scholarly journals Glycosaminoglycans as Biomarkers for Mucopolysaccharidoses and Other Disorders

Diagnostics ◽  
2021 ◽  
Vol 11 (9) ◽  
pp. 1563
Author(s):  
Paige Amendum ◽  
Shaukat Khan ◽  
Seiji Yamaguchi ◽  
Hironori Kobayashi ◽  
Yasuhiko Ago ◽  
...  
Keyword(s):  
Developmental Disorders ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Conclusive Evidence ◽  
Liver Disorders ◽  
Designed Experiments ◽  
Diagnosis And Prognosis ◽  
Clinical Diagnoses ◽  
Larger Sample ◽  
Potential Biomarkers

Glycosaminoglycans (GAGs) are present in proteoglycans, which play critical physiological roles in various tissues. They are known to be elevated in mucopolysaccharidoses (MPS), a group of rare inherited metabolic diseases in which the lysosomal enzyme required to break down one or more GAG is deficient. In a previous study, we found elevation of GAGs in a subset of patients without MPS. In the current study, we aim to investigate serum GAG levels in patients with conditions beyond MPS. In our investigated samples, the largest group of patients had a clinical diagnosis of viral or non-viral encephalopathy. Clinical diagnoses and conditions also included epilepsy, fatty acid metabolism disorders, respiratory and renal disorders, liver disorders, hypoglycemia, developmental disorders, hyperCKemia, myopathy, acidosis, and vomiting disorders. While there was no conclusive evidence across all ages for any disease, serum GAG levels were elevated in patients with encephalopathy and some patients with other conditions. These preliminary findings suggest that serum GAGs are potential biomarkers in MPS and other disorders. In conclusion, we propose that GAGs elevated in blood can be used as biomarkers in the diagnosis and prognosis of various diseases in childhood; however, further designed experiments with larger sample sizes are required.

Abstract 49: The Transcriptional Repressor MafG Regulates Cholesterol Catabolism

2015 ◽  
Vol 35 (suppl_1) ◽  
Author(s):  
Thomas Q de Aguiar Vallim ◽  
Elizabeth J Tarling ◽  
Hannah Ahn ◽  
Lee R Hagey ◽  
Casey E Romanoski ◽  
...  
Keyword(s):  
Bile Acid ◽  
Bile Acids ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Cholesterol Metabolism ◽  
Transcriptional Repressor ◽  
Acid Synthesis ◽  
Bile Acid Synthesis ◽  
Bile Acid Metabolism ◽  
Biliary Bile Acid

Elevated circulating cholesterol levels is a major risk factor for cardiovascular diseases (CVD), and therefore understanding pathways that affect cholesterol metabolism are important for potential treatment of CVD. The major route for cholesterol excretion is through its catabolism to bile acids. Specific bile acids are also potent signaling molecules that modulate metabolic pathways affecting lipid, glucose and bile acid homeostasis. Bile acids are synthesized from cholesterol in the liver, and the key enzymes involved in bile acid synthesis ( Cyp7a1 , Cyp8b1 ) are regulated transcriptionally by the nuclear receptor FXR. We have identified an FXR-regulated pathway upstream of a transcriptional repressor that controls multiple bile acid metabolism genes. We identify MafG as an FXR target gene and show that hepatic MAFG overexpression represses genes of the bile acid synthetic pathway, and modifies the biliary bile acid composition. In contrast, MafG loss-of-function studies cause de-repression of the bile acid genes with concordant changes in biliary bile acid levels. Finally, we identify functional MafG response elements in bile acid metabolism genes using ChIP-Seq analysis. Our studies identify a molecular mechanism for the complex feedback regulation of bile acid synthesis controlled by FXR. The identification of this pathway will likely have important implications in metabolic diseases.

scholarly journals Causes of death in goats in Rio Grande do Sul state, Brazil: analysis of 322 cases (2000-2016)

2018 ◽  
Vol 38 (11) ◽  
pp. 2080-2087 ◽  
Author(s):  
Daniele M. Bassuino ◽  
Guilherme Konradt ◽  
Matheus V. Bianchi ◽  
Gustavo G.M. Snel ◽  
Luciana Sonne ◽  
...  
Keyword(s):  
Infectious Diseases ◽  
Developmental Disorders ◽  
Metabolic Diseases ◽  
Rio Grande ◽  
Nutritional Deficiencies ◽  
Rio Grande Do Sul ◽  
Viral Origin ◽  
Pregnancy Toxemia ◽  
Rumen Acidosis ◽  
Conclusive Diagnosis

ABSTRACT: The diagnosis of the cause of death in goats submitted to necropsy from January 2000 to December 2016 by Setor de Patologia Veterinária from the Universidade Federal do Rio Grande do Sul was reviewed. Epidemiological features, such as the breed, sex and age, in addition to the clinical and pathological features were evaluated. During this period, 322 goats were necropsied, in which a conclusive diagnosis was obtained in 290 (90%) goats. Goats that were part of other experimental study were excluded from this study. From these 290 cases, 167 (57.6%) corresponded to diseases of infectious origin and toxinfectious diseases, while 123 (42.4%) were classified as non-infectious conditions. Infectious diseases included 55 cases of bacterial origin, 59 cases with parasitary involvement, 14 cases of viral origin, and 39 toxinfectious cases. Non-infectious conditions were grouped into metabolic diseases (44 cases), plants or chemical substances poisoning (36), mineral and nutritional deficiencies (20), and neoplasms and developmental disorders (5). In the remaining 18 cases, a conclusive diagnosis was obtained, however the conditions did not fit into those criteria and were classified as “others”. The age range of the goats in this study was from 1 day-old to 10 years-old. Most of the goats were females (201), while 121 were males. Affected breeds included Boer, Saanen, Anglo-Nubian, Toggenburg and mixed breeds. Parasitic, infectious and toxin-infectious diseases were the main cause of deaths, especially haemonchosis, pleuropneumonia, eimeriosis and enterotoxemia. Among the non-infectious conditions, metabolic disorders, especially rumen acidosis, pregnancy toxemia and urolithiasis, were directly related to the management employed in the property. Plant poisoning diagnosis was also highlighted with locally present plants, such as Sida carpinifolia, as the most important.

scholarly journals Metabolome and exposome profiling of the biospecimens from COVID-19 patients in India

2021 ◽  
Vol 98 (4) ◽  
pp. 397-415
Author(s):  
Sh. Aggarwal ◽  
Sh. Parihari ◽  
A. Banerjee ◽  
J. Roy ◽  
N. Banerjee ◽  
...  
Keyword(s):  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Indian Population ◽  
Acid Metabolism ◽  
Clinical Applications ◽  
Rapid Diagnosis ◽  
Plasma Samples ◽  
Metabolism Pathway ◽  
Diagnosis And Prognosis ◽  
Metabolome Profiling

Introduction. COVID-19 has become a global impediment by bringing everything to a halt starting from January 2020. India underwent the lockdown starting from 22nd March 2020 with the sudden spike in the number of COVID-19 patients in major cities and states. This study focused on how metabolites play a crucial role in SARSCoV-2 prognosis.Materials and methods. Metabolome profiling of 106 plasma samples and 24 swab samples from symptomatic patients in the Indian population of the Mumbai region was done. COVID-19 positive samples were further segregated under the non-severe COVID-19 and severe COVID-19 patient cohort for both plasma and swab.Results. After analyzing the raw files, total 7,949 and 12,871 metabolites in plasma and swab were found. 11 and 35 significantly altered metabolites were found in COVID-19 positive compared to COVID-19 negative plasma and swab samples, respectively. Also, 9 and 23 significantly altered metabolites were found in severe COVID-19 positive to non-severe COVID-19 positive plasma and swab samples, respectively. The majorly affected pathways in COVID-19 patients were found to be the amino acid metabolism pathway, sphingosine metabolism pathway, and bile salt metabolism pathway.Conclusion. This study facilitates identification of potential metabolite-based biomarker candidates for rapid diagnosis and prognosis for clinical applications.

Experience in the use of transcranial micro polarization in children with autism spectrum disorders

2021 ◽  
Vol 2 (1) ◽  
pp. 22-28
Author(s):  
Ludmila M. Kuzenkova ◽  
Anna V. Lashkova ◽  
Olga M. Konova ◽  
Tatyana G. Petelguzova
Keyword(s):  
Autism Spectrum Disorders ◽  
Developmental Disorders ◽  
Children With Autism ◽  
Social Situation ◽  
Treatment Method ◽  
Autism Spectrum ◽  
Clinical Diagnoses ◽  
Spectrum Disorders ◽  
Autistic Disorders ◽  
Positive Effect

Introduction. Autism is a disorder characterized by social interaction disorders, social-emotional reciprocity, responses to other people’s emotions, social use of speech skills, lack of modulations of behavior under the social situation, and limited interest stereotypes. The comprehensive approach using medical and psychological correction with physical methods of influence provides the best result in treating and rehabilitating children with autism. The original study examined the effects of transcranial micro polarization (TCMP) on the dynamics of autistic disorders. TCMP is a modern treatment method consisting of a directed polarizing impact of a low-power DC on specific brain areas. Materials and methods. There were observed 25 children aged from 2 years five months to 6 years with varying degrees of severity of autism spectrum disorders (ASD). For the study, three groups were identified according to the corresponding clinical diagnoses: Childhood autism, Atypical autism, and Other general developmental disorders. The vast majority of children from the first two groups had an intellectual disability of varying severity. The TCMP method was used to assess the technique’s effectiveness, the CARS diagnostic scale and the ATEK test. Results. At the end of the course, with the use of TCMP in all the analyzed groups, there was a shift towards a milder degree of autistic disorders. The most significant positive effect was recorded in children with mild forms of autism in the group of other general developmental disorders due to the initially higher level of development in this group. Conclusion. The results obtained demonstrate the effectiveness of TCMP in ASD children. According to the results of the study, the positive effect of this method was revealed in the form of reducing the severity of autistic disorders.

scholarly journals Glucagon Receptor Signaling and Glucagon Resistance

2019 ◽  
Vol 20 (13) ◽  
pp. 3314 ◽  
Author(s):  
Janah ◽  
Kjeldsen ◽  
Galsgaard ◽  
Winther-Sørensen ◽  
Stojanovska ◽  
...  
Keyword(s):  
Lipid Metabolism ◽  
Amino Acid ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Metabolic Diseases ◽  
Physiological Role ◽  
Glucagon Receptor ◽  
Metabolomic Profiling ◽  
Hepatic Fat

Hundred years after the discovery of glucagon, its biology remains enigmatic. Accurate measurement of glucagon has been essential for uncovering its pathological hypersecretion that underlies various metabolic diseases including not only diabetes and liver diseases but also cancers (glucagonomas). The suggested key role of glucagon in the development of diabetes has been termed the bihormonal hypothesis. However, studying tissue-specific knockout of the glucagon receptor has revealed that the physiological role of glucagon may extend beyond blood-glucose regulation. Decades ago, animal and human studies reported an important role of glucagon in amino acid metabolism through ureagenesis. Using modern technologies such as metabolomic profiling, knowledge about the effects of glucagon on amino acid metabolism has been expanded and the mechanisms involved further delineated. Glucagon receptor antagonists have indirectly put focus on glucagon’s potential role in lipid metabolism, as individuals treated with these antagonists showed dyslipidemia and increased hepatic fat. One emerging field in glucagon biology now seems to include the concept of hepatic glucagon resistance. Here, we discuss the roles of glucagon in glucose homeostasis, amino acid metabolism, and lipid metabolism and present speculations on the molecular pathways causing and associating with postulated hepatic glucagon resistance.

scholarly journals Hippocampus Metabolic Disturbance and Autophagy Deficiency in Olfactory Bulbectomized Rats and the Modulatory Effect of Fluoxetine

2019 ◽  
Vol 20 (17) ◽  
pp. 4282 ◽  
Author(s):  
Yunfeng Zhou ◽  
Xue Tao ◽  
Zhi Wang ◽  
Li Feng ◽  
Lisha Wang ◽  
...  
Keyword(s):  
Metabolic Profile ◽  
Amino Acid Metabolism ◽  
Acid Metabolism ◽  
Memory Deficits ◽  
Memory Deficit ◽  
Metabolic Disturbance ◽  
Behavioral Changes ◽  
Post Surgery ◽  
Fluoxetine Treatment ◽  
Potential Biomarkers

An olfactory bulbectomy (OBX) rodent is a widely-used model for depression (especially for agitated depression). The present study aims to investigate the hippocampus metabolic profile and autophagy-related pathways in OBX rats and to explore the modulatory roles of fluoxetine. OBX rats were given a 30-day fluoxetine treatment after post-surgery rehabilitation, and then behavioral changes were evaluated. Subsequently, the hippocampus was harvested for metabonomics analysis and Western blot detection. As a result, OBX rats exhibited a significantly increased hyperemotionality score and declined spatial memory ability. Fluoxetine reduced the hyperemotional response, but failed to restore the memory deficit in OBX rats. Sixteen metabolites were identified as potential biomarkers for the OBX model including six that were rectified by fluoxetine. Disturbed pathways were involved in amino acid metabolism, fatty acid metabolism, purine metabolism, and energy metabolism. In addition, autophagy was markedly inhibited in the hippocampus of OBX rats. Fluoxetine could promote autophagy by up-regulating the expression of LC3 II, beclin1, and p-AMPK/AMPK, and down-regulating the levels of p62, p-Akt/Akt, p-mTOR/mTOR, and p-ULK1/ULK1. Our findings indicated that OBX caused marked abnormalities in hippocampus metabolites and autophagy, and fluoxetine could partly redress the metabolic disturbance and enhance autophagy to reverse the depressive-like behavior, but not the memory deficits in OBX rats.

scholarly journals Untargeted metabolomics reveals the effect of lovastatin on steroid-induced necrosis of the femoral head in rabbits

2020 ◽  
Vol 15 (1) ◽  
Author(s):  
Xiangnan Ren ◽  
Zixing Shao ◽  
Wu Fan ◽  
Zixuan Wang ◽  
Kaiyun Chen ◽  
...  
Keyword(s):  
Femoral Head ◽  
Least Squares ◽  
Partial Least Squares ◽  
Acid Metabolism ◽  
Mass Spectrometry Analysis ◽  
Sphingolipid Metabolism ◽  
Control Group ◽  
Group Model ◽  
Alpha Linolenic Acid ◽  
Potential Biomarkers

Abstract Purpose Lovastatin is an important medicine and it shows a significant effect against glucocorticoid-induced necrosis of the femoral head. This study aimed to investigate the effect of lovastatin on preventing necrosis of the femoral head of by serum metabolomics strategy. Methods Adult healthy adult Japanese white rabbits were divided into three groups: control group, model group, and drug group. The pathologic changes of femoral head were assessed with magnetic resonance imaging and microscope. Metabolomics based on ultra-high performance liquid chromatography tandem mass spectrometry analysis was used to analyze the collected serum sample. Data were analyzed using principal component analysis, partial least squares-discriminate analysis, and orthogonal partial least squares-discriminant analysis. All potential metabolites were identified by comparing with human metabolome database, Metlin database, lipid maps, and chemspider database. Results Eleven potential biomarkers were noted and identified as potential biomarkers. The change of biomarkers suggested that lovastatin on preventing necrosis of the femoral head may affect glycerophospholipid metabolism, linoleic acid metabolism, sphingolipid metabolism, alpha-linolenic acid metabolism, pyrimidine metabolism, and arachidonic acid metabolism. Conclusion The study suggested that lovastatin could prevent the glucocorticoid-induced necrosis of the femoral head of rabbits. The possible reasons were closely associated with adjusting the lipid metabolism, inhibiting adipogenesis, and delaying the osteocyte apoptosis.

scholarly journals Metabolomic Biomarkers of Multiple Sclerosis: A Systematic Review

2020 ◽  
Vol 7 ◽  
Author(s):  
Lachlan Porter ◽  
Alireza Shoushtarizadeh ◽  
George A. Jelinek ◽  
Chelsea R. Brown ◽  
Chai K. Lim ◽  
...  
Keyword(s):  
Multiple Sclerosis ◽  
Magnetic Resonance ◽  
High Throughput Sequencing ◽  
Cochrane Library ◽  
Clinical Criteria ◽  
Diagnosis And Prognosis ◽  
Csf Analysis ◽  
Potential Biomarker ◽  
Magnetic Resonance Imaging Mri ◽  
Potential Biomarkers

BackgroundMagnetic resonance imaging (MRI), cerebrospinal fluid (CSF) analysis, and the McDonald’s clinical criteria are currently utilized tools in diagnosing multiple sclerosis. However, a more conclusive, consistent, and efficient way of diagnosing multiple sclerosis (MS) is yet to be discovered. A potential biomarker, discovered using advances in high-throughput sequencing such as nuclear magnetic resonance (NMR) spectroscopy and other “Omics”-based techniques, may make diagnosis and prognosis more reliable resulting in a more personalized and targeted treatment regime and improved outcomes. The aim of this review was to systematically search the literature for potential biomarkers from any bodily fluid that could consistently and accurately diagnose MS and/or indicate disease progression.MethodsA systematic literature review of EMBASE, PubMed (MEDLINE), The Cochrane Library, and CINAHL databases produced over a thousand potential studies. Inclusion criteria stated studies with potential biomarker outcomes for people with MS were to be included in the review. Studies were limited to those with human participants who had a clinically defined diagnosis of MS and published in English, with no limit placed on date of publication or the type of bodily fluid sampled.ResultsA total of 1,805 studies were recorded from the literature search. A total of 1,760 studies were removed based on their abstract, with a further 18 removed after considering the full text. A total of 30 studies were considered relevant and had their data retrieved and analyzed. Due to the heterogeneity of focus and results from the refined studies, a narrative synthesis was favored.ConclusionSeveral promising candidate biomarkers suitable for clinical application in MS have been studied. It is recommended follow-up studies with larger sample sizes be completed on several potential biomarkers.

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