Comparative study on glutathione transferases of rat brain and testis under the stress of phenobarbitol and β-methylcholanthrene

A comparative study was made on the tissue specific expression of glutathione transferases (GST) in brain and testis after exposure of rat to phenobarbitol (PB) and β-methylcholanthrene (MC). Glutathione transferases, a family of multifunctional proteins are involved in intracellular transport processes and in detoxication of electrophilic xenobiotics by catalyzing reactions such as conjugation, isomerization, reduction and thiolysis. On purification, the yield of GST proteins by affinity chromatography was 39% in testis and 32% in brain. The affinity purified testis GSTs were resolved by chromatofocusing into six anionic and four cationic isozymes, and in brain glutathione transferases were resolved into four anionic and three cationic isozymes, suggesting the presence of multiple isozymes with Yc, Yb, Yβ and Yδ in both of them. In testis and brain, these isozymes at identical pI values showed variable functions with a battery of substrates and the cationic isozymes of brain and testis showed identical properties in CHP (cumene hydroperoxide) at pH values of above 7.0. Substrate specificity studies and immunoblot analysis of testis and brain proteins revealed that they play a predominant role in the detoxication of phenobarbitol or β-methylcholanthrene. Expression of the isozymes in testis and brain on exposure to PB and MC indicated elevated subunit variation. In both testis and brain, Yδ of π class was expressed on PB treatment and Yc of α class and Yβ of μ class was expressed in MC treated testis and only Yc was predominantly expressed in MC treated brain. Thus these subunits expression is considered as markers for carcinogenesis and specific to chemical toxicity under phenobarbitol and β-methylcholanthrene stress.

Glutathione S-transferases M1,T1 genotypes and the risk of gastric cancer:A case-control study

AIM: Glutathione S-transferases (GSTs) are involved in the detoxification of many potential carcinogens and appear to play a critical role in the protection from the effects of carcinogens. The contribution of glutathione S-transferases M1 and T1 genotypes to susceptibility to the risk of gastric cancer and their interaction with cigarette smoking are still unclear. The aim of this study was to determine whether there was any relationship between genetic polymorphisms of GSTT1 and GSTT1 and gastric cancer. METHODS: A population based case-control study was carried out in a high-risk area, Changle County, Fujian Province, China. The epidemiological data were collected by a standard questionnaire and blood samples were obtained from 95 incidence gastric cancer cases and 94 healthy controls. A polymerase chain reaction method was used to detect the presence or absence of the GSTT1 and GSTT1 genes in genomic DNA. Logistic regression model was employed in the data analysis. RESULTS: An increase in risk for gastric cancer was found among carriers of GSTT1 null genotype. The adjusted odds ratio (OR) was 2.63 95% Confidence Interval (95% CI) 1.17-5.88, after controlling for age, gender, cigarette smoking, alcohol drinking, and fish sauce intake. The frequency of GSTT1 null genotype in cancer cases (43.16%) was not significantly different from that in controls (50.00%). However, the risk for gastric cancer in those with GSTT1 null and GSTT1 non-null genotype was significantly higher than in those with both GSTT1 and GSTT1 non-null genotype (OR = 2.77, 95% CI 1.15-6.77). Compared with those subjects who never smoked and had normal GSTT1 genotype, ORs were 1.60 (95% CI:0.62-4.19) for never smokers with GSTT1 null type, 2.33 (95% CI 0.88-6.28) for smokers with normal GSTT1, and 8.06 (95% CI 2.83-23.67) for smokers with GSTT1 null type. CONCLUSIONS: GSTT1 gene polymorphisms may be associated with genetic susceptibility of stomach cancer and may modulate tobacco-related carcinogenesis of gastric cancer.

Purification and characterization of rat testicular glutathione S-transferases:role in the synthesis of eicosanoids

Aim: Purification of glutathione S-transferases (GSTs) from rat testis; separation and identificationunits and their role in eicosanoid biosynthesis. Methods: Purification of mt testicular GSTs by affit?phy, employing S-hexylglutathione-linked epoxy-activated Sepharose 6B column and separation of indiby reverse phase-high pressure liquid chromatography (RP-HPLC). Characterization of affinity purified,um dodecyl sulfate-polyacrylamide gel electrophoresis (SDS-PAGE) and Westem blot analysis. The roGSTs in eicosanoid biosynthesis was determined by incubating GSTs with 5, 6-Leukotriene A_4Me (prostaglandin H_2 (PGH_2) and analyzing the products formed on HPLC/TLC. Results: The present stumajority of rat testicular GSTs are of Y_b size (60%) with molecular weight of 27 kDa. The most preunits, however, are GST Y_(n2) (27% ), followed by GST Y_c (24% ) and GST Y_(nl) (20%). These testiculavery high Leukotriene C_4 (LTC_4) synthase activity with 5, 6-Leukotriene A4Me (LTA_4Me) as theprostaglandin D (PGD) synthase activity with prostaglandin H_2 (PGH_2) as the substrate. Conclusion:testicular GSTs are Y_b sized and are involved in the synthesis of eicosanoids like LTC_4 and PGD_2.(Asian J Androl 2000 Dec; 2: 277-282)

Function of hydroxycinnamoyl transferases for the biosynthesis of phenolamides in rice resistance to Magnaporthe oryzae

Phenolamide(PA)metabolites play important roles in the interaction between plants and pathogens.The putrescine hydroxycinnamoyl transferase genes Os PHT3 and Os PHT4 positively regulate rice cell death and resistance to Magnaporthe oryzae.The b ZIP transcription factor APIP5,a negative regulator of cell death and rice immunity,directly binds to the Os PHT4 promoter to regulate putrescine-derived PAs.Whether other hydroxycinnamoyl transferase(HT)genes also participate in APIP5-mediated immunity remains unclear.Surprisingly,we find that genes encoding agmatine hydroxycinnamoyl transferases Os AHT1 and Os AHT2,tryptamine hydroxycinnamoyl transferases Os TBT1 and Os TBT2,and tyramine hydroxycinnamoyl transferases Os THT1 and Os THT2,responsible for the biosynthesis of polyamine-derived PAs are all up-regulated in APIP5-RNAi transgenic plants compared with segregated wild-type rice.Furthermore,both Os AHT1/2 and Os TBT1/2 are induced during M.oryzae infection,showing expression patterns similar to those previously reported for Os THT1/2 and Os PHT3/4.Transgenic plants overexpressing either Os AHT2-GFP or Os TBT1-GFP show enhanced resistance against M.oryzae and accumulated more PA metabolites and lignin compared with wild-type plants.Interestingly,as demonstrated for Os PHT4,APIP5 directly binds to the promoters of Os AHT1/2,Os TBT1/2,and Os THT1/2,repressing their transcription.Together,these results indicate that the HT genes are common targets of APIP5 and that PAs play critical roles in rice immunity.

Gamma-glutamyl transferase 5 overexpression in cerebrovascular endothelial cells improves brain pathology,cognition,and behavior in APP/PS1 mice

In patients with Alzheimer’s disease,gamma-glutamyl transferase 5(GGT5)expression has been observed to be downregulated in cerebrovascular endothelial cells.However,the functional role of GGT5 in the development of Alzheimer’s disease remains unclear.This study aimed to explore the effect of GGT5 on cognitive function and brain pathology in an APP/PS1 mouse model of Alzheimer’s disease,as well as the underlying mechanism.We observed a significant reduction in GGT5 expression in two in vitro models of Alzheimer’s disease(Aβ_(1-42)-treated hCMEC/D3 and bEnd.3 cells),as well as in the APP/PS1 mouse model.Additionally,injection of APP/PS1 mice with an adeno-associated virus encoding GGT5 enhanced hippocampal synaptic plasticity and mitigated cognitive deficits.Interestingly,increasing GGT5 expression in cerebrovascular endothelial cells reduced levels of both soluble and insoluble amyloid-βin the brains of APP/PS1 mice.This effect may be attributable to inhibition of the expression ofβ-site APP cleaving enzyme 1,which is mediated by nuclear factor-kappa B.Our findings demonstrate that GGT5 expression in cerebrovascular endothelial cells is inversely associated with Alzheimer’s disease pathogenesis,and that GGT5 upregulation mitigates cognitive deficits in APP/PS1 mice.These findings suggest that GGT5 expression in cerebrovascular endothelial cells is a potential therapeutic target and biomarker for Alzheimer’s disease.

Inhibitory potential of three Yin-tonification herbal formulas on the activities of human major cytochrome P450 and UDP-glucuronosyltransferases isozymes in vitro

OBJECTIVE:To investigate the influence of Yin-tonification herbal formulas Jaeumganghwa-tang(Ziyin Jianghuo Tang,JEGHT),Ssanghwa-tang(Shuanghe Tang,SHT) and Yukmijihwang-tang(Liuwei Di huang Tang,YMJHT) on the activities of human major cytochrome P450(CYP450 s) and UDP-glucuronosyltransferases isozymes(UGTs) in vitro.METHODS:The activities of CYP450 s(CYP1 A2,CYP3 A4,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6 and CYP2 E1) and UGTs(UGT1 A1,UGT1 A4 and UGT2 B7)were assessed using in vitro fluorescence-and luminescence-based enzyme assays,respectively.The effects of herbal formulas on the activities of CYP450 s and UGTs were presented as IC50 values.RESULTS:JEGHT showed the potent inhibition of the CYP2 D6 activity,with weak inhibition on the activities of CYP1 A2,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 E1,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7.SHT inhibited the activities of CYP1 A2 and CYP2 E1,whereas the negligible inhibition of the activities of CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7 through SHT was observed.YMJHT inhibited CYP2 E1 activity,with a negligible inhibition on the activities of CYP1 A2,CYP2 B6,CYP2 C9,CYP2 C19,CYP2 D6,CYP3 A4,UGT1 A1,UGT1 A4 and UGT2 B7.CONCLUSION:These findings provide information about the potential interactions between three Yin-tonification herbal formulas and conventional drugs.

Gamma-glutamyl transferases： A structural, mechanistic and physiological perspective

Gamma glutamyl transferases （GGT） are highly conserved enzymes that occur from bacteria to humans. They remove terminal y-glutamyl residue from peptides and amides. GGTs play an important role in the homeostasis of glutathione （a major cellular antioxidant） and in the detoxification of xenobiotics in mammals. They are implicated in diseases like diabetes, inflammation, neurodegenerative diseases and cardiovascular diseases. The physiological role of GGTs in bacteria is still unclear. Nothing is known about the basis for the strong conservation of the enzyme across the living system. The review focuses on the enzyme＇s physiology, chemistry and structural properties of the enzyme with emphasis on the evolutionary relationships. The available data indicate that the members of the GGT family share common structural features but are functionally heterogenous.

Kinases and glutathione transferases:selective and sensitive targeting

Kinases,representing almost 500 proteins in the human genome,are responsible for catalyzing the phosphorylation reaction of amino acid residues at their targets.As the largest family of kinases,the protein tyrosine kinases(PTKs)have roles in controlling the essential cellular activities,and their deregulation is generally related to pathologic conditions.The recent efforts on identifying their signal transducer or mediator role in cellular signaling revealed the interaction of PTKs with numerous enzymes of different classes,such as Ser/Thr kinases(STKs),glutathione transferases(GSTs),and receptor tyrosine kinases(RTKs).In either regulation or enhancing the signaling,PTKs are determined in close interaction with these enzymes,under specific cellular conditions,such as oxidative stress and inflammation.In this concept,intensive research on thiol metabolizing enzymes recently showed their involvement in the physiologic functions in cellular signaling besides their well known traditional role in antioxidant defense.The shared signaling components between PTK and GST family enzymes will be discussed in depth in this research review to evaluate the results of recent studies important in drug targeting for therapeutic intervention,such as cell viability,migration,differentiation and proliferation.

Single-neuron neurodegeneration as a degenerative model for Parkinson’s disease

The positive effect of levodopa in the treatment of Parkinson’s disease,although it is limited in time and has severe side effects,has encouraged the scientific community to look for new drugs that can stop the neurodegenerative process or even regenerate the neuromelanin-containing dopaminergic nigrostriatal neurons.Successful preclinical studies with coenzyme Q10,mitoquinone,isradipine,nilotinib,TCH346,neurturin,zonisamide,deferiprone,prasinezumab,and cinpanemab prompted clinical trials.However,these failed and after more than 50 years levodopa continues to be the key drug in the treatment of the disease,despite its severe side effects after 4–6 years of chronic treatment.The lack of translated successful results obtained in preclinical investigations based on the use of neurotoxins that do not exist in the human body as new drugs for Parkinson’s disease treatment is a big problem.In our opinion,the cause of these failures lies in the experimental animal models involving neurotoxins that do not exist in the human body,such as 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine and 6-hydroxydopamine,that induce a very fast,massive and expansive neurodegenerative process,which contrasts with the extremely slow one of neuromelanin-containing dopaminergic neurons.The exceedingly slow progress of the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s patients is due to(i)a degenerative model in which the neurotoxic effect of an endogenous neurotoxin affects a single neuron,(ii)a neurotoxic event that is not expansive and(iii)the fact that the neurotoxin that triggers the neurodegenerative process is produced inside the neuromelanin-containing dopaminergic neurons.The endogenous neurotoxin that fits this degenerative model involving one single neuron at a time is aminochrome,since it(i)is generated within neuromelanin-containing dopaminergic neurons,(ii)does not cause an expansive neurotoxic effect and(iii)triggers all the mechanisms involved in the neurodegenerative process of the nigrostriatal neurons in idiopathic Parkinson’s disease.In conclusion,based on the hypothesis that the neurodegenerative process of idiopathic Parkinson’s disease corresponds to a single-neuron neurodegeneration model,we must search for molecules that increase the expression of the neuroprotective enzymes DT-diaphorase and glutathione transferase M2-2.It has been observed that the activation of the Kelch-like ECH-associated protein 1/nuclear factor(erythroid-derived 2)-like 2 pathway is associated with the transcriptional activation of the DT-diaphorase and glutathione transferase genes.

Rethinking neurodegenerative diseases:neurometabolic concept linking lipid oxidation to diseases in the central nervous system

Currently,there is a lack of effective medicines capable of halting or reve rsing the progression of neurodegenerative disorde rs,including amyotrophic lateral sclerosis,Parkinson s disease,multiple sclerosis,or Alzheimer s disease.Given the unmet medical need,it is necessary to reevaluate the existing para digms of how to to rget these diseases.When considering neurodegenerative diseases from a systemic neurometabolic perspective,it becomes possible to explain the shared pathological features.This innovative approach presented in this paper draws upon exte nsive research conducted by the authors and researchers worldwide.In this review,we highlight the importance of metabolic mitochondrial dysfunction in the context of neurodegenerative diseases.We provide an overview of the risk factors associated with developing neurodegenerative disorders,including genetic,epigenetic,and environmental fa ctors.Additionally,we examine pathological mechanisms implicated in these diseases such as oxidative stress,accumulation of misfolded proteins,inflammation,demyelination,death of neurons,insulin resistance,dysbiosis,and neurotransmitter disturbances.Finally,we outline a proposal for the restoration of mitochondrial metabolism,a crucial aspect that may hold the key to facilitating curative therapeutic interventions for neurodegenerative disorders in forthcoming advancements.

Transformation of marginal zone lymphoma into high-grade B-cell lymphoma expressing terminal deoxynucleotidyl transferase:A case report

BACKGROUND High-grade B-cell lymphoma(HGBL)is an unusual malignancy that includes myelocytomatosis viral oncogene(MYC),B-cell lymphoma-2(BCL-2),and/or BCL-6 rearrangements,termed double-hit or triple-hit lymphomas,and HGBL-not otherwise specific(HGBL-NOS),which are morphologically characteristic of HGBL but lack MYC,BCL-2,or BCL-6 rearrangements.HGBL is partially transformed by follicular lymphoma and other indolent lymphoma,with few cases of marginal zone lymphoma(MZL)transformation.HGBL often has a poor prognosis and intensive therapy is currently mainly advocated,but there is no good treatment for these patients who cannot tolerate chemotherapy.CASE SUMMARY We reported a case of MZL transformed into HGBL-NOS with TP53 mutation and terminal deoxynucleotidyl transferase expression.Gene analysis revealed the gene expression profile was identical in the pre-and post-transformed tissues,suggesting that the two diseases are homologous,not secondary tumors.The chemotherapy was ineffective and the side effect was severe,so we tried combination therapy including venetoclax and obinutuzumab.The patient tolerated treatment well,and reached partial response.The patient had recurrence of hepatocellular carcinoma and died of multifunctional organ failure.He survived for 12 months after diagnosis.CONCLUSION Venetoclax combined with obinutuzumab might improve the survival in some HGBL patients,who are unsuitable for chemotherapy.

Case Report: Carnitine Palmitoyl Transferase II (CPT II) Deficiency

Carnitine Palmitoyl Transferase II (CPTII) is a very important enzyme that helps with the oxidation of long-chain fatty acid to produce energy. Deficiency in CPTII will lead to energy deficiency in the case of fasting and the accumulation of the long chain fatty in the body. There are three types of CPT II deficiency, the myopathic form, the severe infantile hepatocardiomuscular form and the lethal neonatal form. They are all inherited as an autosomal recessive. Diagnosis of the CPTII are 1) tandem mass spectrometry (MS/MS) in adult form and 2) CPTII polymorphism (F352C), which is linked to reducing the activity of CPTII in infantile form [1]. Glucose is the primary management and medium-chain fatty acid is an alternative due to the bypass of the CPTII enzyme in the pathway. For the prevention of CPTII deficiency are to avoid long chain fatty acid (C12-fatty acid), fasting, prolonged exercise, known triggers, and certain medications such as anti-epileptics and general anesthesia. During the rhabdomyolysis and myoglobinuria attack, it is very important to maintain hydration to avoid acute renal failure. If, however, renal failure occurs, dialysis is recommended. We present a case of a 27-year-old African American woman with the significant past medical history of CPT II deficiency leading to recurrent rhabdomyolysis and myoglobinuria. Together with all the research studies from diagnosis to treatment of CPTII deficiency will help in clinical management of patients. And this case report will add to the existing case reports of patients who have CPTII deficiency in terms of how we diagnose, how we treat, and how we prevent symptoms from re-occurring.

Advances in drug resistance of triple negative breast cancer caused by pregnane X receptor

Breast cancer is the most common malignancy in women worldwide.Triplenegative breast cancer(TNBC),refers breast cancer negative for estrogen receptor,progesterone receptor and human epidermal growth factor receptor 2,characterized by high drug resistance,high metastasis and high recurrence,treatment of which is a difficult problem in the clinical treatment of breast cancer.In order to better treat TNBC clinically,it is a very urgent task to explore the mechanism of TNBC resistance in basic breast cancer research.Pregnane X receptor(PXR)is a nuclear receptor whose main biological function is to participate in the metabolism,transport and clearance of allobiological agents in PXR.PXR plays an important role in drug metabolism and clearance,and PXR is highly expressed in tumor tissues of TNBC patients,which is related to the prognosis of breast cancer patients.This reviews synthesized the important role of PXR in the process of high drug resistance to TNBC chemotherapeutic drugs and related research progress.

Effect of Boschniakia rossica on expression of GSTP,p53 and p21^(ras)proteins in early stage of chemical hepatocarcinogenesis and its anti-inflammatory activities in rats

AIM To investigate the effect of Boschniakiarossica（BR）extract on expression of GST-P,p53 and p21rasproteins in early stage of chemicalhepatocarcinogenesis in rats and its anti-inflammatory activities.METHODS The expression of tumor marker-placental form glutathione S-transferase（GST-P）,p53 and p21rasproteins were investigated byimmunohistochemical techniques and ABCmethod.Anti-inflammatory activities of BR werestudied by xylene and croton oil-induced mouseear edema,carrageenin,histamine and hotscald-induced rat pow edema,adjuvant-inducedrat arthritis and cotton pellet-induced mousegranuloma formation methods.RESULTS The 500 mg/kg of BR-H2O extractfractionated from BR-Methanol extract hadinhibitory effect on the formation of DEN-inducedGST-P-positive foci in rat liver（GST-P stainingwas 78% positive in DEN+AAF group vs 20%positive in DEN+AAF+BR group,P【0.05）andthe expression of mutant p53 and p21rasproteinwas lower than that of hepatic preneoplasticlesions（33% and 22% positive respectively inDEN+AAF group vs negative in DEN+AAF+BRgroup）.Both CH2Cl2 and H2O extracts from BRhad anti-inflamatory effect in xylene and crotonoil-induced mouse ear edema（inhibitory rateswere 26%-29% and 35%-59%,respectively）. BR-H2O extract exhibited inhibitory effect incarrageenin,histamine and hot scald-inducedhind paw edema and adjuvant-induced arthritis inrats and cotton pellet-induced granulomaformation in mice.CONCLUSION BR extract exhibited inhibitory effect on formation of preneoplastic hepatic foci in early stage of rat chemical hepato-carcinogenesis. Both CH2CI2 and H2O extracts from BR exerted anti-inflammatory effect in rats and mice.

GSTM1,GSTT1,GSTP1 and CYP1A1 genetic polymorphisms and susceptibility to esophageal cancer in a French population:Different pattern of squamous cell carcinoma and adenocarcinoma

AIM:To evaluate the association between CYP1A1 and GSTs genetic polymorphisms and susceptibility to esophageal squamous cell carcinoma(SCC)and esophageal adenocarcinoma(ADC)in a high risk area of northwest of France. METHODS:A case-control study was conducted to investigate the genetic polymorphisms of these enzymes (CYPIAI*2C and GSTP1 exon 7 Val alleles,GSTMI*2/*2 and GSTTl *2/*2 null genotypes).A total of 79 esophageal cancer cases and 130 controls were recruited. RESULTS:GSTMI*2/*2 and CYPIAI*IA/*2C genotype frequencies were higher among squamous cell carcinomas at a level dose to statistical significance(OR =1.83,95% CI 0.88-3.83,P=0.11;OR=3.03,95% CI 0.93-9.90,P=0.07, respectively).For GSTP1 polymorphism,no difference was found between controls and cases,whatever their histological status.Lower frequency of GSTT1 deletion was observed in ADC group compared to controls with a statistically significant difference(OR=13.31,95% CI 1.66-106.92,P<0.01). CONCLUSION:In SCC,our results are consistent with the strong association of this kind of tumour with tobacco exposure.In ADC,our results suggest 3 distinct hypotheses: (1)activation of exogenous procarcinogens,such as small halogenated compounds by GSTT1;(2)contribution of GSTT1 to the inflammatory response of esophageal mucosa,which is known to be a strong risk factor for ADC, possibly through leukotriene synthesis;(3)higher sensitivity to the inflammatory process associated with intracellular depletion of glutathione.

Expression of Presenilin-2 and Glutathione S Transferase π and Their Clinical Significance in Breast Infiltrating Ductal Carcinoma

To investigate the expressions of presenilin-2 (PS2) and glutathione Stransferase π (GSTπ) and their roles in prognosis and therapy of breast infiltrating ductalcarcinoma. Methods: The paraffin-embedded specimens of 210 patients with breast infiltrating ductalcarcinoma were examined by using LSAB immunohistochemistry for the expression of PS2 and GSTπ.Results: The expression rate of PS2 and GSTπ was 49.5% (104/210) and 48.1% (101/210) respectively.The 5-year and 10-year postoperative survival rates in 4 groups, from high to low, were group 1 (PS2positive expression/GSTπ negative expression), group 2 (PS2 positive expression/GSTπ positiveexpression), group 3 (PS2 negative expression/GSTπ negative expression) and group 4 (PS2 negativeexpression/GSTπ positive expression) in turn. Conclusion: The prognosis of the group 1 was thebest, followed by the group 2, group 3 and group 4 in turn. These results suggested that thereasonable use of endocrinotherapy and chemotherapy for patients with breast infiltrating ductalcarcinoma is necessary.

Human GSTs Polymorphisms in the Hakka Population of South China and Their Associations with Family History of Several Chronic Diseases

Objective To investigate the associations of genetic polymorphisms in GSTs genes of the Hakka population of south China with family histories of certain chronic diseases.Methods Five hundred and thirty‐nine healthy Hakka natives of Meizhou city of Guangdong province in south China were involved.The genotypes of GSTM1,GSTT1,GSTP1,GSTM3,and GSTA1 were determined using PCR and restriction fragment length polymorphism analysis.The observed polymorphisms were analyzed by Chi‐square and Hardy‐Weinberg equilibrium tests.Logistic regression analysis was used to determine the associations of the distributions of GST genotypes with family history of certain chronic diseases.Results The distributions of polymorphisms in GSTP1,GSTM3,and GSTA1 conformed to the Hardy‐Weinberg equilibrium.Compared to the Cantonese,the Hakka had a lower distribution of the GSTM3 deletion genotype （3.15% vs.11.9%）.A weak association was observed between the GSTM1 genetic polymorphism and family history of hypertension.Alcohol drinkers had a higher frequency of the null‐GSTM1 genotype,while smokers had a higher frequency of a variant GSTP1 genotype.Conclusion The results suggest that the Hakka is a special and distinctive Han Chinese ethnic group with different GSTs genetic polymorphisms.Smoking and drinking might be related to the distribution of GST genotypes.

Challenges in diagnosing mesenteric ischemia

Early identification of acute mesenteric ischemia (AMI) is challenging. The wide variability in clinical presentation challenges providers to make an early accurate diagnosis. Despite major diagnostic and treatment advances over the past decades, mortality remains high. Arterial embolus and superior mesenteric artery thrombosis are common causes of AMI. Non-occlusive causes are less common, but vasculitis may be important, especially in younger people. Because of the unclear clinical presentation and non-specific laboratory findings, low clinical suspicion may lead to loss of valuable time. During this diagnostic delay, progression of ischemia to transmural bowel infarction with peritonitis and septicemia may further worsen patient outcomes. Several diagnostic modalities are used to assess possible AMI. Multi-detector row computed tomographic angiography is the current gold standard. Although computed tomographic angiography leads to an accurate diagnosis in many cases, early detection is a persistent problem. Because early diagnosis is vital to commence treatment, new diagnostic strategies are needed. A non-invasive simple biochemical test would be ideal to increase clinical suspicion of AMI and would improve patient selection for radiographic evaluation. Thus, AMI could be diagnosed earlier with follow-up computed tomographic angiography or high spatial magnetic resonance imaging. Experimental in vitro and in vivo studies show promise for alpha glutathione S transferase and intestinal fatty acid binding protein as markers for AMI. Future research must confirm the clinical utility of these biochemical markers in the diagnosis of mesenteric ischemia.

Expression and alterations of different molecular form γ-glutamyl transferase and total RNA concentration during the carcinogenesis of rat hepatoma

ＩＮＴＲＯＤＵＣＴＩＯＮＣａｒｃｉｎｏｇｅｎｅｓｉｓｉｓｃｌｏｓｅｌｙｒｅｌａｔｅｄｗｉｔｈＤＮＡｓｙｎｔｈｅｓｉｓａｎｄｈｙｐｅｒｍｅｔａｂｏｌｉｓｍｏｆｎｕｃｌｅｉｃａｃｉｄ．γｇｌｕｔａｍｙｌｔｒａｎｓｆｅｒａｓｅ（ＧＧＴ，ＥＣ２．３．２．２...

Increased liver markers are associated with higher risk of type 2 diabetes

AIM: To investigate the association between liver markers and the risk of type 2 diabetes(T2DM) and impaired fasting glucose(IFG).METHODS: A total of 8863 participants(3408 men and 5455 women) over 30 years of age were analyzed from the fifth Korean National Health and Nutrition Examination Survey(2010-2011). The associations of serum liver markers such as aspartate aminotransferase(AST), alanine aminotransferase(ALT), AST/ALT, and gamma-glutamyltransferase(GGT) with T2 DM and IFG were analyzed using logistic regression models. Participants were divided into sex-specific quartiles on the basis of liver markers.RESULTS: The prevalence of T2 DM and IFG were 11.3% and 18.3%. Increasing quartiles of ALT and GGT were positively and AST/ALT were negatively correlated with T2 DM and IFG. Analysis of the liver marker combinations showed that if any two or more markers were in the highest risk quartile, the risks of both T2 DM and IFG increased significantly. The risk was greatest when the highest ALT and GGT and lowest AST/ALT quartile were combined, with the riskof T2 DM at 3.21(95%CI: 1.829-5.622, P < 0.001) in men and 4.60(95%CI: 3.217-6.582, P < 0.001) in women. Men and women with the highest AST and ALT and lowest AST/ALT quartile had a 1.99 and 2.40 times increased risk of IFG.CONCLUSION: Higher levels of GGT and ALT and lower AST/ALT within the physiological range are independent, additive risk factors of T2 DM and IFG.