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Scientific Reports Oct 2023Intravenous iron is commonly used to treat iron deficiency anemia in non-dialysis chronic kidney disease (ND-CKD). There is a paucity of information on the potential... (Randomized Controlled Trial)
Randomized Controlled Trial
Patient reported outcome measures and cardiovascular outcomes following high dose modern intravenous iron in non-dialysis dependent chronic kidney disease: secondary analysis of ExplorIRON-CKD.
Intravenous iron is commonly used to treat iron deficiency anemia in non-dialysis chronic kidney disease (ND-CKD). There is a paucity of information on the potential impact of intravenous iron on patient reported outcome measures, functional status and markers of cardiovascular health. As part of the secondary analysis of this double-blind exploratory randomized controlled trial focusing on patients with iron deficiency (+ /- anemia) and ND-CKD (serum ferritin < 200 µg/L or transferrin saturation ≤ 20% and serum ferritin 200-299 µg/L; CKD stages: 3a-5), 26 patients were randomized in a 1:1 ratio to receive ferric derisomaltose or ferric carboxymaltose. Participants received 1000 mg at baseline and 500-1000 mg at one month to achieve iron repletion. Quality of life and fatigue status were assessed using the Short-Form (36) questionnaire and the fatigue severity scale. Functional status was evaluated using the Duke Activity Status Index and the 1-min-sit-to-stand test. Cardiac markers such as NT-proBNP, Troponin T and pulse wave velocity were monitored. Intravenous iron was associated with similar improvements in most domains of the Short-Form (36) questionnaire, fatigue status, and 1-min-sit-to-stand ability increased significantly by the end of the trial in both groups (p < 0.001). Markers of cardiac function remained stable, with no arterial stiffness impact. Longer term studies are required to further evaluate the impact of intravenous iron on quality of life and cardiac safety in patients with ND-CKD.
Topics: Humans; Iron; Pulse Wave Analysis; Quality of Life; Renal Dialysis; Ferric Compounds; Renal Insufficiency, Chronic; Anemia, Iron-Deficiency; Maltose; Ferritins; Patient Reported Outcome Measures
PubMed: 37884522
DOI: 10.1038/s41598-023-44578-6 -
Anais Da Academia Brasileira de Ciencias 2023The objective of this study was to evaluate the β-glucosidase activity in the non-conventional yeasts under cellulose, glucose and sucrose substrates. The participation...
The objective of this study was to evaluate the β-glucosidase activity in the non-conventional yeasts under cellulose, glucose and sucrose substrates. The participation of the enzyme β-glucosidase and its contribution to the enzymatic degradation of tannins is known. Within the classification of tannins are ellagitannins, molecules of gallic acid and ellagic acid, which are considered as nutraceutical compounds due to the properties that they present and that they can be used in the design of food and new drugs, synthesis of materials with antimicrobial capacity. The extracellular β-glucosidase activity was mainly presented in the Candida and Pichia strains, being the glucose and sucrose media the most capable for inducing the activity that showed maximum values with P. pastoris in glucose (0.1682±0.00 µmol/min mg protein), and C. utilis in cellulose (0.1129±0.1349 µmol/min mg of protein), and sucrose (0.0657±0.0214 µmol/min mg protein). Additionally, I. terricola and P. kluyvery stood out in a qualitative cellulose degradation approach measured by Congo red method (9.60±0.04 mm and 9.20±0.05 mm respectively). These indicate that P. pastoris and C. utilis have potential as β-glucosidase producers, especially when growing under complex carbon sources for biomass conversion, new biofuels production and polyphenol degradation with more manageable bioreactor process.
Topics: Tannins; Yeasts; Cellulose; Glucose; Sucrose; Cellulases; beta-Glucosidase
PubMed: 38055563
DOI: 10.1590/0001-3765202320221118 -
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 -
Journal of Plant Physiology Mar 2024Sugar homeostasis is a critical feature of biological systems. In humans, raised and dysregulated blood sugar is a serious health issue. In plants, directed changes in... (Review)
Review
Sugar homeostasis is a critical feature of biological systems. In humans, raised and dysregulated blood sugar is a serious health issue. In plants, directed changes in sucrose homeostasis and allocation represent opportunities in crop improvement. Plant tissue sucrose varies more than blood glucose and is found at higher concentrations (cytosol and phloem ca. 100 mM v 3.9-6.9 mM for blood glucose). Tissue sucrose varies with developmental stage and environment, but cytosol and phloem exhibit tight sucrose control. Sucrose homeostasis is a consequence of the integration of photosynthesis, synthesis of storage end-products such as starch, transport of sucrose to sinks and sink metabolism. Trehalose 6-phosphate (T6P)-SnRK1 and TOR play central, still emerging roles in regulating and coordinating these processes. Overall, tissue sucrose levels are more strongly related to growth than to photosynthesis. As a key sucrose signal, T6P regulates sucrose levels, transport and metabolic pathways to coordinate source and sink at a whole plant level. Emerging evidence shows that T6P interacts with meristems. With careful targeting, T6P manipulation through exploiting natural variation, chemical intervention and genetic modification is delivering benefits for crop yields. Regulation of cereal grain set, filling and retention may be the most strategically important aspect of sucrose allocation and homeostasis for food security.
Topics: Humans; Sucrose; Blood Glucose; Sugar Phosphates; Plants; Photosynthesis; Trehalose; Homeostasis
PubMed: 38295650
DOI: 10.1016/j.jplph.2024.154188 -
BMC Nephrology May 2024Exit-site infection (ESI) is a common recurring complication in patients undergoing peritoneal dialysis (PD). Sucrose and povidone-iodine (SPI) mixtures, antimicrobial... (Observational Study)
Observational Study
BACKGROUND
Exit-site infection (ESI) is a common recurring complication in patients undergoing peritoneal dialysis (PD). Sucrose and povidone-iodine (SPI) mixtures, antimicrobial ointments that promote wound healing, have been used for the treatment of ulcers and burns, but their efficacy in exit-site care is still unclear.
METHODS
This single-center retrospective observational study included patients who underwent PD between May 2010 and June 2022 and presented with episodes of ESI. Patients were divided into SPI and non-SPI groups and followed up from initial ESI onset until PD cessation, death, transfer to another facility, or June 2023.
RESULTS
Among the 82 patients (mean age 62, [54-72] years), 23 were treated with SPI. The median follow-up duration was 39 months (range, 14-64), with an overall ESI incidence of 0.70 episodes per patient-year. Additionally, 43.1% of second and 25.6% of third ESI were caused by the same pathogen as the first. The log-rank test demonstrated significantly better second and third ESI-free survival in the SPI group than that in the non-SPI group (p < 0.01 and p < 0.01, respectively). In a Cox regression analysis, adjusting for potential confounders, SPI use was a significant predictor of decreased second and third ESI episodes (hazard ratio [HR], 0.22; 95% confidence interval [CI], 0.10-0.52 and HR, 0.22; 95%CI, 0.07-0.73, respectively).
CONCLUSIONS
Our results showed that the use of SPI may be a promising option for preventing the incidence of ESI in patients with PD.
TRIAL REGISTRATION
This study was approved by the Keio University School of Medicine Ethics Committee (approval number 20231078) on August 28, 2023. Retrospectively registered.
Topics: Humans; Povidone-Iodine; Middle Aged; Retrospective Studies; Male; Female; Aged; Sucrose; Anti-Infective Agents, Local; Peritoneal Dialysis; Catheter-Related Infections; Catheters, Indwelling; Treatment Outcome
PubMed: 38698327
DOI: 10.1186/s12882-024-03591-1 -
Contact Lens & Anterior Eye : the... Aug 2023Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and...
BACKGROUND AND OBJECTIVES
Dry eye disease (DED) is common in postmenopausal women. This study evaluated efficacy of a 3-month daily treatment with artificial tears containing trehalose and hyaluronic acid (HA) in women aged 42-54 years (mixed-hormonal status) versus ≥ 55 years (postmenopausal) and with moderate and severe DED.
METHODS
This was a post-hoc analysis of three clinical trials assessing the efficacy of artificial tears containing trehalose (3%) and HA (0.15%) in women with an Ocular Surface Disease Index (OSDI) ≥ 18. Patients instilled one drop of the artificial tears in each eye 3 to 6 times daily and were evaluated at baseline and after 84 ± 7 days for DED symptom severity (OSDI), hyperemia (McMonnies scale), tear break-up time (TBUT), corneal and conjunctival staining (Oxford and Van Bjisterveld scales), tear production (Schirmer I test), and ocular symptoms.
RESULTS
A total of 273 women were evaluated, 61 of age 42-54 years; 212 of ≥ 55 years. DED symptoms, as measured by the OSDI, decreased significantly with the treatment in both age groups (p < 0.0001). Conjunctival hyperemia decreased significantly and TBUT increased significantly in both groups, especially in women of age 42-54 (both p < 0.0001). The global (corneal and conjunctival) staining score decreased significantly in both groups, but also more in women of age 42-54 years. No differences were observed between age groups for any of the variables measured, except for visual acuity. DED symptoms were consistently reported more frequently by the mixed hormonal status women, but also the effect of the treatment was more pronounced in this group.
CONCLUSIONS
Artificial tears with trehalose and HA significantly improved the symptoms of DED in women aged 42-54 and ≥ 55 years. The decrease in symptoms was more pronounced in women of age 42-54 years, suggesting better mechanisms of recovery from inflammation and loss of ocular surface homeostasis.
Topics: Humans; Female; Male; Lubricant Eye Drops; Hyaluronic Acid; Trehalose; Hyperemia; Dry Eye Syndromes; Tears
PubMed: 37117131
DOI: 10.1016/j.clae.2023.101845 -
Molecules (Basel, Switzerland) Nov 2023Glycosidases are essential for the industrial production of functional oligosaccharides and many biotech applications. A novel β-galactosidase/α-L-arabinopyranosidase...
Glycosidases are essential for the industrial production of functional oligosaccharides and many biotech applications. A novel β-galactosidase/α-L-arabinopyranosidase (PpBGal42A) of the glycoside hydrolase family 42 (GH42) from KF-1 was identified and functionally characterized. Using NPG as a substrate, the recombinant PpBGal42A (77.16 kD) was shown to have an optimal temperature and pH of 30 °C and 6.0. Using NPαArap as a substrate, the optimal temperature and pH were 40 °C and 7.0. PpBGal42A has good temperature and pH stability. Furthermore, Na, K, Li, and Ca (5 mmol/L) enhanced the enzymatic activity, whereas Mn, Cu, Zn, and Hg significantly reduced the enzymatic activity. PpBGal42A hydrolyzed NP-β-D-galactoside and NP-α-L-arabinopyranoside. PpBGal42A liberated galactose from β-1,3/4/6-galactobiose and galactan. PpBGal42A hydrolyzed arabinopyranose at C20 of ginsenoside Rb2, but could not cleave arabinofuranose at C20 of ginsenoside Rc. Meanwhile, the molecular docking results revealed that PpBGal42A efficiently recognized and catalyzed lactose. PpBGal42A hydrolyzes lactose to galactose and glucose. PpBGal42A exhibits significant degradative activity towards citrus pectin when combined with pectinase. Our findings suggest that PpBGal42A is a novel bifunctional enzyme that is active as a β-galactosidase and α-L-arabinopyranosidase. This study expands on the diversity of bifunctional enzymes and provides a potentially effective tool for the food industry.
Topics: Paenibacillus polymyxa; Lactose; Molecular Docking Simulation; Galactose; Glycoside Hydrolases; Cloning, Molecular; beta-Galactosidase; Hydrogen-Ion Concentration; Substrate Specificity; Paenibacillus
PubMed: 38005185
DOI: 10.3390/molecules28227464 -
International Journal of Molecular... Nov 2023The apricot ( L.) is a fruit that belongs to the Rosaceae family; it has a unique flavor and is of important economic and nutritional value. The composition and content...
The apricot ( L.) is a fruit that belongs to the Rosaceae family; it has a unique flavor and is of important economic and nutritional value. The composition and content of soluble sugars and organic acids in fruit are key factors in determining the flavor quality. However, the molecular mechanism of sugar and acid accumulation in apricots remains unclear. We measured sucrose, fructose, glucose, sorbitol, starch, malate, citric acid, titratable acid, and pH, and investigated the transcriptome profiles of three apricots (the high-sugar cultivar 'Shushanggan', common-sugar cultivar 'Sungold', and low-sugar cultivar 'F43') at three distinct developmental phases. The findings indicated that 'Shushanggan' accumulates a greater amount of sucrose, glucose, fructose, and sorbitol, and less citric acid and titratable acid, resulting in a better flavor; 'Sungold' mainly accumulates more sucrose and less citric acid and starch for the second flavor; and 'F43' mainly accumulates more titratable acid, citric acid, and starch for a lesser degree of sweetness. We investigated the DEGs associated with the starch and sucrose metabolism pathways, citrate cycle pathway, glycolysis pathway, and a handful of sugar transporter proteins, which were considered to be important regulators of sugar and acid accumulation. Additionally, an analysis of the co-expression network of weighted genes unveiled a robust correlation between the brown module and sucrose, glucose, and fructose, with being identified as a hub gene that interacted with four sugar transporter proteins (, , , and ), as well as three structural genes for sugar and acid metabolism (, , and ). Furthermore, we found some lncRNAs and miRNAs that regulate these genes. Our findings provide clues to the functional genes related to sugar metabolism, and lay the foundation for the selection and cultivation of high-sugar apricots in the future.
Topics: Transcriptome; Sugars; Prunus armeniaca; Fruit; Carbohydrates; Glucose; Acids; Sucrose; Citric Acid; Starch; Fructose; Metabolome; Sorbitol
PubMed: 38069317
DOI: 10.3390/ijms242316992 -
ACS Infectious Diseases Apr 2024Tuberculosis (TB), caused by (Mtb), is the leading cause of death worldwide by infectious disease. Treatment of Mtb infection requires a six-month course of multiple...
Tuberculosis (TB), caused by (Mtb), is the leading cause of death worldwide by infectious disease. Treatment of Mtb infection requires a six-month course of multiple antibiotics, an extremely challenging regimen necessitated by Mtb's ability to form drug-tolerant persister cells. Mtb persister formation is dependent on the trehalose catalytic shift, a stress-responsive metabolic remodeling mechanism in which the disaccharide trehalose is liberated from cell surface glycolipids and repurposed as an internal carbon source to meet energy and redox demands. Here, using a biofilm-persister model, metabolomics, and cryo-electron microscopy (EM), we found that azidodeoxy- and aminodeoxy-d-trehalose analogues block the Mtb trehalose catalytic shift through inhibition of trehalose synthase TreS (Rv0126), which catalyzes the isomerization of trehalose to maltose. Out of a focused eight-member compound panel constructed by chemoenzymatic synthesis, the natural product 2-trehalosamine exhibited the highest potency and significantly potentiated first- and second-line TB drugs in broth culture and macrophage infection assays. We also report the first structure of TreS bound to a substrate analogue inhibitor, obtained via cryo-EM, which revealed conformational changes likely essential for catalysis and inhibitor binding that can potentially be exploited for future therapeutic development. Our results demonstrate that inhibition of the trehalose catalytic shift is a viable strategy to target Mtb persisters and advance trehalose analogues as tools and potential adjunctive therapeutics for investigating and targeting mycobacterial persistence.
Topics: Humans; Mycobacterium tuberculosis; Trehalose; Cryoelectron Microscopy; Tuberculosis; Catalysis
PubMed: 38485491
DOI: 10.1021/acsinfecdis.4c00138 -
Journal of Gastrointestinal and Liver... Dec 2023Lactulose is the first-line drug for both treatment and secondary prophylaxis for overt hepatic encephalopathy (HE). The use of lactulose for the primary prophylaxis of... (Meta-Analysis)
Meta-Analysis
BACKGROUND AND AIMS
Lactulose is the first-line drug for both treatment and secondary prophylaxis for overt hepatic encephalopathy (HE). The use of lactulose for the primary prophylaxis of HE in patients with cirrhosis and acute upper gastrointestinal bleeding (AUGIB) has been debated. Hence, we conducted this meta-analysis to assess the role of lactulose in HE prophylaxis in patients with cirrhosis and AUGIB.
METHODS
A comprehensive search of literature from inception to December 2022 was performed of three databases for randomized studies comparing lactulose and placebo in patients with cirrhosis and AUGIB. Risk ratios (RR) with 95% confidence intervals were calculated for all the dichotomous outcomes.
RESULTS
A total of five studies were included in the final analysis, out of which three studies had a low risk of bias, and two had a moderate risk of bias. Lactulose therapy was associated with a significantly lower risk of OHE compared to placebo, with a RR of 0.38 (0.23-0.62) and a number needed to treat of 6. There was no difference in the risk of mortality between the groups, with a RR of 0.71 (0.29-1.76). The pooled incidence rates of overall adverse events (AEs) and diarrhea with the use of lactulose therapy were 53.2% (42.2- 64.2) and 34.7% (17.7-51.7), but a majority did not require drug discontinuation. The certainty of the evidence was moderate to low.
CONCLUSIONS
Prophylactic lactulose reduces the incidence of HE after AUGIB but has no effect on mortality. Diarrhea and abdominal discomfort are common AEs but do not need drug discontinuation.
Topics: Humans; Lactulose; Randomized Controlled Trials as Topic; Hepatic Encephalopathy; Liver Cirrhosis; Diarrhea; Gastrointestinal Hemorrhage
PubMed: 38147599
DOI: 10.15403/jgld-4975