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The Yale Journal of Biology and Medicine Jun 2024The blood-brain barrier (BBB) prevents the use of many drugs for the treatment of neurological disorders. Recently, nitrogen-doped carbon dots (NCDs) have emerged as...
The blood-brain barrier (BBB) prevents the use of many drugs for the treatment of neurological disorders. Recently, nitrogen-doped carbon dots (NCDs) have emerged as promising nanocarriers to cross BBB. The primary focus of our study was to evaluate the effectiveness of NCDs for the symptomatic treatment of Alzheimer's disease (AD). In this study, we developed and characterized NCDs bound to rutin, a flavonoid with known benefits for AD. Despite its benefits, the transportation of rutin via NCDs for AD therapy has not been explored previously. We characterized the particles using FTIR and UV-visible spectroscopy followed by atomic force microscopy. Once the design was optimized and validated, we performed testing via a hemolytic assay to optimize the dosage. Preliminary testing was performed in AlCl3-induced rat models of AD whereby a single dose of 10 mg/kg NCDs-rutin was administered intraperitoneally. Interestingly, this single dose of 10 mg/kg NCDs-rutin produced the same behavioral effects as 50 mg/kg rutin administered intraperitoneally for 1 month. Similarly, histological and biomarker profiles ( and ) also presented significant protective effects of NCDs-rutin against neuronal loss, inflammation, and oxidative stress. Hence, NCDs-rutin are a promising approach for the treatment of neurological diseases.
Topics: Rutin; Animals; Alzheimer Disease; Carbon; Nitrogen; Rats; Glucose; Male; Quantum Dots; Disease Models, Animal; Oxidative Stress; Humans
PubMed: 38947101
DOI: 10.59249/EWOI2166 -
The Pan African Medical Journal 2024the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the... (Comparative Study)
Comparative Study
Impact of haemoglobin variants on the diagnostic sensitivity of glycated haemoglobin (HbA1c) assay methodologies in sub-Saharan Africa: a laboratory-based method validation study.
INTRODUCTION
the utility of glycated haemoglobin (HbA1c) for the diagnosis and monitoring of diabetes in sub-Saharan Africa is uncertain due to limited data on the performance of the available HbA1c assay methods in this population, which has a high prevalence of haemoglobin variants. We aimed to compare the diagnostic accuracy of the major HbA1c methodologies (Boronate Affinity, Capillary Electrophoresis, High Performance Liquid Chromatography, Immunoassay) in an African population, and assess the impact of the common haemoglobin variant HbAS (sickle cell trait).
METHODS
whole blood samples were obtained from 182 individuals living with type 2 diabetes in Uganda. HbA1c values for each method were compared to average glucose measured over 14 days by continuous glucose monitoring (CGM). To determine concordance, the three HbA1c assay methods were compared to the capillary electrophoresis method.
RESULTS
there was a strong correlation between CGM average glucose levels and all four HbA1c methodologies (r=0.81-0.89) which did not differ in those with and without HbAS (present in 37/182 participants). The presence of HbAS did not alter the relationship between HbA1c and CGM glucose for any assay (p for interaction >0.2 for all methods). Diagnostic accuracy for CGM average glucose thresholds of 7 and 10mmol/L was similar across methods (area under the receiver operating characteristic curve 0.80-0.84 and 0.76-0.84 respectively). The maximum bias between the HbA1c assay methodologies was 2 mmol/mol (2.07%).
CONCLUSION
all major HbA1c technologies offer accurate and comparable HbA1c measurement even in this population with high prevalence of haemoglobin variants.
Topics: Humans; Glycated Hemoglobin; Diabetes Mellitus, Type 2; Electrophoresis, Capillary; Female; Blood Glucose; Male; Middle Aged; Sensitivity and Specificity; Chromatography, High Pressure Liquid; Uganda; Adult; Immunoassay; Blood Glucose Self-Monitoring; Aged; Hemoglobins, Abnormal
PubMed: 38946743
DOI: 10.11604/pamj.2024.48.10.41679 -
Journal of the American Chemical Society Jun 2024bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent...
bacteria are becoming increasingly resistant against multiple antibiotics. Therefore, the development of vaccines to prevent infections with these bacteria is an urgent medical need. While the immunological activity of lipopolysaccharide O-antigens in is well-known, the specific protective epitopes remain unidentified. Herein, we present the first chemical synthesis of highly functionalized aminoglycoside trisaccharide and its acetamido derivative found in the serotype O5 O-antigen. The synthesis of the trisaccharide targets is based on balancing the reactivity of disaccharide acceptors and monosaccharide donors. Glycosylations were analyzed by quantifying the reactivity of the hydroxyl group of the disaccharide acceptor using the orbital-weighted Fukui function and dual descriptor. The stereoselective formation of 1,2--α-fucosylamine linkages was achieved through a combination of remote acyl participation and reagent modulation. The simultaneous S2 substitution of azide groups at C2' and C2″ enabled the efficient synthesis of 1,2--β-linkages for both 2,3-diamino-D-mannuronic acids. Through a strategic orthogonal modification, the five amino groups on target trisaccharide were equipped with a rare acetamidino (Am) and four acetyl (Ac) groups. Glycan microarray analyses of sera from patients infected with indicated that trisaccharides and are key antigenic epitopes of the serotype O5 O-antigen. The acetamidino group is not an essential determinant of antibody binding. The β-D-ManNAc3NAcA residue is a key motif for the antigenicity of serotype O5 O-antigen. These findings serve as a foundation for the development of glycoconjugate vaccines targeting serotype O5.
PubMed: 38946080
DOI: 10.1021/jacs.4c03814 -
Journal of Nutritional Science and... 2024D-Allulose has blood glucose suppression effects in both animal and clinical studies. The mechanism mediating glucose suppression in animals is controlled by several... (Randomized Controlled Trial)
Randomized Controlled Trial
D-Allulose has blood glucose suppression effects in both animal and clinical studies. The mechanism mediating glucose suppression in animals is controlled by several actions including the inhibition of sucrase. To investigate the dose-response effects of D-allulose with a sucrose beverage on glucose tolerance and insulin levels using Thai volunteers. This was a prospective, randomized, double-blinded, crossover study. Subjects had five oral sucrose tolerance tests (OSTT) with escalating doses of D-allulose (0, 2.5, 5, 7.5 or 10 g) with a 50 g sucrose beverage in a random order once a week for five consecutive weeks. The five drinks were consumed in a random order; the order being blinded for both subjects and investigators. Blood samples were drawn immediately before consumption and at 30, 60, 90 and 120 min after consumption of the study product for measurement of plasma glucose and insulin levels. Thirty healthy subjects (11 men and 19 women) completed the study. The peak postprandial glucose (PePPG) and insulin levels (PePPI) were lower when D-allulose was added in a dose-dependent manner. The lowest plasma glucose and insulin levels occurred at 120 min after OSTT in all five products and they were raised when D-allulose was added in a dose-dependent manner. D-Allulose has a suppression response on glucose and insulin shown by the decrease in postprandial plasma glucose and insulin levels following the addition of D-allulose to sucrose in a dose-dependent manner. The more D-allulose added, the less marked the glucose and insulin response occurred.
Topics: Humans; Male; Cross-Over Studies; Insulin; Blood Glucose; Adult; Double-Blind Method; Female; Young Adult; Postprandial Period; Thailand; Sucrose; Fructose; Glucose Tolerance Test; Dose-Response Relationship, Drug; Prospective Studies; Beverages; Healthy Volunteers; Sugar-Sweetened Beverages; Southeast Asian People
PubMed: 38945885
DOI: 10.3177/jnsv.70.203 -
Food Research International (Ottawa,... Aug 2024Undaria pinnatifida (UP) contains multiple bioactive substances, such as polyphenols, polysaccharides, and amino acids, which are associated with various biological... (Comparative Study)
Comparative Study
Undaria pinnatifida (UP) contains multiple bioactive substances, such as polyphenols, polysaccharides, and amino acids, which are associated with various biological properties. This study aimed to evaluate the antihyperglycemic effects of three extracts obtained from UP. UP was extracted under three different conditions: a low-temperature water extract at 50 °C (UPLW), a high-temperature water extract at 90 °C (UPHW), and a 70 % ethanol extract (UPE). Nontargeted chemical profiling using high-performance liquid chromatography-triple/time-of-flight mass spectrometry (HPLC-Triple TOF-MS/MS) was conducted on the three UP extracts. Subsequently, α-glucosidase inhibitory (AGI) activity, glucose uptake, and the mRNA expression of sodium/glucose cotransporter 1 (SGLT1) and glucose transporter 2 (GLUT2) were evaluated in Caco-2 cell monolayers. Furthermore, an oral carbohydrate tolerance test was performed on C57BL/6 mice. The mice were orally administered UP at 300 mg/kg body weight (B.W.), and the blood glucose level and area under the curve (AUC) were measured. Compared with glucose, UPLW, UPHW and UPE significantly inhibited both glucose uptake and the mRNA expression of SGLT1 and GLUT2 in Caco-2 cell monolayers. After glucose, maltose, and sucrose loading, the blood glucose levels and AUC of the UPLW group were significantly lower than those of the control group. These findings suggest that UPLW has antihyperglycemic effects by regulating glucose uptake through glucose transporters and can be expected to alleviate postprandial hyperglycemia. Therefore, UPLW may have potential as a functional food ingredient for alleviating postprandial hyperglycemia.
Topics: Animals; Hypoglycemic Agents; Undaria; Plant Extracts; Humans; Caco-2 Cells; Male; Mice, Inbred C57BL; Blood Glucose; Mice; Sodium-Glucose Transporter 1; Glucose Transporter Type 2; Glycoside Hydrolase Inhibitors; Tandem Mass Spectrometry; Chromatography, High Pressure Liquid; Edible Seaweeds
PubMed: 38945577
DOI: 10.1016/j.foodres.2024.114623 -
Journal of Gastrointestinal and Liver... Jun 2024There has been a growing emphasis on dietary therapies for irritable bowel syndrome (IBS). Furthermore, there has been an evolving evidence base for the low fermentable...
BACKGROUND AND AIMS
There has been a growing emphasis on dietary therapies for irritable bowel syndrome (IBS). Furthermore, there has been an evolving evidence base for the low fermentable oligosaccharides, disaccharides, monosaccharides and polyols (FODMAP) diet, gluten-free diet (GFD), and lactose-free diet. This study examines the dietary approaches employed and the factors influencing dietetic decision-making for IBS interventions.
METHODS
Participants, including registered dietitians and nutritionists, were recruited from diverse healthcare settings at the point of registration for the 4th Sheffield National Dietetic Gastroenterology Symposium, 2023. A 15-question online survey investigated the practices of dietitians and nutritionists in managing IBS patients, covering dietary approaches, decision-making factors, and patient education. The evidence base for different dietary interventions was provided and a follow-up survey assessed symposium attendees, views on current IBS dietary practices.
RESULTS
Out of 731 respondents, primarily registered dietitians (93%) and females (93%), 54% spent 10-50% of clinic time on IBS. Respondents noted that a GFD (34%), low lactose (32%), and traditional dietary advice (TDA) (18%) were the most frequently used dietary interventions that patients try before seeking professional advice. Delegates were asked to rank their dietary intervention preferences pre- and post-meeting (after the evidence base had been presented): TDA pre-meeting 75% versus post-meeting 87% (p=0.04), fibre modification 59% versus 6% (p<0.0001), low FODMAP 25% versus 10% (p=0.0001), low lactose 12% versus 62% (p<0.0001) and GFD 6% to 23% (p<0.0001).
CONCLUSIONS
TDA remains the choice of diet for dietitians. After our educational event, the use of low-lactose and gluten-free diet significantly increased. Factors influencing the decision-making process were based on patient acceptability, counselling time, supporting evidence base and dietary triggers.
Topics: Humans; Irritable Bowel Syndrome; Female; Male; Nutritionists; Patient Education as Topic; Diet, Gluten-Free; Diet, Carbohydrate-Restricted; Surveys and Questionnaires; Health Care Surveys; Adult; Middle Aged; Clinical Decision-Making
PubMed: 38944865
DOI: 10.15403/jgld-5466 -
Mymensingh Medical Journal : MMJ Jul 2024Both of neurological emergencies and hyperglycemia are independently associated risk factors of mortality in the ICU patients. In critically ills, hyperglycemia is...
Both of neurological emergencies and hyperglycemia are independently associated risk factors of mortality in the ICU patients. In critically ills, hyperglycemia is secondary to already existing DM or stress-induced hyperglycemia (SIH). Admission glycemic gap (AGG) is considered as a reliable indicator of SIH. This study aimed to explore the association of AGG on diabetic neuro-critical patients' short-term mortality, and understand the potential of AGG as the predictor of outcome. Sixty adult diabetic neuro-critical patients admitted in ICU and stayed at least for 24 hours, were prospectively observed for 30 days, or until discharge or death, whichever came first. The patients' initial clinical assessment and HbA1c, CBC, ABG, and blood glucose level were done within 24 hours of admission. A1c derived admission glucose (ADAG) was calculated as, ADAG = (1.59 × HbA1c) - 2.59 (mmol/L). The AGG was calculated by subtracting ADAG from admission blood glucose level (ABGL). Death or survival of 30 days was our primary outcome and participants were divided between survivor or non-survivor groups according to primary outcome. Statistical comparisons of the study variables between the groups were performed and the relationship between parameters derived from blood glucose and mortality was prospected. Among the 60 patients enrolled, 35(58.3%) were non-survivors and 25(41.7%) were survivors. Age, sex, residence, primary diagnosis, co-morbidity, or drug history had no association with survival/non-survival. Among the initial clinical assessment parameters, lower GCS had significant association with non-survival. AGG, HbA1c, ADAG and ABGL were significantly different between the groups, with higher values in the non-survivors. Lower GCS, and higher AGG, HbA1c, ADAG and ABGL showed significant odds of non-survival. The highest odds of non- survival was for AGG (OR 2.95, 95% CI: 1.83-4.75; p<0.001). For ABGL and HbA1c the OR were 2.03 (95% CI: 1.44-2.86; p<0.001) and 1.93 (95% CI: 1.04-3.58; p<0.04) respectively. The final adjusted odds (aOR) of non-survival for higher AGG was 3.25 (95% CI: 1.71-6.16; p<0.001), signifying that AGG is independently associated with non-survival. AGG, GCS level, ABGL, HbA1c level, and ADAG can predict short-term outcome (mortality). However, AGG has the greatest potential to predict short-term outcome in diabetic neuro-critical patients.
Topics: Humans; Female; Male; Middle Aged; Blood Glucose; Aged; Prospective Studies; Glycated Hemoglobin; Adult; Critical Illness; Intensive Care Units; Hyperglycemia; Diabetes Mellitus
PubMed: 38944734
DOI: No ID Found -
Mymensingh Medical Journal : MMJ Jul 2024Stroke is one of the most common neurological disorder and third most common cause of death in the world. Low vitamin D concentrations have been shown to predict risk of...
Stroke is one of the most common neurological disorder and third most common cause of death in the world. Low vitamin D concentrations have been shown to predict risk of cardiovascular disease and all-cause of mortality. The aim of this study was to estimate serum vitamin D level in acute ischemic stroke patients. This comparative cross-sectional type of study was conducted in the Department of Neurology and Department of Medicine at Mymensingh Medical College and Hospital, Bangladesh from November 2017 to June 2019 with a total number of 100 study subjects. Total fifty patients with acute ischemic stroke were enrolled in Group A and another fifty age and sex matched volunteer subjects were enrolled in Group B with no prior history of stroke or transient ischemic attacks. Serum vitamin D levels, fasting plasma glucose and lipid profile were assessed in both groups and compared with each other. P value <0.05 was considered as significant in the study. Mean fasting blood sugar, serum fasting total cholesterol (TC), serum fasting triglycerides, serum fasting Low density lipoprotein (LDL) were significantly higher in Group A than Group B (p<0.05). Serum vitamin D level in Group A was 25.28±8.47ng/ml and in Group B was 30.90±5.80, (p=0.001). Insufficient vitamin D level was found in 52.0% of ischemic stroke patients and in 30% of healthy controls (p=0.0002). Vitamin D deficiency was found in 20.0% ischemic stroke patients and 10.0% in healthy controls. This study demonstrates a positive association between low serum vitamin D level and acute ischemic stroke. Further studies are required to determine whether vitamin D supplementation could improve functional outcome in patients with ischemic stroke.
Topics: Humans; Male; Female; Vitamin D; Ischemic Stroke; Cross-Sectional Studies; Middle Aged; Vitamin D Deficiency; Bangladesh; Aged; Adult; Case-Control Studies; Blood Glucose
PubMed: 38944725
DOI: No ID Found -
Advances in Pediatrics Aug 2024To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the... (Review)
Review
To provide a more appropriate foundation for dealing with the problem of hypoglycemia in newborn infants, this article focuses on the mechanisms which underlie the various forms of neonatal hypoglycemia and discusses their implications for newborn care. Evidence indicates that all of the major forms of neonatal hypoglycemia are the result of hyperinsulinism due to dysregulation of pancreatic islet insulin secretion. Based on these observations, the authors propose that routine measurement of B-hydroxybutyrate should be considered an essential part of glucose monitoring in newborn infants.
Topics: Humans; Infant, Newborn; Hypoglycemia; Blood Glucose; Insulin; Hyperinsulinism
PubMed: 38944478
DOI: 10.1016/j.yapd.2024.03.001 -
The Journal of Biological Chemistry Jun 2024L-Fucose (6-deoxy-L-galactose), a monosaccharide abundant in glycolipids and glycoproteins produced by mammalian cells, has been extensively studied for its role in...
L-Fucose (6-deoxy-L-galactose), a monosaccharide abundant in glycolipids and glycoproteins produced by mammalian cells, has been extensively studied for its role in intracellular biosynthesis and recycling of GDP-L-fucose for fucosylation. However, in certain mammalian species, L-fucose is efficiently broken down to pyruvate and lactate in a poorly understood metabolic pathway. In the 1970s, L-fucose dehydrogenase, an enzyme responsible for the initial step of this pathway, was partially purified from pig and rabbit livers and characterized biochemically. However, its molecular identity remained elusive until recently. This study reports the purification, identification, and biochemical characterization of the mammalian L-fucose dehydrogenase. The enzyme was purified from rabbit liver approximately 340-fold. Mass spectrometry analysis of the purified protein preparation identified mammalian hydroxysteroid 17-β dehydrogenase 14 (HSD17B14) as the sole candidate enzyme. Rabbit and human HSD17B14 were expressed in HEK293T and Escherichia coli, respectively, purified and demonstrated to catalyze the oxidation of L-fucose to L-fucono-1,5-lactone, as confirmed by mass spectrometry and NMR analysis. Substrate specificity studies revealed that L-fucose is the preferred substrate for both enzymes. The human enzyme exhibited a catalytic efficiency for L-fucose that was 359-fold higher than its efficiency for estradiol. Additionally, recombinant rat HSD17B14 exhibited negligible activity towards L-fucose, consistent with the absence of L-fucose metabolism in this species. The identification of the gene encoding mammalian L-fucose dehydrogenase provides novel insights into the substrate specificity of enzymes belonging to the 17-β-hydroxysteroid dehydrogenase family. This discovery also paves the way for unraveling the physiological functions of the L-fucose degradation pathway, which remains enigmatic.
PubMed: 38944119
DOI: 10.1016/j.jbc.2024.107501