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Journal of Cardiac Failure May 2024In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of... (Randomized Controlled Trial)
Randomized Controlled Trial
The Impact of Ferric Derisomaltose on Cardiovascular and Noncardiovascular Events in Patients With Anemia, Iron Deficiency, and Heart Failure With Reduced Ejection Fraction.
BACKGROUND
In some countries, intravenous ferric derisomaltose (FDI) is only licensed for treating iron deficiency with anemia. Accordingly, we investigated the effects of intravenous FDI in a subgroup of patients with anemia in the IRONMAN (Effectiveness of Intravenous (IV) Iron Treatment Versus Standard Care in Patients With Heart Failure and Iron Deficiency) trial.
METHOD AND RESULTS
IRONMAN enrolled patients with heart failure, a left ventricular ejection fraction of ≤45%, and iron deficiency (ferritin <100 µg/L or transferrin saturation of <20%), 771 (68%) of whom had anemia (hemoglobin <12 g/dL for women and <13 g/dL for men). Patients were randomized, open label, to FDI (n = 397) or usual care (n = 374) and followed for a median of 2.6 years. The primary end point, recurrent hospitalization for heart failure and cardiovascular death, occurred less frequently for those assigned to FDI (rate ratio 0.78, 95% confidence interval 0.61-1.01; P = .063). First event analysis for cardiovascular death or hospitalization for heart failure, less affected by the coronavirus disease 2019 pandemic, gave similar results (hazard ratio 0.77, 95% confidence interval 0.62-0.96; P = .022). Patients randomized to FDI reported a better Minnesota Living with Heart Failure quality of life, for overall (P = .013) and physical domain (P = .00093) scores at 4 months.
CONCLUSIONS
In patients with iron deficiency anemia and heart failure with reduced left ventricular ejection fraction, intravenous FDI improves quality of life and may decrease cardiovascular events.
Topics: Humans; Female; Male; Heart Failure; Stroke Volume; Anemia, Iron-Deficiency; Middle Aged; Aged; Ferric Compounds; Treatment Outcome; COVID-19; Maltose; Quality of Life
PubMed: 37926238
DOI: 10.1016/j.cardfail.2023.10.006 -
Cellular Signalling Jan 2024The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to... (Review)
Review
The rewiring of cellular metabolism is a defining characteristic of cancer, as tumor cells adapt to acquire essential nutrients from a nutrient-poor environment to sustain their viability and biomass. While hypoxia has been identified as a major factor depriving cancer cells of nutrients, recent studies have revealed that cancer cells distant from supporting blood vessels also face nutrient limitations. To overcome this challenge, hypoxic cancer cells, which heavily rely on glucose as an energy source, employ alternative pathways such as glycogen metabolism and reductive carboxylation of glutamine to meet their energy requirements for survival. Our preliminary studies, alongside others in the field, have shown that under glucose-deficient conditions, hypoxic cells can utilize mannose and maltose as alternative energy sources. This review aims to comprehensively examine the hypoxic cancer microenvironment, its association with drug resistance, and potential therapeutic strategies for targeting this unique niche. Furthermore, we will critically evaluate the current literature on hypoxic cancer microenvironments and explore state-of-the-art techniques used to analyze alternate carbohydrates, specifically mannose and maltose, in complex biological fluids. We will also propose the most effective analytical methods for quantifying mannose and maltose in such biological samples. By gaining a deeper understanding of the hypoxic cancer cell microenvironment and its role in drug resistance, novel therapeutic approaches can be developed to exploit this knowledge.
Topics: Humans; Cell Hypoxia; Maltose; Mannose; Neoplasms; Hypoxia; Glucose; Tumor Microenvironment; Drug Resistance
PubMed: 37805102
DOI: 10.1016/j.cellsig.2023.110911 -
Carbohydrate Polymers Dec 2023Fucosylated chondroitin sulfate (FCS) extracted from Phyllophorella kohkutiensis (PkFCS) is composed of d-GalNAc, d-GlcA, l-Fuc and -SO. According to the defined...
Fucosylated chondroitin sulfate (FCS) extracted from Phyllophorella kohkutiensis (PkFCS) is composed of d-GalNAc, d-GlcA, l-Fuc and -SO. According to the defined structures revealed by NMR spectra of the branches released by mild acid hydrolysis and oligosaccharides generated by β-eliminative depolymerization, the backbone of PkFCS is CS-E, and the branch types attached to C-3 of d-GlcA include l-Fuc, l-Fuc, l-Fuc and the disaccharide α-d-GalNAc-1,2-α-l-Fuc with the ratio of 43:13:22:22. Notably, novel heptasaccharide and hendecasaccharide were identified that are branched with continuous distribution of the disaccharide. The structural sequences of the oligosaccharides indicate that three unique structural motifs are present in the entire PkFCS polymer, including a motif branched with randomly distributed different sulfated l-Fuc units, a motif containing regular l-Fuc branches and a motif enriched in α-d-GalNAc-1,2-α-l-Fuc. This is the first report about the distribution pattern of diverse branches in natural FCS. Natural PkFCS exhibited potent anticoagulant activity on APTT prolonging and anti-iXase activity. Regarding the structurally defined oligosaccharides with sulfated fucosyl side chains, octasaccharide (Pk4b) is the minimum fragment responsible for its anticoagulant activity correlated with anti-iXase. However, further glycosyl modification with a non-sulfated d-GalNAc at the C-2 position of l-Fuc could significantly decrease the anticoagulant and anti-iXase activity.
Topics: Animals; Sea Cucumbers; Anticoagulants; Chondroitin Sulfates; Disaccharides; Sulfates; Sulfur Oxides
PubMed: 37739534
DOI: 10.1016/j.carbpol.2023.121304 -
Journal of Intensive Care Medicine Mar 2024Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of... (Observational Study)
Observational Study
BACKGROUND
Sepsis-associated destruction of the pulmonary microvascular endothelial glycocalyx (EGCX) creates a vulnerable endothelial surface, contributing to the development of acute respiratory distress syndrome (ARDS). Constituents of the EGCX shed into circulation, glycosaminoglycans and proteoglycans, may serve as biomarkers of endothelial dysfunction. We sought to define the patterns of plasma EGCX degradation products in children with sepsis-associated pediatric ARDS (PARDS), and test their association with clinical outcomes.
METHODS
We retrospectively analyzed a prospective cohort (2018-2020) of children (≥1 month to <18 years of age) receiving invasive mechanical ventilation for acute respiratory failure for ≥72 h. Children with and without sepsis-associated PARDS were selected from the parent cohort and compared. Blood was collected at time of enrollment. Plasma glycosaminoglycan disaccharide class (heparan sulfate, chondroitin sulfate, and hyaluronan) and sulfation subtypes (heparan sulfate and chondroitin sulfate) were quantified using liquid chromatography tandem mass spectrometry. Plasma proteoglycans (syndecan-1) were measured through an immunoassay.
RESULTS
Among the 39 mechanically ventilated children (29 with and 10 without sepsis-associated PARDS), sepsis-associated PARDS patients demonstrated higher levels of heparan sulfate (median 639 ng/mL [interquartile range, IQR 421-902] vs 311 [IQR 228-461]) and syndecan-1 (median 146 ng/mL [IQR 32-315] vs 8 [IQR 8-50]), both = 0.01. Heparan sulfate subtype analysis demonstrated greater proportions of -sulfated disaccharide levels among children with sepsis-associated PARDS (0.01). Increasing sulfated disaccharide levels by quartile were associated with severe PARDS (n = 9/29) with the highest quartile including >60% of the severe PARDS patients (test for trend, = 0.04). Higher total heparan sulfate and sulfated disaccharide levels were independently associated with fewer 28-day ventilator-free days in children with sepsis-associated PARDS (all 0.05).
CONCLUSIONS
Children with sepsis-associated PARDS exhibited higher plasma levels of heparan sulfate disaccharides and syndecan-1, suggesting that EGCX degradation biomarkers may provide insights into endothelial dysfunction and PARDS pathobiology.
Topics: Humans; Child; Retrospective Studies; Syndecan-1; Chondroitin Sulfates; Prospective Studies; Glycocalyx; Respiratory Distress Syndrome; Sepsis; Heparitin Sulfate; Biomarkers; Proteoglycans; Disaccharides
PubMed: 37670670
DOI: 10.1177/08850666231200162 -
Bioorganic Chemistry Jul 2024Bacterial infections are the second leading cause of death worldwide, and the evolution and widespread distribution of antibiotic-resistance elements in bacterial... (Review)
Review
Bacterial infections are the second leading cause of death worldwide, and the evolution and widespread distribution of antibiotic-resistance elements in bacterial pathogens exacerbate the threat crisis. Carbohydrates participate in bacterial infection, drug resistance and the process of host immune regulation. Numerous antimicrobials derived from carbohydrates or contained carbohydrate scaffolds that are conducive to an increase in pathogenic bacteria targeting, the physicochemical properties and druggability profiles. In the paper, according to the type and number of sugar residues contained in antimicrobial molecules collected from the literatures ranging from 2014 to 2024, the antimicrobial activities, action mechanisms and structure-activity relationships were delineated and summarized, for purpose to provide the guiding template to select the type and size of sugars in the design of oligosaccharide-based antimicrobials to fight the looming antibiotic resistance crisis.
Topics: Structure-Activity Relationship; Oligosaccharides; Anti-Bacterial Agents; Microbial Sensitivity Tests; Molecular Structure; Bacteria; Humans; Monosaccharides; Disaccharides
PubMed: 38728907
DOI: 10.1016/j.bioorg.2024.107406 -
Voprosy Pitaniia 2024The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology.... (Review)
Review
The study of the genetic determinants of the disaccharidase activity opens up new prospects for improving diagnostics and choosing medical tactics in gastroenterology. of the study was to systematize the data on the role of the sucrase-isomaltase gene (SI) in regulating sucrose metabolism and the contribution of SI mutations to the prevalence of sucrose malabsorption disorders (sucrase-isomaltase deficiency, SID) and certain forms of enterological pathology in different population groups. . A review of the peer-reviewed scientific literature, mainly in the PubMed database (https://pubmed.ncbi.nlm.nih.gov) and eLibrary (https://elibrary.ru), was conducted using key words: carbohydrate malabsorption, sucrase, sucrase-isomaltase deficiency, sucrase-isomaltase SI gene. The search depth was not specified, but particular attention was paid to recent publications. The gnomAD database (https://www.ncbi.nlm. nih.gov/snp/rs781470490) was also used. . According to the review results, 37 out of 150 known SI gene mutations have been confirmed to contribute to reduced sucrase activity or restricted sucrase production. The prevalence of point mutations in the SI gene is estimated at 0.0006%, but carrier rates of the SI delAG deletion (rs781470490), manifested as homozygosity in SID, are very high (5-21%) in indigenous populations of Arctic regions in East Asia and America. Medicalgenetic research methods improve the accuracy of differential diagnosis of primary and secondary SID and other forms of disaccharide and polysaccharide malabsorption. The formation of databases on the prevalence of genetic determinants of sucrase-isomaltase insufficiency is a promising way to refine the epidemiology of SID. There is an increased (0.2-2.3%) risk of clinical manifestations of SID in homozygous carriers of the SI delAG mutation in the Chukotka, Kamchatka, and Northern Priochotye populations. Verification of reports on a less pronounced tendency to lipid metabolism disorders in SI delAG carriers compared with the control group is recommended. . Manifestations of mutant SI variants in the phenotype are associated with the presence of accompanying carbohydrate malabsorption variants and specific gut microbiota. The SI 15Phe variant (rs9290264) may contribute to the development of irritable bowel syndrome.
Topics: Humans; Carbohydrate Metabolism, Inborn Errors; Sucrase-Isomaltase Complex; Mutation; Sucrose; Malabsorption Syndromes
PubMed: 38809799
DOI: 10.33029/0042-8833-2024-93-2-52-62 -
Journal of Insect Science (Online) Nov 2023In temperate climates, honey bees rely on stored carbohydrates to sustain them throughout the winter. In nature, honey serves as the bees' source of carbohydrates, but...
In temperate climates, honey bees rely on stored carbohydrates to sustain them throughout the winter. In nature, honey serves as the bees' source of carbohydrates, but when managed, beekeepers often harvest honey and replace it with cheaper, artificial feed. The effects of alternative carbohydrate sources on colony survival, strength, and individual bee metabolic health are poorly understood. We assessed the impacts of carbohydrate diets (honey, sucrose syrup, high-fructose corn syrup, and invert syrup) on colony winter survival, population size, and worker bee nutritional state (i.e., fat content and gene expression of overwintered bees and emerging callow bees). We observed a nonsignificant trend for greater survival and larger adult population size among colonies overwintered on honey compared to the artificial feeds, with colonies fed high-fructose corn syrup performing particularly poorly. These trends were mirrored in individual bee physiology, with bees from colonies fed honey having significantly larger fat bodies than those from colonies fed high-fructose corn syrup. For bees fed honey or sucrose, we also observed gene expression profiles consistent with a higher nutritional state, associated with physiologically younger individuals. That is, there was significantly higher expression of vitellogenin and insulin-like peptide 2 and lower expression of insulin-like peptide 1 and juvenile hormone acid methyltransferase in the brains of bees that consumed honey or sucrose syrup relative to those that consumed invert syrup or high-fructose corn syrup. These findings further our understanding of the physiological implications of carbohydrate nutrition in honey bees and have applied implications for colony management.
Topics: Humans; Bees; Animals; Honey; Carbohydrates; Sucrose; Fructose
PubMed: 38055947
DOI: 10.1093/jisesa/iead084 -
Plant Communications Mar 2024Anthocyanins play diverse roles in plant physiology and stress adaptation. In Arabidopsis, the MYB-bHLH-WD40 (MBW) complex has a crucial role in the regulation of...
Anthocyanins play diverse roles in plant physiology and stress adaptation. In Arabidopsis, the MYB-bHLH-WD40 (MBW) complex has a crucial role in the regulation of anthocyanin synthesis. Here, we report that the R2R3-MYB transcription factor MYB30 and the ubiquitin E3 ligase RHA2b participate in anthocyanin biosynthesis through regulation of the MBW complex. MYB30 was found to negatively regulate sucrose-induced anthocyanin biosynthesis in Arabidopsis seedlings. Expression of multiple genes involved in flavonoid or anthocyanin biosynthesis was affected in the myb30 mutant, and MYB30 directly repressed the expression of MYB75, which encodes a core component of the MBW complex, by binding to its promoter. Moreover, MYB30 physically interacted with MYB75 to inhibit its activity by repressing MBW complex assembly. In addition, sucrose treatment significantly promoted MYB30 degradation via the action of RHA2b. The ubiquitination and degradation of MYB30 were significantly attenuated in the rha2b mutant under high-sucrose treatment, and further analysis showed that MYB75 directly promoted RHA2b expression in response to high sucrose. Our work thus reveals an anthocyanin biosynthetic regulatory module, RHA2b-MYB30, that controls the function of the MBW complex via MYB75. The repression of MYB75 by MYB30 is released by MYB75-induced RHA2b expression, thus ensuring the self-activation of MYB75 when anthocyanin synthesis is needed.
Topics: Arabidopsis; Anthocyanins; Arabidopsis Proteins; Seedlings; Sucrose; Transcription Factors
PubMed: 37946410
DOI: 10.1016/j.xplc.2023.100744 -
Pharmaceutical Research Jan 2024The purpose of the present study was to investigate the effect of food viscosity on the dissolution rate of a drug. There are two types of viscosity, macroviscosity and...
PURPOSE
The purpose of the present study was to investigate the effect of food viscosity on the dissolution rate of a drug. There are two types of viscosity, macroviscosity and microviscosity. Macroviscosity affects the diffusion layer thickness, whereas microviscosity affects the molecular diffusion coefficient. The mass transfer coefficient (k) in the intrinsic dissolution rate (IDR) depends on the viscosity (η) as k ∝ η (a is an exponent on η). In theory, for rotating flow over a disk, if a thickener increases only macroviscosity, a = -1/6, and if it increases both macroviscosity and microviscosity equally, a = -7/6.
METHOD
Benzocaine was used as a model drug. Hydroxypropyl cellulose (HPC) and methylcellulose (MC) were employed as control thickeners that increase only macroviscosity. Sucrose was employed as a control thickener for both macroviscosity and microviscosity. The FDA breakfast homogenate (BFH) was diluted with distilled water or 1 mM HCl with/without pepsin digestion. The IDR value was measured by the paddle-over-disk method.
RESULTS
The η value of 30% BFH distilled water was 209 mPa∙s, about 300 times higher than distilled water. It was further increased by HCl (430 mPa∙s), and reduced by pepsin digestion (35 mPa∙s). The k value was little affected by BFH (a = 0.00 to -0.09), slightly less than those in HPC (a = -0.19) and MC (a = -0.21). Sucrose decreased the k value more significantly (a = -0.70).
CONCLUSION
The IDR and k values of benzocaine were little affected by BFH, suggesting that BFH increased only macroviscosity.
Topics: Drug Liberation; Benzocaine; Viscosity; Pepsin A; Methylcellulose; Water; Sucrose
PubMed: 37884679
DOI: 10.1007/s11095-023-03620-y -
Pediatric Research Feb 2024Music for neonatal pain has not been exclusively studied in term neonates in a well-designed trial compared to the standard of care. This study aims to assess the... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND
Music for neonatal pain has not been exclusively studied in term neonates in a well-designed trial compared to the standard of care. This study aims to assess the effectiveness of music intervention as an adjuvant in relieving acute pain in term newborns undergoing minor painful procedures.
METHODS
This randomized, controlled, blinded trial included any term neonate undergoing heel prick. Both control and intervention groups received oral sucrose 2 min before heel prick. Intervention group was exposed to 'Bedtime Mozart' lullaby recorded music via bedside speakers. Pain was measured using Neonatal Infant Pain Scale (NIPS) at 1-min intervals. Investigators were blinded using noise-canceling headphones that played random music.
RESULTS
A total of 100 neonates were enrolled. Mean gestational age was 39.2 weeks, and mean duration of the procedure was 113 s. Music group was found to have significantly lower pain scores [OR = 0.42 (0.31, 0.56), p < 0.001]. Baseline NIPS scores were similar across groups and there was no interaction effect between groups and time. When NIPS were categorized as pain and no pain, there continued to be statistically significant lower NIPS scores in the music group (p < 0.001).
CONCLUSION
Recorded music, in addition to sucrose, is efficacious in reducing pain, encouraging its use in term neonates.
IMPACT
Recorded music effectively reduces pain induced by minor procedures in term neonates. Clinical studies have shown that live and recorded music induces changes in vital signs and pain scores in the NICU's predominantly preterm population. Most of these studies were also conducted in the white ethnic population. Our study objectively proves reduction in pain scores by using recorded music in a randomized, controlled, blinded study of predominantly non-white, term neonates. Recorded music is effective in reducing acute pain in term neonates and can be widely used even in low-resource nurseries.
Topics: Infant, Newborn; Humans; Infant; Music; Punctures; Acute Pain; Pain Management; Sucrose
PubMed: 37640940
DOI: 10.1038/s41390-023-02746-4