Schisandra chinensis Oil Attenuates Aristolochic Acid I-Induced Nephrotoxicity in vivo and in vitro / 中国结合医学杂志

OBJECTIVE@#To investigate the protective effects of Schisandra chinensis oil (SCEO) against aristolochic acid I (AA I)-induced nephrotoxicity in vivo and in vitro and elucidate the underlying mechanism.@*METHODS@#C57BL/6 mice were randomly divided into 5 groups according to a random number table, including control group, AA I group, and AA I +SCEO (0.25, 0.5 and 1 g/kg) groups (n=5 per group). Pretreatment with SCEO was done for 2 days by oral administration, while the control and AA I groups were treated with sodium carboxymethyl cellulose. Mice of all groups except for the control group were injected intraperitoneally with AA I (5 mg/kg) from day 3 until day 7. Histopathological examination and apoptosis of kidney tissue were observed by hematoxylin and eosin and TdT-mediated dUTP nick-end labeling (TUNEL) staining, respectively. The levels of serum alanine aminotransferase (ALT), aspartate aminotransferase (AST), blood urea nitrogen (BUN), and serum creatinine (SCr), as well as renal malondialdehyde (MDA), glutathione, r-glutamyl cysteingl+glycine (GSH), and superoxide dismutase (SOD) were analyzed using enzyme-linked immunosorbent assay (ELISA). Expressions of hepatic cytochrome P450 1A1 (CYP1A1), CYP1A2, and nad(p)hquinonedehydrogenase1 (NQO1) were analyzed using ELISA, quantitative real-time polymerase chain reaction (qPCR) and Western blot, respectively. In vitro, SCEO (40 µ g/mL) was added 12 h before treatment with AA I (40 µ mol/mL for 48 h) in human renal proximal tubule cell line (HK-2), then apoptosis and reactive oxygen species (ROS) were analyzed by flow cytometry.@*RESULTS@#SCEO 0.5 and 1 g/kg ameliorated histopathological changes and TUNEL+ staining in the kidney tissues of mice with AA I-induced nephrotoxicity, and reduced serum levels of ALT, AST, BUN and SCr (P<0.01 or P<0.05). SCEO 0.5 and 1 g/kg alleviated the ROS generation in kidney, containing MDA, GSH and SOD (P<0.01 or P<0.05). SCEO 1 g/kg increased the expressions of CYP1A1 and CYP1A2 and decreased NQO1 level in the liver tissues (P<0.01 or P<0.05). Besides, in vitro studies also demonstrated that SCEO 40 µ g/mL inhibited apoptosis and ROS generation (P<0.05 or P<0.01).@*CONCLUSIONS@#SCEO can alleviate AA I-induced kidney damage both in vivo and in vitro. The protective mechanism may be closely related to the regulation of metabolic enzymes, thereby inhibiting apoptosis and ROS production.

Effects of ophiopogonin D on fatty acid metabolic enzymes in cardiomyocytes / 中国中药杂志

To explore the effect of ophiopogonin D on main fatty acid metabolic enzymes in human cardiomyocyte AC-16,so as to provide reference for cardiovascular protection mechanism and safe clinical application of Ophiopogon japonicus.CCK-8 (cell counting kit-8) was used to detect the effect of different concentrations of ophiopogonin D on the viability of cardiomyocytes.Meanwhile,the effect of different concentrations of ophiopogonin D on the morphology and quantity of cardiomyocytes was observed under microscope.The effect of ophiopogonin D on the mRNA expression of CYP2J2,CYP4F3,CYP4A11,CYP4A22 and CYP4F2 in cardiomyocytes was detected by RT-PCR.Western blot was used to detect the protein expression of CYP4F3 in different concentrations of ophiopogonin D.Compared with the control group,low-concentration ophiopogonin D had no effect on the viability of cardiomyocytes.However,ophiopogonin D with a concentration of higher than 20μmol·L~(-1)could promote the viability.Under the microscope,ophiopogonin D with a concentration of below 100μmol·L~(-1)had no significant effect on the morphology and number of cardiomyocytes.RT-PCR results showed that compared with the control group,5μmol·L~(-1)ophiopogonin D could slightly up-regulate mRNA expressions of CYP2J2 and CYP4F3,while high-concentration ophiopogonin D (10 and 20μmol·L~(-1)) could significantly induce mRNA expressions of CYP2J2and CYP4F3 in a dose-dependent manner (P<0.05).The same concentration of ophiopogonin D had a little effect on the mRNA expressions of CYP4A11,CYP4A22 and CYP4F2.Western blot results showed that 20μmol·L~(-1)ophiopogonin D could significantly induce the protein expression of CYP4F3 in a dose-dependent manner (P<0.05).Based on the above results,ophiopogonin D (less than100μmol·L~(-1)) has no effect on the viability of AC-16 cardiomyocytes.Ophiopogonin D (less than 100μmol·L~(-1)) can selectively induce the expressions of CYP2J2 and CYP4F3,regulate the metabolic pathway of fatty acid signaling molecules,and thus protecting the cardiovascular system.

Impact of metabolic enzymes overexpression on transient expression of anti-hLAG3 by CHO cells / 生物工程学报

To enhance recombinant protein production by CHO cells, We compared the impact of overexpression of metabolic enzymes, namely pyruvate carboxylase 2 (PYC2), malate dehydrogenase Ⅱ (MDH2), alanine aminotransferase Ⅰ (ALT1), ornithine transcarbamylase (OTC), carbamoyl phosphate synthetase Ⅰ (CPSⅠ), and metabolism related proteins, namely taurine transporter (TAUT) and Vitreoscilla hemoglobin (VHb), on transient expression of anti-hLAG3 by ExpiCHO-S. Overexpression of these 7 proteins could differentially enhance antibody production. OTC, CPSI, MDH2, and PYC2 overexpression could improve antibody titer by 29.2%, 27.6%, 24.1%, and 20.3%, respectively. Specifically, OTC and MDH2 could obviously improve early-stage antibody production rate and the culture period was shortened by 4 days compared with that of the control. In addition, OTC and MDH2 had little impact on the affinity of anti-hLAG3. In most cases, overexpression of these proteins had little impact on the cell growth of ExpiCHO-S. MDH2 and ALT1 overexpression in H293T cells could also improve antibody production. Overall, overexpression of enzymes involved in cellular metabolism is an effective tool to improve antibody production in transient expression system.

Advances in pharmacogenomics of new oral anticoagulants / 第二军医大学学报

Novel oral anticoagulants (NOACs) play an important role in the prevention and treatment of cardiovascular and cerebrovascular thrombosis. Different individuals have different pharmacokinetic parameters in vivo after taking the same dose of NOACs, which may be related to gene polymorphisms of transporters and metabolic enzymes involved in the in vivo process of NOACs. Compared with drug transporters, gene polymorphisms of drug metabolizing enzymes have a greater impact on the pharmacokinetic properties of NOACs, but there have been few related studies up to now. In this paper we summarized the effects of gene polymorphisms on the pharmacokinetic properties of NOACs..

Advances on metabolizing enzyme and transporter mediated potential interactions between ciprofloxacin and Chinese materia medica / 中草药

The combination of Chinese and Western medicine is common in clinical practice. Ciprofloxacin is one of the most commonly used fluoroquinolones for the treatment of infectious diseases. In order to improve the therapeutic effect of infectious diseases or cope with patients with multiple diseases at the same time, the combination of ciprofloxacin with one or more traditional Chinese medicines is more common. The herb-drug interactions produced by the combination of Chinese materia medica and ciprofloxacin may play an active role in increasing efficacy and reducing toxicity, and may also lead to treatment failure or adverse reactions. The herb-drug interaction mechanisms will occur in the course of absorption (A), distribution (D), metabolism (M), and excretion (E). The effects of drug-metabolizing enzymes and transporters on the ADME process of ciprofloxacin have received much attention in recent years. Therefore, this paper reviews the potential interaction between common Chinese medicine and ciprofloxacin from the perspective of drug-metabolizing enzymes and transporters. It is expected to provide the basis on the rational use of ciprofloxacin and Chinese materia medica.

Effects of low dose persistent organic pollutants on rats / 预防医学

Objective @#To evaluate the health effects of persistent organic pollutants（POPs）on body weight,food intake,internal organs,blood biochemistry,metabolic enzymes and antioxidant ingredients of rats. @*Methods @#Sixteen healthy Sprague-Dawley（SD）rats were randomly divided into the experimental group exposed to 10 mL/kg mixture of POPs（10 ng/mL PCBs,5 ng/mL PBDEs,1 ng/mL PCDD/F）everyday for 28 days by gavage,and the control group exposed to the same volume of soybean oil in the same way. Body weight and food intake of the rats were recorded regularly;blood routine and biochemical indices were detected;liver,kidney,spleen and testicles（ovary）of the rats were weighed to calculate organ coefficients;metabolic enzymes and antioxidant ingredients were detected from livers of the rats. @*Results @#No obviously abnormal symptoms and no deaths were found in both groups. Compared to the control group,the weekly food intake in the experimental group increased more for there was an interaction between grouping and time（P< 0.05）. The ratio of liver to body weight of male rats in the experimental group was higher than that in the control group [（3.87± 0.19）% vs.（3.53± 0.06）%,P< 0.05]. The haemoglobin and red blood cell of female rats in the experimental group were lower than those in the control group[（145.25± 6.18）g/L vs.（154.50± 4.20）g/L;（6.90± 0.14）× 1012/L vs.（7.39± 0.24）× 1012/L;both P< 0.05]. The glutathione-S-transferase（GST）of female rats in the experimental group was higher than that in the control group [（13.37± 1.05）U/mgprot vs.（9.43± 1.08）U/mgprot,P< 0.05]. The cytochrome P4501A1of rats in the experimental group was higher than that in the control group [female：（88.23± 5.81）ng/mgprot vs.（73.85± 5.86）ng/mgprot;male：（96.80± 13.32）ng/mgprot vs.（ 72.20± 2.01）ng/mgprot;both P< 0.05].@*Conclusion @#After exposed to low dose of POPs,the cytochrome P4501A1 increased in all rats,the liver to body weight ratio increased in male rats,GST activity increased while red blood cell and haemoglobin decreased in female rats,which indicated possible body damages in rats.

2018 DMPK research progress in China / 药学学报

This paper summarizes research progresses of Chinese scholars in the field of drug metabolism and pharmacokinetics (DMPK) in 2018. Chinese scholars focused on drug metabolizing enzymes and transporters, and carried out studies on the mechanisms of drug metabolism and transport of active molecules. Topics of research included regulatory mechanisms of drug metabolizing enzymes or transporters, and their implications in drug development and disease etiology or progression. Here, we summarized studies on drug toxicity based on drug metabolism or transport, rational drug use in the clinic, drug metabolism mediated by intestinal flora, metabolism of traditional Chinese medicines, and new technologies or models in DMPK. In recent years, the research focus of drug metabolism in China has transformed from serving for new drug discovery and rational use, to innovation driven and mechanism oriented research. The domestic research topics and technology utilization are gradually aligning with the international conventions.

Corrigendum: Effects of Aqueous Fraction of Ethanolic Extract of Balanites aegyptiaca Stem-bark on Glucose Metabolic Enzymes in Streptozotocin-induced Diabetic Rats

Aims:The study examines effect of aqueous-fraction of ethanolic extractof Balanites aegyptiacastem-bark on enzymes of glucose metabolism in streptozotocin (STZ)-induced diabetic rats in a bid to ascertain its anti-hyperglycemic and possible mechanism of action.Methodology:Diabetes was induced in male rats by intra-peritoneal injection of 60 mg/kg body weight of STZ. Dried powdered Balanitesaegyptiacastem-bark was defatted with hexane and extracted using ethanol followed by solvent-solvent fractionation with water and ethyl acetate. The aqueous fraction (ASF) obtained was subjected to acute toxicity on wistar rats using a gradient dosage, where 1/10thof lethal dose was calculated and used for the study. It was orally administered at a dose of 400 mg/kg body weight of diabetic rats, metformin (200 mg/kg body wt) serve as reference drug and diabetic/normal untreated rats received 10 % dimethyl sulfurdioxide for the 28 days treatment period. On day 29th, rats were sacrificed; blood and liver samples were collected. Liver tissues were homogenized, centrifuged and the supernatants were used for assay of glucose metabolic enzymes while serum was used for biochemical markers estimations.Results:Results obtained showed no death or lethal effect in the acute toxicity study up to a dose of 4000 mg/kg body wt. Therefore, the LD50value was considered to be more than 4000 mg/kg body wt.Streptozotocin-induced diabetic rats treated with ASF showed a significant (P<0.05) reversal effect in activities of the glucose metabolic enzymes assayed compare to untreated diabetic rats. Glucokinase activity was enhanced (2.98±2.23U/min/mg Protein) against untreated diabetic (2.22±0.02 U/min/mg Protein) as well as glycogen synthase (12.48±0.11x10-2U/min/mg Protein) against untreated diabetic (9.41±0.34x10-2U/min/mg Protein. Glucose-6-phosphatase activity was suppressed in the diabetic rats received ASF (0.26±0.03 U/min/mg Protein) compare to the untreated diabetic (1.44±0.05 U/min/mg Protein). Glycogen content of the treated diabetic ratswas elevated to 13.77±0.32 mg/g liver against the diabetic untreated rats (10.69±0.32 mg/g liver).A significant reduction in fasting blood glucose was recorded from the ASF treated diabetic rats (290.4±18.4mg/dL) compared to diabetic untreated rats (336.0±11.9mg/dL). Conclusion: The study suggested that Balanites aegyptiacastem-bark may contained compound(s) that has the capacity to reverse the activity of glucose metabolic enzymes to exert antihyperglycemic activity.

Hepatotoxicity of Eight Components of Radix Polygonum multiflorum Thunb. in Rat Liver Microsome System in Vitro / 中国药学杂志

OBJECTIVE: To investigate the hepatic toxicity of 8 monomers in Polygonum multiflorum using a combination of UDPglucuronic acid transferase 1A1(UGT1A1 enzyme). METHODS: Bilirubin was used as the substrate for UGT1A1. Incubation method in RLM in vitro was adopted to test the apparent inhibition constants(Ki) of different components. Furthermore the structure-activity relationship between the 8 components and UGT1A1 was analyzed. RESULTS: The inhibition effects on UGT1A1 enzyme of the 8 components were in the following sequence: emodin-8-O-glc > emodin > citreorosein > (+) -catechin > gallic acid > physcion > rhein > emodin-6-O-glc. Moreover, there was a structure-activity relationship, and it was presumed that the 6-position hydroxyl group is an active and necessary group. CONCLUSION: The established method in vitro is stable and feasible. Experimental results shows that the enzyme inhibition has structural selectivity, which provides an experimental basis for predicting the enzyme inhibition activity of the analogues of components of Polygonum multiflorum.

Role of hepatic transporters and metabolic enzymes in chemical substances-induced liver injury / 药物评价研究

Liver is an important metabolic and detoxification organ in the body.Hepatic transporters are a series of functional membrane proteins that are extensively expressed in the liver.They are responsible for the uptake of endogenous and exogenous substances such as medicines into hepatocytes and excretion of their metabolic products into bile.Recent studies have provided that transporters and metabolic enzymes play important roles in the chemical substances-induced liver injury,and its various regulatory mechanisms have become hot topics of research.In this paper,we summarize the classification of hepatic transporters and metabolic enzymes and the changes of transporters and metabolic enzymes in the chemical substances-induced liver injury and its regulatory mechanism.

Mechanism of hepatic transporters and metabolic enzymes in cholestatic liver injury / 药物评价研究

Cholestatic liver injury,which is mainly caused by the disruption of bile acids,is common in the clinic.The pathogenesis of cholestatic liver injury is directly related to the changes of bile acid-related transporters,synthetic and metabolic enzymes.Nuclear receptors play a crucial part in cholestatic liver injury by regulating the expression of transporters and metabolic enzymes that maintaining the homeostasis of bile acids.In this review,we focus on the role of hepatic transporters and metabolic enzymes in cholestatic liver injury and the mechanism of nuclear receptors on the regulation of transporters and metabolic enzymes.

Research Progress of ABC Membrane Transporters and Their Regulation in Tumor Drug Resistance and New Mechanism of Detoxification / 中国药学杂志

Multidrug resistance of tumor cells is a material cause of chemotherapy failure, and the overexpression of adenosine triphosphate-binding cassette(ABC) membrane transporters is an important factor in multidrug resistance. Significant progress has been made in reversing multidrug resistance by reducing the expression of drug transporters on tumor cells; inspired by the mechanism of multidrug resistance, speeding up the efflux of poisons by increasing the expression of drug transporters is attracting more and more attention. In this review, We summarized the research progress on mechanism of membrane transp-orters in drug resistance in recent years, and new mechanism of detoxification based on these theories.

Study on Activities of Phase Ⅰ and Ⅱ Drug-metabolic Enzymes in Spleen of Rats with Spleen-Kidney Yang Deficiency Syndrome / 广州中医药大学学报

Objective To study the changes of activities of phase Ⅰ and Ⅱ drug-metabolic enzymes in the spleen of rats with spleen-kidney yang deficiency syndrome.Methods The rat model of spleen-kidney yang deficiency syndrome was established by gastric gavage of Radix et Rhizoma Rhei decoction combined with injection of hydrocortisone for 17 continuous days.And then we detected the activities of 6 kinds of phase Ⅰ drug-metabolic enzymes of CYP2C19,CYP2D6,CYP2C9,CYP1A2,CYP2C8,CYP3A4,and 4 kinds of phase Ⅱ drugmetabolic enzymes of phenol sulfotransferase (PST),uridine diphosphate glucuronosyl transferase 1 (UGT1),glutathione transferase (GST),estrogen sulfotransferase (SULT1E1) in the spleen.Results Compared with the normal control group,the activities of PST,UGT1,GST and SULT1E1 in the model group were significantly decreased (P ＜ 0.05 or P ＜ 0.01),and the activity of CYP1A2 was significantly increased (P ＜ 0.01),while CYP2C19,CYP2D6,CYP2C8,CYP3A4,CYP2C9 enzymes showed no obvious changes(P ＞ 0.05).Conclusion The activities of splenic drug-metabolic enzymes,in particular the phase Ⅱ enzymes,are significantly varied under the state of spleen-kidney yang deficiency.

The research of the hepatotoxicity of polygonum multiflorum on the basic of the inhibition of the UGT1A1 enzyme in vivo and in vitro / 中国药学杂志

OBJECTIVE: To study the hepatotoxicity of Polygonum multiflorum on the basic of the bilirubin metabolism mediated by glucuronidation of UGT1A1 enzyme. METHODS: Inspected the enzyme kinetic parameters after giving the rats Polygonum multiflorum extract orally(in vivo), and added the Polygonum multiflorum extract into the human liver microsome(rat liver microsome; human recombinant UGT1A1 enzyme) to test the hepatotoxicity using the bilirubin as UGT1A1 enzyme substrate, investigating the inhibition of the UGT1A1 enzyme(in vitro). Apparent inhibition constant Ki and enzyme kinetic parameters were used to evaluate the hepatotoxicity. RESULTS: Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in all the three systems in vitro. All the type of inhibition is the competitive inhibition. While Polygonum multiflorum extract has a strong inhibiton to the UGT1A1 enzyme in vivo, but the type of inhibition is the uncompetitive inhibition. CONCLUSION: The method we had established in our study provides a new idea and a new method to evaluate the hepatotoxicity and the safety of Chinese herbs.

Post-transcription regulation of drug metabolic enzymes by miRNAs / 中国药理学通报

microRNAs ( miRNAs) are a family of short non-cod-ing RNAs that regulate the expression of target genes by binding to complementary regions. The miRNAs expression is readily al-tered by drugs, carcinogens, hormones, stress or diseases, and that might lead to changes in the drug metabolism, pharmacoki-netics or potency. Moreover, the evaluation of drug metabolic enzyme-related miRNAs would provide useful information for per-sonalized medicine. This review describes the current knowledge on the post-transcription regulation of drug metabolic enzymes by miRNAs.

Advances in study on compatibility of licorice and its mechanism of detoxification based on pharmacokinetics / 中草药

Licorice is one of Chinese materia medica (CMM) widely used in Chinese medicinal formulae as assistant and guiding medicines, it plays a role in restricting the main drug's toxicity and moderating the property of herbs. Licorice is regarded as a herb that can moderate the property of each herb and remove the hundreds of toxicants. Based on the above characteristics, toxic CMM is always used with licorice. However, the mechanism of the compatibility of licorice is not very clear. It is a good way for us to understand the principle and law of the compatibility of licorice, and to know the relationship between the process and compatibility detoxifying mechanism of licorice through studying on how the licorice has an effect on intracorporal process of the main components in the toxic CMM. The paper mainly summarizes the study on the pharmacokinetics of toxic CMM by compatibility of licorice and its mechanism of pharmacokinetic detoxification.

Progress in Genetic Polymorphism of Related Metabolic Enzymes Influencing Individualized Thiopurine Therapy / 中国药师

Thiopurines, one kind of immunosuppressants, represent an effective and widely prescribed therapy in clinic. Howev-er, the narrow therapeutic window and pharmacokinetic individual differences are always the problems in the clinical application of these drugs. Many factors can affect the metabolism and pharmacological effects of thiopurines, and the genetic polymorphisms of relat-ed metabolic enzymes involved in the metabolic process are considered to be the main factors. Recently, there is growing attention to the influence of the pharmacogenetics of related metabolic enzymes on the pharmacokinetics and pharmacodynamics of thiopurines. Therefore, based on the literature data, this review summarizes the correlation between the genetic polymorphisms of related metabolic enzymes ( TPMT, ITPA, GST, HPRT, XO, IMPDH and GMPS) and efficacy and side effects of thiopurines in order to provide guid-ance for the individualized thiopurine treatment in the clinical practice.

Vitamin C Stimulates Epidermal Ceramide Production by Regulating Its Metabolic Enzymes

Ceramide is the most abundant lipid in the epidermis and plays a critical role in maintaining epidermal barrier function. Overall ceramide content in keratinocyte increases in parallel with differentiation, which is initiated by supplementation of calcium and/or vitamin C. However, the role of metabolic enzymes responsible for ceramide generation in response to vitamin C is still unclear. Here, we investigated whether vitamin C alters epidermal ceramide content by regulating the expression and/or activity of its metabolic enzymes. When human keratinocytes were grown in 1.2 mM calcium with vitamin C (50 mug/ml) for 11 days, bulk ceramide content significantly increased in conjunction with terminal differentiation of keratinocytes as compared to vehicle controls (1.2 mM calcium alone). Synthesis of the ceramide fractions was enhanced by increased de novo ceramide synthesis pathway via serine palmitoyltransferase and ceramide synthase activations. Moreover, sphingosine-1-phosphate (S1P) hydrolysis pathway by action of S1P phosphatase was also stimulated by vitamin C supplementation, contributing, in part, to enhanced ceramide production. However, activity of sphingomyelinase, a hydrolase enzyme that converts sphingomyelin to ceramide, remained unaltered. Taken together, we demonstrate that vitamin C stimulates ceramide production in keratinocytes by modulating ceramide metabolic-related enzymes, and as a result, could improve overall epidermal barrier function.

Anti-bacterial activity of Achatina CRP and its mechanism of action.

The physiological role of C-reactive protein (CRP), the classical acute-phase protein, is not well documented, despite many reports on biological effects of CRP in vitro and in model systems in vivo. It has been suggested that CRP protects mice against lethal toxicity of bacterial infections by implementing immunological responses. In Achatina fulica CRP is a constitutive multifunctional protein in haemolymph and considered responsible for their survival in the environment for millions of years. The efficacy of Achatina CRP (ACRP) was tested against both Salmonella typhimurium and Bacillus subtilis infections in mice where endogenous CRP level is negligible even after inflammatory stimulus. Further, growth curves of the bacteria revealed that ACRP (50 µg/mL) is bacteriostatic against gram negative salmonellae and bactericidal against gram positive bacilli. ACRP induced energy crises in bacterial cells, inhibited key carbohydrate metabolic enzymes such as phosphofructokinase in glycolysis, isocitrate dehydrogenase in TCA cycle, isocitrate lyase in glyoxylate cycle and fructose-1,6-bisphosphatase in gluconeogenesis. ACRP disturbed the homeostasis of cellular redox potential as well as reduced glutathione status, which is accompanied by an enhanced rate of lipid peroxidation. Annexin V-Cy3/CFDA dual staining clearly showed ACRP induced apoptosis-like death in bacterial cell population. Moreover, immunoblot analyses also indicated apoptosis-like death in ACRP treated bacterial cells, where activation of poly (ADP-ribose) polymerase-1 (PARP) and caspase-3 was noteworthy. It is concluded that metabolic impairment by ACRP in bacterial cells is primarily due to generation of reactive oxygen species and ACRP induced anti-bacterial effect is mediated by metabolic impairment leading to apoptosis-like death in bacterial cells.

Effects of altered metabolic enzymes on epigenetic status in gliomas / 实用肿瘤学杂志

Alteration of metabolism and epigenetic status are two new focuses in the field of cancer re -search.Recently,more and more reports have demonstrated that the changes of both metabolic enzymes and al -tered epigenetic status have close interrelationship with the pathogenesis and development of gliomas in human . We discuss here the effects of altered metabolic enzymes on epigenetic status in gliomas based on two important altered metabolic enzymes ,with the aim to unlock the molecular mechanism on how gliomas occur and progress . This newfound molecular mechanism of how altered metabolic enzymes impact on epigenetic status in gliomas may contribute to the identification of novel therapeutic targets to gliomas in the future .