinegar to afford vinegar-baked Radix Bupleuri (VBRB), which is used in Traditional Chinese Medicine (TCM) for liver diseases treatment. In the present study, nuclear magnetic resonance-based metabolomic approach was used to compare the liver protective effect of RB and two types of VBRBs, which were prepared by two kinds of vinegar. The contents of 14 metabolites in the liver of carbon tetrachloride (CCl4) treated mice were significantly altered in comparison with control group, and VBRB prepared by Shanxi vinegar showed best effect as revealed by the amount and regulatory degree of the perturbed metabolites. The metabolism pathways analysis showed that the liver protective effect was related with the energy metabolism, lipid metabolism, ketone body metabolism, glutathione metabolism, amino acids metabolism and nucleotide synthesis. The results presented here showed that metabolomic approach made it possible to disclose the subtle biological difference between two types of VBRB, which highlight the potential of metabolomic approach to quantitatively compare the pharmacological effect of the herbal drugs.

[Investigation of the potentially effective components of Semen Ziziphi Spinosae based on "in vitro to in vivo" translation approach].

The study aims to investigate the effective components of Semen Ziziphi Spinosae (SZR) in nourishing the heart and tranquilizing the mind. A method of ultra high liquid chromatography (UHPLC) coupled with Q Exactive high resolution mass spectrometry (HR-MS) was developed. Based on the UV spectra, retention time and MS spectra, 25 compounds of SZR extract were identified or tentatively characterized, including 12 flavonoids, 8 triterpenoids saponins, 2 fatty acid and 3 alakoids. The study illuminated the major chemical components. Twenty bioactive components were determined in rat urine after oral administration of SZR extract by "in vitro to in vivo" translation approach, including 16 prototype compounds and 4 metabolites. Spinosin, swertisin, jujuboside A and B were considered as the effective and active constituents in SZR of the sedative and hypnotic effects, which emodies characteristics of multiple components. It was beneficial exploration for searching the effective and active constituents of SZR in nourishing the heart and tranquilizing the mind.

[Rationality of commodity criteria and traditional breeding of Polygala tenuifolia based on agronomic traits and determination of chemical components].

The agronomic traits (plant height, root diameter, root length, first lateral root height, lateral root amount, root weight) of 18 Polygala tenuifolia samples with different agronomic traits were analyzed, respectively. HPLC was used to analyze three main characteristic components including tenuifolin, polygalaxanthone Ⅲ, and 3,6'-disinapoyl sucrose. At last, the correlation between six agronomic traits and three main characteristic components were analyzed by scatter plot. We found no significant correlation between root diameter and three main characteristic components. There were no obvious correlations between tenuifolin and the remaining five agronomic traits. Short root length and first lateral root height as well as high lateral root amount resulted in high levels of polygalaxanthone Ⅲ in P. tenuifolia samples. High levels of 3,6'-disinapoyl sucrose were observed in P. tenuifolia samples with longer root. So, the current commodity criteria and traditional breeding of P. tenuifolia did not conform to pharmacopoeia standards, which excellent medicinal materials should have high contents of the main characteristic components. It was urgent to revise the current commodity criteria and breeding methods.

[Oxidation of mercury by CuBr2 decomposition under controlled-release membrane catalysis condition].

CuBr2 in the multi-porous ceramic membrane can release Br2 at high temperature, which was employed as the oxidant for Hg0 oxidation. Hg0 oxidation efficiency was studied by a membrane catalysis device. Meanwhile, a reaction and in situ monitoring device was designed to avoid the impact of Br2 on the downstream pipe. The result showed that the MnO(x)/alpha-Al2O3 catalysis membrane had a considerable "controlled-release" effect on Br2 produced by CuBr2 decomposition. The adsorption and reaction of Hg0 and Br2 on the surface of catalysis membrane obeyed the Langmuir-Hinshelwood mechanism. The removal efficiency of Hg0 increased with the rising of Br2 concentration. However, when Br2 reached a certain concentration, the removal efficiency was limited by adsorption rate and reaction rate of Hg0 and Br2 on the catalysis membrane. From 473 K to 573 K, the variation of Hg0 oxidation efficiency was relatively stable. SO2 in flue gas inhibited the oxidation of Hg0 while NO displayed no obvious effect.

[NMR-based analysis of water soluble extracts of different Astragali Radix].

Water soluble extract (WSE) is an important index for the quality evaluation of Astragali Radix (AR). In this study, the WSE of the wild AR from Shanxi province (SX) and the cultivated AR from Gansu Province (GS) were compared. The WSEs of two types of AR were determined according to the appendix of Chinese pharmacopoeia. Then the WSEs were subjected to NMR analysis, and the obtained data were analyzed using HCA, PCA, OPLS-DA, microarray analysis, and Spearman rank analysis. In addition, the Pearson correlation of differential metabolites were also calculated. The results showed that the WSE content of GS-AR (37.80%) was higher than that of SX-AR (32.13%). The main constituent of WSE was sucrose, and other 18 compounds, including amino acids, organic acids, were also detected. Multivariate analysis revealed that SX-AR contained more choline, succinic acid, citric acid, glutamate, taurine and aspartate, while GS samples contained more sucrose, arginine and fumaric acid. In addition, the Pearson correlations between different metabolites of the two types of AR also showed apparent differences. The results suggested that the WSE of two types of AR differs not only in the content, but also in the chemical compositions. Thus, the cultivation way is important to the quality of AR. This study supplied a new method for the comparison of extract of herbal drugs.

Metabolomic profiling of the antitussive and expectorant plant Tussilago farfara L. by nuclear magnetic resonance spectroscopy and multivariate data analysis.

This study aims to find metabolites responsible for antitussive and expectorant activities of Tussilago farfara L. by metabolomic approach. Different parts (roots, flower buds, and leaves) of the title plant were analyzed systematically. The in vivo study revealed that the leaves and flower buds had strong antitussive and expectorant effects. Then ¹H NMR spectrometry together with principal component analysis (PCA) and partial least squares discriminant (PLS-DA) analysis were used to investigate the compounds responsible for the bioactivities. PCA was used to find the differential metabolites, while PLS-DA confirmed a strong correlation between the observed effects and the metabolic profiles of the plant. The result revealed that chlorogenic acid, 3,5-dicaffeoylquinic acid, and rutin may be closely related with the antitussive and expectorant activities. The overall results of this study confirm the benefits of using metabolic profiling for screening active principles in medicinal plants.

Metabolomic profiling of the flower bud and rachis of Tussilago farfara with antitussive and expectorant effects on mice.

ETHNOPHARMACOLOGICAL RELEVANCE: Flower bud of Tussilago farfara L. is widely used for the treatment of cough, bronchitis and asthmatic disorders in the Traditional Chinese Medicine. However, due to the increasing demands, adulteration with rachis is frequently encountered in the marketplace. No report demonstrated the chemical and pharmacological differences between flower bud and rachis before. MATERIALS AND METHODS: The water extracts were orally administrated to mice. Ammonia induced mice coughing model was used to evaluate the antitussive activity. The expectorant activity was evaluated by volume of phenol red in mice's tracheas. Metabolites were identified directly from the crude extracts through 1D- and 2D-NMR spectra. A metabolic profiling carried out by (1)H NMR spectroscopy and multivariate data analysis was applied to crude extracts from flower bud and rachis. RESULTS: Flower bud significantly lengthened the latent period of cough, decreased cough frequency caused by ammonia and enhanced tracheal phenol red output in expectorant evaluation. Principal component analysis (PCA) yielded good separation between flower bud and rachis, and corresponding loading plot showed that the phenolic compounds, organic acid, sugar, amino acid, terpene and sterol contributed to the discrimination. CONCLUSIONS: These findings provide pharmacological and chemical evidence that only flower bud can be used as the antitussive and expectorant herbal drug. The high concentration of chlorogenic acid, 3,5-dicaffeoylquinic acid, rutin in flower buds may be related with the antitussive and expectorant effects of Flos Farfara. To guarantee the clinical effect, rachis should be picked out before use.

Electro-thermal treatment optimization of high concentration ammonia nitrogen by gaseous oxidation in liquid phase (GOLP).

This study is focused on optimizing the treatment parameters for high concentration ammonia using gaseous oxidation in liquid phase (GOLP). The conversion of ammonia was achieved electrothermally over mono-crystalline silicon supported CoOx catalyst. The experimental results demonstrated that factors including the co-anions, pH of the solutions, air flowrate and the current showed apparent influences on the ammonia removal. The higher the Cl(-) concentration and/or current, the better the efficiency of ammonia degradation. The increase of the air flowrate would increase the ammonia removal accordingly. And it was also observed that the pH declined during the ammonia conversion, and the neutral and alkaline pH were beneficial to the ammonia removal. The preliminary cost analysis based on lab data was also provided for future reference.

[Expression of peroxisome proliferator-activated receptor gamma in glioma].

OBJECTIVE: To investigate the expression and significance of peroxisome proliferators-activated receptor gamma (PPAR gamma) in human glioma. METHODS: Immunohistochemical staining for PPAR gamma was performed using biopsy specimens of human glioma of various histological types. Expression of PPAR gamma and GFAP in glioma cell lines SWO-38, U251 and SHG-44 were analyzed using Western blotting and reverse transcription-polymerase chain reaction (RT-PCR). RESULTS: Immunohistochemical study showed that PPAR gamma was expressed in glioma tissues with positive rate of 37.5%. Western blotting and RT-PCR showed that PPAR gamma was expressed in both glioma cell lines SWO-38 and U251, but not in SHG-44 cells. However, high expression of GFAP was detected in SHG-44 cells. CONCLUSION: PPAR gamma is associated with carcinogens of glioma. Actived PPAR gamma by agonist may be a novel approach to the treatment of glioma.

[Clinical observation on treatment of albuminuria in patients with pregnancy-induced hypertension syndrome in puerperium by Xiaobai Decoction].

OBJECTIVE: To observe the effects of Xiaobai Decoction (XBD) in reducing albuminuria and shortening the duration of albuminuria in patients with pregnancy-induced hypertension syndrome (PIH) in puerperium. METHODS: Eighty-five patients were given the conventional treatment with magnesium sulfate for relieving convulsion and lowering hypertension, at the same time, the treated group was given XBD additionally with the modification according to the symptoms. The treatment course for both groups was 14 days. Routine test of midstream urine was performed every three days, and 24 h-urinary protein was measured every week. RESULTS: The therapeutic effect on the 43 patients of the treated group was markedly effective in 11 (25.6 % ), effective in 26 (60.4%) and ineffective in 6 cases (14.0%), the total effective rate being 86.0%; while in the 42 patients of the control group, the corresponding numbers were 5 (11.9%), 21 (50.0%), 16 (38.1%) and 61.9%, respectively, the efficacy of the former was significantly better (P < 0.05). CONCLUSION: XBD is a simple, safe and effective drug for reducing albuminuria and shortening the duration of albuminuria in puerperium of PIH patients.

[Expression of PTEN gene in human glioma cell lines U251 and SHG-44 and its effect on cell proliferation].

BACKGROUND & OBJECTIVE: Mutation or deletion of PTEN gene is related to a variety of tumors. PTEN gene abnormality is closely related to the tumorigenesis of glioma. This study aimed to investigate the expression of PTEN gene in human glioma cell lines U251 and SHG-44, and explore its effect on cell proliferation. METHODS: The expression of PTEN gene in U251 and SHG-44 cells was detected by reverse transcription-polymerase chain reaction (RT-PCR). The recombinant eukaryotic expression vector containing wild-type PTEN gene was transfected into U251 and SHG-44 cells by cation polymex. The stably transfected cells were selected by G418 and amplified. Cell morphology was observed under microscope. The effect of PTEN gene on cell proliferation was assessed. The expression of PTEN protein and glial fibrillary acidic protein (GFAP) were detected by Western blot and immunohistochemistry. RESULTS: Point mutation and deletion of PTEN mRNA were observed respectively in U251 and SHG-44 cells. The proliferation rates of U251 and SHG-44 cells were inhibited by 39.1% and 27.8% of control at 7 days after transfection. The expression of PTEN and GFAP were both increased. The stably transfected U251 cells differentiated toward astrocytes, but SHG-44 cells had no obvious morphologic changes. CONCLUSION: Restoring expression of wild-type PTEN could induce differentiation of glioma cells differently.

Expression of c-fos in rat brain as a prelude marker of central nervous system injury in response to methylmercury-stimulation.

OBJECTIVE: To probe into the prelude marker of central nervous system injury in response to methyl mercury chloride (MMC) stimulation and the signal transduction molecular mechanism of injury in rat brain induced by MMC. METHODS: The expression of c-fos mRNA in brain and the expression of c-FOS protein in cortex, hippocampus and ependyma were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The control group was injected with physiological saline of 0.9%, while the concentrations for the exposure groups were 0.05 and 0.5, 5 mg/kg MMC respectively, and the sampling times points were 20, 60, 240, 1440 min. RESULTS: The expression of c-FOS protein in cortex and hippocampus increased significantly, the accumulation of mercury in the brain induced by 0.05 mg/Kg MMC for 20 min had no significant difference compared with the control group. The mean value was 0.0044 mg/Kg, while the protein c-FOS expression had significant difference compared with the control group (P < 0.01). More sensitive expression occurred in hippocampus and cortex, but not in ependyma. Conclusion The expression of c-FOS protein in cortex and hippocampus can predict the neurotoxicity of MMC in the early time, and immediately early gene (IEG) c-fos participates in the process of brain injury induced by MMC.

Effects of mercury contaminated rice from typical chemical plant area in China on nitric oxide changes and c-fos expression of rats brain.

China is one of countries with the highest mercury production in the world. The Guizhou Province in Southwestern China is currently one of the world's most important mercury production areas. In order to study the neurotoxicity of rice from Qingzhen Chemical Plant area and probe into the signal transduction molecular mechanism of injury in rat brain stimulation by mercury contaminated rice. The rats were exposed to mercury contaminated rice for 20 d. Both of the measurements of NO and NOS were processed according to the protocol of the kit. The effect of Hg contaminated rice on the expression of c-fos mRNA in rat brain and the expression of c-FOS protein in cortex, hippocampus were observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. The results showed the neural transmitter NO and NOS in brain were significantly change between exposure groups and control group; the mercury polluted rice induced significantly the expression of c-fos mRNA; the c-FOS positive cells in hippocampus and cortex of exposure groups were significant different from control group (p < 0.01). It could be concluded that nitric oxide was involved in mercury contaminated rice induced immediate early gene c-fos expressions in the rat brain. Through food chain, local ecosystem and health of local people iave been deteriorated seriously by mercury. This serious situation will last a long period. In order to alleviate mercury pollution, more work needs to do.

Effect of methylmercury on some neurotransmitters and oxidative damage of rats.

In order to study the molecular mechanism of injury in rat organs induced by methylmercury, and the relationship between neurotransmitter and oxidative damage in the toxicity process of rat injury by methylmercury was studied. The control group was physiological saline of 0.9%, the concentration of exposure groups were 5 mg/( kg x d) and 10 mg/( kg x d) respectively. The content of AChE, ACh, NOS, NO, MDA, SOD, GSH-Px and GSH in different organs of rats were determined with conventional methods. The results showed that after exposure to methylmercury for 7 d, the mercury content in brain of exposure groups increased clearly and had significant difference compared with the control group (P < 0.01). In rat's brain, serum, liver and kidney, the content of ACh and AChE were all decreased; the content of NOS and NO were all increased; the content of MDA was increased compared with the control group, the exposure groups had significant difference (P < 0.01); the content of SOD, GSH and GSH-Px was decreased compared with the control group, the exposure groups had significant difference (P < 0.01). It could be concluded that methylmercury did effect the change of neurotransmitter and free radical. They participated in the toxicity process of injury by methylmercury. The damage of neurotransmitter maybe cause the chaos of free radical and the chaos of free radical may also do more damage to neurotransmitter vice versa.

Rice from mercury contaminated areas in Guizhou Province induces c-jun expression in rat brain.

OBJECTIVE: Mercury (Hg), as one of the priority pollutants and also a hot topic of frontier environmental research in many countries, has been paid higher attention in the world since the middle of the last century. Guizhou Province (at N24 degrees 30'-29 degrees 13', E103 degrees 1'-109 degrees 30', 1 100 m above the sea level, with subtropical humid climate) in southwest China is an important mercury production center. It has been found that the mercury content in most media of aquatics, soil, atmosphere and in biomass of corns, plants and animals, is higher than the national standard. The present study aims to explore the influence of mercury pollution on the health of local citizens. METHODS: The effect of rice from two mercury polluted experimental plots of Guizhou Province on the expression of c-jun mRNA in rat brain and c-jun protein in cortex, hippocampus and ependyma was observed using reverse transcription polymerase chain reaction (RT-PCR) and immunocytochemical methods. RESULTS: The results showed that the mercury polluted rice induced expression of c-jun mRNA and its protein significantly. Selenium can reduce Hg uptake, an antagonism between selenium and mercury on the expression of c-jun mRNA and c-jun protein. CONCLUSION: c-jun participates in the toxicity process of brain injury by mercury polluted rice, the expression of c-jun mRNA in brain, and c-jun protein in rat cortex and hippocampus can predict neurotoxicity of mercury polluted rice. People should be advised to be cautious in eating any kind of Hg-polluted foods. To reveal the relationship between c-jun induction and apoptosis, further examinations are required.