Humans ; Fibrinogen ; Liver/pathology* ; Liver Diseases/pathology* ; Metabolic Diseases/pathology*

Objective: To investigate the clinicopathological and molecular characteristics of hepatic fibrinogen storage disease (FSD) in children. Methods: The clinical, histopathologic, immunophenotypic, ultrastructural and gene sequencing data of 4 FSD cases were collected from September 2019 to January 2021 in the Children's Hospital of Fudan University, Shanghai, China. Retrospective analysis and literature review were conducted. Results: There were 4 cases of FSD, 3 males and 1 female, aged 3 years and 3 months to 6 years (median age, 3 years and 4 months). The clinical manifestations were abnormal liver function and abnormal blood coagulation function, for which 2 cases had family genetic history. Liver biopsies revealed that, besides liver steatosis, fibrosis and inflammation, there were single or multiple eosinophilic inclusion bodies of various sizes and surrounding transparent pale halo in hepatocytes. Immunohistochemistry showed that the inclusion bodies were positive for anti-fibrinogen. Under the electron microscope, they corresponded to the dilated cisternae of the rough endoplasmic reticulum, which were occupied by compactly packed tubular structures and arranged into a fingerprint-like pattern with curved bundles. Gene sequencing revealed that the 2 cases of FGG mutation were located in exon 8 c.1106A>G (p.His369Arg) and c.905T>C (p.Leu302Pro), and 1 case was located in exon 9 c.1201C>T (p.Arg401Trp). No pathogenic variant was detected in the other case. Conclusions: FSD is a rare genetic metabolic disease and clinically manifests as abnormal liver function with hypofibrinogenemia. In the background of liver steatosis, fibrosis and inflammation, there are eosinophilic inclusions with pale halo in the hepatocytic cytoplasm, which can be identified by anti-fibrinogen immunohistochemical staining. The fingerprint-like structures under electron microscope are helpful for the diagnosis, while FGG sequencing detects the pathogenic mutation of exon 8 or 9 that can clearly explain the phenotype. However, the diagnosis of FSD cannot be completely ruled out if the relevant mutations are not detected.
Child ; Child, Preschool ; China ; Female ; Fibrinogen/chemistry* ; Humans ; Liver/pathology* ; Liver Diseases/pathology* ; Male ; Metabolic Diseases/pathology* ; Retrospective Studies

The expression or dysfunction of long non-coding RNAs (lncRNAs) is closely related to various hereditary diseases, autoimmune diseases, metabolic diseases and tumors. LncRNAs were also recently recognized as functional regulators of fibrosis, which is a secondary process in many of these diseases and a primary pathology in fibrosis diseases. We review the latest findings on lncRNAs in fibrosis diseases of the liver, myocardium, kidney, lung and peritoneum. We also discuss the potential of disease-related lncRNAs as therapeutic targets for the clinical treatment of human fibrosis diseases.
Autoimmune Diseases ; Fibrosis ; Genetic Diseases, Inborn ; Humans ; Kidney ; Liver ; Lung ; Metabolic Diseases ; Myocardium ; Pathology ; Peritoneum ; RNA, Long Noncoding

Calcium pyrophosphate dihydrate (CPPD) crystal deposition disease is a disease of the elderly and extremely rare in young individuals. If young people develop CPPD crystal deposition disease, it may be associated with metabolic diseases such as hemochromatosis, hyperparathyroidism, hypophosphatasia, hypomagnesemia, Wilson's disease, hypothyroidism, gout, acromegaly, and X-linked hypophosphatemic rickets. Therefore, in young-onset polyarticular CPPD crystal deposition disease, investigation for predisposing metabolic conditions is warranted. We report a case of a young male patient with idiopathic CPPD crystal deposition disease, who did not have any evidences of metabolic diseases after thorough evaluations. As far as we know, this is the first report of a young male patient presented with idiopathic CPPD crystal deposition disease.
Adult ; Calcium Pyrophosphate/*metabolism ; Cartilage, Articular/metabolism/pathology ; Diagnosis, Differential ; Human ; Knee Joint/*pathology ; Male ; Metabolic Diseases/metabolism/pathology ; Shoulder Joint/pathology

A complex microbiota colonizes mucosal layers in different regions of the human gut. In the healthy state, the microbial communities provide nutrients and energy to the host via fermentation of non-digestible dietary components in the large intestine. In contrast, they can play roles in inflammation and infection, including gastrointestinal diseases and metabolic syndrome such as obesity. However, because of the complexity of the microbial community, the functional connections between the enteric microbiota and metabolism are less well understood. Nevertheless, major progress has been made in defining dominant bacterial species, community profiles, and systemic characteristics that produce stable microbiota beneficial to health, and in identifying their roles in enteric metabolism. Through studies in both mice and humans, we are recently in a better position to understand what effect the enteric microbiota has on the metabolism by improving energy yield from food and modulating dietary components. Achieving better knowledge of this information may provide insights into new possibilities that reconstitution of enteric microbiota via diet can provide the maintenance of healthy state and therapeutic/preventive strategies against metabolic syndrome such as obesity. This review focuses on enteric microbial composition and metabolism on healthy and diseased states.
Animals ; Bacteria/growth & development/metabolism ; Diet ; Gastrointestinal Diseases/*microbiology/pathology ; Humans ; Inflammation/microbiology/pathology ; Intestines/microbiology ; Metabolic Syndrome X/*microbiology/pathology ; *Microbiota ; Probiotics

Taurine is an abundant, β-amino acid with diverse cytoprotective activity. In some species, taurine is an essential nutrient but in man it is considered a semi-essential nutrient, although cells lacking taurine show major pathology. These findings have spurred interest in the potential use of taurine as a therapeutic agent. The discovery that taurine is an effective therapy against congestive heart failure led to the study of taurine as a therapeutic agent against other disease conditions. Today, taurine has been approved for the treatment of congestive heart failure in Japan and shows promise in the treatment of several other diseases. The present review summarizes studies supporting a role of taurine in the treatment of diseases of muscle, the central nervous system, and the cardiovascular system. In addition, taurine is extremely effective in the treatment of the mitochondrial disease, mitochondrial encephalopathy, lactic acidosis, and stroke-like episodes (MELAS), and offers a new approach for the treatment of metabolic diseases, such as diabetes, and inflammatory diseases, such as arthritis. The review also addresses the functions of taurine (regulation of antioxidation, energy metabolism, gene expression, ER stress, neuromodulation, quality control and calcium homeostasis) underlying these therapeutic actions.
Acidosis, Lactic ; Arthritis ; Brain Diseases ; Calcium ; Cardiovascular System ; Central Nervous System ; Cytoprotection ; Energy Metabolism ; Gene Expression ; Heart Failure ; Japan ; MELAS Syndrome ; Metabolic Diseases ; Mitochondrial Diseases ; Neurodegenerative Diseases ; Pathology ; Quality Control ; Taurine*

Bodycomposition measurement is useful in the diagnosis of pathology, assessment of disease process and response to treatement in many endoclonologic and metabolic diseases. The Techniques used currently are mostly indirect, often expensive, difficult and time-consuming. A new method for estimation of body composition, infrared interactance, is rapid, safe, noninvasive, and may be useful in research and clinical studies. Body composition was assessed in 51 children and adolescants with insulin-dependent diabetes mellitus by infrared interactance method using a Futrex 5000A body fat content analyzer. Percentage body fat of pubertal girls was 26.1+/-7.6%, significantly greater than prepubertal girls (17.9%, 0<0.01) and pubertal boys (19.9%, p<0.05). Body fat content was increased through puberty in girls. but not increased in boys. Our data do not explain why body fat of pubertal boys was not increased. There was no significant association of insulin dose and HbA1C level with percentage body fat. Thus, we had to attempt measure calorie intake, activity level and diet composition. Our data revealed that dietary carbohydrates may prompt fat deposition, but energy balance does not explain the differences between pubertal girls and boys. In conclusion, Body fat increased through puberty in girls, but the etiology of differences in pubertal girls and boys is not clear, and in view of potential adverse effect of fat depostion of long-term health, further larger case-contolled study will be necessary.
Adipose Tissue ; Adolescent* ; Body Composition* ; Child* ; Diabetes Mellitus, Type 1* ; Diagnosis ; Diet ; Dietary Carbohydrates ; Female ; Humans ; Insulin ; Metabolic Diseases ; Pathology ; Puberty

BACKGROUNDGastric cancer (GC) is one of the most common types of cancer in the world. A change in the metabolism of lipids in tumor cells could lead to the pathogenesis of cancer. In this study, we investigated fatty acid and fatty acid amide metabolic perturbations associated with GC morbidity.

METHODSGas chromatography/mass spectrometry (GC/MS) was utilized to analyze fatty acids (FAs) and fatty acid amides (FAAs) of GC tissues and matched normal mucosae from 30 GC patients. Acquired lipid data was analyzed using non parametric Wilcoxon rank sum test to find the differential biomarkers for GC and diagnostic models for GC were established by using orthogonal partial least squares discriminant analysis (OPLS-DA).

RESULTSA total of 13 FAs and 4 FAAs were detected using GC/MS and 5 differential FAs as well as oleamide were identified with significant difference (P<0.05). The OPLS-DA model generated from lipid profile showed adequate discrimination of GC tissues from normal mucosae while the OPLS-DA model failed to separate GC specimens of different TNM stages. A total of 8 variables were obtained for their most contribution in the discriminating model (Variable importance in the projection (VIP) value>1.0), five of which were detected with significant difference (P<0.05).

CONCLUSIONSFA and FAA metabolic profiles have great potential in detecting GC and helping understand perturbations of lipid metabolism associated with GC morbidity.

Amides ; metabolism ; Fatty Acids ; metabolism ; Female ; Gas Chromatography-Mass Spectrometry ; Humans ; In Vitro Techniques ; Male ; Metabolic Diseases ; physiopathology ; Stomach Neoplasms ; metabolism ; pathology

Animal models have been used to elucidate the pathophysiology of varying diseases and to provide insight into potential targets for therapeutic intervention. Although alternatives to animal testing have been proposed to help overcome potential drawbacks related to animal experiments and avoid ethical issues, their use remains vital for the testing of new drug candidates and to identify the most effective strategies for therapeutic intervention. Particularly, the study of metabolic diseases requires the use of animal models to monitor whole-body physiology. In line with this, the National Institute of Food and Drug Safety Evaluation (NIFDS) in Korea has established their own animal strains to help evaluate both efficacy and safety during new drug development. The objective of this study was to characterize the response of C57BL/6NKorl mice from the NIFDS compared with that of other mice originating from the USA and Japan in a chemical-induced diabetic condition. Multiple low-dose treatments with streptozotocin were used to generate a type-1 diabetic animal model which is closely linked to the known clinical pathology of this disease. There were no significantly different responses observed between the varying streptozotocin-induced type-1 diabetic models tested in this study. When comparing control and diabetic mice, increases in liver weight and disturbances in serum amino acids levels of diabetic mice were most remarkable. Although the relationship between type-1 diabetes and BCAA has not been elucidated in this study, the results, which reveal a characteristic increase in diabetic mice of all origins are considered worthy of further study.
Amino Acids ; Amino Acids, Branched-Chain ; Animal Experimentation ; Animal Testing Alternatives ; Animals ; Ethics ; Japan ; Korea ; Liver ; Metabolic Diseases ; Metabolomics* ; Mice* ; Models, Animal ; Pathology, Clinical ; Physiology ; Streptozocin

Brain and the gastrointestinal (GI) tract are intimately connected to form a bidirectional neurohumoral communication system. The communication between gut and brain, knows as the gut-brain axis, is so well established that the functional status of gut is always related to the condition of brain. The researches on the gut-brain axis were traditionally focused on the psychological status affecting the function of the GI tract. However, recent evidences showed that gut microbiota communicates with the brain via the gut-brain axis to modulate brain development and behavioral phenotypes. These recent findings on the new role of gut microbiota in the gut-brain axis implicate that gut microbiota could associate with brain functions as well as neurological diseases via the gut-brain axis. To elucidate the role of gut microbiota in the gut-brain axis, precise identification of the composition of microbes constituting gut microbiota is an essential step. However, identification of microbes constituting gut microbiota has been the main technological challenge currently due to massive amount of intestinal microbes and the difficulties in culture of gut microbes. Current methods for identification of microbes constituting gut microbiota are dependent on omics analysis methods by using advanced high tech equipment. Here, we review the association of gut microbiota with the gut-brain axis, including the pros and cons of the current high throughput methods for identification of microbes constituting gut microbiota to elucidate the role of gut microbiota in the gut-brain axis.
Brain ; metabolism ; Central Nervous System ; metabolism ; Gastrointestinal Tract ; metabolism ; microbiology ; High-Throughput Nucleotide Sequencing ; Humans ; Liver ; metabolism ; Metabolic Diseases ; metabolism ; pathology ; Metagenome ; Receptors, G-Protein-Coupled ; metabolism