Systematic studies on the kinetic process of 20(S)-protopanaxadiol in rats and dogs: absorption, distribution, metabolism and excretion.

Background and Objective: Ginseng has been regarded as a precious medicinal herb with miraculous effects in Eastern culture. The primary chemical constituents of ginseng are saponins, and the physiological activities of ginsenosides determine their edible and medicinal value. The aim of this study is to comprehensively and systematically investigate the kinetic processes of 20(S)-protopanaxadiol (PPD) in rats and dogs, in order to promote the rational combination of ginseng as a drug and dietary ingredient. Methods: PPD was administered, and drug concentration in different biological samples were detected by liquid chromatography tandem mass spectrometry (LC/MS/MS) and radioactive tracer methods. Pharmacokinetic parameters such as absorption, bioavailability, tissue distribution, plasma protein binding rate, excretion rate, and cumulative excretion were calculated, along with inference of major metabolites. Results: This study systematically investigated the absorption, distribution, metabolism, excretion (ADME) of PPD in rats and dogs for the first time. The bioavailabilities of PPD were relatively low, with oral absorption nearly complete, and the majority underwent first-pass metabolism. PPD had a high plasma protein binding rate and was relatively evenly distributed in the body. Following oral administration, PPD underwent extensive metabolism, potentially involving one structural transformation and three hydroxylation reactions. The metabolites were primarily excreted through feces and urine, indicating the presence of enterohepatic circulation. The pharmacokinetic processes of PPD following intravenous administration aligned well with a three-compartment model. In contrast, after gastric administration, it fitted better with a two-compartment model, conforming to linear pharmacokinetics and proportional elimination. There were evident interspecies differences between rats and dogs regarding PPD, but individual variations of this drug were minimal within the same species. Conclusion: This study systematically studied the kinetic process of PPD in rats and also investigated the kinetic characteristics of PPD in dogs for the first time. These findings lay the foundation for further research on the dietary nutrition and pharmacological effects of PPD.

Reprogramming of regulatory T cells in inflammatory tumor microenvironment: can it become immunotherapy turning point?

Overcoming the immunosuppressive tumor microenvironment and identifying widely used immunosuppressants with minimal side effects are two major challenges currently hampering cancer immunotherapy. Regulatory T cells (Tregs) are present in almost all cancer tissues and play an important role in preserving autoimmune tolerance and tissue homeostasis. The tumor inflammatory microenvironment causes the reprogramming of Tregs, resulting in the conversion of Tregs to immunosuppressive phenotypes. This process ultimately facilitates tumor immune escape or tumor progression. However, current systemic Treg depletion therapies may lead to severe autoimmune toxicity. Therefore, it is crucial to understand the mechanism of Treg reprogramming and develop immunotherapies that selectively target Tregs within tumors. This article provides a comprehensive review of the potential mechanisms involved in Treg cell reprogramming and explores the application of Treg cell immunotherapy. The interference with reprogramming pathways has shown promise in reducing the number of tumor-associated Tregs or impairing their function during immunotherapy, thereby improving anti-tumor immune responses. Furthermore, a deeper understanding of the mechanisms that drive Treg cell reprogramming could reveal new molecular targets for future treatments.

Nanoplastic Exposure at Environmental Concentrations Disrupts Hepatic Lipid Metabolism through Oxidative Stress Induction and Endoplasmic Reticulum Homeostasis Perturbation.

In this study, we investigated the mechanism underlying the perturbation of hepatic lipid metabolism in response to micro/nanoplastic (MP/NP) exposure at environmentally relevant concentrations. Polystyrene (PS) MPs/NPs with different sizes (0.1, 0.5, and 5.0 µm) were studied for their effects on the homeostasis and function of Nile tilapia (Oreochromis niloticus) liver. Results showed that PS MPs/NPs were readily internalized and accumulated in various internal organs/tissues, especially in fish liver and muscle. Smaller-sized NPs caused more severe toxicity than larger MPs, including hepatic steatosis, inflammatory response, and disturbed liver function. Mechanistically, PS NPs with a particle size of 100 nm perturbed protein homeostasis in the endoplasmic reticulum (ER) by inhibiting the expression of chaperone proteins and genes involved in ER-associated degradation. This led to the activation of the PERK-eIF2α pathway, which caused dysfunction of hepatic lipid metabolism. Induction of oxidative stress and activation of the Nrf2/Keap1 pathway were also involved in the PS NP-induced hepatic lipid accumulation. These findings highlight the potential adverse effects of environmental MPs/NPs on aquatic organisms, raising concerns about their ecotoxicity and food safety.

Influences of continuous and pulse atrazine exposure on intestinal flora and metabolites of Pelophylax nigromaculatus tadpoles.

Atrazine, a widely used herbicide, has adverse effects on the growth and metabolism of amphibians. Due to the cyclical application use of the pesticide atrazine in agricultural production, atrazine concentrations in water occur in the form of pulses. However, knowledge of the effects of atrazine pulse exposure on the gut microbiota and metabolism of amphibians is limited. In this study, Pelophylax nigromaculatus tadpoles (Gs 26) were exposed to continuous and pulse atrazine (100 µg/L) for 60 days. The results showed that continuous exposure and pulse exposure had different effects on the diversity of gut microbiota. At the phyla level, pulse exposure significantly increased the relative abundance of Actinobacteria, and decreased the relative abundance of Firmicutes compared to continuous exposure. At the genus level, continuous and pulse exposure to atrazine significantly altered the relative abundance of Acetobacterium, Microbacterium, Bacteroides, Eulopiscium and Leuconostoc. Compared to continuous exposure, pulse exposure significantly increased the relative abundance of Microbacterium, and significantly decreased the relative abundance of Acetobacterium and Eplopiscium. In terms of metabolism, pulse exposure significantly increased the relative abundance of creatine, guanine, and inosine and significantly decreased the relative abundance of 3-hydroxysebacic acid, ganoderic acid F, hypoxanthine, and withaperuvin H compared to continuous exposure. Continuous and pulse exposure to atrazine significantly altered the relative abundance of metabolites of the pymidine metabolism, purine metabolism, beta-alanine metabolism and other pathways in the gut of P. nigromaculatus tadpoles. In addition, changes in most metabolites had a significant correlation with changes in gut microorganisms. In conclusion, our study confirmed that pulse exposure to atrazine has a greater effect on the composition of the gut microflora and the metabolism of P. nigromaculatus tadpoles than continuous exposure.

Thyroid dysfunction in young, first-episode and drug-naïve patients with major depressive disorder: prevalence and associated clinical factors.

Objective: The incidence of thyroid dysfunction (TD) and major depressive disorder (MDD) is increasing year by year in the general population. However, the prevalence and correlates of TD in first-episode drug-naive (FEDN) MDD patients have not been explored. This study sought to fill this gap and examine the association between TD and MDD. Methods: We recruited 1,289 FEDN MDD patients aged 18 ~ 45 years. A total of 1,289 FEDN MDD outpatients were recruited. Demographical and suicide data were collected for each patient, and lipid profiles, thyroid function, and fasting blood glucose (FBG) levels were measured. The Hamilton Depression Scale 17 (HAMD-17) was assessed for depression. Results: The prevalence of TD in young FEDN MDD patients was 64.86%. Compared with those without TD, patients with TD had longer duration of illness, greater HAMD score, higher BMI, TG, TC, and LDL-C levels, and higher suicide attempt rates, but lower HDL-C and FBG levels. Further logistic regression indicated that duration of illness, HAMD score, TC, HDL-C, BMI, and FBG levels were significantly associated with TD. Limitations: No causal relationship can be drawn due to the cross-sectional design. Conclusion: TD is common in young FEDN MDD patients. So clinicians should monitor thyroid function in patients with MDD.

Phylogenetic and expression analysis of the angiopoietin-like gene family and their role in lipid metabolism in pigs.

OBJECTIVE: The objective of this study was to investigate the phylogenetic and expression analysis of the angiopoietin-like (ANGPTL) gene family and their role in lipid metabolism in pigs. METHODS: In this study, the amino acid sequence analysis, phylogenetic analysis, and chromosome adjacent gene analysis were performed to identify the ANGPTL gene family in pigs. According to the body weight data from 60 Jinhua pigs, different tissues of 6 pigs with average body weight were used to determine the expression profile of ANGPTL1-8. The ileum, subcutaneous fat, and liver of 8 pigs with distinct fatness were selected to analyze the gene expression of ANGPTL3, ANGPTL4, and ANGPTL8. RESULTS: The sequence length of ANGPTLs in pigs was between 1,186 and 1,991 bp, and the pig ANGPTL family members shared common features with human homologous genes, including the high similarity of the amino acid sequence and chromosome flanking genes. Amino acid sequence analysis showed that ANGPTL1-7 had a highly conserved domain except for ANGPTL8. Phylogenetic analysis showed that each ANGPTL homologous gene shared a common origin. Quantitative reverse-transcription polymerase chain reaction analysis showed that ANGPTL family members had different expression patterns in different tissues. ANGPTL3 and ANGPTL8 were mainly expressed in the liver, while ANGPTL4 was expressed in many other tissues, such as the intestine and subcutaneous fat. The expression levels of ANGPTL3 in the liver and ANGPTL4 in the liver, intestine and subcutaneous fat of Jinhua pigs with low propensity for adipogenesis were significantly higher than those of high propensity for adipogenesis. CONCLUSION: These results increase our knowledge about the biological role of the ANGPTL family in this important economic species, it will also help to better understand the role of ANGPTL3, ANGPTL4, and ANGPTL8 in lipid metabolism of pigs, and provide innovative ideas for developing strategies to improve meat quality of pigs.

Correlation analysis of lipid metabolism genes with the immune microenvironment in gastric cancer and the construction of a novel gene signature

Background Lipid metabolism reprogramming plays an important role in cell growth, proliferation, angiogenesis and invasion of cancer. However, the prognostic value of lipid metabolism during gastric cancer (GC) progression and the relationship with the immune microenvironment are still unclear. The aim of this study was to clarify the correlation between lipid metabolism genes and GC immunity. Method We obtained 350 patients from The Cancer Genome Atlas (TCGA) and 355 patients from Gene Expression Omnibus (GEO) databases. Lipid metabolism-related gene datasets were obtained from the Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular subtypes were obtained by Consensus clustering, and subtype immune status was analyzed using ESTIMATE, TIMER and microenvironmental cell population counter (MCP Counter) algorithm for immune analysis. Functional analyses included the application of Gene Set Enrichment Analysis (GSEA), KEGG, gene ontology (GO), and Protein–Protein Interaction Networks (PPI) to evaluate the molecular mechanisms of different subtypes. Weighted gene co-expression network analysis (WGCNA) was used to identify genes associated with immunity. The LASSO algorithm and multivariate Cox regression analysis were used to construct prognostic risk models. Result Based on the lipid metabolism genes found in GC, patients with GC can be divided into two subgroups with significantly different survival. The subgroup with a better prognosis presented higher immune scores and immune infiltrating cell abundance. 1170 immune-related genes were screened by WGCNA, and further screening by PPI network analysis revealed that PTPRC, CD4, ITGB2 and LCP2 were closely associated with immune cells. Combined with the TIDE score results, it was found that the population with high expression of the above genes might be more sensitive to immunotherapy (AU)

A novel metabolism-related prognostic gene development and validation in gastric cancer

Background The importance of metabolism-related alterations in the development of gastric cancer (GC) is increasingly recognized. The present study aimed to identify metabolism-related genes to facilitate prognosis of GC patients. Methods Gene expression datasets and clinical information of GC patients were downloaded from TCGA and GEO databases. We scored the enrichment of human metabolism-related pathways (n = 86) in GC samples by GSV, constructed prognostic risk models using LASSO algorithm and multivariate Cox regression analysis, combined with clinical information to construct a nomogram, and finally cis score algorithm to analyze the abundance of immune-related cells in different subtypes. We used Weka software to screen for prognosis-related marker genes and finally validated the expression of the selected genes in clinical cancer patient tissues. Results We identified that two GC metabolism-related signatures were strongly associated with OS and the levels of immune cell infiltration. Moreover, a survival prediction model for GC was established based on six GC metabolism-related genes. Time-dependent ROC analysis showed good stability of the risk prediction scoring model. The model was successfully validated in an independent ACRG cohort, and the expression trends of key genes were also verified in the GC tissues of patients. DLX1, LTBP2, FGFR1 and MMP2 were highly expressed in the cluster with poorer prognosis while SLC13A2 and SLCO1B3 were highly expressed in the cluster with better prognosis. Conclusions We identified a risk predictive score model based on six metabolism-related genes related to survival, which may serve as prognostic indicators and potential therapeutic targets for GC (AU)

Correlation analysis of lipid metabolism genes with the immune microenvironment in gastric cancer and the construction of a novel gene signature.

BACKGROUND: Lipid metabolism reprogramming plays an important role in cell growth, proliferation, angiogenesis and invasion of cancer. However, the prognostic value of lipid metabolism during gastric cancer (GC) progression and the relationship with the immune microenvironment are still unclear. The aim of this study was to clarify the correlation between lipid metabolism genes and GC immunity. METHOD: We obtained 350 patients from The Cancer Genome Atlas (TCGA) and 355 patients from Gene Expression Omnibus (GEO) databases. Lipid metabolism-related gene datasets were obtained from the Reactome and Kyoto Encyclopedia of Genes and Genomes (KEGG) databases. Molecular subtypes were obtained by Consensus clustering, and subtype immune status was analyzed using ESTIMATE, TIMER and microenvironmental cell population counter (MCP Counter) algorithm for immune analysis. Functional analyses included the application of Gene Set Enrichment Analysis (GSEA), KEGG, gene ontology (GO), and Protein-Protein Interaction Networks (PPI) to evaluate the molecular mechanisms of different subtypes. Weighted gene co-expression network analysis (WGCNA) was used to identify genes associated with immunity. The LASSO algorithm and multivariate Cox regression analysis were used to construct prognostic risk models. RESULT: Based on the lipid metabolism genes found in GC, patients with GC can be divided into two subgroups with significantly different survival. The subgroup with a better prognosis presented higher immune scores and immune infiltrating cell abundance. 1170 immune-related genes were screened by WGCNA, and further screening by PPI network analysis revealed that PTPRC, CD4, ITGB2 and LCP2 were closely associated with immune cells. Combined with the TIDE score results, it was found that the population with high expression of the above genes might be more sensitive to immunotherapy. In addition, a survival prediction model for GC was developed based on five survival-related lipid metabolism genes, PIAS4, PLA2R1, PRKACA, SLCO1A2 and STARD4. The ROC analysis over time showed that the risk prediction score model had good stability. CONCLUSION: Lipid metabolism gene expression is correlated with the immune microenvironment in GC patients and can accurately predict their prognosis. Studies on lipid metabolism and GC immunity can help to screen the population for immunotherapy benefits.

A novel metabolism-related prognostic gene development and validation in gastric cancer.

BACKGROUND: The importance of metabolism-related alterations in the development of gastric cancer (GC) is increasingly recognized. The present study aimed to identify metabolism-related genes to facilitate prognosis of GC patients. METHODS: Gene expression datasets and clinical information of GC patients were downloaded from TCGA and GEO databases. We scored the enrichment of human metabolism-related pathways (n = 86) in GC samples by GSV, constructed prognostic risk models using LASSO algorithm and multivariate Cox regression analysis, combined with clinical information to construct a nomogram, and finally cis score algorithm to analyze the abundance of immune-related cells in different subtypes. We used Weka software to screen for prognosis-related marker genes and finally validated the expression of the selected genes in clinical cancer patient tissues. RESULTS: We identified that two GC metabolism-related signatures were strongly associated with OS and the levels of immune cell infiltration. Moreover, a survival prediction model for GC was established based on six GC metabolism-related genes. Time-dependent ROC analysis showed good stability of the risk prediction scoring model. The model was successfully validated in an independent ACRG cohort, and the expression trends of key genes were also verified in the GC tissues of patients. DLX1, LTBP2, FGFR1 and MMP2 were highly expressed in the cluster with poorer prognosis while SLC13A2 and SLCO1B3 were highly expressed in the cluster with better prognosis. CONCLUSIONS: We identified a risk predictive score model based on six metabolism-related genes related to survival, which may serve as prognostic indicators and potential therapeutic targets for GC.

Insights into the Dynamic Succession of Microbial Community and Related Factors of Vanillin Content Change Based by High-Throughput Sequencing and Daqu Quality Drivers.

Daqu is an important saccharifying starter in the fermentation of Nongxiangxing Baijiu in China. Vanillin is a health and flavor factor in Baijiu. However, only a few research studies on the vanillin content of Daqu are currently not systematic. In order to investigate the metabolic mechanism of vanillin in the fermentation process of Daqu, we analyzed the changes in microorganisms, influencing factors, and enzymes related to vanillin in Daqu. This research found that there were differences between bacterial and fungal genera in each sample, and the abundance of bacteria was greater than that of fungi. Among the microbial genera, Klebsiella, Escherichia, Acinetobacter, Saccharopolyspora, Aerococcus, and Puccinia were positively correlated with vanillin. Meanwhile, we also found that moisture and reducing sugar were the main physicochemical factors affecting the formation of vanillin. The functional annotation results indicate that carbohydrate metabolism and energy metabolism were important microbial metabolic pathways that impacted vanillin production in solid-state fermentation. The feruloyl-CoA hydratase/lyase (EC 4.1.2.61) and acylamidase (EC 3.5.1.4) were positively correlated with vanillin content (p ≤ 0.05) and promote the increase in vanillin content. These findings contribute to furthering our understanding of the functional microorganisms, physicochemical factors, and enzymes related to the change in vanillin content during the fermentation of Daqu and can help to further explore the flavor substances in Baijiu fermentation in the future.

NMMHC IIA triggered lipid metabolize reprogramming resulting in vascular endothelial cellular tight junction injury.

BACKGROUND AND PURPOSE: Nonmuscle myosin heavy chain IIA, played an essential role in the promotion of tight junction injury in vascular endothelial cells under oxygen glucose deprivation condition. Rat microvascular endothelial cells had been confirmed to have the susceptibility to ox-LDL stimulation under OGD condition. We proposed the hypothesis that lipid metabolic reprogramming might be the root cause for damage to RBMCs tight junction. METHODS: Untargeted shotgun and targeted lipid metabolomics mass spectrometry approaches combined with principal component analysis was applied to better define the lipids contributing to the variance observed between control and different OGD time. The protein expression of tight junction of RBMCs: occludin, claudin-5, and ZO-1 were detected with immunofluorescence staining and western blot. The proof of the interaction between NMMHC IIA and SREBP1 was investigated via GST-pull down, while their specific binding fragments were also confirmed. The regulation mechanism of NMMHC IIA on SREBP1 was investigated to explore downstream regulatory signaling pathways. RESULTS: Untargeted and targeted shotgun lipidomics data revealed that OGD might be the conditional factor in reshaping lipid components. Mechanistic studies showed that with the increase of OGD time, PCA analysis of lipidomics obtained from RBMCs indicated their specificity in reshaping lipid components, while ≥80% major lipid components phospholipids and sphingolipids transferred from phospholipids, sphingolipids, and neutral lipids, of which neutral lipids taken the largest proportion with OGD time course. Perturbing reprogramming of lipid composition was less susceptible to OGD condition via knockdown of NMMHC IIA of vascular endothelial cells. Knockdown of NMMHC IIA could promote tight junction defense to OGD condition. NMMHC IIA could directly bind with SREBP1, then could affect sterol regulatory element binding protein-1 to adjust lipid metabolize reprogramming of RBMCs. CONCLUSIONS: Mechanistic studies showed that perturbing reprogramming of lipid composition could enhance tight junction damage, which was mediated by the opposing effects of NMMHC IIA.

[Toxicological research and safety consideration of coumarins].

Coumarin is an important class of natural organic compounds, which widely exists in a variety of plants and microorganisms. Coumarins have many biological activities and wide clinical applications, such as anti-tumor, anti-HIV, anti-bacterial, anti-inflammatory, anti-oxidation, anti-coagulation, but they have obvious toxic effects in rodents. It was found that the toxicity of coumarins in different animals and organs was significantly different, and high dose oral administration was more likely to produce toxic reactions. Based on the research and analysis of domestic and foreign literatures in recent 60 years, this paper mainly summarized the hepatotoxicity and pulmonary toxicity induced by coumarins, and probed into their possible mechanisms. It was found that the toxicity of coumarins had metabolic differences and species differences. The liver of rats and lungs of mice were more susceptible to coumarins. Toxic reactions occurred mainly in the second metabolic pathway of coumarin metabolism in vivo. In order to put forward safety considerations and evaluate the impact of coumarin on human body, it was found that coumarin is unlikely to produce hepatotoxicity at normal exposure level. It was also suggested that species differences due to different metabolic patterns in model animals should be carefully considered when assessing coumarin toxicity, in order to provide reference for clinical research and rational use of coumarins and improve the rational use of coumarins.

Toxicological research and safety consideration of coumarins / 中国中药杂志

Coumarin is an important class of natural organic compounds, which widely exists in a variety of plants and microorganisms. Coumarins have many biological activities and wide clinical applications, such as anti-tumor, anti-HIV, anti-bacterial, anti-inflammatory, anti-oxidation, anti-coagulation, but they have obvious toxic effects in rodents. It was found that the toxicity of coumarins in different animals and organs was significantly different, and high dose oral administration was more likely to produce toxic reactions. Based on the research and analysis of domestic and foreign literatures in recent 60 years, this paper mainly summarized the hepatotoxicity and pulmonary toxicity induced by coumarins, and probed into their possible mechanisms. It was found that the toxicity of coumarins had metabolic differences and species differences. The liver of rats and lungs of mice were more susceptible to coumarins. Toxic reactions occurred mainly in the second metabolic pathway of coumarin metabolism in vivo. In order to put forward safety considerations and evaluate the impact of coumarin on human body, it was found that coumarin is unlikely to produce hepatotoxicity at normal exposure level. It was also suggested that species differences due to different metabolic patterns in model animals should be carefully considered when assessing coumarin toxicity, in order to provide reference for clinical research and rational use of coumarins and improve the rational use of coumarins.

CYP enzymes, expressed within live human suspension cells, are superior to widely-used microsomal enzymes in identifying potent CYP1A1/CYP1B1 inhibitors: Identification of quinazolinones as CYP1A1/CYP1B1 inhibitors that efficiently reverse B[a]P toxicity and cisplatin resistance.

Microsomal cytochrome P450 (CYP) enzymes, isolated from recombinant bacterial/insect/yeast cells, are extensively used for drug metabolism studies. However, they may not always portray how a developmental drug would behave in human cells with intact intracellular transport mechanisms. This study emphasizes the usefulness of human HEK293 kidney cells, grown in 'suspension' for expression of CYPs, in finding potent CYP1A1/CYP1B1 inhibitors, as possible anticancer agents. With live cell-based assays, quinazolinones 9i/9b were found to be selective CYP1A1/CYP1B1 inhibitors with IC50 values of 30/21 nM, and > 150-fold selectivity over CYP2/3 enzymes, whereas they were far less active using commercially-available CYP1A1/CYP1B1 microsomal enzymes (IC50, >10/1.3-1.7 µM). Compound 9i prevented CYP1A1-mediated benzo[a]pyrene-toxicity in normal fibroblasts whereas 9b completely reversed cisplatin resistance in PC-3/prostate, COR-L23/lung, MIAPaCa-2/pancreatic and LS174T/colon cancer cells, underlining the human-cell-assays' potential. Our results indicate that the most potent CYP1A1/CYP1B1 inhibitors would not have been identified if one had relied merely on microsomal enzymes.

Feeding and metabolism effects of three common microplastics on Tenebrio molitor L.

Mealworms from three different regions: Guangzhou, Tai'an and Shenzhen, were fed with three commonly used microplastics of polystyrene (PS), polyvinyl chloride (PVC) and low-density polyethylene (LDPE) for 1 month under favorable conditions, respectively. The survival rate and average weight of mealworms, the mass loss of microplastics and the production of frass were recorded every 4 days. Samples collected were characterized by X-ray diffraction, fourier transform infrared spectroscopy, thermogravimetric analyzer and gel permeation chromatography. The results showed that mealworms from Tai'an and Shenzhen could effectively metabolize the whole microplastics tested, while those from Guangzhou could only metabolize PS and LDPE. Besides, LDPE could be degraded by mealworms from Tai'an and Shenzhen, while those from Guangzhou showed no such capability, indicating that mealworms from different regions present different metabolism effects. Furthermore, PS and LDPE are more likely to be metabolized compared with PVC.

Glutamine and tumor / 国际外科学杂志

Glutamine,a coding amino acid in the process of synthesis of protein,could be absorbed by endothelial cells of the small intestine in most cases,or converted from other amino acid and glucose in the assistance of concerned enzyme.This nonessential amino acid maintains homeostasis in rivo.In recent years,a large number of researches reveal that glutamine plays an extremely important role in the tumor metabolism and therefore influences the process and treatment of cancer.In the study,the netabolism of glutamine in normal cells and tumor cells and its effects on tumor therapy were reviewed.

Metabolism of glycyrrhizin and glycyrrhetinic acid in the in situ vascularly perfused rat intestine-liver model / 中国药理学通报

Aim To study the biotransformation of gly-cyrrhizin in rat intestine-liver. Methods The in situ vascularly perfused rat intestine-liver model was estab-lished with a validated LC-MS/MS method for assay of the model perfusate glycyrrhizin and glycyrrhetinic acid. Results The steady state intestinal and liver ex-traction ratios in the once-through perfused rat intes-tine-liver model for glycyrrhizin were ( 4. 2 ± 0. 6 )%and (28. 0 ± 3. 0)%, respectively; the first-order ab-sorption rate constant for glycyrrhizin in the recircula-tion of perfusate to the intestine model was ( 0. 33 ± 0. 06 ) min-1;after intraduodenal administration of gly-cyrrhizin,the main active metabolite in was the perfu-sate glycyrrhetinic acid, which was also found in intes-tinal luminal fluids. Conclusions The first-pass effi-cacy of glycyrrhizin is obvious and there is only a small amount of metabolite in the intestinal mucosa cells;gly-cyrrhizin is metabolized by gut bacteria or liver cells af-ter oral administration;the in situ vascularly perfused rat intestine-liver model can be used in glycyrrhizin pharmacokinetic studies.

The Research of Managing MS Sufferers / 中国实用内科杂志

Objective Inquire a method to treat,interfere and control the conditions of MS sufferers.Methods Discover MS sufferers through the healthy management center check-up.Divide them into the intervention set and matched control random.Synthesize an intervention towards interfering set to carry on valuation,change life style,the medicine treatment Two years later statistics to analyze index signs,such as two sets of dangerous factor,blood sugar fat,weight index numbers and blood pressure...etc.Result The management rate of the interfering set is 94.24%.After interfering,the Treatment rate,the understanding rate,the controlling rate have been increased by 53.56%,55.07%and 69.93%.The empty stomach blood sugar,the blood glycerin three esters,the total cholesterols,the weight index numbers,systolic pressure and diastolic pressure have obviously improved compared with those before interfering(P

Role of SREBP-1C and GRP-94 in hepatocytes lipids metabolism of mice / 基础医学与临床

Objective To explore the expression of sterol regulatory element binding protein 1C (SREBP-1C) and glucose-regulated protein 94(GRP-94)in hyperhomocysteinmia and to evaluate the effects of endoplasmic reticulum stress proteins on hepatocytes lipids metabolism. Methods After hyperhomocysteinmia C57BL/6 mice model being induced by high methionine diet, TGE and CHO of Hepatocytes were determined, and the expression of SREBP-1C and GRP-94 was assessed by RT-PCR and Western blot. All data were compared to those in control group′s. Results The level of plasmic homocysteine(Hcy) and hepatocytes TGE or CHO of high methionine diet mice at different time point significantly ascended(P