scholarly journals Analysis of site and structure specific core fucosylation in liver cirrhosis using exoglycosidase-assisted data-independent LC-MS/MS

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Miloslav Sanda ◽  
Jaeil Ahn ◽  
Petr Kozlik ◽  
Radoslav Goldman

AbstractCarbohydrates form one of the major groups of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation. Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer. Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored. We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides to their nonfucosylated glycoforms derived from 18 serum proteins in liver disease of different etiologies. Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment. In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans. Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.

2020 ◽  
Author(s):  
Miloslav Sanda ◽  
Jaeil Ahn ◽  
Petr Kozlik ◽  
Radoslav Goldman

ABSTRACTCarbohydrates form one of the major groups of biological macromolecules in living organisms. Many biological processes including protein folding, stability, immune response, and receptor activation are regulated by glycosylation. Fucosylation of proteins regulates such processes and is associated with various diseases including autoimmunity and cancer. Mass spectrometry efficiently identifies structures of fucosylated glycans or sites of core fucosylated N-glycopeptides but quantification of the glycopeptides remains less explored. We performed experiments that facilitate quantitative analysis of the core fucosylation of proteins with partial structural resolution of the glycans and we present results of the mass spectrometric SWATH-type DIA analysis of relative abundances of the core fucosylated glycoforms of 45 glycopeptides derived from 18 serum proteins in liver disease of different etiologies. Our results show that a combination of soft fragmentation with exoglycosidases is efficient at the assignment and quantification of the core fucosylated N-glycoforms at specific sites of protein attachment. In addition, our results show that disease-associated changes in core fucosylation are peptide-dependent and further differ by branching of the core fucosylated glycans. Further studies are needed to verify whether tri- and tetra-antennary core fucosylated glycopeptides could be used as markers of liver disease progression.


Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1894-P
Author(s):  
JIANDI CHEN ◽  
JIANXU CHEN ◽  
HUIRONG FU ◽  
YUN LI ◽  
SHUNKUI LUO ◽  
...  

2013 ◽  
Vol 8 (2) ◽  
pp. 159-178 ◽  

Atrazine, a chlorinated s-triazine group of herbicide is one of the most widely used pesticides in the World. Due to its extensive use, long half-life and various toxic properties, it has very high environmental significance. Up to 22 mg l-1 of atrazine was found in ground water whereas permissible limit of atrazine is in ppb level in drinking water. As per Indian standard there should not be any pesticide present in drinking water. Among many other treatment processes available, Incineration, adsorption, chemical treatment, phytoremediation and biodegradation are the most commonly used ones. Biological degradation of atrazine depends upon various factors like the operating environment, external carbon and nitrogen sources, carbon/ nitrogen ratio (C/N), water content and the bacterial strain. Although, general atrazine degradation pathways are available, the specific pathways in specific conditions are not yet clearly defined. In this paper extensive review has been made on the occurrence of atrazine in surface and ground water bodies, probable sources and causes of its occurrence in water environment, the toxicity of atrazine on various living organisms and its removal by biological processes.


Author(s):  
Xiao Zhou ◽  
Xiao-Fei Zhang ◽  
Dong-Yan Guo ◽  
Yan-Jun Yang ◽  
Lin Liu ◽  
...  

Objective: Lingzhu San (LZS) is a traditional Chinese medicine (TCM) prescription which can be effective in treating febrile seizures (FS) and has few researches on the mechanisms. In order to better guide the clinical use of LZS, we used the research ideas and methods of network pharmacology to find the potential core compounds, targets and pathways of LZS in the complex TCM system for the treatment of FS, and predict the mechanism. Materials and Methods: Databases such as BATMAN, TCMSP, TCMID, and SWISS TARGET are used to mine the active compounds and targets of LZS, and the target information of FS was obtained through GENECARDS and OMIM. Using Venny2.1.0 and Cytoscape software to locked the potential core compounds and targets of FS. The R language and ClusterProfiler software package were adopt to enrich and analyze the KEGG and GO pathways of the core targets and the biological processes and potential mechanisms of the core targets were revealed. Results: 187 active compounds and 2113 target proteins of LZS were collected. And 38 potential core compounds, 35 core targets and 775 metabolic and functional pathways were screened which involved in mediating FS. Finally, the role of the core compounds, targets and pivotal pathways of LZS regulated FS in the pathogenesis and therapeutic mechanism of FS was discussed and clarified. Conclusions: In this paper, the multi-compounds, multi-targets and multi-pathways mechanism of LZS in the treatment of FS was preliminarily revealed through the analysis of network pharmacology data, which is consistent with the principle of multi-compounds compatibility of TCM prescriptions and unified treatment of diseases from multiple angles, and it provides a new way for TCM to treat complex diseases caused by multiple factors.


2019 ◽  
Vol 20 (7) ◽  
pp. 727-735 ◽  
Author(s):  
Yi Wu ◽  
Zhibin Cheng ◽  
Yueyu Bai ◽  
Xi Ma

Nutrients can regulate metabolic activities of living organisms through epigenetic mechanisms, including DNA methylation, histone modification, and RNA regulation. Since the nutrients required for early embryos and postpartum lactation are derived in whole or in part from maternal and lactating nutrition, the maternal nutritional level affects the growth and development of fetus and creates a profound relationship between disease development and early environmental exposure in the offspring’s later life. Protein is one of the most important biological macromolecules, involved in almost every process of life, such as information transmission, energy processing and material metabolism. Maternal protein intake levels may affect the integrity of the fetal genome and alter DNA methylation and gene expression. Most amino acids are supplied to the fetus from the maternal circulation through active transport of placenta. Some amino acids, such as methionine, as dietary methyl donor, play an important role in DNA methylation and body’s one-carbon metabolism. The purpose of this review is to describe effects of maternal dietary protein and amino acid intake on fetal and neonatal growth and development through epigenetic mechanisms, with examples in humans and animals.


2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Nghiem Xuan Hoan ◽  
Pham Thi Minh Huyen ◽  
Mai Thanh Binh ◽  
Ngo Tat Trung ◽  
Dao Phuong Giang ◽  
...  

AbstractThe inhibitory effects of programmed cell death 1/programmed cell death ligand 1 (PD-1/PD-L1) modulates T-cell depletion. T-cell depletion is one of the key mechanisms of hepatitis B virus (HBV) persistence, in particular liver disease progression and the development of hepatocellular carcinoma (HCC). This case–control study aimed to understand the significance of PD-1 polymorphisms (PD-1.5 and PD-1.9) association with HBV infection risk and HBV-induced liver disease progression. Genotyping of PD-1.5 and PD-1.9 variants was performed by direct Sanger sequencing in 682 HBV-infected patients including chronic hepatitis (CHB, n = 193), liver cirrhosis (LC, n = 183), hepatocellular carcinoma (HCC, n = 306) and 283 healthy controls (HC). To analyze the association of PD-1 variants with liver disease progression, a binary logistic regression, adjusted for age and gender, was performed using different genetic models. The PD-1.9 T allele and PD-1.9 TT genotype are significantly associated with increased risk of LC, HCC, and LC + HCC. The frequencies of PD-1.5 TT genotype and PD-1.5 T allele are significantly higher in HCC compared to LC patients. The haplotype CT (PD-1.5 C and PD-1.9 T) was significantly associated with increased risk of LC, HCC, and LC + HCC. In addition, the TC (PD-1.5 T and PD-1.9 C) haplotype was associated with the risk of HCC compared to non-HCC. The PD-1.5 CC, PD-1.9 TT, genotype, and the CC (PD-1.5 C and PD-1.9) haplotype are associated with unfavorable laboratory parameters in chronic hepatitis B patients. PD-1.5 and PD1.9 are useful prognostic predictors for HBV infection risk and liver disease progression.


2021 ◽  
Vol 12 (2) ◽  
pp. 155-165
Author(s):  
Ahmed Hashem ◽  
Yogesh Shastri ◽  
Malfi Al Otaibi ◽  
Elwin Buchel ◽  
Hussam Saleh ◽  
...  

Non-alcoholic fatty disease (NAFLD) is amongst the leading causes of chronic liver disease worldwide. The prevalence of NAFLD in the Middle East is 32%, similar to that observed worldwide. The clinicians in this region face several challenges in diagnosing and treating patients with NAFLD. Additionally, there are no national or regional guidelines to address the concerns faced with current treatment options. Silymarin, derived from milk thistle, provides a rational and clinically proven approach to hepatoprotection. This article focuses on addressing regional diagnostic challenges and provides clear guidance and potential solutions for the use of Silymarin in the treatment of NAFLD in the Middle East. Both clinical and preclinical studies have highlighted the efficiency of Silymarin in managing NAFLD by reducing liver disease progression and improving patient symptoms and quality of life, alongside being safe and well tolerated. An expert panel of professionals from the Middle East convened to establish a set of regional-specific diagnostics. A consensus was established to aid general physicians to address the diagnostic challenges in the region. In conclusion, Silymarin can be considered beneficial in treating NAFLD and should be initiated as early as possible and continued as long as necessary.


2021 ◽  
Vol 22 (9) ◽  
pp. 4495
Author(s):  
Hyunmi Kim ◽  
Da Som Lee ◽  
Tae Hyeon An ◽  
Hyun-Ju Park ◽  
Won Kon Kim ◽  
...  

Liver disease is the spectrum of liver damage ranging from simple steatosis called as nonalcoholic fatty liver disease (NAFLD) to hepatocellular carcinoma (HCC). Clinically, NAFLD and type 2 diabetes coexist. Type 2 diabetes contributes to biological processes driving the severity of NAFLD, the primary cause for development of chronic liver diseases. In the last 20 years, the rate of non-viral NAFLD/NASH-derived HCC has been increasing rapidly. As there are currently no suitable drugs for treatment of NAFLD and NASH, a class of thiazolidinediones (TZDs) drugs for the treatment of type 2 diabetes is sometimes used to improve liver failure despite the risk of side effects. Therefore, diagnosis, prevention, and treatment of the development and progression of NAFLD and NASH are important issues. In this review, we will discuss the pathogenesis of NAFLD/NASH and NAFLD/NASH-derived HCC and the current promising pharmacological therapies of NAFLD/NASH. Further, we will provide insights into “adipose-derived adipokines” and “liver-derived hepatokines” as diagnostic and therapeutic targets from NAFLD to HCC.


2021 ◽  
Vol 22 (13) ◽  
pp. 6921
Author(s):  
Norihisa Nishimura ◽  
Kosuke Kaji ◽  
Koh Kitagawa ◽  
Yasuhiko Sawada ◽  
Masanori Furukawa ◽  
...  

Recent studies have suggested that an alteration in the gut microbiota and their products, particularly endotoxins derived from Gram-negative bacteria, may play a major role in the pathogenesis of liver diseases. Gut dysbiosis caused by a high-fat diet and alcohol consumption induces increased intestinal permeability, which means higher translocation of bacteria and their products and components, including endotoxins, the so-called “leaky gut”. Clinical studies have found that plasma endotoxin levels are elevated in patients with chronic liver diseases, including alcoholic liver disease and nonalcoholic liver disease. A decrease in commensal nonpathogenic bacteria including Ruminococaceae and Lactobacillus and an overgrowth of pathogenic bacteria such as Bacteroidaceae and Enterobacteriaceae are observed in cirrhotic patients. The decreased diversity of the gut microbiota in cirrhotic patients before liver transplantation is also related to a higher incidence of post-transplant infections and cognitive impairment. The exposure to endotoxins activates macrophages via Toll-like receptor 4 (TLR4), leading to a greater production of proinflammatory cytokines and chemokines including tumor necrosis factor-alpha, interleukin (IL)-6, and IL-8, which play key roles in the progression of liver diseases. TLR4 is a major receptor activated by the binding of endotoxins in macrophages, and its downstream signal induces proinflammatory cytokines. The expression of TLR4 is also observed in nonimmune cells in the liver, such as hepatic stellate cells, which play a crucial role in the progression of liver fibrosis that develops into hepatocarcinogenesis, suggesting the importance of the interaction between endotoxemia and TLR4 signaling as a target for preventing liver disease progression. In this review, we summarize the findings for the role of gut-derived endotoxemia underlying the progression of liver pathogenesis.


2017 ◽  
Vol 66 (1) ◽  
pp. S711-S712
Author(s):  
W. Zanjir ◽  
R. Maan ◽  
B. Hansen ◽  
O. Cerocchi ◽  
H. Janssen ◽  
...  

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