Biotin-tagged fluorescent probe for in situ visualization of γ-glutamyl transpeptidase in cancerous cells and tissues.

γ-Glutamyl transpeptidase (GGT), a cell-surface enzyme, is strongly implicated in mammalian malignancy growth and migration processes including human hepatocarcinogens. However, simply and conveniently detect of GGT on the cell membrane remains highly challenging. In this study, a biotin-tagged fluorescent probe Nap-biotin-glu was developed using glutamic acid, naphthalimide, and biotin as the reaction site, fluorescent reporter, and membrane-targeting group, which required only three steps. Colocalization fluorescence imaging and immunofluorescence analysis indicated that probe Nap-biotin-glu was successfully realized in situ visualizing of GGT on the cell membrane.Owing to the significant over-expressed GGT level in tumor, the probe was successfully applied to distinguish cancer tissues from adjacent normal tissues.

TyG-GGT is a Reliable Non-Invasive Predictor of Advanced Liver Fibrosis in Overweight or Obese Individuals.

BACKGROUND: Liver fibrosis is a predisposing factor for liver cancer. This study will investigate the predictive role of the Triglyceride-glucose and Gamma-glutamyl transferase index (TyG-GGT) as a non-invasive indicator of advanced liver fibrosis in individuals with obesity or overweight. METHOD: We enrolled patients who underwent metabolic and bariatric surgery as well as intraoperative liver biopsies at Zhejiang provincial people's hospital from August 2020 to March 2023. Clinical characteristics, comorbidities, laboratory data, and pathological variables of patients were collected and analysed. Then, we conducted logistics regression model to compare the performance of the TyG-GGT index with other 4 non-invasive models. RESULTS: A total of 65 patients were included in this study. 43(66.2%) of them were female, with the mean body mass index (BMI) of 39.0 ± 7.3 kg/m2. Meanwhile, 24(36.9%) patients were diagnosed with diabetes. Advanced liver fibrosis were observed in 16.9% of patients, while liver cirrhosis was found in 4.6% of patients. The multivariable logistics regression showed that TyG-GGT was an independent risk factor of advanced liver fibrosis (OR = 6.989, P = 0.049). Additionally, compared to another 4 non-invasive liver fibrosis models (NFS = 0.66, FIB4 = 0.65, METS-IR = 0.68, APRI = 0.65), TyG-GGT exhibits the highest AUC value of 0.75. CONCLUSIONS: More than one-third of patients undergoing metabolic and bariatric surgery are afflicted with nonalcoholic steatohepatitis (NASH), and a significant proportion exhibit advanced fibrosis. TyG-GGT was a potentially reliable predictor for screening individuals with overweight or obesity at high risk of advanced liver fibrosis, thus providing clinical guidance for early intervention in this targeted group.

Near-infrared imaging of hepatocellular carcinoma and its medicinal treatment with a γ-glutamyl transpeptidase-monitoring fluorescence probe.

Herein, the Near-infrared imaging of hepatocellular carcinoma (HCC) and its medicinal treatment was achieved with a γ-glutamyl transpeptidase (GGT)-monitoring fluorescence probe KYZ-GGT which consisted of the typical recognition group γ-glutamyl and the structurally modified signal reporting group hemicyanine-thioxanthene. Compared with the recently reported probes, KYZ-GGT suggested practical and steady capability for monitoring the GGT level in the cellular, xenograft, induced as well as medicinal treatment HCC models. It realized the mitochondrial targeting intracellular imaging to reflect the GGT dynamics in the induction or medicinal treatment of HCC. In the xenograft and induced model mice with multiple factors, KYZ-GGT showed stable performance for visualizing the HCC status. In the medicinal treatment of the long-period-induced HCC model mice verified by the serum indexes and histopathological analysis, KYZ-GGT successfully imaged the medicinal treatment process of HCC with two marketed drugs (Sorafenib and Lenvatinib) respectively, with an applicative penetration depth. The information here was meaningful for investigating effective medicinal strategies for overcoming HCC.

A ratiometric fluorescent probe for detection of γ-glutamyl transpeptidase in blood serum and living cells.

γ-Glutamyl transpeptidase (GGT) is one of the biomarker of cancer, hepatitis, and numerous other diseases. The accurate analysis of GGT is useful for the early diagnosis of these diseases. In this work, Probe 1, a ratiometric fluorescent probe based on 2,3,5,6-tetrafluoroterephthalonitrile, was designed for GGT detection. The results indicated that Probe 1 can sensitively and selectively detect GGT in phosphate buffered solution and complex biological systems (e.g., blood serum). Furthermore, Probe 1 has been successfully applied for ratiometric imaging of GGT in cancer cells and normal cells.

[Diagnostic value of gamma-glutamyl transferase and alkaline phosphatase for cholecystolithiasis complicated with occult pancreaticobiliary reflux].

Objective: To explore the diagnostic value of the preoperative liver function for occult pancreaticobiliary reflux (OPBR) in patients with gallstones. Methods: Patients with gallstones in Shanghai East Hospital were enrolled from December 2020 to June 2021. Their intraoperative bile and clinical data were collected. According to the gallbladder bile amylase level, patients were divided into the OPBR group (bile amylase>110 U/L) and the control group (bile amylase ≤ 110 U/L). Preoperative liver function levels of the two groups were compared, and the differential parameters were accessed by the receiver operating characteristic (ROC) curve. And the risk factors for OPBR were tested by multiple logistic regression analysis. Results: Among 249 patients, 83 were male and 166 were female, aged 50 (37, 62) years; There were 218 cases in control group, including 70 males and 148 females, aged 49 (36, 61) years; There were 31 patients in the OPBR group, including 13 males and 18 females, aged 58 (51, 65) years. For preoperative liver function, gamma-glutamyl transferase (GGT) and alkaline phosphatase (ALP) in the OPBR group were higher than those in the control group [35 (18, 59) vs 19 (13, 34) U/L, 80 (71, 97) vs 69 (57, 83) U/L; both P<0.01]. ROC indicated that preoperative GGT and ALP had important predictive values for OPBR in gallstone patients. Their respective optimal cut-off value and area under the ROC curve [AUC (95%CI)] were GGT ≥ 30 U/L, 0.656 (0.542-0.770), P=0.005; ALP≥70 U/L, 0.693 (0.613-0.773), P=0.001, respectively. In addition, multivariate logistic regression analysis showed that the levels of GGT [OR (95%CI)=2.856 (1.260-6.473), P=0.012] and ALP [OR (95%CI)=3.685 (1.314-10.333), P=0.013] were independent-related factors for OPBR in patients with gallstones. Conclusion: Preoperative liver function assessment is of great significance for patients with gallstones, while GGT and ALP are important for predicting OPBR in patients with gallstones.

Rotating night shift work, sleep duration and elevated gamma-glutamyl transpeptidase among steelworkers: cross-sectional analyses from a Chinese occupational cohort.

OBJECTIVES: This study aimed to evaluate the separate and combined effects of rotating night shift work and lifestyle factors with elevated gamma-glutamyl transpeptidase (GGT) among steelworkers. DESIGN, SETTING AND PARTICIPANTS: This cross-sectional study used the baseline information from a Chinese occupational cohort. The in-service workers of the production department of Tangsteel Company who participated in the occupational health examination in Tangshan from February to June 2017 were selected as the research objects. MAIN OUTCOME MEASURES: The separate and combined effects of rotating night shift work and lifestyle factors with elevated GGT among steelworkers. RESULTS: The information of 7031 subjects from the production department of Tangsteel Company was analysed. Results showed that the current shift workers and the workers with the duration of night shifts>19 years, the cumulative number of night shifts>1774 nights, the average frequency of night shifts≤7 nights/month and the average frequency of night shifts>7 nights/month had elevated odds of elevated GGT, compared with those who never worked night shifts, and ORs, (95% CIs) were 1.39, (1.10 to 1.75), 1.46, (1.15 to 1.86), 1.46, (1.15 to 1.85), 1.34, (1.04 to 1.73) and 1.37, (1.09 to 1.74) after adjustment for potential confounders. The independent effect of shorter sleep duration (<7 hours/day) on elevated GGT was not statistically significant. Among workers who had shorter sleep duration, the association between rotating night shift work and elevated GGT was statistically significant, but no associations were found among workers with the sleep duration of ≥7 hours/day. In addition, other lifestyle factors affected the association between rotating night shift work and elevated GGT. CONCLUSIONS: Rotating night shift work is associated with elevated GGT among steelworkers. In particular, the effect of rotating night shift work on elevated GGT was affected by sleep duration and other lifestyle factors.

A de novo strategy to develop NIR precipitating fluorochrome for long-term in situ cell membrane bioimaging.

Cell membrane-targeted bioimaging is a prerequisite for studying the roles of membrane-associated biomolecules in various physiological and pathological processes. However, long-term in situ bioimaging on the cell membrane with conventional fluorescent probes leads to diffusion into cells from the membrane surface. Therefore, we herein proposed a de novo strategy to construct an antidiffusion probe by integrating a fluorochrome characterized by strong hydrophobicity and low lipophilicity, with an enzyme substrate to meet this challenge. This precipitating fluorochrome HYPQ was designed by conjugating the traditionally strong hydrophobic solid-state fluorochrome 6-chloro-2-(2-hydroxyphenyl) quinazolin-4(3H)-one (HPQ) with a 2-(2-methyl-4H-chromen-4-ylidene) malononitrile group to obtain closer stacking to lower lipophilicity and elongate emission to the far-red to near-infrared wavelength. As proof-of-concept, the membrane-associated enzyme γ-glutamyltranspeptidase (GGT) was selected as a model enzyme to design the antidiffusion probe HYPQG. Then, benefiting from the precipitating and stable signal properties of HYPQ, in situ imaging of GGT on the membrane was successfully realized. Moreover, after HYPQG was activated by GGT, the fluorescence signal on the cell membrane remained unchanged, with incubation time even extending to 6 h, which is significant for in situ monitoring of enzymatic activity. In vivo testing subsequently showed that the tumor region could be accurately defined by this probe after long-term in situ imaging of tumor-bearing mice. The excellent performance of HYPQ indicates that it may be an ideal alternative for constructing universal antidiffusion fluorescent probes, potentially providing an efficient tool for accurate imaging-guided surgery in the future.

COVID-19 and liver injury: a meta-analysis.

BACKGROUND/AIMS: The number of cases with coronavirus disease 2019 (COVID-19) has exceeded seven million worldwide. However, the data describing the global prevalence of liver injury associated with COVID-19 is lacking secondary to the novelty of this ongoing pandemic. Therefore, we conducted a meta-analysis to determine the association between COVID-19 and liver injury. METHODS: A systematic literature search of indexed databases including, PubMed, Medline, and Embase databases from inception to 14 April 2020, was used to identify studies that reported data of liver chemistry in patients diagnosed with COVID 19. The overall prevalence of abnormal liver chemistry and relevant 95% confidence interval was used to estimate the pooled results studies. RESULTS: Sixty-four studies with 11 245 patients with COVID-19 were included. The pattern of abnormal liver enzymes was notable for higher aspartate aminotransferase (AST) than alanine aminotransferase (ALT) levels. The overall global prevalence of elevated AST, ALT, total bilirubin, gamma-glutamyltransferase (GGT), and alkaline phosphatase was 23.2, 21.2, 9.7, 15.0, and 4.0%, respectively. The prevalence of elevated AST was substantially higher among those with severe cases (45.5%) compared to non-severe cases (15.0%). Co-existing chronic liver disease presented up to 37.6% of patients with COVID-19. CONCLUSION: A fourth of COVID-19 patients had elevated liver enzymes and associated with disease severity. Our study may be used as a guide for clinicians and epidemiologists to proactively identify other sources of injury and illness in patients diagnosed with COVID-19. Intensive monitoring for liver injury may be needed in cases with severe COVID-19.

Ácido úrico y gamma-glutamiltransferasa como biomarcadores de enfermedad cardiovascular a través del estrés oxidativo / Uric acid and gamma-glutamyltransferase as biomarkers of cardiovascular disease via oxidative stress

Introducción: Las enfermedades cardiovasculares constituyen la principal causa de mortalidad y morbilidad a nivel mundial. Reconocidas como problemas de salud de impacto social, han motivado a muchos científicos a tratar de explicar su patogénesis. Actualmente se plantea de la existencia de otros factores de riesgo, independientemente de los clásicos. Entre estos factores se describen el papel de las altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre, biomarcadores de estrés oxidativo. Estos elementos que de manera individual pudieran contribuir a las enfermedades cardiovasculares, parecen tener un efecto sinérgico. Objetivo: Revisar las evidencias que sostienen que altas concentraciones de ácido úrico y la actividad de la enzima gamma-glutamiltransferasa en sangre pueden constituir factores de riesgo que desde el estrés oxidativo contribuyan a las enfermedades cardiovasculares. Métodos: Se recopiló la información a partir de las bases de datos de diferentes buscadores (Medline-Pubmed, Cochrane, Scopus y SciELO) entre el 1 de marzo del 2019 y el 23 de mayo 2020. Conclusiones: Se encontró que, tanto el ácido úrico como la gamma-glutamiltransferasa son productos horméticos que a bajas concentraciones tienen efecto antioxidante en el organismo, pero al elevarse involucran la ocurrencia de procesos oxidativos que conducen a la disfunción endotelial y las enfermedades cardiovasculares(AU)

Introduction: Cardiovascular diseases are the leading cause of mortality and morbidity worldwide. Recognized as a health problem of social impact; they have prompted many scientists to try to explain their pathogenesis. New risk factors are currently acknowledged alongside the classic ones. These factors include the role of high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood, both of which are biomarkers of oxidative stress. These elements may individually contribute to the development of cardiovascular diseases, and seem to have a synergistic effect. Objective: Review the evidence supporting the idea that high uric acid concentrations and the activity of the enzyme gamma-glutamyltransferase in blood may be risk factors contributing to the development of cardiovascular diseases via oxidative stress. Methods: Data were collected from the databases of various search engines (Medline-Pubmed, Cochrane, Scopus and SciELO) from 1 March 2019 to 23 May 2020. Conclusions: It was found that uric acid and gamma-glutamyltransferase are hormetic products causing an antioxidant effect on the organism at low concentrations. However, when concentrations rise, they are involved in the occurrence of oxidative processes leading to endothelial dysfunction and cardiovascular diseases(AU)

A two-photon fluorescent probe for sensitive detection and imaging of γ-glutamyl transpeptidase.

A GGT-activated two-photon fluorescent probe (4F-2CN-GSH) was developed based on a cascade reaction. 4F-2CN-GSH could selectivily detect GGT with low detection limit and distinguish ovarian cancer cells from normal cells using both one-photon and two-photon fluorescence imaging.

Cell-Membrane-Localizing, Two-Photon Probe for Ratiometric Imaging of γ-Glutamyl Transpeptidase in Cancerous Cells and Tissues.

γ-Glutamyl transpeptidase (GGT), a cell surface-bound protease, is associated with various diseases including cancer. The detection of the enzyme activity is an important subject, leading to about 40 activatable fluorescent probes so far. All of them, however, lack the membrane-localizing ability, raising a reliability issue in the quantitative analysis. Disclosed is the first fluorescent probe that senses the cell surface-bound enzyme, which, furthermore, is capable of ratiometric as well as two-photon imaging with desirable features. Ratiometric imaging of cancer cell lines reveals a 6.4-8.4-fold higher GGT levels than those in normal cell lines. A comparison of the enzyme activity in organ tissues of normal and tumor xenograft mice reveals notably different levels of enzyme activity depending on the kind of tissue. Normal tissues exhibited comparable levels of enzyme activity, except the kidney that has significantly higher GGT activity (2.7-4.0-fold) than the other organs. Compared with the normal tissues, considerably higher enzyme activity was observed in the tumor tissues of the thigh (4.0-fold), colon (2.5-fold), lung (3.6-fold), and liver (2.1-fold), but essentially no enhanced activity in the tumor tissues of the spleen, stomach, and pancreas and a comparable level in both the tumor and normal kidney tissues were observed. The probe offers practical means for studying GGT-associated biology in cells and tissues by one- as well as two-photon ratiometric imaging.

Routine blood tests as a potential diagnostic tool for COVID-19.

Objectives The outbreak of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) to date, the epidemic has gradually spread to 209 countries worldwide with more than 1.5 million infected people and 100,000 deaths. Amplification of viral RNA by rRT-PCR serves as the gold standard for confirmation of infection, yet it needs a long turnaround time (3-4 h to generate results) and shows false-negative rates as large as 15%-20%. In addition, the need of certified laboratories, expensive equipment and trained personnel led many countries to limit the rRT-PCR tests only to individuals with pronounced respiratory syndrome symptoms. Thus, there is a need for alternative, less expensive and more accessible tests. Methods We analyzed the plasma levels of white blood cells (WBCs), platelets, C-reactive protein (CRP), aspartate aminotransferase (AST), alanine aminotransferase (ALT), γ-glutamyl transpeptidase (GGT), alkaline phosphatase and lactate dehydrogenase (LDH) of 207 patients who, after being admitted to the emergency room of the San Raffaele Hospital (Milan, Italy) with COVID-19 symptoms, were rRT-PCR tested. Of them, 105 tested positive, whereas 102 tested negative. Results Statistically significant differences were observed for WBC, CRP, AST, ALT and LDH. Empirical thresholds for AST and LDH allowed the identification of 70% of either COVID-19-positive or -negative patients on the basis of routine blood test results. Conclusions Combining appropriate cutoffs for certain hematological parameters could help in identifying false-positive/negative rRT-PCR tests. Blood test analysis might be used as an alternative to rRT-PCR for identifying COVID-19-positive patients in those countries which suffer from a large shortage of rRT-PCR reagents and/or specialized laboratory.

Gamma glutamil transferasa, marcador de eficacia clínica del ozono médico y su papel en la artritis reumatoide y la osteoartritis de rodilla / Gamma glutamyl transferase: an indicator of medical ozone clinical efficacy and its pathological role in rheumatoid arthritis and knee osteoarthritis

Introducción: El ozono médico tiene eficacia clínica e incrementa la relación beneficio/riesgo en pacientes con artritis reumatoide tratados con la terapia combinada metotrexate + ozono. Hoy, la gamma glutamil transferasa se considera como un marcador de riesgo de enfermedades de una alta morbilidad y mortalidad, y tiene particular valor en la artritis reumatoide por desempeñar un papel patológico asociado al estrés oxidativo y a la remodelación ósea, lo que causa daño al cartílago y al hueso. Objetivo: Evaluar los efectos del ozono médico sobre los niveles de gamma glutamil transferasa. Métodos: Se estudiaron pacientes portadores de dos enfermedades artríticas: artritis reumatoide (n = 100; grupo tratado con metotrexate [n = 50] y grupo con metotrexate + ozono [n = 50]) y osteoartritis de rodilla (n = 40; grupo precondicionado con ozono antes de la artroscopía [n = 20] y grupo sin pretratamiento con ozono antes de la artroscopía [n = 20]). Los pacientes con artritis reumatoide fueron valorados con indicadores clínicos específicos, incluidos los niveles de anticuerpos contra péptidos cíclicos citrulinados, así como las concentraciones de glutatión reducido, importante antioxidante endógeno. Resultados: El ozono médico reguló la actividad sérica de gamma glutamil transferasa. Correlacionó de forma inversamente proporcional con los niveles de glutatión reducido que, a su vez, fue el único marcador redox que para los pacientes tratados con la terapia combinada metotrexate + ozono fue directamente proporcional con todas las variables clínicas evaluadas. Conclusión: Se debe considerar a la gamma glutamil transferasa un indicador de la eficacia clínica del ozono médico en las enfermedades estudiadas, por su doble función: biomarcador de estrés oxidativo e indicador de la remodelación patológica del hueso(AU)

Introduction: Medical ozone has demonstrated its clinical efficacy as well as the increase of beneficial/risk relationship in rheumatoid arthritis patients treated with metotrexate+ozone combined therapy. At present, gamma-glutamyl transpeptidase is considered as risk indicator of high morbimortality diseases. It has a special value in arthritis diseases due to its pathologic role associated to oxidative stress and in the abnormal bone remodeling processes. Objective: Assess the ozone medical effects on gamma-glutamyl transpeptidase levels. Method: Patients who suffered of two arthritic diseases: rheumatoid arthritis (n=100; Group treated with Metotrexate (n=50) and metotrexate+ozone (n=50) and knee osteoarthritis (n=40); Group preconditioned with ozone before arthroscopy (n=20) and Group without previous treatment with ozone before arthroscopy (n=20). Rheumatoid arthritis patients were assessed through specific clinic indicators which included antibodies against cyclic citrullinate peptides as well as reduced gluthatione concentrations which are an important endogenous antioxidant. Results: Medical ozone regulated serum gamma-glutamyl transpeptidase activity which correlated in inverse proportion to reduced glutathione levels which was the only one redox marker that correlated with all clinical variables (p < 0.05) when patients were treated with metotrexate+ozone. Conclusion: Gamma-glutamyl transpeptidase should be considered as biomarker of medical ozone clinical efficacy in rheumatoid arthritis and knee osteoarthritis due to GGT´s both pathologic functions: indicator of oxidative stress and abnormal bone remodeling processes(AU)

Induction of lactation in dairy heifers: milk production, inflammatory and metabolic aspects / Indução de lactação em novilhas leiteiras: produção de leite, aspectos inflamatórios e metabólicos

The aim of this study was to evaluate the metabolic, inflammatory, and hepatic aspects, as well as the milk yield in heifers submitted to protocol for induction of lactation compared to primiparous cows. Sixty Holstein heifers were selected and enrolled into two groups: Control (n= 30), pregnant heifers and Induction heifers (n= 30), non-pregnant femeales, submitted to a lactation induction protocol. Blood samples were collected at: pre-lactation period (weeks -3, -2 and -1) and post-lactation period (weeks 1, 2 and 3), aiming to evaluate glucose, non-esterified fatty acids, paraoxonase-1, albumin, ALT, GGT and cortisol. The protocol efficiently induced lactation in all the heifers, which produced 74.54% of the total production of milk from primiparous cows. In the pre-lactation period, induced animals presented higher concentrations of non-esterified fatty acids than the Control heifers, and the opposite was observed in the post lactation period. In both moments albumin and ALT were lower in the Induction group, and paraoxonase-1 activity and GGT concentrations were higher, compared to the Control. Thus, lactation induction protocol is efficient to initiate milk production in dairy heifers with no considerable changes in energetic, metabolic and hepatic profile when compared to heifers in physiological lactation.(AU)

O objetivo deste estudo foi avaliar os perfis metabólico, inflamatório, hepático e a produção de leite de novilhas induzidas à lactação comparadas a primíparas. Sessenta novilhas da raça Holandês foram selecionadas e alocadas em grupos: controle (n=30), novilhas prenhas, e indução (n=30), novilhas vazias submetidas a um protocolo de indução de lactação. As amostras de sangue foram coletadas nas semanas -3, -2 e -1 (pré-lactação) e nas semanas 1, 2 e 3 (pós-início de lactação) para avaliação de glicose, ácidos graxos não esterificados, paraoxonase-1, albumina, ALT, GGT e cortisol. O protocolo induziu eficientemente a lactação em todas as novilhas, que produziram 74,54% da produção total de leite do controle. No período pré-lactação, o grupo indução apresentou maiores concentrações de ácidos graxos não esterificados que o controle, e o oposto foi observado pós-lactação. Em ambos os momentos, albumina e ALT foram menores no grupo indução, e a atividade da paraoxonase-1 e as concentrações de GGT foram maiores, em comparação ao controle. Assim, o protocolo de indução de lactação foi eficiente para iniciar a produção de leite em novilhas induzidas, além de terem sido observadas alterações nos perfis energético, metabólico e hepático em comparação a novilhas em lactação fisiológica.(AU)

Body mass index and γ-glutamyl transferase expression in normal and cancerous breast tissue.

BACKGROUND: Localized to cell membrane, γ-glutamyl transferase (GGT) is a reliable marker for the evaluation of cell distress occurring in several pathological conditions including obesity, metabolic syndrome, and cancer. In particular, high GGT serum levels are associated with breast cancer incidence and progression. METHODS: The tissue expression of GGT1, the gene coding for GGT, was investigated in silico in a large case series of paired samples of breast cancer and adjacent histologically normal (HN) tissue, and in a collection of healthy breast tissues from reduction mammoplasty. The association of GGT1 with patient's body mass index (BMI), and the relationship between GGT1 and a panel of genes involved in apoptosis, IGF-1 signaling, or coding for adipokines and adipokine receptors were also investigated. RESULTS: GGT1 expression was significantly higher in tumor than in the adjacent HN tissue (P = 0.0002). Unexpectedly, the expression of GGT1 was inversely associated with BMI in normal and HN tissue, whereas no correlation was found in cancerous tissue. In all tissues, GGT1 correlated positively with TP53 and negatively with BCL2 and LEPR, whereas only in normal and HN tissue GGT1 correlated positively with IGF1R. The linear regression model, adjusted for BMI, showed no confounding effect on any correlation, except for the correlation of GGT1 with LEPR in normal tissue from healthy women. CONCLUSIONS: Even if present results provide interesting insights on the still elusive mechanism(s) underlying the association between obesity and epithelial cell proliferation, possibly promoting neoplastic transformation, such relationship deserves further investigation in other independent datasets.

Inappropriate use of laboratory tests: How availability triggers demand - Examples across Europe.

INTRODUCTION: The appropriate use of laboratory diagnostics is increasingly at stake. The aim of this study was to depict some paradigmatic examples of under- and overutilization, as well as possible solutions across Europe. METHODS: We collected six examples from five European countries where a rise or decline of orders for specific laboratory parameters was observed after organizational changes but without evidence of changes in patient collective characteristics as source of this variation. RESULTS: The collected examples were the following: 1-Germany) Switch from a Brain-Natriuretic-Peptide assay to NT-pro Brain-Natriuretic-Peptide assay, resulting in a 374% increase in these analytics; 2-Spain) Implementation of a gatekeeping strategy in tumor marker diagnostics, resulting in a 15-61% reduction of these diagnostics; 3-Croatia) Stepwise elimination of creatine-kinase-MB assay from the laboratory portfolio; 4-UK) Removal of γ-glutamyl transferase from a "liver function" profile, resulting in 82% reduction of orders; 5-Austria) Implementation of a new device for rapid Influenza-RNA detection, resulting in a 450% increase of Influenza testing; 6-Spain) Insourcing of 1,25-(OH)2-Vitamin D measurements, leading to a 378% increase of these analyses. CONCLUSION: The six paradigmatic examples described in this manuscript show that availability of laboratory resources may considerably catalyze the demand, thus underscoring that inappropriate use of laboratory resources may be commonplace in routine laboratories all across Europe and most probably beyond. They also demonstrate that the application of simple strategies may assist in overcoming this issue. We believe that laboratory specialists need to refocus on the extra-analytical parts of the testing process and engage more in interdisciplinary patient-care.

Serum gamma-glutamyltransferase activity and Parkinson's disease risk in men and women.

We evaluated serum gamma-glutamyltransferase (GGT) and the risk of Parkinson's disease (PD). Using data from the National Health Insurance Service (NHIS) database, we constructed a cohort consisting of individuals aged above 40 years who underwent a health check-up in 2009. After excluding individuals with heavy alcohol consumption, hepatobiliary and pancreatic disorders, and a previous history of PD, each quartile group of baseline serum GGT levels was monitored for the development of PD for 7 years. Adjusted hazard ratios (HRs) for PD were estimated by Cox proportional hazard models adjusting for potential confounding variables. We additionally analyzed the possible interaction between GGT and obesity or metabolic syndrome. Among the 6,098,405 individuals who were included, PD developed in 20,895 individuals during the follow-up (0.34%, 9,512 men and 11,383 women). The top quartile of serum GGT (geometric means, 90.44 IU/L in men and 41.86 IU/L in women) was associated with a lower risk in men (adjusted HR = 0.72 (95% CI: 0.67-0.76)) and a higher risk in women (adjusted HR = 1.30 (95% CI: 1.23-1.37)) using the lower GGT quartiles as a reference. Obesity and metabolic syndrome increased PD risk in both sexes, and there was only a subadditive interaction between serum GGT and obesity in women.

A New γ-Glutamyltranspeptidase-Based Intracellular Self-Assembly of Fluorine-18 Labeled Probe for Enhancing PET Imaging in Tumors.

γ-Glutamyltranspeptidase (GGT) is a cell -membrane-associated enzyme which has been recognized as a promising biomarker for the diagnosis of many malignant tumors. Herein, we rationally designed a fluorine-18 labeled small-molecule probe, [18F]γ-Glu-Cys(StBu)-PPG(CBT)-AmBF3 (18F-1G), by applying a biocompatible CBT-Cys condensation reaction and ingeniously decorating it with a GGT-recognizable substrate, γ-glutamate (γ-Glu), for enhancing PET imaging to detect GGT level of tumors in living nude mice. The probe had exceptional stability at physiological conditions, but could be efficiently cleaved by GGT, followed by a reduction-triggered self-assembly and formation of nanoparticles (NPs) progressively that could be directly observed by transmission electron microscopy (TEM). In in vitro cell experiments, 18F-1G showed GGT-targeted uptake contrast of 2.7-fold to that of 18F-1 for the detection of intracellular GGT level. Moreover, the higher uptake in GGT overexpressed HCT116 tumor cells (∼4-fold) compared to GGT-deficient L929 normal cells demonstrated that 18F-1G was also capable of distinguishing some tumor cells from normal cells. In vivo PET imaging revealed enhanced and durable radioactive signal in tumor regions after 18F-1G coinjecting with 1G, thus allowing real-time detection of endogenous GGT level with high sensitivity and noninvasive effect. We anticipated that our probe could serve as a new tool to investigate GGT-related diseases in the near future.

Liver Enzymes and the Risk of Atrial Fibrillation: A Meta-Analysis of Prospective Cohort Studies.

Background: The association between liver enzymes and the future development of atrial fibrillation (AF) from observational studies is unclear. We, therefore, performed a meta-analysis to systematically evaluate the relationship between liver enzymes and AF risk. Methods: We searched the PubMed and Embase databases for observational cohort studies assessing the association between liver enzymes and AF risk. Pooled relative risks (RRs) with 95% confidence intervals (CIs) were calculated using a random effects model. Results: Five prospective studies with 282,615 participants and 7062 AF events were included. The pooled fully adjusted RRs (95% CIs) for AF were 1.10 (1.06-1.14) per 1-standard deviation change in log baseline level of gamma glutamyltransferase (GGT). No positive association was found between alanine aminotransferase (ALT, RR 1.04, 95% CI 0.90-1.20, p = 0.607) or aspartate aminotransferase (AST, RR 1.05, 95% CI 0.96-1.15, p = 0.268) and the risk of AF. Conclusions: The baseline GGT level is positively associated with the AF risk in a log-linear manner. We found no significant association between ALT or AST and the risk of AF. However, further well-designed prospective studies are needed to confirm these findings and elucidate the pathophysiological mechanisms.