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Glycoconjugate Journal Aug 2023Every eukaryotic cell is covered with a thick layer of complex carbohydrates with essential roles in their social life. In Deuterostoma, sialic acids present at the... (Review)
Review
Every eukaryotic cell is covered with a thick layer of complex carbohydrates with essential roles in their social life. In Deuterostoma, sialic acids present at the outermost positions of glycans of glycoconjugates are known to be key players in cellular interactions including host-pathogen interactions. Their negative charge and hydrophilic properties enable their roles in various normal and pathological states and their expression is altered in many diseases including cancers. Sialylation of glycoproteins and glycolipids is orchestrated by the regulated expression of twenty sialyltransferases in human tissues with distinct enzymatic characteristics and preferences for substrates and linkages formed. However, still very little is known on the functional organization of sialyltransferases in the Golgi apparatus and how the sialylation machinery is finely regulated to provide the ad hoc sialome to the cell. This review summarizes current knowledge on sialyltransferases, their structure-function relationships, molecular evolution, and their implications in human biology.
Topics: Animals; Humans; Sialyltransferases; Sialic Acids; Vertebrates; Glycoproteins; Evolution, Molecular
PubMed: 37247156
DOI: 10.1007/s10719-023-10123-w -
EMBO Reports Nov 2023Fate determination of primordial germ cells (PGCs) is regulated in a multi-layered manner, involving signaling pathways, epigenetic mechanisms, and transcriptional...
Fate determination of primordial germ cells (PGCs) is regulated in a multi-layered manner, involving signaling pathways, epigenetic mechanisms, and transcriptional control. Chemical modification of macromolecules, including epigenetics, is expected to be closely related with metabolic mechanisms but the detailed molecular machinery linking these two layers remains poorly understood. Here, we show that the hexosamine biosynthetic pathway controls PGC fate determination via O-linked β-N-acetylglucosamine (O-GlcNAc) modification. Consistent with this model, reduction of carbohydrate metabolism via a maternal ketogenic diet that decreases O-GlcNAcylation levels causes repression of PGC formation in vivo. Moreover, maternal ketogenic diet intake until mid-gestation affects the number of ovarian germ cells in newborn pups. Taken together, we show that nutritional and metabolic mechanisms play a previously unappreciated role in PGC fate determination.
Topics: Infant, Newborn; Humans; Signal Transduction; Acetylglucosamine; Gene Expression Regulation; Epigenesis, Genetic; Germ Cells; Protein Processing, Post-Translational
PubMed: 37842859
DOI: 10.15252/embr.202356845 -
Gut Microbes Dec 2023subsp. utilizes oligosaccharides secreted in human milk as a carbohydrate source. These human milk oligosaccharides (HMOs) integrate the nitrogenous residue...
subsp. utilizes oligosaccharides secreted in human milk as a carbohydrate source. These human milk oligosaccharides (HMOs) integrate the nitrogenous residue N-acetylglucosamine (NAG), although HMO nitrogen utilization has not been described to date. Herein, we characterize the nitrogen utilization phenotype on two NAG-containing HMO species, LNT and LNnT. This was characterized through growth kinetics, incorporation of isotopically labeled NAG nitrogen into the proteome, as well as modulation of intracellular 2-oxoglutarate levels while utilizing HMO nitrogen. Further support is provided by comparative transcriptomics and proteomics that identified global regulatory networks deployed during HMO nitrogen utilization. The aggregate data demonstrate that strains utilize HMO nitrogen with the potential to significantly impact fundamental and clinical studies, as well as enable applications.
Topics: Humans; Bifidobacterium longum subspecies infantis; Acetylglucosamine; Milk, Human; Gastrointestinal Microbiome; Oligosaccharides; Nitrogen
PubMed: 37609905
DOI: 10.1080/19490976.2023.2244721 -
Journal of Nanobiotechnology May 2024With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as "Gou qi zi" in China, is a traditional...
With the increasing trend of global aging, sarcopenia has become a significant public health issue. Goji berry, also known as "Gou qi zi" in China, is a traditional Chinese herb that can enhance the structure and function of muscles and bones. Otherwise, previous excellent publications illustrated that plant-derived exosome-like nanoparticles can exert good bioactive functions in different aging or disease models. Thus, we issued the hypothesis that Gouqi-derived nanovesicles (GqDNVs) may also have the ability to improve skeletal muscle health, though the effect and its mechanism need to be explored. Hence, we have extracted GqDNVs from fresh berries of Lycium barbarum L. (goji) and found that the contents of GqDNVs are rich in saccharides and lipids. Based on the pathway annotations and predictions in non-targeted metabolome analysis, GqDNVs are tightly associated with the pathways in metabolism. In muscle atrophy model mice, intramuscular injection of GqDNVs improves the cross-sectional area of the quadriceps muscle, grip strength and the AMPK/SIRT1/PGC1α pathway expression. After separately inhibiting AMPK or PGC1α in C2C12 cells with dexamethasone administration, we have found that the activated AMPK plays the chief role in improving cell proliferation induced by GqDNVs. Furthermore, the energy-targeted metabolome analysis in the quadriceps muscle demonstrates that the GqDNVs up-regulate the metabolism of amino sugar and nucleotide sugar, autophagy and oxidative phosphorylation process, which indicates the activation of muscle regeneration. Besides, the Spearman rank analysis shows close associations between the quality and function of skeletal muscle, metabolites and expression levels of AMPK and SIRT1. In this study, we provide a new founding that GqDNVs can improve the quality and function of skeletal muscle accompanying the activated AMPK/SIRT1/PGC1α signaling pathway. Therefore, GqDNVs have the effect of anti-aging skeletal muscle as a potential adjuvant or complementary method or idea in future therapy and research.
Topics: Animals; Sirtuin 1; Peroxisome Proliferator-Activated Receptor Gamma Coactivator 1-alpha; Mice; Signal Transduction; Dexamethasone; AMP-Activated Protein Kinases; Muscular Atrophy; Cell Line; Drugs, Chinese Herbal; Male; Muscle, Skeletal; Mice, Inbred C57BL; Nanoparticles; Exosomes
PubMed: 38778385
DOI: 10.1186/s12951-024-02563-9 -
The Journal of Clinical Endocrinology... Oct 2023Intermediate-term glycemic control metrics may represent a viable alternative to continuous glucose monitoring (CGM) in patients without access to CGM.
CONTEXT
Intermediate-term glycemic control metrics may represent a viable alternative to continuous glucose monitoring (CGM) in patients without access to CGM.
OBJECTIVE
This work aimed to compare the relationship between CGM parameters and glycated albumin (GA), glycated hemoglobin A1c (HbA1c), and fructosamine for 24 weeks.
METHODS
We conducted exploratory comparative analyses of CGM subgroup data from a previously published 24-week prospective study of assay performance in 8 US clinics. Participants included 34 individuals with type 1 (n = 18) and type 2 diabetes (n = 16) undergoing changes to improve glycemic control (n = 22; group 1) or with stable diabetes therapy (n = 12; group 2). Main outcome measures included Pearson correlations between CGM and glycemic indices and receiver operating characteristic (ROC) analysis of glycemic index values predictive of time in range (TIR) greater than 70%.
RESULTS
At weeks 4 and 8, GA correlations with TIR were higher than HbA1c correlations in group 1. In group 2, GA correlations with TIR were statistically significant, whereas HbA1c correlations were not. In both groups over the first 12 weeks, GA correlations with TIR were higher than fructosamine-TIR correlations. In the ROC analysis, GA predicted a TIR greater than 70% during weeks 2 to 24 (area under the curve >0.80); HbA1c was predictive during weeks 12 to 24. Cutoff values for TIR greater than 70% were 17.5% (sensitivity and specificity, 0.88) for GA and 7.3% (0.86) for HbA1c.
CONCLUSION
GA is the most accurate predictor of TIR over 8 weeks compared with other glycemic indices, which may assist in clinical evaluation of changes in treatment where CGM is not possible and it is too early to use HbA1c (NCT02489773).
Topics: Humans; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Fructosamine; Blood Glucose; Blood Glucose Self-Monitoring; Prospective Studies; Glycated Serum Albumin; Glycation End Products, Advanced; Serum Albumin
PubMed: 37259605
DOI: 10.1210/clinem/dgad298 -
The Journal of Clinical Endocrinology... Oct 2023There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be...
CONTEXT
There is no early, first-trimester risk estimation available to predict later (gestational week 24-28) gestational diabetes mellitus (GDM); however, it would be beneficial to start an early treatment to prevent the development of complications.
OBJECTIVE
We aimed to identify early, first-trimester prediction markers for GDM.
METHODS
The present case-control study is based on the study cohort of a Hungarian biobank containing biological samples and follow-up data from 2545 pregnant women. Oxidative-nitrative stress-related parameters, steroid hormone, and metabolite levels were measured in the serum/plasma samples collected at the end of the first trimester from 55 randomly selected control and 55 women who developed GDM later.
RESULTS
Pregnant women who developed GDM later during the pregnancy were older and had higher body mass index. The following parameters showed higher concentration in their serum/plasma samples: fructosamine, total antioxidant capacity, testosterone, cortisone, 21-deoxycortisol; soluble urokinase plasminogen activator receptor, dehydroepiandrosterone sulfate, dihydrotestosterone, cortisol, and 11-deoxycorticosterone levels were lower. Analyzing these variables using a forward stepwise multivariate logistic regression model, we established a GDM prediction model with a specificity of 96.6% and sensitivity of 97.5% (included variables: fructosamine, cortisol, cortisone, 11-deoxycorticosterone, SuPAR).
CONCLUSION
Based on these measurements, we accurately predict the development of later-onset GDM (24th-28th weeks of pregnancy). Early risk estimation provides the opportunity for targeted prevention and the timely treatment of GDM. Prevention and slowing the progression of GDM result in a lower lifelong metabolic risk for both mother and offspring.
Topics: Female; Humans; Pregnancy; Cortisone; Desoxycorticosterone; Diabetes, Gestational; Fructosamine; Hydrocortisone; Pregnancy Trimester, First; Case-Control Studies
PubMed: 37247379
DOI: 10.1210/clinem/dgad301 -
Scientific Reports Sep 2023The human polysialyltransferases ST8Sia II and ST8Sia IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles...
The human polysialyltransferases ST8Sia II and ST8Sia IV catalyze the transfer of several Neu5Ac residues onto glycoproteins forming homopolymers with essential roles during different physiological processes. In salmonids, heterogeneous set of sialic acids polymers have been described in ovary and on eggs cell surface and three genes st8sia4, st8sia2-r1 and st8sia2-r2 were identified that could be implicated in these heteropolymers. The three polysialyltransferases from the salmonid Coregonus maraena were cloned, recombinantly expressed in HEK293 cells and the ST8Sia IV was biochemically characterized. The MicroPlate Sialyltransferase Assay and the non-natural donor substrate CMP-SiaNAl were used to demonstrate enzyme activity and optimize polysialylation reactions. Polysialylation was also carried out with natural donor substrates CMP-Neu5Ac, CMP-Neu5Gc and CMP-Kdn in cell-free and cell-based assays and structural analyses of polysialylated products using the anti-polySia monoclonal antibody 735 and endoneuraminidase N and HPLC approaches. Our data highlighted distinct specificities of human and salmonid polysialyltransferases with notable differences in donor substrates use and the capacity of fish enzymes to generate heteropolymers. This study further suggested an evolution of the biological functions of polySia. C. maraena ST8Sia IV of particular interest to modify glycoproteins with a variety of polySia chains.
Topics: Animals; Female; Humans; N-Acetylneuraminic Acid; Salmonidae; HEK293 Cells; Biological Assay
PubMed: 37730806
DOI: 10.1038/s41598-023-42095-0 -
International Journal of Nanomedicine 2023Silybin (SLB) as an effective hepatoprotective phytomedicine has been limited by its hydrophobicity, poor bioavailability and accumulation at lesion sites. Additionally,...
INTRODUCTION
Silybin (SLB) as an effective hepatoprotective phytomedicine has been limited by its hydrophobicity, poor bioavailability and accumulation at lesion sites. Additionally, present drug loading methods are impeded by their low drug loading capacity, potential hazard of materials and poor therapeutic effects. Consequently, there is a pressing need to devise an innovative approach for preparing nanosuspensions loaded with both SLB and Silybin Meglumine salt (SLB-M), as well as to investigate the therapeutic effects of SLB nanosuspensions against hepatic fibrosis.
METHODS
The SLB nanosuspension (NS-SLB) was prepared and further modified with a hyaluronic acid-cholesterol conjugate (NS-SLB-HC) to improve the CD44 targeting proficiency of NS-SLB. To validate the accumulation of CD44 and ensure minimal cytotoxicity, cellular uptake and cytotoxicity assessments were carried out for the nanosuspensions. Western blotting was employed to evaluate the anti-hepatic fibrosis efficacy in LX-2 cells by inhibiting the secretion of collagen I. Hepatic fibrosis mouse models were used to further confirm the effectiveness of NS-SLB and NS-SLB-HC against hepatic fibrosis in vivo.
RESULTS
Uniform nanosuspensions were prepared through self-assembly, achieving high drug loading rates of 89.44% and 60.67%, respectively. Both SLB nanosuspensions showed minimal cytotoxicity in cellular environments and mitigated hepatic fibrosis in vitro. NS-SLB-HC was demonstrated to target activated hepatic stellate cells by receptor-ligand interaction between HA and CD44. They can reverse hepatic fibrosis in vivo by downregulating TGF-β and inhibiting the secretion of α-SMA and collagen I.
CONCLUSION
Designed as a medical excipient analogue, SLB-M was aimed to establish an innovative nanosuspension preparation method, characterized by high drug loading capacity and a notable impact against hepatic fibrosis.
Topics: Animals; Mice; Silybin; Biological Availability; Collagen Type I; Disease Models, Animal; Liver Cirrhosis; Meglumine
PubMed: 37720597
DOI: 10.2147/IJN.S407762 -
PeerJ 2024Ferroptosis is a form of cell death, , programmed cell death characterized by lipid peroxidation and iron dependence, which has unique morphological and biochemical... (Review)
Review
Ferroptosis is a form of cell death, , programmed cell death characterized by lipid peroxidation and iron dependence, which has unique morphological and biochemical properties. This unique mode of cell death is driven by iron-dependent phospholipid peroxidation and regulated by multiple cell metabolic pathways, including redox homeostasis, iron metabolism, mitochondrial activity, and the metabolism of amino acids, lipids, and sugars. Many organ injuries and degenerative pathologies are caused by ferroptosis. Ferroptosis is closely related to central nervous system injury diseases and is currently an important topic of research globally. This research examined the relationships between ferroptosis and the occurrence and treatment of central nervous system injury diseases. Additionally, ferroptosis was assessed from the aspect of theory proposal, mechanism of action, and related signaling pathways per recent research. This review provides a relevant theoretical basis for further research on this theory, the prospect of its development, and the prevention and treatment of such diseases.
Topics: Humans; Ferroptosis; Amino Acids; Antifibrinolytic Agents; Central Nervous System Diseases; Iron; Central Nervous System
PubMed: 38313006
DOI: 10.7717/peerj.16741 -
International Journal of Molecular... Sep 2023Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An...
Gestational diabetes mellitus (GDM) is a condition characterized by glucose intolerance, with hyperglycemia of varying severity with onset during pregnancy. An uncontrolled GDM can lead to an increased risk of morbidity in the fetus and newborn, and an increased risk of obesity or developing type 2 diabetes, hypertension or neurocognitive developmental impairment in adulthood. In this study, we used nuclear magnetic resonance (NMR) spectroscopy and gas chromatography-mass spectrometry (GS-MS) to analyze the urinary metabolomic profile of newborns of diabetic mothers (NDMs) with the aim of identifying biomarkers useful for the monitoring of NDMs and for early diagnosis of predisposition to develop related chronic diseases. A total of 26 newborns were recruited: 21 children of diabetic mothers, comprising 13 in diet therapy (NDM-diet) and 8 in insulin therapy (NDM-insulin), and 5 control children of non-diabetic mothers (CTR). Urine samples were collected at five time points: at birth (T1), on the third day of life (T2), one week (T3), one month (T4) and six months postpartum (T5). At T1, variations were observed in the levels of seven potential biomarkers (acetate, lactate, glycylproline/proline, isocitrate, N,N-dimethylglycine, N-acetylglucosamine and N-carbamoyl-aspartate) in NMD-insulin infants compared to NDM-diet and CTR infants. In particular, the altered metabolites were found to be involved in several metabolic pathways such as citrate metabolism, glycine, serine and threonine metabolism, arginine and proline metabolism, amino sugar and nucleotide sugar metabolism, and pyruvate metabolism. In contrast, these changes were not visible at subsequent sampling times. The impact of early nutrition (maternal and formula milk) on the metabolomic profile was considered as a potential contributing factor to this finding.
PubMed: 37762025
DOI: 10.3390/ijms241813724