Γ-glutamyl Transpeptidase Activity Research Articles

A ratiometric fluorescent probe for the detection of γ-glutamyl transpeptidase activity and its application in garlic

A novel ratiometric fluorescent probe for the detection of γ-glutamyl transpeptidase (GGT) activity was developed. The recognition of GGT by this probe is achieved by its enzymatic hydrolysis of peptide bonds in the probe. Under optimized conditions, the probe exhibited obvious ratiometric fluorescence responsiveness after interaction with GGT, avoiding potential background interference. The linear concentration range was 0.0350–2 U / mL, with good selectivity and stability. Under a 365 nm UV lamp, as the concentration of GGT increased, the probe aqueous solution gradually changed from dark blue to light blue. In addition, the B/G value of the probe's solution and the GGT activity were linearly correlated. More significantly, the probe was able to effectively identify the GGT activity of garlic.

A sensitive benzothiazole fluorescent probe for the detection of γ-glutamyl transpeptidase activity and its application.

A sensitive benzothiazole fluorescent probe (PBZO) for the detection of γ-glutamyl transpeptidase (GGT) activity was developed. Based on the enzymatic hydrolysis of peptide bonds by glutamyl transpeptidase, it can be specifically recognized by PBZO. The PBZO has a good linear relationship with different gradients of GGT activity at the emission wavelength of 560 nm, the Stokes shift reached 215 nm, and the detection limit of GGT activity is 0.1644 U/ml. With the increase of GGT concentration in the probe solution, the color of the solution gradually changed from orange to dark yellow under the 365 nm UV lamp. The same color change was also observed on the probe test paper. In addition, there is a linear relationship between the GGT activity and the R-value of the probe solution. More importantly, the probe has a good recovery rate in serum. Therefore, this probe can be used as a convenient tool for detecting GGT activity.

Supplementation of Saccharomycopsis fibuligera nucleotides in soybean-based diets enhanced growth, intestinal health, and reduced inflammatory responses of turbot juveniles (Scophthalmus maximus L.)

In this study, Saccharomycopsis fibuligera nucleotides (SFN) were extracted for exploring the influence on growth, inflammatory response and intestinal health level in turbot juveniles (initial weight 7.16 ± 0.01 g) for 10 weeks. Five isonitrogenous and isolipidic experimental feeds were formulated to include fishmeal-based diet (FM) that contained no SFN, while the other four soybean meal-based diet (SBM), that replaced 30 % FM, contained 0.25, 0.5 or 0.75 % SFN hereafter referred to as SBM0.25, SBM0.5 and SBM0.75, respectively. The feed efficiency exhibited a significantly quadratic or linear increase with the increase of SFN intake and the values reached the peak in the SBM0.5 treatment (P < 0.05). With the increase of SFN supplementation, the specific growth rate presented a significantly linear increase tendency (P < 0.05), and reached a peak in the SBM0.5 treatment. The hepatic antioxidant ability of turbot juveniles was significantly linear or quadratic promoted with dietary SFN supplementation in SBM-based diets (P < 0.05). Moreover, activities of plasma transaminases and γ-glutamyl transpeptidase of turbots showed significantly linear and quadratic decreasing trends with the SFN supplementation increasing (P < 0.05). The hepatic pro-inflammatory factor mRNA expressions were significantly linear or quadratic down-regulated and the anti-inflammatory factor mRNA expression was significantly linear and quadratic up-regulated with the SFN supplementation increasing (P < 0.05). Moreover, the height of villi and microvilli, the thickness of the muscularis and the tight junction proteins mRNA expression level exhibited significantly linear or quadratic increasing trends with the increasing dietary SFN supplementation (P < 0.05). The relative abundance of Lactobacillus plantarum of hindgut was significantly higher of fish fed the SBM0.75 diet compared with the SBM treatment. In conclusion, SFN supplementation was beneficial to the growth and health level of turbot juveniles, the appropriate amount of SFN supplemented was above 0.5 % in this study.

A dual-site fluorescent probe for the detection of γ-glutamyl transpeptidase activity and its application in garlic

Developing convenient γ-glutamyl transpeptidase (GGT) activity detection methods is of great significance for soaking Laba garlic and human diseases detection. A dual-site fluorescent probe (probe 1) was developed for detection the activity of GGT. Probe 1 could recognize GGT by the enzymatic hydrolysis of peptide bond by GGT. There has a linear relationship between the fluorescence intensity of probe 1 at 416 nm and the activity of GGT. And the color of the probe solution gradually changed from colorless to blue with the increase of GGT activity under 365 nm ultraviolet light. Importantly, it has a linear relationship between the activity of GGT and the blue (B) value of probe solution photo. Therefore, probes can serve as a convenient tool for detecting GGT activity. More importantly, the probe has been successfully applied to detect of GGT activity in garlic.

Simple isomeric pyridine-based fluorescence-off probes for in vitro monitoring γ-glutamyltranspeptidase activity: Design, synthesis and application

γ-Glutamyltranspeptidase (GGT) is a cell surface-associated enzyme, which has been proven to be closely related to many diseases. Thus, development of simple and effective GGT-activatable fluorescent probes for early diagnosis of diseases is of great significance. Herein, a series of simple isomeric pyridine-based GGT-activatable fluorescent probes has been successfully designed and synthesized. The preliminary experimental results indicate that Py-GGT-1 has a significant fluorescence response to GGT via a rare fluorescence-off approach. Further fluorescence response experiments, such as the time-/dose-dependent fluorescence change and the selectivity/specificity estimation, reveal that Py-GGT-1 has an excellent ability to monitor endogenous GGT activity. Mechanism studies through HRMS analysis, DFT calculations and molecular docking have theoretically verified the catalytic process between Py-GGT-1 and GGT. To develop its practical application, live-cell imaging and serum-sample analysis were carried out, demonstrating that Py-GGT-1 coud effectively track GGT within cells and organisms. Based its high selectivity and reasonable sensitivity, we expect that the probe will be applied in clinical diagnosis of GGT-related diseases in the future.

IMPACT OF CORONARY ARTERY DISEASE ON STEATOTIC LIVER DISEASE PROGRESSION

Introduction. Metabolic dysfunction-associated steatotic liver disease and coronary artery disease often exacerbate each other, leading to a more severe course of both conditions. The aim of this study is to evaluate the role of coronary artery disease in dislipidemia and liver fibrosis progression in patients with metabolic dysfunction-associated steatotic liver disease. Materials and methods. Forty-six patients with metabolic dysfunction-associated steatotic liver disease were examined. Patients were divided into two groups based on the presence of concomitant coronary artery disease: group I (n=24) included patients with both metabolic dysfunction-associated steatotic liver disease and coronary artery disease, while group II (n=22) included patients with metabolic dysfunction-associated steatotic liver disease only. A third group (Group III) comprised healthy individuals. Specific lipid metabolism parameters, obesity stage, alanine aminotransferase (ALT), aspartate aminotransferase (AST), γ-glutamyl transpeptidase (GGT) activity, and platelet count were examined. Fibrosis stage was evaluated using the FIB-4 score. The findings obtained were statistically processed. Results. Arterial hypertension was more prevalent in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease. In group I, arterial hypertension was observed in 95.8% of cases, whereas in group II, it was observed in 40.9% of cases (χ2=16.35, p=0.00005). Patients with metabolic dysfunction-associated steatotic liver disease exhibited elevated levels of total cholesterol, low-density lipoproteins, and triglycerides, leading to an increased atherogenic index. Conversely, high-density lipoprotein levels were decreased (p&gt;0.05). The degree of fibrosis according to the FIB-4 score was 1.45 times higher in patients with metabolic dysfunction-associated steatotic liver disease and concomitant coronary artery disease compared to those without coronary artery disease.

Effects of oral exposure to iron oxide nanoparticles on reproductive system of male rats

To investigate the effects of oral exposure to iron oxide nanoparticles(Fe_2O_3NPs) on the reproductive system of male rats. Forty male SD rats were randomly divided into control group and low, medium, high dose groups, 10 rats in each group, normal saline and 50, 100 and 200 mg/kg Fe_2O_3NPs suspension were given by gavage, respectively. The volume of gavage was 10 mL/kg for 28 days. The body weight was weighed every three days, and the body weight changes of rats were recorded. After intraperitoneal anesthesia with 10% chloral hydrate, the rats were sacrificed by cervical dislocation, and the testis and epididymis were collected. Weigh and calculate the testicular coefficient and epididymal coefficient, the pathological sections of rat testis were observed by hematoxylin-eosin staining, the number of epididymal sperm was counted under an optical microscope and the sperm deformity rate was calculated. The activities of acid phosphatase(ACP), alkaline phosphatase(AKP), lactate dehydrogenase(LDH) and γ-glutamyl transpeptidase(γ-GT), the activity of superoxide dismutase(SOD), and the contents of glutathione(GSH) and malondialdehyde(MDA) in rat testis homogenate were detected by kit method. Compared with control group, there was no significant difference in body weight, testicular coefficient and epididymal coefficient in each dose group. In the medium and high dose groups, the arrangement of spermatogenic epithelium was disordered and spermatogenic cells decreased. The number of sperm in high dose group was decreased, and the sperm deformity rate in medium and high dose groups was increased(P&lt;0.01). The activity of ACP in medium and high dose groups increased(P&lt;0.05), and the activity of γ-GT decreased(P&lt;0.01). There was no significant change in the activity of AKP and LDH in testicular homogenate of rats in each group(P&gt;0.05). The level of GSH in medium dose group was increased(P&lt;0.05), and the content of MDA in medium and high dose groups was increased(P&lt;0.01). There was no significant difference in SOD activity among the groups(P&gt;0.05). Under the conditions of this experiment, Fe_2O_3NPs can cause damage to the structure of rat testicular tissue, reduce the number of sperm, increase the rate of sperm deformity, interfere with the activity of marker enzymes in testicular tissue and induce oxidative stress injury, which has a negative impact on the reproductive system of male rats.

Subsequent development of cholangiocarcinoma caused by exposure to 1,2-dichloropropane and/or dichloromethane in the printing company in Osaka, Japan.

After the report of 17 patients with occupational cholangiocarcinoma caused by long-term exposure to high concentrations of 1,2-dichloropropane and/or dichloromethane in a printing company in Osaka in 2014, additional five patients were diagnosed to have such cholangiocarcinoma. Cholangiocarcinoma was detected during regular health examination or follow-up for liver dysfunction in four of the five patients. Nearly all five patients presented with clinicopathological findings such as an elevated γ-glutamyl transpeptidase activity at the diagnosis, regional dilatation of intrahepatic bile ducts without tumor-induced obstruction, chronic bile duct injury, and precancerous/early cancerous lesions (biliary intraepithelial neoplasia and intraductal papillary neoplasm of the bile duct) at various sites of the bile duct. These findings were similar to those of the previous 17 patients. In total, cholangiocarcinoma developed in 22 of 95 workers exposed to 1,2-dichloropropane in the printing company. Of 22 patients with cholangiocarcinoma, 18 patients were members of 19 high exposure workers (≥1,500 ppm-years). These findings strengthen further the theory that 1,2-dichloropropane causes occupational cholangiocarcinoma. Regular health examination of workers exposed to 1,2-dichloropropane and/or dichloromethane is necessary to detect such cholangiocarcinoma because the potential of the carcinogenesis risk persists over the long term.

Synergistic Protective Effect of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Mixture in the Ethanol-Induced Hepatotoxicity.

Schizandrae Fructus (SF), fruits of Schisandra chinensis (Turcz.) Baill. and Hoveniae Semen cum Fructus (HSCF), the dried peduncle of Hovenia dulcis Thunb., have long been used for alcohol detoxification in the traditional medicine of Korea and China. In the current study, we aimed to evaluate the potential synergistic hepatoprotective effect of a combination mixture (MSH) comprising fermented SF pomace (fSFP) and HSCF hot water extracts at a 1:1 (w:w) ratio against ethanol-induced liver toxicity. Subacute ethanol-mediated hepatotoxicity was induced by the oral administration of ethanol (5 g/kg) in C57BL/6J mice once daily for 14 consecutive days. One hour after each ethanol administration, MSH (50, 100, and 200 mg/kg) was also orally administered daily. MSH administration significantly reduced the serum activities of alanine aminotransferase, aspartate aminotransferase, alkaline phosphatase, and γ-glutamyl transpeptidase. Histological observation indicated that MSH administration synergistically and significantly decreased the fatty changed region of hepatic parenchyma and the formation of lipid droplet in hepatocytes. Moreover, MSH significantly attenuated the hepatic triglyceride accumulation through reducing lipogenesis genes expression and increasing fatty acid oxidation genes expression. In addition, MSH significantly inhibited protein nitrosylation and lipid peroxidation by lowering cytochrome P450 2E1 enzyme activity and restoring the glutathione level, superoxide dismutase and catalase activity in liver. Furthermore, MSH synergistically decreased the mRNA level of tumor necrosis factor-α in the hepatic tissue. These findings indicate that MSH has potential for preventing alcoholic liver disease through inhibiting hepatic steatosis, oxidative stress, and inflammation.

A Mixture of Fermented Schizandrae Fructus Pomace and Hoveniae Semen cum Fructus Extracts Synergistically Protects against Oxidative Stress-Mediated Liver Injury.

Schizandrae Fructus (SF) and Hoveniae Semen cum Fructus (HSCF) have long been used as medicinal herbs for treating various diseases in Asian traditional medicine. In the current study, we investigated the protective effect of fermented SF pomace and HSCF extract 1:1 (w:w) combination mixture (MSH) against carbon tetrachloride (CCl4)-induced acute liver injury mice. After MSH (50-200 mg/kg) oral administration for 7 consecutive days, animals were injected intraperitoneally with CCl4 (0.5 mL/kg). Histopathological observation revealed that administration of MSH synergistically decreased the degeneration of hepatocytes and the infiltration of inflammatory cells induced by CCl4. Moreover, MSH administration reduced the activities of alanine aminotransferase, aspartate aminotransferase, and γ-glutamyl transpeptidase in serum, and mitigated apoptotic cell death in hepatic parenchyma. In addition, MSH alleviated CCl4-mediated lipid peroxidation by restoring endogenous antioxidants capacities including glutathione contents, superoxide dismutase, and catalase activities. In vitro assessments using tert-butyl hydroperoxide-induced oxidative stress in HepG2 cells revealed that MSH protects hepatocytes by lowering ROS generation and lipid peroxidation via upregulating the transcriptional activity of nuclear factor erythroid-2-related factor 2 and the expression of antioxidant genes. Furthermore, MSH synergistically attenuated the expression of proinflammatory cytokines in CCl4-injured liver and lipopolysaccharide-stimulated RAW 264.7 cells. Taken together, these findings suggest that MSH has the potential to prevent acute liver damage by effectively suppressing oxidative stress and inflammation.

Activatable Raman Probes Utilizing Enzyme-Induced Aggregate Formation for Selective Ex Vivo Imaging

Detecting multiple enzyme activities simultaneously with high spatial specificity is a promising strategy to investigate complex biological phenomena, and Raman imaging would be an excellent tool for this purpose due to its high multiplexing capabilities. We previously developed activatable Raman probes based on 9CN-pyronins, but specific visualization of cells with target enzyme activities proved difficult due to leakage of the hydrolysis products from the target cells after activation. Here, focusing on rhodol bearing a nitrile group at the position of 9 (9CN-rhodol), we established a novel mechanism for Raman signal activation based on a combination of aggregate formation (to increase local dye concentration) and the resonant Raman effect along with the bathochromic shift of the absorption, and utilized it to develop Raman probes. We selected the 9CN-rhodol derivative 9CN-JCR as offering a suitable combination of increased stimulated Raman scattering (SRS) signal intensity and high aggregate-forming ability, resulting in good retention in target cells after probe activation. By using isotope-edited 9CN-JCR-based probes, we could simultaneously detect β-galactosidase, γ-glutamyl transpeptidase, and dipeptidyl peptidase-4 activities in live cultured cells and distinguish cell regions expressing target enzyme activity in Drosophila wing disc and fat body ex vivo.

Improvement in salt-tolerance of Aspergillus oryzae γ-glutamyl transpeptidase via protein chimerization with Aspergillus sydowii homolog

γ-Glutamyl transpeptidase is one of the key enzymes involved in glutamate production during high-salt fermentation of soy sauce and miso by koji mold, Aspergillus oryzae. However, the activity of γ-glutamyl transpeptidase from A. oryzae (AOggtA) is markedly reduced in the presence of NaCl, thus classifying it as a non-salt-tolerant enzyme. In contrast, the homologous protein from the xerophilic mold, A. sydowii (ASggtA) maintains its activity under high-salt conditions. Therefore, in this study, a chimeric enzyme, ASAOggtA, was designed and engineered to improve salt-tolerance in AOggtA by swapping the N-terminal region, based on sequence and structure comparisons between salt-tolerant ASggtA and non-salt-tolerant AOggtA. The parental AOggtA and ASggtA and their chimera, ASAOggtA, were heterologously expressed in A. oryzae and purified. The chimeric enzyme inherited the superior activity and stability from each of the two parent enzymes. ASAOggtA showed > 2-fold greater tolerance than AOggtA in the presence of 18% NaCl. In addition, the chimera showed a broader range of pH stability and greater thermostability than ASggtA. AOggtA and ASAOggtA were sy over the range pH 3.0 to pH 10.5. Thermal stability was found to be in the order AOggtA (57.5 °C, t1/2 = 32.5 min) > ASAOggtA (55 °C, t1/2 = 20.5 min) > ASggtA (50 °C, t1/2 = 12.5 min). The catalytic and structural characteristics indicated that non-salt-tolerant AOggtA would not undergo irreversible structural changes in the presence of NaCl, but rather a temporary conformational change, which might result in reducing the substrate binding and catalytic activity, on the basis of kinetic properties. In addition, the chimeric enzyme showed hydrolytic activity toward L-glutamine that was as high as that of AOggtA. The newly-designed chimeric ASAOggtA might have potential applications in high-salt fermentation, such as miso and shoyu, to increase the content of the umami-flavor amino acid, L-glutamate.

Immobilization of E. coli expressing γ-glutamyltranspeptidase on its surface for γ-glutamyl compound production

An Escherichia coli strain expressing γ-glutamyltranspeptidase on its extracellular surface using the Met1 to Arg232 fragment of YiaT of E. coli as an anchor protein was immobilized with alginate for repeated use. Measurement of γ-glutamyltranspeptidase activity of the immobilized cells was performed repeatedly at pH 8.73 and 37 °C for 10 days using γ-glutamyl-p-nitroanilide in the presence of 100 mM CaCl2 and 3% NaCl with and without glycylglycine. Even after the 10th day, the enzyme activity did not decrease from the initial levels. The production of γ-glutamylglutamine from glutamine using the immobilized cells was performed repeatedly at pH 10.5 and 37 °C for 10 days in the presence of 250 mM glutamine, 100 mM CaCl2, and 3% NaCl. Sixty-four % of glutamine was converted to γ-glutamylglutamine in the first cycle. While repeating the production 10 times, the surface of the beads gradually became covered with white precipitate, and the conversion efficiency gradually decreased, but 72% of the initial value still remained even at the 10th measurement.

Alteration of Glutathione and Antioxidant Status with Exercise in Unfed and Refed Rats

The influences of food deprivation and refeeding on glutathione (GSH) status, antioxidant enzyme activity and lipid peroxidation in response to an acute bout of exercise were investigated in the liver and skeletal muscles of male Sprague-Dawley rats randomly divided into three groups: starved for 48 h without refeeding; starved for 48 h and refed for 24 or 48 h. Half of each group of rats was exercised on a treadmill until exhaustion and killed immediately, whereas the other half group was killed at rest. Food-deprived rats had significantly lower liver GSH concentration and GSH:glutathione disulfide (GSSG) ratio. Malondialdehyde concentrations in the liver and skeletal muscle were both higher in the starved than in the refed rats (P < 0.05). Refed rats had significantly greater liver GSH level, γ-glutamylcysteine synthetase and glucose 6-phosphate dehydrogenase activities and plasma insulin concentration than unfed rats. Exercised 24- and 48-h refed rats had 27% and 31% lower liver GSH (P < 0.05), respectively, and a 21% lower GSH:GSSG ratio (P < 0.05) than their rested counterparts. Plasma insulin concentrations were significantly lower, whereas glucagon concentrations were greater in the exercised than in the rested rats. Muscle GSH concentration was significantly lower in the food-deprived than in the refed rats (P < 0.05) but was unaffected by exercise. Exercised 24-h refed rats had significantly elevated muscle GSSG concentration compared with rested rats, along with a higher GSH peroxidase and a lower γ-glutamyltranspeptidase activity (P < 0.05). These data indicate that both food deprivation-refeeding and exhaustive exercise influence liver and skeletal muscle glutathione status and that these changes may be controlled by hepatic glutathione synthesis and release due to hormonal stimulation.

Evaluation of Cottonseed Meal as an Alternative to Fish Meal in Diet for Juvenile Asian Red-Tailed Catfish Hemibagrus wyckioides.

A 10-week trial was performed to investigate the effects of replacing fishmeal with cottonseed meal (CSM) on the growth rate, protein metabolism, and antioxidant response of Asian red-tailed catfish Hemibagrus wyckioides. Five isonitrogenous and isocaloric diets (C0, C8.5, C17.2, C25.7, and C34.4) were prepared to contain 0%, 8.5%, 17.2%, 25.7%, and 34.4% CSM replacing fishmeal, respectively. The weight gain, daily growth coefficient, pepsin, and intestinal amylase activities initially increased and then decreased with the raising dietary CSM levels; the highest values were observed in the C17.2 group (P < 0.05). However, feed cost exhibited the opposite trend. With the increasing dietary CSM levels, the protein efficiency ratio and intestinal trypsin activity decreased but feed conversion rate increased gradually; while no differences were observed among the C0, C8.5, and C17.2 groups (P > 0.05). Dietary CSM inclusion regardless of levels increased the plasma growth hormone level as well as hepatic aspartate aminotransferase (AST) and γ-glutamyl transpeptidase activities but decreased the plasma glutamate dehydrogenase and AST activities (P < 0.05). With the increasing dietary CSM levels, the plasma alkaline phosphatase (AKP) and hepatic superoxide dismutase activities decreased but malondialdehyde content increased gradually, while no differences were observed among the C0, C8.5, and C17.2 groups (P > 0.05). The plasma immunoglobulin M content and hepatic glutathione reductase activity initially increased but then decreased with the raising dietary CSM levels; the highest values were found in the C17.2 group. These results indicated that dietary CSM inclusion level up to 17.2% improved the growth rate, feed cost, digestive enzyme activity, and protein metabolism without compromising antioxidant capacity of H. wyckioide, whereas these parameters were depressed by further inclusion of CSM. CSM is a potentially cost-effective alternative plant protein source in diet of H. wyckioide.

First Example of the Extracellular Surface Expression of Intrinsically Periplasmic Escherichia coli γ-Glutamyltranspeptidase, a Member of the N-Terminal Nucleophile Hydrolase Superfamily, and the Use of Cells as a Catalyst for γ-Glutamylvalylglycine Production.

Although the purified Escherichia coli γ-glutamyltranspeptidase has much higher transpeptidation activity than hydrolysis activity, almost all γ-glutamyltranspeptidase activity is hydrolysis activity in vivo, that is when measured using the whole cells. By using the Met1 to Arg232 fragment of E. coli YiaT or the CapA of Bacillus subtilis subsp. Natto as an anchor protein, we succeeded in expressing E. coli γ-glutamyltranspeptidase on the extracellular surface of the cells, and these cells showed higher transpeptidation activity than hydrolysis activity in the presence of NaCl. Furthermore, E. coli cells overexpressing γ-glutamyltranspeptidase without an anchor from the T5 promoter maintained γ-glutamyltranspeptidase on the extracellular surface of the cells immediately after being harvested from the culture medium, but the enzyme was released from the extracellular surface of the cells subsequently in the absence of NaCl. Using these cells expressing γ-glutamyltranspeptidase on the extracellular surface, γ-Glu-Val-Gly, a kokumi compound, was successfully produced.

Ameliorative Effects of Vanadyl Sulfate on Some Biochemical Parameters of Experimental Diabetic Rat Kidneys

Diabetes mellitus (DM), closely related to diabetic nephropathy, is one of the major public health problems worldwide. Today, with the increasing understanding of the underlying pathophysiology of DM, new oral anti-diabetic treatment strategies are being developed. Vanadium is a transition element that is widely distributed in nature, and its oral administration has been reported to improve DM in humans and a variety of diabetic animal models. The purpose of the research is to explore the effect of vanadyl sulfate (VS) administration on the different enzyme activities associated with kidney injury in streptozotocin- (STZ) induced diabetic rats. Male rats were assigned into groups as follows: untreated control, control animals given VS (100 mg/kg), diabetic (a single dose of intraperitoneal STZ, 65 mg/kg), and diabetic + VS (same dose) group. VS was administered orally for 60 days after the induction of diabetes. On the 60th day of experiment, kidney samples were taken for analysis. According to the data obtained from the biochemical analysis, the activities of transaminases, alkaline phosphatase, carbonic anhydrase, and γ-glutamyl transpeptidase decreased, whereas superoxide dismutase activity elevated in the kidney tissue of VS treated hyperglycemic animals. The results suggested that VS improved the diabetic renal injury, probably by VS insulin-mimic and antioxidant behavior through decreased oxidative stress and increased antioxidant capacity. Therefore, vanadyl sulfate might be used as a potential oral anti-diabetic compound in the treatment of the diabetic nephropathy, and as an important control for elevated blood glucose levels in the diabetic state.

Association of serum brain-derived neurotrophic factor with hepatic enzymes, AST/ALT ratio, and FIB-4 index in middle-aged and older women.

Substantial evidence suggests an important role of liver function in brain health. Liver function is clinically assessed by measuring the activity of hepatic enzymes in the peripheral blood. Brain-derived neurotrophic factor (BDNF) is an important regulator of brain function. Therefore, we hypothesized that blood BDNF levels are associated with liver function and fibrosis. To test this hypothesis, in this cross-sectional study, we investigated whether serum BDNF concentration is associated with liver enzyme activity, aspartate aminotransferase (AST)/ alanine aminotransferase (ALT) ratio, and fibrosis-4 (FIB-4) index in middle-aged and older women. We found that serum BDNF level showed a significant positive association with ALT and γ-glutamyltranspeptidase (GGT) activity and negative association with FIB-4 index, and a trend of negative association with the AST/ALT ratio after adjustment for age. Additionally, these associations remained statistically significant even after adjustment for body mass index (BMI) and fasting blood glucose level. These results demonstrate associations of serum BDNF levels with liver enzymes and hepatic fibrosis-related indices, which may underlie liver-brain interactions.

A water-soluble fluorescent probe for real-time visualization of γ-glutamyl transpeptidase activity in living cells

γ-glutamyl transpeptidase (GGT) is a kind of cell-surface enzyme that is overexpressed in many cancer cells. It is of great significance to develop an ideal tool for the diagnosis of GGT-rich cancer cells. Here, we reported a simple-structured but effective imaging probe for the detection of GGT activity. In the presence of GGT, the γ-glutamyl linkage could be cleaved specifically to produce amino-substituted product, resulting in significant fluorescence enhancement at 578 nm. Moreover, we successfully employed the probe to monitor GGT activity in HepG2 cells. We envisaged that such a simple but effective imaging tool could improve the practical applications for bioimaging.

Sensitive sensing of alkaline phosphatase and γ-glutamyltranspeptidase activity for tumor imaging.

Alkaline phosphatase (ALP) and γ-glutamyltranspeptidase (GGT) are regarded as two important biomarkers in several human cancers. There are many probes for ALP or GGT detection but no probe was reported to sense the activity of both ALP and GGT in vitro or in vivo. Herein, a bioluminescent probe P-Bz-Luc was designed for realizing sensitive and specific tumor imaging via the co-cleavage of ALP and GGT. In solution experiments showed that an excellent linear relationship was found between the bioluminescence signal of the P-Bz-Luc solution and the enzyme concentration at limits of detection of 0.172 for ALP and 0.634 U L-1 for GGT. Eventually, the BL probe P-Bz-Luc was successfully applied for sensitive imaging of the ALP and GGT co-overexpressed fLuc-231 breast cancer cells and tumors, with the help of the coordination cleavage of P-Bz-Luc by ALP and GGT.