UGT1A1 dysfunction increases liver burden and aggravates hepatocyte damage caused by long-term bilirubin metabolism disorder

2021 ◽  
pp. 114592
Author(s):  
Dan Liu ◽  
Qi Yu ◽  
Zibo Li ◽  
Lin Zhang ◽  
Ming Hu ◽  
...  
Keyword(s):  
Metabolism Disorder ◽  
Bilirubin Metabolism ◽  
Hepatocyte Damage

scholarly journals Ameliorative Effects of Nano-Selenium Against Fluoride Stress Induced Hepatocytes Autophagy and Apoptosis in Mice

2020 ◽  
Author(s):  
Yajing Wang ◽  
Bingxian Liu ◽  
Qingyue Han ◽  
Khalid Mehmood ◽  
Fazul Nabi ◽  
...  
Keyword(s):  
Caspase 3 ◽  
Beclin 1 ◽  
Protective Effects ◽  
Human Beings ◽  
Caspase 9 ◽  
Nano Material ◽  
Cyt C ◽  
Hepatocyte Damage

Abstract Background: Fluorine is widespread in the environment, and the injurious impacts of fluoride underscore its significance for public health. The long-term presence of fluorine in environment could be a risk in hepatotoxicity for both human beings and animals. Important role of selenium in mitigation of heavy metal toxicity via regulating autophagy and apoptosis is well-known. Further, nano-Se is a common artificial nano material, with higher biological activity and lower toxicity. The aim of the current study was to examine whether nano-Se supplementation can reduce the effects of fluoride-induced hepatocytes autophagy and apoptosis. Results: Here, we report that fluoride exposure induces apoptosis and autophagy with nucleus broken, dissolved and disappeared of hepatocyte, contributing to its hepatotoxicity. More importantly, Cyt-C and Beclin-1/Bcl-2 pathways are involved in the regulation of autophagy and apoptosis via targeting Caspase-9, Caspase-3, P53, Bax, LC3, ATG-5, P62 and mTOR expressions. Conclusion: Nano-Se is capable to alleviate fluoride-induced hepatocyte damage, that selenium can be prefer to prevent chronic fluorosis-induced autophagy and apoptosis by regulating Cyt-C and Beclin-1/Bcl-2 signaling pathway. In precisely, NaF-induced the liver injury by activating autophagy and apoptosis, which indicate that fluorine exposure, pose an ecological risk to human beings and animals. Nano-Se has protective effects against fluoride-induced hepatocytes.

scholarly journals Relationship between Renal Dysfunction and Bone Metabolism Disorder in Male Rats after Long-Term Oral Quantitative Cadmium Administration.

2000 ◽  
Vol 38 (4) ◽  
pp. 339-355 ◽  
Author(s):  
Hisayoshi OHTA ◽  
Youji YAMAUCHI ◽  
Minoru NAKAKITA ◽  
Hideyuki TANAKA ◽  
Satoshi ASAMI ◽  
...  
Keyword(s):  
Renal Dysfunction ◽  
Bone Metabolism ◽  
Male Rats ◽  
Metabolism Disorder

scholarly journals Long-term outcome of the survivors of infantile hypercalcaemia with CYP24A1 and SLC34A1 mutations

2020 ◽  
Author(s):  
Agnieszka Janiec ◽  
Paulina Halat-Wolska ◽  
Łukasz Obrycki ◽  
Elżbieta Ciara ◽  
Marek Wójcik ◽  
...  
Keyword(s):  
Renal Transplantation ◽  
Vitamin D3 ◽  
Risk Level ◽  
Renal Ultrasound ◽  
Active Metabolites ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Metabolism Disorder ◽  
Biallelic Mutations

Abstract Background Infantile hypercalcaemia (IH) is a vitamin D3 metabolism disorder. The molecular basis for IH is biallelic mutations in the CYP24A1 or SLC34A1 gene. These changes lead to catabolism disorders (CYP24A1 mutations) or excessive generation of 1,25-dihydroxyvitamin D3 [1,25(OH)2D3] (SLC34A1 mutations). The incidence rate of IH in children and the risk level for developing end-stage renal disease (ESRD) are still unknown. The aim of this study was to analyse the long-term outcome of adolescents and young adults who suffered from IH in infancy. Design Forty-two children (23 girls; average age 10.7 ± 6.3 years) and 26 adults (14 women; average age 24.2 ± 4.4 years) with a personal history of hypercalcaemia with elevated 1,25(OH)2D3 levels were included in the analysis. In all patients, a genetic analysis of possible IH mutations was conducted, as well as laboratory tests and renal ultrasonography. Results IH was confirmed in 20 studied patients (10 females). CYP24A1 mutations were found in 16 patients (8 females) and SLC34A1 in 4 patients (2 females). The long-term outcome was assessed in 18 patients with an average age of 23.8 years (age range 2–34). The average glomerular filtration rate (GFR) was 72 mL/min/1.73 m2 (range 15–105). Two patients with a CYP24A1 mutation developed ESRD and underwent renal transplantation. A GFR <90 mL/min/1.73 m2 was found in 14 patients (77%), whereas a GFR <60 mL/min/1.73 m2 was seen in 5 patients (28%), including 2 adults after renal transplantation. Three of 18 patients still had serum calcium levels >2.6 mmol/L. A renal ultrasound revealed nephrocalcinosis in 16 of 18 (88%) patients, however, mild hypercalciuria was detected in only one subject. Conclusions Subjects who suffered from IH have a greater risk of progressive chronic kidney disease and nephrocalcinosis. This indicates that all survivors of IH should be closely monitored, with early implementation of preventive measures, e.g. inhibition of active metabolites of vitamin D3 synthesis.

scholarly journals Neonatal jaundice causes and management

2018 ◽  
Vol 5 (11) ◽  
pp. 4992
Author(s):  
Ruya Althomali ◽  
Renad Aloqayli ◽  
Basma Alyafi ◽  
Ahela Nono ◽  
Suhaib Alkhalaf ◽  
...  
Keyword(s):  
Exchange Transfusion ◽  
Neonatal Jaundice ◽  
Intravenous Immunoglobulins ◽  
Pharmacological Agents ◽  
Abo Incompatibility ◽  
Search Terms ◽  
Bilirubin Metabolism ◽  
Comprehensive Search ◽  
Neonates And Infants

80% of healthy neonates present with some degree of hyperbilirubinemia after birth, however, only 5-10% would require therapy to prevent damage or treat the cause of jaundice. Neonatal jaundice can be classified as physiological and pathological and can have several causes such as breast milk feeding, blood group incompatibility, hemolysis, or genetic defects of enzymes in the bilirubin metabolism pathway. We tried to understand the various types of neonatal jaundice, and also focus on its management. We conducted this review using a comprehensive search of MEDLINE, PubMed and EMBASE from January 2001 to March 2017. The following search terms were used: neonatal jaundice, hyperbilirubinemia, ABO incompatibility, neonatal hemolysis, kernicterus, phototherapy, exchange transfusion. Hyperbilirubinemia and jaundice are common issues encountered neonates and infants. Most cases of neonatal hyperbilirubinemia and jaundice are physiological and benign. However, some severe cases may progress to develop severe and permanent long-term complications. Therefore, early diagnosis and management is essential. Neonatal jaundice can be treated using phototherapy, pharmacological agents, intravenous immunoglobulins and exchange transfusion in severe cases.

The UGT1A1*28 gene variant predicts long-term mortality in patients undergoing coronary angiography

2018 ◽  
Vol 56 (4) ◽  
pp. 560-564 ◽  
Author(s):  
Barbara Zulus ◽  
Gerda Grünbacher ◽  
Marcus E. Kleber ◽  
Winfried März ◽  
Wilfried Renner
Keyword(s):  
Cardiovascular Health ◽  
Multivariate Regression Analysis ◽  
Health Study ◽  
Cardiovascular Health Study ◽  
Uridine Diphosphate ◽  
Gene Variant ◽  
Bilirubin Metabolism ◽  
Exogenous Compounds

AbstractBackground:Uridine diphosphate glycosyltransferases 1A1 (UGT1A1) plays an essential role in detoxification and excretion of several endogenous and exogenous compounds. A functional polymorphism in the promoter of theUGT1A1gene (TA repeat insertion,UGT1A1*28, rs3064744) has been associated with reducedUGT1A1enzyme activity. The purpose of the present study was to investigate the role ofUGT1A1genotypes in mortality.Methods:UGT1A1genotypes as well as baseline plasma bilirubin levels were analyzed in participants of the Ludwigshafen Risk and Cardiovascular Health study (n=3316).UGT1A1*28 genotypes were determined on an ABI PRISM 3730 genetic analyzer.Results:As expected,UGT1A1genotypes were associated with baseline bilirubin levels (*1/*1 genotype: 9.1±4.6 µmol/L; *1/*28 genotype: 10.8±5.3; *28/*28: 16.9±9.2; p<0.001). During a median follow-up of 10.4 years, 995 subjects (30.0%) died. In a multivariate regression analysis adjusting for age, sex, smoking, type 2 diabetes, dyslipidemia, alanine aminotransferase (ALT) levels and bilirubin levels, theUGT1A1*28 variant predicted lower overall mortality (hazard ratio [HR], 0.86; 95% confidence interval [CI], 0.78–0.95; p=0.003). Contrary to expected, higher baseline bilirubin levels predicted increased mortality (HR, 1.014; 95% CI, 1.002–1.025; p=0.019).Conclusions:TheUGT1A1*28 gene variant is associated with lower mortality rates. The protective effect of theUGT1A1*28 variant likely includes mechanism other than bilirubin metabolism.

scholarly journals Molecular Physiology and Pathophysiology of Bilirubin Handling by the Blood, Liver, Intestine, and Brain in the Newborn

2020 ◽  
Vol 100 (3) ◽  
pp. 1291-1346 ◽  
Author(s):  
Thor W. R. Hansen ◽  
Ronald J. Wong ◽  
David K. Stevenson
Keyword(s):  
Newborn Infant ◽  
Newborn Infants ◽  
The Body ◽  
Older Children ◽  
Molecular Physiology ◽  
Current State ◽  
Oxidation Reduction ◽  
Bilirubin Metabolism ◽  
The Brain

Bilirubin is the end product of heme catabolism formed during a process that involves oxidation-reduction reactions and conserves iron body stores. Unconjugated hyperbilirubinemia is common in newborn infants, but rare later in life. The basic physiology of bilirubin metabolism, such as production, transport, and excretion, has been well described. However, in the neonate, numerous variables related to nutrition, ethnicity, and genetic variants at several metabolic steps may be superimposed on the normal physiological hyperbilirubinemia that occurs in the first week of life and results in bilirubin levels that may be toxic to the brain. Bilirubin exists in several isomeric forms that differ in their polarities and is considered a physiologically important antioxidant. Here we review the chemistry of the bilirubin molecule and its metabolism in the body with a particular focus on the processes that impact the newborn infant, and how differences relative to older children and adults contribute to the risk of developing both acute and long-term neurological sequelae in the newborn infant. The final section deals with the interplay between the brain and bilirubin and its entry, clearance, and accumulation. We conclude with a discussion of the current state of knowledge regarding the mechanism(s) of bilirubin neurotoxicity.

scholarly journals Glucose Metabolism Disorder Induces Spermatogenic Dysfunction in Northern Pig-Tailed Macaques (Macaca leonina) With Long-Term SIVmac239 Infection

2021 ◽  
Vol 12 ◽  
Author(s):  
Tian-Zhang Song ◽  
Ming-Xu Zhang ◽  
Han-Dan Zhang ◽  
Xue-Hui Wang ◽  
Wei Pang ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Pancreatic Islet ◽  
Lactate Production ◽  
Whole Body ◽  
Β Cell ◽  
Metabolism Disorder ◽  
Immunodeficiency Virus ◽  
Glucose Metabolism Disorder ◽  
Sivmac239 Infection

Although spermatogenic dysfunction is widely found in patients with human immunodeficiency virus (HIV), the underlying reasons remain unclear. Thus far, potential hypotheses involving viral reservoirs, testicular inflammation, hormone imbalance, and cachexia show inconsistent correlation with spermatogenic dysfunction. Here, northern pig-tailed macaques (NPMs) exhibited marked spermatogenic dysfunction after long-term infection with simian immunodeficiency virus (SIVmac239), with significant decreases in Johnsen scores, differentiated spermatogonial stem cells, and testicular proliferating cells. The above hypotheses were also evaluated. Results showed no differences between SIV− and SIV+ NPMs, except for an increase in follicle stimulating hormone (FSH) during SIV infection, which had no direct effect on the testes. However, long-term SIVmac239 infection undermined pancreatic islet β cell function, partly represented by significant reductions in cellular counts and autophagy levels. Pancreatic islet β cell dysfunction led to glucose metabolism disorder at the whole-body level, which inhibited lactate production by Sertoli cells in testicular tissue. As lactate is the main energy substrate for developing germ cells, its decrease was strongly correlated with spermatogenic dysfunction. Therefore, glucose metabolism disorder appears to be a primary cause of spermatogenic dysfunction in NPMs with long-term SIVmac239 infection.

Therapy and prevention for mental health: What if mental diseases are mostly not brain disorders?

2019 ◽  
Vol 42 ◽  
Author(s):  
John P. A. Ioannidis
Keyword(s):  
Mental Health ◽  
Mental Disease ◽  
Brain Disorders ◽  
Social Stressors ◽  
Labor Education ◽  
Mental Diseases ◽  
Long Term Follow Up ◽  
Political Decisions

AbstractNeurobiology-based interventions for mental diseases and searches for useful biomarkers of treatment response have largely failed. Clinical trials should assess interventions related to environmental and social stressors, with long-term follow-up; social rather than biological endpoints; personalized outcomes; and suitable cluster, adaptive, and n-of-1 designs. Labor, education, financial, and other social/political decisions should be evaluated for their impacts on mental disease.

Conceptual short-term memory (CSTM) supports core claims of Christiansen and Chater

2016 ◽  
Vol 39 ◽  
Author(s):  
Mary C. Potter
Keyword(s):  
Working Memory ◽  
Rapid Serial Visual Presentation ◽  
Language Comprehension ◽  
Short Term Memory ◽  
Visual Presentation ◽  
Long Term Memory ◽  
Short Term ◽  
Term Memory ◽  
Use Of Knowledge

AbstractRapid serial visual presentation (RSVP) of words or pictured scenes provides evidence for a large-capacity conceptual short-term memory (CSTM) that momentarily provides rich associated material from long-term memory, permitting rapid chunking (Potter 1993; 2009; 2012). In perception of scenes as well as language comprehension, we make use of knowledge that briefly exceeds the supposed limits of working memory.

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