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Chembiochem : a European Journal of... Mar 2024Carbohydrates are common co-solutes for the stabilization of proteins. The effect of carbohydrate solutions on the stability of collagen, the most abundant protein in...
Carbohydrates are common co-solutes for the stabilization of proteins. The effect of carbohydrate solutions on the stability of collagen, the most abundant protein in mammals, is, however, underexplored. In this work, we studied the thermal stability of collagen triple helices derived from a molecularly defined collagen model peptide (CMP), Ac-(Pro-Hyp-Gly) -NH , in solutions of six common mono- and disaccharides. We show that the carbohydrates stabilize the collagen triple helix in a concentration-dependent manner, with an increase of the melting temperature of up to 17 °C. In addition, we show that the stabilizing effect is similar for all studied sugars, including trehalose, which is otherwise considered a privileged bioprotectant. The results provided insight into the effects of sugar co-solutes on collagen triple helices and can aid the selection of storage environments for collagen-based materials and probes.
Topics: Animals; Collagen; Disaccharides; Temperature; Trehalose; Mammals
PubMed: 38233350
DOI: 10.1002/cbic.202300860 -
Journal of Human Nutrition and... Feb 2024The present study aimed to evaluate the effects of fermented oligosaccharide, disaccharide, monosaccharide and polyols (FODMAP) diet therapy and probiotics on irritable... (Clinical Trial)
Clinical Trial
BACKGROUND
The present study aimed to evaluate the effects of fermented oligosaccharide, disaccharide, monosaccharide and polyols (FODMAP) diet therapy and probiotics on irritable bowel syndrome (IBS) symptoms, quality of life and depression in women diagnosed with IBS.
METHODS
For the study, 52 female IBS patients between the ages of 20 and 55 were enrolled. Individuals were monitored for 6 weeks in two groups. A low-FODMAP diet was given to the first group and a low-FODMAP diet plus a probiotic supplement was given to the second group (Lactobacillus rhamnosus). Three-day food intake records were kept at the start of the study and continued up to its conclusion, with a weekly check-in in between. At the start and end of the trial, participants completed the Hospital Anxiety and Depression Scale, IBS Quality of Life Scale (IBS-QOL) and IBS Symptom Severity Score (IBS-SSS). The Bristol Stool Scale was also used by the subjects to record their daily stool densities.
RESULTS
At the end of the study, it was determined that the daily intake of FODMAP (lactose [g] + oligosaccharides [g] + mannitol [g] + sorbitol [g]) decreased significantly in both groups (p < 0.05). At the end of the study, it was determined that the IBS-SSS, anxiety and depression scores of the individuals in both groups decreased significantly and their IBS-QOL scores increased significantly (p < 0.05). However, the difference between these values between the groups was not statistically significant (p > 0.05).
CONCLUSIONS
A low-FODMAP diet has been demonstrated to benefit people by lessening the severity of their IBS symptoms and enhancing their quality of life. No evidence was found, however, to indicate that the FODMAP diet would be more beneficial on these metrics if additional probiotics were used. It should be emphasised that the reaction of probiotic strains may vary depending on the IBS subtype.
Topics: Adult; Female; Humans; Middle Aged; Young Adult; Depression; Diet; Disaccharides; Fermentation; FODMAP Diet; Irritable Bowel Syndrome; Monosaccharides; Oligosaccharides; Probiotics; Quality of Life; Treatment Outcome
PubMed: 37430435
DOI: 10.1111/jhn.13194 -
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 -
International Journal of Pharmaceutics Jul 2023This study aims to examine (i) the effect of diluent types (lactose monohydrate, corn starch, and microcrystalline cellulose) and granulation liquids (20%...
This study aims to examine (i) the effect of diluent types (lactose monohydrate, corn starch, and microcrystalline cellulose) and granulation liquids (20% polyvinylpyrrolidone K30, 65% alcohol, and dispersion containing 40% model drug- Pithecellobium clypearia Benth extracted powder) on granule properties and tablet quality for high shear wet granulation and tableting (HSWG-T) and, more importantly, (ii) the attribute transmission in the process. In general, the impact of diluents on granule properties and tablet quality was more dominant than that of granulation liquids. Attribute transmission patterns were revealed as follows. The granules' ISO. Roundness and density correlated with raw material (i.e., model drug, diluent, and/or granulation liquid) properties such as density and viscosity. The granules' compressibility parameter a correlated with the granules' Span, and parameter y correlated with the granules' flowability and friability. Compactibility parameters k and k correlated mainly with granules' flowability and density, and parameter b correlated significantly and positively with tablet tensile strength. The compressibility correlated negatively with tablet solid fraction (SF) and friability, while the compactibility correlated positively with tablet disintegration time. Moreover, the rearrangement and elasticity of granules correlated positively with SF and friability, respectively. Overall, this study provides some guides for achieving high-quality tablets via HSWG-T.
Topics: Excipients; Tablets; Starch; Tensile Strength; Lactose; Particle Size; Drug Compounding; Technology, Pharmaceutical
PubMed: 37364781
DOI: 10.1016/j.ijpharm.2023.123177 -
Clinical Nutrition (Edinburgh, Scotland) Jun 2024A diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) has been shown to effectively reduce irritable bowel syndrome (IBS) symptoms. Effects resulting... (Meta-Analysis)
Meta-Analysis
The efficacy and real-world effectiveness of a diet low in fermentable oligo-, di-, monosaccharides and polyols in irritable bowel syndrome: A systematic review and meta-analysis.
BACKGROUND & AIMS
A diet low in fermentable oligo-, di-, monosaccharides, and polyols (LFD) has been shown to effectively reduce irritable bowel syndrome (IBS) symptoms. Effects resulting from real-world studies may differ from those seen in efficacy studies because of the diversity of patients in real-world settings. This systematic review and meta-analysis aimed to compare the effect of the LFD on reducing IBS symptoms and improving the quality of life (QoL) in efficacy trials and real-world studies.
METHODS
Major databases, trial registries, dissertations, and journals were systematically searched for studies on the LFD in adults with IBS. Meta-analysis was conducted using a random effects model with standardized mean differences (SMD) and 95% confidence intervals (CI). Outcomes of interest were all patient-reported: stool consistency, stool frequency, abdominal pain, overall symptoms, adequate symptom relief, IBS-specific QoL and adherence to the LFD.
RESULTS
Eleven efficacy and 19 real-world studies were reviewed. The meta-analysis results for abdominal pain (SMD 0.35, 95% CI 0.16 to 0.54) and QoL (SMD 0.23, 95% CI -0.05 to 0.50) showed the LFD was beneficial in efficacy studies with no statistically significant results for stool frequency (SMD 0.71, 95% CI 0.34 to 1.07). Real-world studies found improvements in abdominal pain and QoL. Due to heterogeneity, no meta-analysis was done for stool consistency and overall symptoms. In these outcomes, results were mostly supportive of the LFD, but they were not always statistically significant.
CONCLUSIONS
The results of this systematic review and meta-analysis suggest the LFD improves outcomes compared to a control diet (efficacy studies) or baseline data (real-world studies). Because of diverse study designs and heterogeneity of results, a clear superiority of the LFD over control diets could not be concluded. There are no indications of an efficacy-effectiveness gap for the LFD in adults with IBS.
Topics: Irritable Bowel Syndrome; Humans; Monosaccharides; Quality of Life; Fermentation; Polymers; Oligosaccharides; Disaccharides; Diet, Carbohydrate-Restricted; Treatment Outcome
PubMed: 38754307
DOI: 10.1016/j.clnu.2024.05.014 -
Biomedical Materials (Bristol, England) Sep 2023In the past few decades, although tissue engineering has made significant progress and achieved many accomplishments, there are still some key problems that remain...
In the past few decades, although tissue engineering has made significant progress and achieved many accomplishments, there are still some key problems that remain unsolved. One of the urgent research challenges in this field is how to prepare large-scale tissue engineering scaffolds with spatially complex structures. In this work, a sacrificial template process using sucrose as the sacrificial material and a gelatin/microbial transglutaminase mixed solution as the bio-scaffold material is proposed to fabricate a bio-scaffold with multi-level branching and spatially complex vascular network channels that mimic the structure and function of the human vascular network. To validate the feasibility of the fabrication process and the rationality of the process parameters, the morphological characteristics, connectivity of vascular network channels, shaping accuracy, and mechanical properties of the bio-scaffold were tested and analyzed. The results showed that the bio-scaffold fabricated using this process had a complete morphology and excellent connectivity. The diameter of the sucrose sacrificial template showed a linear relationship with the feeding speed, and the average diameter error rate between the sucrose sacrificial template and the vascular network channels inside the bio-scaffold was less than 8%. The mechanical properties of the bio-scaffold met the requirements for large-scale tissue defect repair. To evaluate the effect of the bio-scaffold on cell activity, human umbilical vein endothelial cells (HUVECs) were seeded into the vascular network channels of the bio-scaffold, and their attachment, growth, and proliferation on the surface of the vascular network channels were observed. To further assess the biocompatibility of the bio-scaffold, the bio-scaffold was implanted subcutaneously in the dorsal tissue of rats, and the tissue regeneration status was compared and analyzed through immunohistochemical analysis. The results showed that the vascular network channels within the bio-scaffold allowed uniform cell attachment, growth, with fewer dead cells and high cell viability. Moreover, clear cell attachment and growth were observed within the vascular network channels of the bio-scaffold after implantation in rats. These results indicate that the fabricated bio-scaffold meets the basic performance requirements for the repair and regeneration of large-scale tissue defects, providing a new approach for oxygen and nutrient transport in large-scale tissues and opening up new avenues for clinical applications.
Topics: Humans; Animals; Rats; Cell Survival; Gelatin; Human Umbilical Vein Endothelial Cells; Oxygen; Sucrose
PubMed: 37691568
DOI: 10.1088/1748-605X/acf541 -
Carbohydrate Polymers May 2024Heparin is one of the most widely used natural drugs, and has been the preferred anticoagulant and antithrombotic agent in the clinical setting for nearly a century.... (Review)
Review
Heparin is one of the most widely used natural drugs, and has been the preferred anticoagulant and antithrombotic agent in the clinical setting for nearly a century. Heparin also shows increasing therapeutic potential for treating inflammation, cancer, and microbial and viral diseases, including COVID-19. With advancements in synthetic biology, heparin production through microbial engineering of heparosan offers a cost-effective and scalable alternative to traditional extraction from animal tissues. Heparosan serves as the starting carbon backbone for the chemoenzymatic synthesis of bioengineered heparin, possessing a chain length that is critically important for the production of heparin-based therapeutics with specific molecular weight (MW) distributions. Recent advancements in metabolic engineering of microbial cell factories have resulted in high-yield heparosan production. This review systematically analyzes the key modules involved in microbial heparosan biosynthesis and the latest metabolic engineering strategies for enhancing production, regulating MW, and optimizing the fermentation scale-up of heparosan. It also discusses future studies, remaining challenges, and prospects in the field.
Topics: Metabolic Engineering; Fermentation; Disaccharides; Heparin
PubMed: 38388039
DOI: 10.1016/j.carbpol.2024.121881 -
Gastroenterology Jul 2024The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND & AIMS
The efficacy of a low fermentable oligo-, di-, monosaccharides and polyols (FODMAP) diet in irritable bowel syndrome (IBS) is well established. After the elimination period, a reintroduction phase aims to identify triggers. We studied the impact of a blinded reintroduction using FODMAP powders to objectively identify triggers and evaluated the effect on symptoms, quality of life, and psychosocial comorbidities.
METHODS
Responders to a 6-week low FODMAP diet, defined by a drop in IBS symptom severity score (IBS-SSS) compared with baseline, entered a 9-week blinded randomized reintroduction phase with 6 FODMAP powders (fructans, fructose, galacto-oligosaccharides, lactose, mannitol, sorbitol) or control (glucose). A rise in IBS-SSS (≥50 points) defined a FODMAP trigger. Patients completed daily symptom diaries and questionnaires for quality of life and psychosocial comorbidities.
RESULTS
In 117 recruited patients with IBS, IBS-SSS improved significantly after the elimination period compared with baseline (150 ± 116 vs 301 ± 97, P < .0001, 80% responders). Symptom recurrence was triggered in 85% of the FODMAP powders, by an average of 2.5 ± 2 FODMAPs/patient. The most prevalent triggers were fructans (56%) and mannitol (54%), followed by galacto-oligosaccharides, lactose, fructose, sorbitol, and glucose (respectively 35%, 28%, 27%, 23%, and 26%) with a significant increase in abdominal pain at day 1 for sorbitol/mannitol, day 2 for fructans/galacto-oligosaccharides, and day 3 for lactose.
CONCLUSION
We confirmed the significant benefit of the low FODMAP diet in tertiary-care IBS. A blinded reintroduction revealed a personalized pattern of symptom recurrence, with fructans and mannitol as the most prevalent, and allows the most objective identification of individual FODMAP triggers. Ethical commission University hospital of Leuven reference number: s63629; Clinicaltrials.gov number: NCT04373304.
Topics: Humans; Irritable Bowel Syndrome; Female; Male; Adult; Quality of Life; Middle Aged; Oligosaccharides; Fermentation; Mannitol; Diet, Carbohydrate-Restricted; Treatment Outcome; Lactose; Monosaccharides; Disaccharides; Polymers; Fructose; Sorbitol; Fructans; Severity of Illness Index; Double-Blind Method; Surveys and Questionnaires; Powders; Recurrence; Young Adult; FODMAP Diet
PubMed: 38401741
DOI: 10.1053/j.gastro.2024.02.008 -
PeerJ 2023Storage of potato tubers is an essential stage of the supply chain, from farm to consumer, to efficiently match supply and demand. However, the quality and yield of...
BACKGROUND
Storage of potato tubers is an essential stage of the supply chain, from farm to consumer, to efficiently match supply and demand. However, the quality and yield of potatoes are influenced by physiological changes during storage.
METHODS
This study tested the physiological and biochemical indices in three potato varieties (YunSu 108, YunSu 304 and YunSu 306) during their dormancy periods.
RESULTS
Three potato varieties with different dormancy periods were used to follow changes in starch, protein and several enzymes during storage. The starch and sugar content of the long-dormant variety (YunSu 108, LDV) were stable, whereas those of the short-dormant variety (YunSu 306, SDV) were variable. Starch synthase activity in the three varieties was initially high, then decreased; the starch content of LDV was relatively stable, that of the medium-dormant variety (YunSu 304, MDV) increased with storage time and peaked at sprouting, and that of SDV was low but variable. The sucrose synthase activity of LDV was significantly higher ( < 0.05) than MDV and SDV in the middle storage period. Two spikes were observed in the invertase activity of SDV, whereas those of MDV and LDV were stable. The reducing sugar content of LDV increased significantly before sprouting, that of MDV slowly decreased and that of SDV dropped sharply. During the whole storage period, pectinase activity in LDV did not change significantly, whereas pectinase in MDV and SDV decreased. The cellulase and protein contents initially increased and then decreased in LDV, and steadily decreased in MDV and SDV.
CONCLUSION
The metabolic indices related to starch and sugar in the LDV were relatively stable during storage, whereas those of the SDV varied greatly. SDV showed increased sucrose, reducing sugars and cellulose; LDV PCA plots clustered in the positive quadrant of PC1 and the negative quadrant of PC2, with increased protein, sucrose synthase and starch; MDV had increased soluble starch synthase.
Topics: Solanum tuberosum; Polygalacturonase; Starch Synthase; Starch; Sucrose
PubMed: 37663286
DOI: 10.7717/peerj.15923 -
American Journal of Physiology.... Sep 2023Diet is considered a culprit for symptoms in irritable bowel syndrome (IBS), although the mechanistic understanding of underlying causes is lacking. Metabolomics, i.e.,... (Randomized Controlled Trial)
Randomized Controlled Trial
Diet is considered a culprit for symptoms in irritable bowel syndrome (IBS), although the mechanistic understanding of underlying causes is lacking. Metabolomics, i.e., the analysis of metabolites in biological samples may offer a diet-responsive fingerprint for IBS. Our aim was to explore alterations in the plasma metabolome after interventions with fermentable oligosaccharides, disaccharides, monosaccharides, and polyols (FODMAPs) or gluten versus control in IBS, and to relate such alterations to symptoms. People with IBS ( = 110) were included in a double-blind, randomized, crossover study with 1-wk provocations of FODMAPs, gluten, or placebo. Symptoms were evaluated with the IBS severity scoring system (IBS-SSS). Untargeted metabolomics was performed on plasma samples using LC-qTOF-MS. Discovery of metabolite alterations by treatment was performed using random forest followed by linear mixed modeling. Associations were studied using Spearman correlation. The metabolome was affected by FODMAP [classification rate (CR) 0.88, < 0.0001], but less by gluten intake CR 0.72, = 0.01). FODMAP lowered bile acids, whereas phenolic-derived metabolites and 3-indolepropionic acid (IPA) were higher compared with placebo. IPA and some unidentified metabolites correlated weakly to abdominal pain and quality of life. Gluten affected lipid metabolism weakly, but with no interpretable relationship to IBS. FODMAP affected gut microbial-derived metabolites relating to positive health outcomes. IPA and unknown metabolites correlated weakly to IBS severity. Minor symptom worsening by FODMAP intake must be weighed against general positive health aspects of FODMAP. The gluten intervention affected lipid metabolism weakly with no interpretable association to IBS severity. Registration: www.clinicaltrials.gov as NCT03653689. In irritable bowel syndrome (IBS), fermentable oligo-, di-, monosaccharides, and polyols (FODMAPs) affected microbial-derived metabolites relating to positive health outcomes such as reduced risk of colon cancer, inflammation, and type 2 diabetes, as shown in previous studies. The minor IBS symptom induction by FODMAP intake must be weighed against the positive health aspects of FODMAP consumption. Gluten affected lipids weakly with no association to IBS severity.
Topics: Humans; Disaccharides; Irritable Bowel Syndrome; Glutens; Monosaccharides; Tryptophan; Quality of Life; Cross-Over Studies; Bile Acids and Salts; Diabetes Mellitus, Type 2; Fermentation; Oligosaccharides; Lipids; Diet, Carbohydrate-Restricted
PubMed: 37399002
DOI: 10.1152/ajpregu.00016.2023