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1.
Sultan Qaboos Univ Med J ; 24(2): 243-249, 2024 May.
Article in English | MEDLINE | ID: mdl-38828248

ABSTRACT

Objectives: This study aimed to evaluate the safety and efficacy of remogliflozin compared to vildagliptin as an add-on drug to metformin in type 2 diabetes mellitus (T2DM) treatment. Metformin is considered a first-line drug in T2DM. However, as the disease progresses with heightened insulin resistance and declining ß-cell function, the use of metformin alone is often inadequate to achieve optimum glucose levels. Methods: This prospective, randomised study was conducted at Maulana Azad Medical College and Associated Hospital in New Delhi, India, between February 2020 to January 2021. This study recruited 60 T2DM patients aged 35-70 years with glycated haemoglobin (HbA1c) >6.5% taking metformin at a daily dosage of 1,500-3,000 mg for ≥3 months. Patients were randomly assigned in a 1:1 ratio to receive either vildagliptin (50 mg) or remogliflozin (100 mg) twice daily for 90 days. The primary endpoint was a change in HbA1c levels from baseline to the end of 90 days whereas secondary endpoints were changes in lipid profile and weight. Results: The decrement in mean HbA1c levels was significantly higher in the remogliflozin group than in the vildagliptin group (-8.1% versus -2.4%; P <0.001). In addition, more significant weight loss was found in remogliflozin-treated patients (-5.2% versus -0.6%; P <0.01). Both treatments were well tolerated throughout the study. Conclusion: Compared to vildagliptin, remoglilflozin was significantly more effective in glycaemic control and weight loss in patients with T2DM and can therefore be considered as an add-on drug in T2DM not adequately controlled by metformin monotherapy.


Subject(s)
Diabetes Mellitus, Type 2 , Drug Therapy, Combination , Hypoglycemic Agents , Metformin , Vildagliptin , Humans , Diabetes Mellitus, Type 2/drug therapy , Diabetes Mellitus, Type 2/blood , Vildagliptin/pharmacology , Vildagliptin/therapeutic use , Metformin/therapeutic use , Metformin/pharmacology , Middle Aged , Male , Female , Hypoglycemic Agents/therapeutic use , Hypoglycemic Agents/pharmacology , Prospective Studies , Aged , Adult , Drug Therapy, Combination/methods , India , Glycated Hemoglobin/analysis , Glycated Hemoglobin/drug effects , Glucosides/therapeutic use , Glucosides/pharmacology , Treatment Outcome , Blood Glucose/analysis , Blood Glucose/drug effects , Sorbitol/analogs & derivatives , Sorbitol/therapeutic use , Sorbitol/pharmacology , Sorbitol/adverse effects , Sorbitol/administration & dosage , Pyrazoles
2.
Sci Rep ; 14(1): 12461, 2024 05 30.
Article in English | MEDLINE | ID: mdl-38816376

ABSTRACT

Contaminated lake water and fish can be sources of bacterial pathogens of public health concern, including pathogenic E. coli. Within Ethiopia, specifically, Central Oromia, raw fish consumption is a common practice. Although there are few reports on occurrence of E. coli O157 in fish destined for human consumption and children under five years, information on the transmission pathways of E. coli O157 and other sorbitol non-fermenting (SN-F) E. coli from water-to-fish-to-human, and their virulence factors and antimicrobial resistant determinants along the fish supply chain is lacking. The study aimed to investigate the occurrence, molecular characteristics, and antimicrobial susceptibility of E. coli O157 and other SN-F E. coli strains in fish, lake water and humans in central Oromia, Ethiopia. A total of 750 samples (450 fish samples, 150 water samples, 150 human stool samples) were collected from five lakes and three health facilities. The samples were processed following the standard protocol recommended by European Food Safety Authority and Kirby-Bauer disc diffusion method for detection of the bacteria, and antimicrobial susceptibility tests, respectively. Molecular characterization of presumptive isolates was performed using Whole-Genome Sequencing (WGS) for serotyping, determination of virulence factors, antimicrobial resistance traits, and genetic linkage of the isolates. Overall, 3.9% (29/750) of the samples had SN-F E. coli; of which 6.7% (n = 10), 1.8% (n = 8) and 7.3% (n = 11) were retrieved from water, fish, and diarrheic human patients, respectively. The WGS confirmed that all the isolates were SN-F non-O157: H7 E. coli strains. We reported two new E. coli strains with unknown O-antigen from fish and human samples. All the strains have multiple virulence factors and one or more genes encoding for them. Genetic relatedness was observed among strains from the same sources (water, fish, and humans). Most isolates were resistant to ampicillin (100%), tetracycline (100%), cefotaxime (100%), ceftazidime (100%), meropenem (100%), nalidixic acid (93.1%) and sulfamethoxazole/trimethoprim (79.3%). Majority of the strains were resistant to chloramphenicol (58.6%) and ciprofloxacin (48.3%), while small fraction showed resistance to azithromycin (3.45%). Isolates had an overall MDR profile of 87.5%. Majority, (62.1%; n = 18) of the strains had acquired MDR traits. Genes encoding for mutational resistance and Extended-spectrum beta-lactamases (ESBL) were also detected. In conclusion, our study revealed the occurrence of virulent and MDR SN-F E. coli strains in water, fish, and humans. Although no genetic relatedness was observed among strains from various sources, the genomic clustering among strains from the same sources strongly suggests the potential risk of transmission along the supply chain at the human-fish-environment interface if strict hygienic fish production is not in place. Further robust genetic study of the new strains with unknown O-antigens, and the epidemiology of SN-F E. coli is required to elucidate the molecular profile and public health implications of the pathogens.


Subject(s)
Escherichia coli , Fishes , Lakes , Sorbitol , Humans , Ethiopia/epidemiology , Animals , Lakes/microbiology , Sorbitol/pharmacology , Fishes/microbiology , Escherichia coli/genetics , Escherichia coli/drug effects , Escherichia coli/isolation & purification , Escherichia coli/pathogenicity , Microbial Sensitivity Tests , Escherichia coli Infections/microbiology , Escherichia coli Infections/epidemiology , Anti-Bacterial Agents/pharmacology , Virulence Factors/genetics , Whole Genome Sequencing , Water Microbiology , Drug Resistance, Bacterial/genetics , Food Microbiology , Feces/microbiology , Escherichia coli O157/genetics , Escherichia coli O157/drug effects , Escherichia coli O157/isolation & purification , Escherichia coli O157/pathogenicity
3.
Mediators Inflamm ; 2024: 7524314, 2024.
Article in English | MEDLINE | ID: mdl-38725539

ABSTRACT

Objective: Microfold cells (M cells) are specific intestinal epithelial cells for monitoring and transcytosis of antigens, microorganisms, and pathogens in the intestine. However, the mechanism for M-cell development remained elusive. Materials and Methods: Real-time polymerase chain reaction, immunofluorescence, and western blotting were performed to analyze the effect of sorbitol-regulated M-cell differentiation in vivo and in vitro, and luciferase and chromatin Immunoprecipitation were used to reveal the mechanism through which sorbitol-modulated M-cell differentiation. Results: Herein, in comparison to the mannitol group (control group), we found that intestinal M-cell development was inhibited in response to sorbitol treatment as evidenced by impaired enteroids accompanying with decreased early differentiation marker Annexin 5, Marcksl1, Spib, sox8, and mature M-cell marker glycoprotein 2 expression, which was attributed to downregulation of receptor activator of nuclear factor kappa-В ligand (RANKL) expression in vivo and in vitro. Mechanically, in the M-cell model, sorbitol stimulation caused a significant upregulation of phosphodiesterase 4 (PDE4) phosphorylation, leading to decreased protein kinase A (PKA)/cAMP-response element binding protein (CREB) activation, which further resulted in CREB retention in cytosolic and attenuated CREB binds to RANKL promoter to inhibit RANKL expression. Interestingly, endogenous PKA interacted with CREB, and this interaction was destroyed by sorbitol stimulation. Most importantly, inhibition of PDE4 by dipyridamole could rescue the inhibitory effect of sorbitol on intestinal enteroids and M-cell differentiation and mature in vivo and in vitro. Conclusion: These findings suggested that sorbitol suppressed intestinal enteroids and M-cell differentiation and matured through PDE4-mediated RANKL expression; targeting to inhibit PDE4 was sufficient to induce M-cell development.


Subject(s)
Cell Differentiation , Cyclic AMP Response Element-Binding Protein , Cyclic Nucleotide Phosphodiesterases, Type 4 , RANK Ligand , Sorbitol , Sorbitol/pharmacology , RANK Ligand/metabolism , Animals , Cyclic Nucleotide Phosphodiesterases, Type 4/metabolism , Cell Differentiation/drug effects , Mice , Cyclic AMP Response Element-Binding Protein/metabolism , Intestinal Mucosa/metabolism , Cyclic AMP-Dependent Protein Kinases/metabolism , Male , Mice, Inbred C57BL , M Cells
4.
Sci Rep ; 14(1): 11285, 2024 05 17.
Article in English | MEDLINE | ID: mdl-38760389

ABSTRACT

Feeding behaviors are determined by two main factors. One is the internal state, such as hunger or previous experiences; the other is external factors, such as sensory stimulation. During starvation, animals must balance food-seeking behavior with energy conservation. The fruit fly, Drosophila melanogaster, serves as a useful model for studying food selectivity and various behaviors related to food intake. However, few studies have directly connected food selectivity with other behaviors, such as locomotor activity and sleep. In this study, we report that flies exhibited a preference for specific positions and spent more time in the proximity of sweet sugars, such as sucrose and sucralose, but not non-sweet and nutritious sugars like xylitol and sorbitol. On the other hand, prolonged exposure to sorbitol increased the staying time of flies in the proximity of sorbitol. Additionally, after starvation, flies immediately exhibited a position preference in the proximity of sorbitol. These findings suggest that flies prefer the proximity of sweet food, and starvation alters their preference for nutritious food, which may be beneficial for their survival.


Subject(s)
Drosophila melanogaster , Feeding Behavior , Sugars , Animals , Drosophila melanogaster/physiology , Feeding Behavior/physiology , Starvation , Food Preferences/physiology , Sorbitol/pharmacology , Sucrose/metabolism
5.
PLoS One ; 19(5): e0295735, 2024.
Article in English | MEDLINE | ID: mdl-38696486

ABSTRACT

The stability of monoclonal antibodies (mAbs) is vital for their therapeutic success. Sorbitol, a common mAb stabilizer used to prevent aggregation, was evaluated for any potential adverse effects on the chemical stability of mAb X. An LC-MS/MS based analysis focusing on the post-translational modifications (PTMs) of mAb X was conducted on samples that had undergone accelerated aging at 40°C. Along with PTMs that are known to affect mAbs' structure function and stability (such as deamidation and oxidation), a novel mAb PTM was discovered, the esterification of glutamic acid by sorbitol. Incubation of mAb X with a 1:1 ratio of unlabeled sorbitol and isotopically labeled sorbitol (13C6) further corroborated that the modification was the consequence of the esterification of glutamic acid by sorbitol. Levels of esterification varied across glutamic acid residues and correlated with incubation time and sorbitol concentration. After 4 weeks of accelerated stability with isotopically labeled sorbitol, it was found that 16% of the total mAb possesses an esterified glutamic acid. No esterification was observed at aspartic acid sites despite the free carboxylic acid side chain. This study unveils a unique modification of mAbs, emphasizing its potential significance for formulation and drug development.


Subject(s)
Antibodies, Monoclonal , Glutamic Acid , Sorbitol , Tandem Mass Spectrometry , Sorbitol/chemistry , Esterification , Tandem Mass Spectrometry/methods , Antibodies, Monoclonal/chemistry , Glutamic Acid/chemistry , Chromatography, Liquid/methods , Protein Stability , Protein Processing, Post-Translational , Drug Stability , Liquid Chromatography-Mass Spectrometry
6.
FEMS Yeast Res ; 242024 Jan 09.
Article in English | MEDLINE | ID: mdl-38565313

ABSTRACT

Pretreatment of lignocellulose yields a complex sugar mixture that potentially can be converted into bioethanol and other chemicals by engineered yeast. One approach to overcome competition between sugars for uptake and metabolism is the use of a consortium of specialist strains capable of efficient conversion of single sugars. Here, we show that maltose inhibits cell growth of a xylose-fermenting specialist strain IMX730.1 that is unable to utilize glucose because of the deletion of all hexokinase genes. The growth inhibition cannot be attributed to a competition between maltose and xylose for uptake. The inhibition is enhanced in a strain lacking maltase enzymes (dMalX2) and completely eliminated when all maltose transporters are deleted. High-level accumulation of maltose in the dMalX2 strain is accompanied by a hypotonic-like transcriptional response, while cells are rescued from maltose-induced cell death by the inclusion of an extracellular osmolyte such as sorbitol. These data suggest that maltose-induced cell death is due to high levels of maltose uptake causing hypotonic-like stress conditions and can be prevented through engineering of the maltose transporters. Transporter engineering should be included in the development of stable microbial consortia for the efficient conversion of lignocellulosic feedstocks.


Subject(s)
Maltose , Saccharomyces cerevisiae , Saccharomyces cerevisiae/genetics , Saccharomyces cerevisiae/metabolism , Maltose/metabolism , Microbial Viability , Gene Deletion , Sorbitol/metabolism , Sorbitol/pharmacology , Xylose/metabolism , Monosaccharide Transport Proteins/genetics , Monosaccharide Transport Proteins/metabolism , Saccharomyces cerevisiae Proteins/genetics , Saccharomyces cerevisiae Proteins/metabolism , Glucose/metabolism
7.
Food Chem ; 449: 139213, 2024 Aug 15.
Article in English | MEDLINE | ID: mdl-38631134

ABSTRACT

This study took a novel approach to address the dual challenges of enhancing the ethanol content and aroma complexity in Laiyang pear wine. It focused on sorbitol as a pivotal element in the strategic selection of yeasts with specific sorbitol-utilization capabilities and their application in co-fermentation strategies. We selected two Saccharomyces cerevisiae strains (coded as Sc1, Sc2), two Metschnikowia pulcherrima (coded as Mp1, Mp2), and one Pichia terricola (coded as Tp) due to their efficacy as starter cultures. Notably, the Sc2 strain, alone or with Mp2, significantly increased the ethanol content (30% and 16%). Mixed Saccharomyces cerevisiae and Pichia terricola fermentation improved the ester profiles and beta-damascenone levels (maximum of 150%), while Metschnikowia pulcherrima addition enriched the phenethyl alcohol content (maximum of 330%), diversifying the aroma. This study investigated the efficacy of strategic yeast selection based on sorbitol utilization and co-fermentation methods in enhancing Laiyang pear wine quality and aroma.


Subject(s)
Fermentation , Flavoring Agents , Odorants , Pyrus , Saccharomyces cerevisiae , Sorbitol , Taste , Wine , Wine/analysis , Wine/microbiology , Pyrus/chemistry , Pyrus/microbiology , Pyrus/metabolism , Saccharomyces cerevisiae/metabolism , Saccharomyces cerevisiae/chemistry , Flavoring Agents/metabolism , Flavoring Agents/chemistry , Sorbitol/metabolism , Sorbitol/analysis , Odorants/analysis , Ethanol/metabolism , Ethanol/analysis , Pichia/metabolism , Metschnikowia/metabolism , Fruit/chemistry , Fruit/microbiology , Fruit/metabolism
8.
Food Chem ; 450: 139267, 2024 Aug 30.
Article in English | MEDLINE | ID: mdl-38615526

ABSTRACT

In this study, kimchi-extracted cellulose was utilized to fabricate edible films using a hot synthetic approach, followed by solvent casting, and employing sorbitol and citric acid as the plasticizer and crosslinker, respectively. The chemical, optical, physical, and thermal properties of these films were explored to provide a comparative assessment of their suitability for various packaging applications. Chemical analyses confirmed that the kimchi-extracted cellulose comprised cellulose Iß and amorphous cellulose and did not contain any impurities. Optical analyses revealed that kimchi-extracted cellulose-containing films exhibited better-dispersed surfaces than films fabricated from commercial cellulose. Physical property analyses indicated their hydrophilic characteristics with contact angles <20°. In the thermal analysis, similar Tg results confirmed the comparable thermal stability between films containing commercial microcrystalline cellulose-containing films and kimchi-extracted cellulose-containing films. Edible films produced from kimchi-extracted cellulose through food-upcycling approaches are therefore promising for applications as packaging materials.


Subject(s)
Cellulose , Citric Acid , Edible Films , Food Packaging , Sorbitol , Food Packaging/instrumentation , Cellulose/chemistry , Citric Acid/chemistry , Sorbitol/chemistry
9.
ACS Chem Neurosci ; 15(7): 1366-1377, 2024 Apr 03.
Article in English | MEDLINE | ID: mdl-38503425

ABSTRACT

The pathological misfolding and aggregation of the microtubule associated protein tau (MAPT), a full length Tau2N4R with 441aa, is considered the principal disease relevant constituent in tauopathies including Alzheimer's disease (AD) with an imbalanced ratio in 3R/4R isoforms. The exact cellular fluid composition, properties, and changes that coincide with tau misfolding, seed formation, and propagation events remain obscure. The proteostasis network, along with the associated osmolytes, is responsible for maintaining the presence of tau in its native structure or dealing with misfolding. In this study, for the first time, the roles of natural brain osmolytes are being investigated for their potential effects on regulating the conformational stability of the tau monomer (tauM) and its propensity to aggregate or disaggregate. Herein, the effects of physiological osmolytes myo-inositol, taurine, trimethyl amine oxide (TMAO), betaine, sorbitol, glycerophosphocholine (GPC), and citrulline on tau's aggregation state were investigated. The overall results indicate the ability of sorbitol and GPC to maintain the monomeric form and prevent aggregation of tau, whereas myo-inositol, taurine, TMAO, betaine, and citrulline promote tau aggregation to different degrees, as revealed by protein morphology in atomic force microscopy images. Biochemical and biophysical methods also revealed that tau proteins adopt different conformations under the influence of these osmolytes. TauM in the presence of all osmolytes expressed no toxicity when tested by a lactate dehydrogenase assay. Investigating the conformational stability of tau in the presence of osmolytes may provide a better understanding of the complex nature of tau aggregation in AD and the protective and/or chaotropic nature of osmolytes.


Subject(s)
Alzheimer Disease , Methylamines , tau Proteins , Humans , tau Proteins/metabolism , Betaine , Citrulline , Alzheimer Disease/drug therapy , Alzheimer Disease/metabolism , Taurine/pharmacology , Inositol/metabolism , Sorbitol/metabolism
10.
Air Med J ; 43(2): 116-123, 2024.
Article in English | MEDLINE | ID: mdl-38490774

ABSTRACT

OBJECTIVE: The epidemiology accompanying helicopter emergency medical services (HEMS) transport has evolved as agencies have matured and become integrated into regionalized health systems, as evidenced primarily by nationwide systems in Europe. System-level congruence between Europe and the United States, where HEMS is geographically fragmentary, is unclear. In this study, we provide a temporal, epidemiologic characterization of the largest standardized private, nonprofit HEMS system in the United States, STAT MedEvac. METHODS: We obtained comprehensive timing, procedure, and vital signs data from STAT MedEvac prehospital electronic patient care records for all adult patients transported to UPMC Health System hospitals in the period of January 2012 through October 2021. We linked these data with hospital electronic health records available through June 2018 to establish length of stay and vital status at discharge. RESULTS: We studied 90,960 transports and matched 62.8% (n = 57,128) to the electronic health record. The average patient age was 58.6 years ( 19 years), and most were male (57.9%). The majority of cases were interfacility transports (77.6%), and the most common general medical category was nontrauma (72.7%). Sixty-one percent of all patients received a prehospital intervention. Overall, hospital mortality was 15%, and the average hospital length of stay (LOS) was 8.8 days ( 10.0 days). Observed trends over time included increases in nontrauma transports, level of severity, and in-hospital mortality. In multivariable models, case severity and medical category correlated with the outcomes of mortality and LOS. CONCLUSION: In the largest standardized nonprofit HEMS system in the United States, patient mortality and hospital LOS increased over time, whereas the proportion of trauma patients and scene runs decreased.


Subject(s)
Air Ambulances , Emergency Medical Services , Adult , Humans , Male , United States/epidemiology , Middle Aged , Female , Retrospective Studies , Aircraft , Emergency Medical Services/methods , Critical Care , Sorbitol , Injury Severity Score
11.
Int J Biol Macromol ; 264(Pt 2): 130773, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38467211

ABSTRACT

This work reports on the development of starch-rich thermoplastic based formulations produced by using mango kernel flour, avoiding the extraction process of starch from mango kernel to produce these materials. Glycerol, sorbitol and urea at 15 wt% are used as plasticizers to obtain thermoplastic starch (TPS) formulations by extrusion and injection-moulding processes. Mechanical results show that sorbitol and urea allowed to obtain samples with tensile strength and elongation at break higher than the glycerol-plasticized sample, achieving values of 2.9 MPa of tensile strength and 42 % of elongation at break at 53 % RH. These results are supported by field emission scanning electron microscopy (FESEM) micrographs, where a limited concentration of voids was observed in the samples with sorbitol and urea, indicating a better interaction between starch and the plasticizers. Thermogravimetric analysis (TGA) shows that urea and sorbitol increase the thermal stability of TPS in comparison to the glycerol-plasticized sample. Differential scanning calorimetry (DSC) and dynamic-mechanical-thermal analysis (DMTA) verify the increase in stiffness of the sorbitol and urea plasticized TPS and also illustrate an increase in the glass transition temperature of both samples in comparison to the glycerol-plasticized sample. Glass transition temperatures of 45 °C were achieved for the sample with sorbitol.


Subject(s)
Mangifera , Plasticizers , Plasticizers/chemistry , Starch/chemistry , Glycerol/chemistry , Flour , Plastics , Sorbitol/chemistry , Urea/chemistry
12.
Genes Cells ; 29(5): 432-437, 2024 May.
Article in English | MEDLINE | ID: mdl-38467515

ABSTRACT

The systemic effects of the artificial sweetener sorbitol on older adult individuals have not been elucidated. We assessed the effects of sorbitol consumption on cognitive and gingival health in a mouse model. Aged mice were fed 5% sorbitol for 3 months before their behavior was assessed, and brain and gingival tissues were collected. Long-term sorbitol consumption inhibited gingival tissue aging in aged mice. However, it caused cognitive decline and decreased brain-derived neurotrophic factor (BDNF) in the hippocampus. Sorbitol consumption did not affect homeostatic function; however, it may exert effects within the brain, particularly in the hippocampus.


Subject(s)
Aging , Cognition , Hippocampus , Sorbitol , Animals , Hippocampus/metabolism , Hippocampus/drug effects , Sorbitol/pharmacology , Sorbitol/administration & dosage , Mice , Cognition/drug effects , Male , Brain-Derived Neurotrophic Factor/metabolism , Mice, Inbred C57BL , Cognitive Dysfunction/chemically induced , Cognitive Dysfunction/metabolism , Cognitive Dysfunction/etiology
14.
Environ Sci Pollut Res Int ; 31(17): 25216-25226, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38468002

ABSTRACT

The concentrations of anhydrosugars (levoglucosan, mannosan, and galactosan), polyols (inositol, xylitol, sorbitol, and mannitol), and glucose were measured in PM1 and PM10 samples collected during 1 year at a traffic site in the city of Elche (southeastern Spain). Levoglucosan, mannosan, and galactosan were mainly found in the PM1 fraction since they are mainly emitted from biomass burning (BB). Likewise, inositol, xylitol, and sorbitol were primarily distributed in the fine mode, suggesting a non-negligible contribution from anthropogenic sources (specifically BB) to the levels of these compounds. This was supported by their seasonal variations, with higher concentrations during winter, and their correlations with levoglucosan concentrations. The average contributions of biomass burning and biogenic sources to OC and PM levels were calculated using levoglucosan and mannitol, respectively, as tracers. On average, BB accounted for 12% and 16% of the OC in PM1 and PM10, while the estimated contribution of fungal spores to OC and PM10 levels was 1.2 and 0.8%, respectively. The results of the present study suggest that, at least in the study area, most sugar alcohols are not appropriate tracers of biogenic emissions.


Subject(s)
Air Pollutants , Air Pollutants/analysis , Particulate Matter/analysis , Biomass , Xylitol , Aerosols/analysis , Sorbitol , Inositol , Mannitol , Environmental Monitoring/methods , Seasons
15.
Diabetes Obes Metab ; 26(6): 2339-2348, 2024 Jun.
Article in English | MEDLINE | ID: mdl-38504118

ABSTRACT

AIM: Dipeptidyl peptidase-4 (DPP-4) inhibitors suppress the inactivation of incretin hormones and lower blood glucose levels by inhibiting DPP-4 function. Sodium-glucose cotransporter 2 (SGLT2) inhibitors lower blood glucose levels in an insulin-independent manner by inhibiting renal reabsorption of glucose. DPP-4 and SGLT2 inhibitors each have the potential to improve hepatic steatosis; however, their combined effects remain unclear. In this study, we examined the effects of the combination of these drugs on hepatic steatosis using high-fat diet-fed mice. METHOD: C57BL/6J male mice were fed a 60% high-fat diet for 2 months to induce hepatic steatosis. Mice were divided into four groups (control; DPP-4 inhibitor anagliptin; SGLT2 inhibitor luseogliflozin; anagliptin and luseogliflozin combination), and the effects of each drug and their combination on hepatic steatosis after a 4-week intervention were evaluated. RESULTS: There were no differences in blood glucose levels among the four groups. Anagliptin suppresses inflammation- and chemokine-related gene expression. It also improved macrophage fractionation in the liver. Luseogliflozin reduced body weight, hepatic gluconeogenesis and blood glucose levels in the oral glucose tolerance test. The combination treatment improved hepatic steatosis without interfering with the effects of anagliptin and luseogliflozin, respectively, and fat content and inflammatory gene expression in the liver were significantly improved in the combination group compared with the other groups. CONCLUSION: The combination therapy with the DPP-4 inhibitor anagliptin and the SGLT2 inhibitor luseogliflozin inhibits fat deposition in the liver via anti-inflammatory effects during the early phase of diet-induced liver steatosis.


Subject(s)
Diet, High-Fat , Dipeptidyl-Peptidase IV Inhibitors , Fatty Liver , Sodium-Glucose Transporter 2 Inhibitors , Animals , Male , Mice , Blood Glucose/drug effects , Blood Glucose/metabolism , Diet, High-Fat/adverse effects , Dipeptidyl-Peptidase IV Inhibitors/pharmacology , Dipeptidyl-Peptidase IV Inhibitors/therapeutic use , Drug Synergism , Drug Therapy, Combination , Fatty Liver/prevention & control , Fatty Liver/drug therapy , Glucosides/pharmacology , Glucosides/therapeutic use , Liver/drug effects , Liver/metabolism , Mice, Inbred C57BL , Non-alcoholic Fatty Liver Disease/drug therapy , Non-alcoholic Fatty Liver Disease/metabolism , Non-alcoholic Fatty Liver Disease/etiology , Pyrimidines/pharmacology , Pyrimidines/therapeutic use , Sodium-Glucose Transporter 2 Inhibitors/pharmacology , Sodium-Glucose Transporter 2 Inhibitors/therapeutic use , Sorbitol/analogs & derivatives , Sorbitol/pharmacology , Sorbitol/therapeutic use
16.
J Tradit Chin Med ; 44(2): 260-267, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38504532

ABSTRACT

OBJECTIVE: To explore the anti-inflammatory components and mechanism of the non-volatile ingredients of patchouli. METHODS: High performance liquid chromatography-heated electron spray ionization-high resolution mass spectroscope (HPLC-HESI-HRMS) was used to analyze the chemical constituents of the non-volatile ingredients of patchouli. The anti-inflammatory activity of ingredients was evaluated using lipopolysaccharide (LPS) induced RAW264.7 cell inflammation model, and the anti-inflammatory mechanism was investigated using multivariate statistical analysis of cell metabolomics. RESULTS: The non-volatile ingredients of patchouli were characterized by HPLC-HESI-HRMS, and 36 flavonoids and 18 other components were identified. These ingredients of patchouli not only had a good protective effect on the LPS-induced inflammation model of RAW264.7 cells, but also regulated the expression levels of arginine, L-leucine, cholesterol, fructose and sorbitol by down-regulating arginine metabolism, aminoacyl-tRNA biosynthesis, polyol/sorbitol pathway, so as to reduce inflammation and reduce cell damage. CONCLUSION: The non-volatile ingredients of patchouli had good anti-inflammatory effect and exerted its curative effect by regulating endogenous metabolic pathway to reduce inflammatory response.


Subject(s)
Lipopolysaccharides , Pogostemon , Humans , Chromatography, High Pressure Liquid , Electrons , Anti-Inflammatory Agents/pharmacology , Metabolomics , Inflammation , Pogostemon/chemistry , Arginine , Sorbitol
17.
Sci Rep ; 14(1): 5563, 2024 03 06.
Article in English | MEDLINE | ID: mdl-38448501

ABSTRACT

Byproducts from the sugarcane manufacturing process, specifically sugarcane molasses (SM) and sugarcane bagasse (SB), can be used as alternative raw materials for sorbitol production via the biological fermentation process. This study investigated the production of sorbitol from SM and sugarcane bagasse hydrolysate (SBH) using a thermally adapted Zymomonas mobilis ZM AD41. Various combinations of SM and SBH on sorbitol production using batch fermentation process were tested. The results revealed that SM alone (FM1) or a mixture of SM and SBH at a ratio of 3:1 (FM2) based on the sugar mass in the raw material proved to be the best condition for sorbitol production by ZM AD41 at 37 °C. Further optimization conditions for sorbitol production revealed that a sugar concentration of 200 g/L and a CaCl2 concentration of 5.0 g/L yielded the highest sorbitol content. The maximum sorbitol concentrations produced by ZM AD41 in the fermentation medium containing SM (FM1) or a mixture of SM and SBH (FM2) were 31.23 and 30.45 g/L, respectively, comparable to those reported in the literature using sucrose or a mixture of sucrose and maltose as feedstock. These results suggested that SBH could be used as an alternative feedstock to supplement or blend with SM for sustainable sorbitol production. In addition, the fermentation conditions established in this study could also be applied to large-scale sorbitol production. Moreover, the thermally adapted Z. mobilis ZM AD41 is also a promising sorbitol-producing bacterium for large-scale production at a relatively high fermentation temperature using agricultural byproducts, specifically SM and SB, as feedstock, which could reduce the operating cost due to minimizing the energy required for the cooling system.


Subject(s)
Saccharum , Zymomonas , Cellulose , Sorbitol , Molasses , Maltose , Sucrose
18.
ACS Appl Bio Mater ; 7(4): 2240-2253, 2024 Apr 15.
Article in English | MEDLINE | ID: mdl-38326107

ABSTRACT

The protein extracted from the discarded eye lenses postcataract surgery, referred to as the cataractous eye protein isolate (CEPI), is employed as a polymer matrix for the construction of solid polymer electrolyte species (SPEs). SPEs are expected to be inexpensive, conductive, and mechanically stable in order to be economically and commercially viable. Environmentally, these materials should be biodegradable and nontoxic. Taking these factors into account, we investigated the possibility of using a discarded protein as a polymer matrix for SPEs. Natural compounds sorbitol and sinapic acid (SA) are used as the plasticizer and cross-linker, respectively, to tune the mechanical as well as electrochemical properties. The specific material formed is demonstrated to have high ionic conductivity ranging from ∼2 × 10-2 to ∼8 × 10-2 S cm-1. Without the addition of any salt, the ionic conductivity of sorbitol-plasticized non-cross-linked CEPI is ∼7.5 × 10-2 S cm-1. Upon the addition of NaCl, the conductivity is enhanced to ∼8 × 10-1 S cm-1. This study shows the possibility of utilizing a discarded protein CEPI as an alternative polymer matrix with further potential for the construction of tunable, flexible, recyclable, biocompatible, and biodegradable SPEs for flexible green electronics and biological devices.


Subject(s)
Electrolytes , Electronics , Electric Conductivity , Polymers , Sorbitol
19.
Int J Biol Macromol ; 262(Pt 2): 130103, 2024 Mar.
Article in English | MEDLINE | ID: mdl-38346616

ABSTRACT

Extraction of seaweed compounds using Deep Eutectic Solvents (DES) has shown high interest. Quantification, however, is challenging due to interactions with DES components. In this research work, three chemical separation techniques were investigated to isolate and quantify alginate from a set of choline chloride-based DES. While choline chloride served as the hydrogen bond acceptor (HBA); Urea, Ethylene Glycol, Propylene Glycol, Glycerol, Sorbitol, Xylitol and Glucose were used as hydrogen bond donors (HBD). DES containing sodium alginate were subjected to precipitation with sulfuric acid 0.2 M (pH 1.6), ethanol-water mixture (80 % v/v) and calcium chloride (1 % w/v CaCl2·2H2O). Alginate in precipitates was quantified and used to evaluate the performance of each separation technique. The highest recovery yields (51.2 ± 1.3 %) were obtained using the ethanol-water mixture followed by calcium chloride (45.7 ± 1.2 %), except for polyols (e.g. sorbitol). The lowest recovery yields were obtained with acid, with a particularly low recovery yield when urea was used as HBD (9.6 ± 1.3 %). Estimations of ManA/GulA ratios showed lower values for precipitates from DES compared to the ones obtained from water. This research shows ethanolic precipitation as a suitable method for alginate separation from the studied set of choline chloride-based DES.


Subject(s)
Choline , Deep Eutectic Solvents , Choline/chemistry , Solvents/chemistry , Alginates , Calcium Chloride , Water , Ethanol , Urea/chemistry , Sorbitol
20.
Int J Biol Macromol ; 263(Pt 1): 130293, 2024 Apr.
Article in English | MEDLINE | ID: mdl-38382791

ABSTRACT

Cellulose nanocrystal (CNC) film is known to be one kind of dynamic color-sensing material, capable of reversible color changes in response to varying humidity levels. However, the brittleness, low hygroscopicity and poor homogeneity of these films have hindered their development. To address this limitation, we present a novel approach where we combine natural deep eutectic solvents (NADES) with sorbitol under the influence of circular shear flow to craft a CNC humidity-sensitive film with enhanced flexibility, hygroscopicity and homogeneity. The inclusion of sorbitol and NADES enhances hygroscopicity and improves the flexibility. Surprisingly, the introduction of circular shear flow was found not only to improve homogeneity, macroscopically and microscopically, but also to further enhance flexibility, toughness, and water absorption capability. The resulting composite films demonstrated highly reversible color changes across the whole visible spectrum depending on the relative humidity, showing their capability to be reliable humidity-sensing materials. Thanks to the improved homogeneity and flexibility, the obtained humidity-sensing composite film can be employed in its entirety without the need for cutting, making it a promising candidate for various applications.


Subject(s)
Cellulose , Nanoparticles , Cellulose/chemistry , Humidity , Nanoparticles/chemistry , Wettability , Sorbitol
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