Exploring Bariatric Surgery's Impact on Weight Loss and Diabetes: Sodium and Glucose Receptor Modulation.

Sodium-glucose cotransporters (SGLT) and glucose transporters (GLUT) have been shown to influence diabetes management by modulating glucose uptake by the intestine. Therefore, alterations in gastrointestinal anatomy during bariatric surgery can change SGLT and GLUT receptor activity. These changes offer an additional mechanism for weight loss and may explain the differential impact of the various bariatric surgical procedures. This review examines the current literature on SGLT and GLUT receptors and their effects on weight loss through genetic studies, pharmacologic inhibition, and how SGLT/GLUT receptors impact surgical physiologic modulation. A better understanding of Type I sodium-glucose cotransport receptors (SGLT-1), GLUT-2, and GLUT-5 could provide insight for improved procedures and allow us to determine the best method to tailor operations to a patient's individual needs.

Spring and fall blood concentrations of adrenocorticotropic hormone, insulin, and thyroxine in healthy horses in Saskatchewan.

Objective: To characterize concentrations of adrenocorticotropic hormone (ACTH), insulin, and thyroxine (T4) at 2 times of the year in healthy horses in Saskatchewan. Animals and procedure: A prospective, observational study was carried out in 52 healthy, client-owned horses. Inclusion criteria were no recent travel outside of Saskatchewan, normal physical examination findings, and no history or evidence of ongoing illness. Blood concentrations of ACTH, insulin and T4 were determined by chemiluminescence. Samples were collected in spring and fall and compared using the paired Student's t-test or Wilcoxon signed-rank test. Generalized estimating equations were used to assess the associations between ACTH, T4, and insulin concentrations and gender, age, season, body condition score, glucose concentration, and breed. Results: There were increases in both ACTH and insulin concentrations in the fall compared to spring (P < 0.001 and P = 0.001, respectively). Other than season, insulin concentration was associated with breed, whereas ACTH concentration was associated with age. Finally, T4 concentration was associated with breed and glucose concentration, but not with season. Conclusion and clinical relevance: These results highlighted the differences between spring and fall concentrations of both ACTH and insulin in healthy horses residing in the Canadian prairie provinces, which are known for extreme differences in summer and winter temperatures as well as day length. Geographically adjusted reference values are necessary to account for these variations, to improve diagnostic accuracy. This is the first published Canadian study evaluating these factors and their associations with hormone concentrations in clinically healthy animals.

Concentrations sanguines printanières et automnales d'hormone adrénocorticotrope, d'insuline et de thyroxine chez des chevaux en bonne santé en Saskatchewan. Objectif: Caractériser les concentrations d'hormone adrénocorticotrope (ACTH), d'insuline et de thyroxine (T4) à 2 moments de l'année chez des chevaux en bonne santé en Saskatchewan. Animaux et procédure: Une étude observationnelle prospective a été réalisée auprès de 52 chevaux en bonne santé appartenant à des clients. Les critères d'inclusion étaient l'absence de voyage récent à l'extérieur de la Saskatchewan, les résultats normaux de l'examen physique et l'absence d'antécédents ou de signes de maladie persistante. Les concentrations sanguines d'ACTH, d'insuline et de T4 ont été déterminées par chimiluminescence. Des échantillons ont été collectés au printemps et à l'automne et comparés à l'aide du test de Student apparié ou du test du rang de signe de Wilcoxon. Des équations d'estimation généralisées ont été utilisées pour évaluer les associations entre les concentrations d'ACTH, de T4 et d'insuline et le sexe, l'âge, la saison, l'état corporel, la concentration de glucose et la race. Résultats: Il y avait une augmentation des concentrations d'ACTH et d'insuline à l'automne par rapport au printemps (P < 0,001 et P = 0,001, respectivement). Hormis la saison, la concentration d'insuline était associée à la race, alors que la concentration d'ACTH était associée à l'âge. Enfin, la concentration de T4 était associée à la race et à la concentration en glucose, mais pas à la saison. Conclusion et pertinence clinique: Ces résultats ont mis en évidence les différences entre les concentrations printanières et automnales d'ACTH et d'insuline chez les chevaux en bonne santé résidant dans les provinces des Prairies canadiennes, reconnues pour leurs différences extrêmes de températures estivales et hivernales ainsi que de durée du jour. Des valeurs de référence géographiquement ajustées sont nécessaires pour tenir compte de ces variations et améliorer la précision du diagnostic. Il s'agit de la première étude canadienne publiée évaluant ces facteurs et leurs associations avec les concentrations d'hormones chez des animaux cliniquement sains.(Traduit par Dr Serge Messier).

Stevioside Ameliorates Palmitic Acid-Induced Abnormal Glucose Uptake via the PDK4/AMPK/TBC1D1 Pathway in C2C12 Myotubes.

BACKGROUND: Stevioside (SV) with minimal calories is widely used as a natural sweetener in beverages due to its high sweetness and safety. However, the effects of SV on glucose uptake and the pyruvate dehydrogenase kinase isoenzyme (PDK4) as an important protein in the regulation of glucose metabolism, remain largely unexplored. In this study, we used C2C12 skeletal muscle cells that was induced by palmitic acid (PA) to assess the effects and mechanisms of SV on glucose uptake and PDK4. METHODS: The glucose uptake of C2C12 cells was determined by 2-NBDG; expression of the Pdk4 gene was measured by quantitative real-time PCR; and expression of the proteins PDK4, p-AMPK, TBC1D1 and GLUT4 was assessed by Western blotting. RESULTS: In PA-induced C2C12 myotubes, SV could significantly promote cellular glucose uptake by decreasing PDK4 levels and increasing p-AMPK and TBC1D1 levels. SV could promote the translocation of GLUT4 from the cytoplasm to the cell membrane in cells. Moreover, in Pdk4-overexpressing C2C12 myotubes, SV decreased the level of PDK4 and increased the levels of p-AMPK and TBC1D1. CONCLUSION: SV was found to ameliorate PA-induced abnormal glucose uptake via the PDK4/AMPK/TBC1D1 pathway in C2C12 myotubes. Although these results warranted further investigation for validation, they may provide some evidence of SV as a safe natural sweetener for its use in sugar-free beverages to prevent and control T2DM.

A novel thermotolerant L-rhamnose isomerase variant for biocatalytic conversion of D-allulose to D-allose.

A novel L-rhamnose isomerase was identified and cloned from an extreme-temperature aquatic habitat metagenome. The deduced amino acid sequence homology suggested the possible source of this metagenomic sequence to be Chloroflexus islandicus. The gene expression was performed in a heterologous host, Escherichia coli, and the recombinant protein L-rhamnose isomerase (L-RIM) was extracted and purified. The catalytic function of L-RIM was characterized for D-allulose to D-allose bioconversion. D-Allose is a sweet, rare sugar molecule with anti-tumour, anti-hypertensive, cryoprotective, and antioxidative properties. The characterization experiments showed L-RIM to be a Co++- or Mn++-dependent metalloenzyme. L-RIM was remarkably active (~ 80%) in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges. Optimal L-RIM activity with D-allulose as the substrate occurred at pH 7.0 and 75 °C. The enzyme was found to be excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively. L-RIM catalysis conducted at slightly acidic pH of 6.0 and 70 °C achieved biosynthesis of about 30 g L-1 from 100 g L-1 D-allulose in 3 h. KEY POINTS: • The present study explored an extreme temperature metagenome to identify a novel gene that encodes a thermostable l-rhamnose isomerase (L-RIM) • L-RIM exhibits substantial (80% or more) activity in a broad spectrum of pH (6.0 to 9.0) and temperature (70 to 80 °C) ranges • L-RIM is excessively heat stable, displaying a half-life of about 12 days and 5 days at 65 °C and 70 °C, respectively.

Metabolic Profile and Long-Term Risk of Depression, Anxiety, and Stress-Related Disorders.

Importance: Biomarkers of lipid, apolipoprotein, and carbohydrate metabolism have been previously suggested to be associated with the risk for depression, anxiety, and stress-related disorders, but results are inconsistent. Objective: To examine whether the biomarkers of carbohydrate, lipid, and apolipoprotein metabolism are associated with the risk of depression, anxiety, and stress-related disorders. Design, Setting, and Participants: This population-based cohort study with longitudinal data collection assessed 211 200 participants from the Apolipoprotein-Related Mortality Risk (AMORIS) cohort who underwent occupational health screening between January 1, 1985, and December 31, 1996, mainly in the Stockholm region in Sweden. Statistical analysis was performed during 2022 to 2023. Exposures: Lipid, apolipoprotein, and carbohydrate biomarkers measured in blood. Main Outcomes and Measures: The associations between biomarker levels and the risk of developing depression, anxiety, and stress-related disorders through the end of 2020 were examined using Cox proportional hazards regression models. In addition, nested case-control analyses were conducted within the cohort, including all incident cases of depression, anxiety, and stress-related disorders, and up to 10 control individuals per case who were individually matched to the case by year of birth, sex, and year of enrollment to the AMORIS cohort, using incidence density sampling. Population trajectories were used to illustrate the temporal trends in biomarker levels for cases and controls. Results: A total of 211 200 individuals (mean [SD] age at first biomarker measurement, 42.1 [12.6] years; 122 535 [58.0%] male; 188 895 [89.4%] born in Sweden) participated in the study. During a mean (SD) follow-up of 21.0 (6.7) years, a total of 16 256 individuals were diagnosed with depression, anxiety, or stress-related disorders. High levels of glucose (hazard ratio [HR], 1.30; 95% CI, 1.20-1.41) and triglycerides (HR, 1.15; 95% CI, 1.10-1.20) were associated with an increased subsequent risk of all tested psychiatric disorders, whereas high levels of high-density lipoprotein (HR, 0.88; 95% CI, 0.80-0.97) were associated with a reduced risk. These results were similar for male and female participants as well as for all tested disorders. The nested case-control analyses demonstrated that patients with depression, anxiety, or stress-related disorders had higher levels of glucose, triglycerides, and total cholesterol during the 20 years preceding diagnosis, as well as higher levels of apolipoprotein A-I and apolipoprotein B during the 10 years preceding diagnosis, compared with control participants. Conclusions and Relevance: In this cohort study of more than 200 000 participants, high levels of glucose and triglycerides and low levels of high-density lipoprotein were associated with future risk of depression, anxiety, and stress-related disorders. These findings may support closer follow-up of individuals with metabolic dysregulations for the prevention and diagnosis of psychiatric disorders.

In-depth correlation analysis between tear glucose and blood glucose using a wireless smart contact lens.

Tears have emerged as a promising alternative to blood for diagnosing diabetes. Despite increasing attempts to measure tear glucose using smart contact lenses, the controversy surrounding the correlation between tear glucose and blood glucose still limits the clinical usage of tears. Herein, we present an in-depth investigation of the correlation between tear glucose and blood glucose using a wireless and soft smart contact lens for continuous monitoring of tear glucose. This smart contact lens is capable of quantitatively monitoring the tear glucose levels in basal tears excluding the effect of reflex tears which might weaken the relationship with blood glucose. Furthermore, this smart contact lens can provide an unprecedented level of continuous tear glucose data acquisition at sub-minute intervals. These advantages allow the precise estimation of lag time, enabling the establishment of the concept called 'personalized lag time'. This demonstration considers individual differences and is successfully applied to both non-diabetic and diabetic humans, as well as in animal models, resulting in a high correlation.

LIN28B induced PCAT5 promotes endometrial cancer progression and glycolysis via IGF2BP3 deubiquitination.

Endometrial cancer (EC) cells exhibit abnormal glucose metabolism, characterized by increased aerobic glycolysis and decreased oxidative phosphorylation. Targeting cellular glucose metabolism in these cells could be an effective therapeutic approach for EC. This study aimed to assess the roles of LIN28B, PCAT5, and IGF2BP3 in the glucose metabolism, proliferation, migration, and invasion of EC cells. LIN28B highly expressed in EC, binds and stabilizes PCAT5. PCAT5, overexpressed in EC, and its 1485-2288nt region can bind to the KH1-2 domain of IGF2BP3 to prevent MKRN2 from binding to the K294 ubiquitination site of IGF2BP3, thus stabilizing IGF2BP3. Finally, IGF2BP3 promotes the aerobic glycolysis, proliferation, migration and invasion of EC cells by stabilizing the key enzymes of glucose metabolism HK2 and PKM2. Taken together, our data reveal that the LIN28B/PCAT5/IGF2BP3 axis is critical for glucose reprogramming and malignant biological behavior in EC cells. Therefore, targeting this axis may contribute to the development of a novel therapeutic strategy for EC metabolism.

GLUT4 localisation with the plasma membrane is unaffected by an increase in plasma free fatty acid availability.

BACKGROUND: Insulin-stimulated glucose uptake into skeletal muscle occurs via translocation of GLUT4 from intracellular storage vesicles to the plasma membrane. Elevated free fatty acid (FFA) availability via a lipid infusion reduces glucose disposal, but this occurs in the absence of impaired proximal insulin signalling. Whether GLUT4 localisation to the plasma membrane is subsequently affected by elevated FFA availability is not known. METHODS: Trained (n = 11) and sedentary (n = 10) individuals, matched for age, sex and body mass index, received either a 6 h lipid or glycerol infusion in the setting of a concurrent hyperinsulinaemic-euglycaemic clamp. Sequential muscle biopsies (0, 2 and 6 h) were analysed for GLUT4 membrane localisation and microvesicle size and distribution using immunofluorescence microscopy. RESULTS: At baseline, trained individuals had more small GLUT4 spots at the plasma membrane, whereas sedentary individuals had larger GLUT4 spots. GLUT4 localisation with the plasma membrane increased at 2 h (P = 0.04) of the hyperinsulinemic-euglycemic clamp, and remained elevated until 6 h, with no differences between groups or infusion type. The number of GLUT4 spots was unchanged at 2 h of infusion. However, from 2 to 6 h there was a decrease in the number of small GLUT4 spots at the plasma membrane (P = 0.047), with no differences between groups or infusion type. CONCLUSION: GLUT4 localisation with the plasma membrane increases during a hyperinsulinemic-euglycemic clamp, but this is not altered by elevated FFA availability. GLUT4 appears to disperse from small GLUT4 clusters located at the plasma membrane to support glucose uptake during a hyperinsulinaemic-euglycaemic clamp.

Triglyceride-glucose-waist circumference index predicts the incidence of cardiovascular disease in Korean populations: competing risk analysis of an 18-year prospective study.

BACKGROUND: The triglyceride and glucose-waist circumference (TyG-WC) index demonstrated a strong association with insulin resistance, especially in Asian population. However, evidence on the association between TyG-WC index and the occurrence of cardiovascular disease (CVD) is limited. This study aimed to verify association between the TyG-WC index and the occurrence of CVD by considering all-cause mortality as a competing risk. METHODS: The study included 7482 participants divided into four groups based on the TyG-WC index quartiles. Kaplan-Meier curves illustrated cumulative incidence rates of CVD and all-cause mortality during the follow-up period. Log-rank tests determined group differences. The Cox proportional hazard spline curve demonstrates the dose-dependent relationship between the TyG-WC index and incident CVD. Modified Cox regression (Fine and Gray) estimated hazard ratios (HRs) with 95% CIs for incident CVD, treating death as a competing risk. Death event after incident CVD was excluded from the death count. RESULTS: During the median 15.94 year of follow-up period, a total of 691 (9.24%) new-onset CVD cases and 562 (7.51%) all-cause mortality cases were confirmed. Cox proportional hazard spline curves suggested that TyG-WC index exhibited a dose-dependent positive correlation with incident CVD. The cumulative incidence rate of CVD was significantly higher in the groups with higher TyG-WC index quartiles in Kaplan-Meier curves. The adjusted HR (95% CI) for incident CVD in Q2-Q4, compared with Q1, was 1.47 (1.12-1.93), 1.91 (1.44-2.54) and 2.24 (1.63-3.07), respectively. There was no significant association between TyG-WC index and all-cause mortality. Specifically, angina and stroke were significantly associated with the TyG-WC index, in contrast to myocardial infarction and peripheral artery disease. CONCLUSIONS: The TyG-WC index was positively associated with incident CVD even considering all-cause mortality as a competing risk. Therefore, TyG-WC index may be a valuable marker for predicting the occurrence of CVD.

Yeast cell responses and survival during periodic osmotic stress are controlled by glucose availability.

Natural environments of living organisms are often dynamic and multifactorial, with multiple parameters fluctuating over time. To better understand how cells respond to dynamically interacting factors, we quantified the effects of dual fluctuations of osmotic stress and glucose deprivation on yeast cells using microfluidics and time-lapse microscopy. Strikingly, we observed that cell proliferation, survival, and signaling depend on the phasing of the two periodic stresses. Cells divided faster, survived longer, and showed decreased transcriptional response when fluctuations of hyperosmotic stress and glucose deprivation occurred in phase than when the two stresses occurred alternatively. Therefore, glucose availability regulates yeast responses to dynamic osmotic stress, showcasing the key role of metabolic fluctuations in cellular responses to dynamic stress. We also found that mutants with impaired osmotic stress response were better adapted to alternating stresses than wild-type cells, showing that genetic mechanisms of adaptation to a persistent stress factor can be detrimental under dynamically interacting conditions.

Effects of Saikosaponin-A on Insulin Resistance in Obesity: Computational and Animal Experimental Study.

Obesity is known to be associated with increased inflammation and dysregulated autophagy, both of which contribute to insulin resistance. Saikosaponin-A (SSA) has been reported to exhibit anti-inflammatory and lipid-lowering properties. In this research, we employed a combination of computational modeling and animal experiments to explore the effects of SSA. Male C57BL/6 mice were categorized into four groups: normal diet, high-fat diet (HFD), HFD + atorvastatin 10 mg/kg, and HFD + SSA 10 mg/kg. We conducted oral glucose and fat tolerance tests to assess metabolic parameters and histological changes. Furthermore, we evaluated the population of Kupffer cells (KCs) and examined gene expressions related to inflammation and autophagy. Computational analysis revealed that SSA displayed high binding affinity to tumor necrosis factor (TNF)-α, nuclear factor (NF)-κB, fibroblast growth factor 21 (FGF21), and autophagy-related 7 (ATG7). Animal study demonstrated that SSA administration improved fasting and postprandial glucose levels, homeostatic model assessment of insulin resistance (HOMA-IR) index, as well as triglyceride, free fatty acid, total cholesterol, low-density lipoprotein cholesterol (LDL-C)-cholesterol, and high-density lipoprotein cholesterol (HDL-C)-cholesterol levels in HFD-fed mice. Moreover, SSA significantly reduced liver weight and fat accumulation, while inhibiting the infiltration and M1 activation of KCs. At the mRNA level, SSA downregulated TNF-α and NF-κB expression, while upregulating FGF21 and ATG7 expression. In conclusion, our study suggests that SSA may serve as a therapeutic agent for addressing the metabolic complications associated with obesity. This potential therapeutic effect is attributed to the suppression of inflammatory cytokines and the upregulation of FGF21 and ATG7.

GSH-responsive degradable nanodrug for glucose metabolism intervention and induction of ferroptosis to enhance magnetothermal anti-tumor therapy.

The challenges associated with activating ferroptosis for cancer therapy primarily arise from obstacles related to redox and iron homeostasis, which hinder the susceptibility of tumor cells to ferroptosis. However, the specific mechanisms of ferroptosis resistance, especially those intertwined with abnormal metabolic processes within tumor cells, have been consistently underestimated. In response, we present an innovative glutathione-responsive magnetocaloric therapy nanodrug termed LFMP. LFMP consists of lonidamine (LND) loaded into PEG-modified magnetic nanoparticles with a Fe3O4 core and coated with disulfide bonds-bridged mesoporous silica shells. This nanodrug is designed to induce an accelerated ferroptosis-activating state in tumor cells by disrupting homeostasis. Under the dual effects of alternating magnetic fields and high concentrations of glutathione in the tumor microenvironment, LFMP undergoes disintegration, releasing drugs. LND intervenes in cell metabolism by inhibiting glycolysis, ultimately enhancing iron death and leading to synthetic glutathione consumption. The disulfide bonds play a pivotal role in disrupting intracellular redox homeostasis by depleting glutathione and inactivating glutathione peroxidase 4 (GPX4), synergizing with LND to enhance the sensitivity of tumor cells to ferroptosis. This process intensifies oxidative stress, further impairing redox homeostasis. Furthermore, LFMP exacerbates mitochondrial dysfunction, triggering ROS formation and lactate buildup in cancer cells, resulting in increased acidity and subsequent tumor cell death. Importantly, LFMP significantly suppresses tumor cell proliferation with minimal side effects both in vitro and in vivo, exhibiting satisfactory T2-weighted MR imaging properties. In conclusion, this magnetic hyperthermia-based nanomedicine strategy presents a promising and innovative approach for antitumor therapy.

Effects of down-regulated carbonic anhydrase 8 on cell survival and glucose metabolism in human colorectal cancer cell lines.

Carbonic anhydrase 8 (CA8) is a member of the α-carbonic anhydrase family but does not catalyze the reversible hydration of carbon dioxide. In the present study, we examined the effects of CA8 on two human colon cancer cell lines, SW480 and SW620, by suppressing CA8 expression through shRNA knockdown. Our results showed that knockdown of CA8 decreased cell growth and cell mobility in SW620 cells, but not in SW480 cells. In addition, downregulated CA8 resulted in a significant decrease of glucose uptake in both SW480 and SW620 cells. Interestingly, stable downregulation of CA8 decreased phosphofructokinase-1 expression but increased glucose transporter 3 (GLUT3) levels in SW620 cells. However, transient downregulation of CA8 fails to up-regulate GLUT3 expression, indicating that the increased GLUT3 observed in SW620-shCA8 cells is a compensatory effect. In addition, the interaction between CA8 and GLUT3 was evidenced by pull-down and IP assays. On the other hand, we showed that metformin, a first-line drug for type II diabetes patients, significantly inhibited cell migration of SW620 cells, depending on the expressions of CA8 and focal adhesion kinase. Taken together, our data demonstrate that when compared to primary colon cancer SW480 cells, metastatic colon cancer SW620 cells respond differently to downregulated CA8, indicating that CA8 in more aggressive cancer cells may play a more important role in controlling cell survival and metformin response. CA8 may affect glucose metabolism- and cell invasion-related molecules in colon cancer, suggesting that CA8 may be a potential target in future cancer therapy.

Transcriptional patterns of human retinal pigment epithelial cells under protracted high glucose.

BACKGROUND: The retinal pigment epithelium (RPE) is essential for retinal homeostasis. Comprehensively exploring the transcriptional patterns of diabetic human RPE promotes the understanding of diabetic retinopathy (DR). METHODS AND RESULTS: A total of 4125 differentially expressed genes (DEGs) were screened out from the human primary RPE cells subjected to prolonged high glucose (HG). The subsequent bioinformatics analysis is divided into 3 steps. In Step 1, 21 genes were revealed by intersecting the enriched genes from the KEGG, WIKI, and Reactome databases. In Step 2, WGCNA was applied and intersected with the DEGs. Further intersection based on the enrichments with the GO biological processes, GO cellular components, and GO molecular functions databases screened out 12 candidate genes. In Step 3, 13 genes were found to be simultaneously up-regulated in the DEGs and a GEO dataset involving human diabetic retinal tissues. VEGFA and ERN1 were the 2 starred genes finally screened out by overlapping the 3 Steps. CONCLUSION: In this study, multiple genes were identified as crucial in the pathological process of RPE under protracted HG, providing potential candidates for future researches on DR. The current study highlights the importance of RPE in DR pathogenesis.

Perineural 5% dextrose versus corticosteroid injection in non-surgical carpal tunnel syndrom treatment.

Background and purpose:

We aimed to investigate the difference of clinical and electrophysiological improvement between perineural corticosteroid injection therapy (PCIT) and perineural 5% dextrose injection therapy (5%PDIT) in carpal tunnel syndrome (CTS).

Total of 92 wrists that were diagnosed as mild-to-moderate idiopathic CTS and completed their follow-up were included in our study. The severity of pain, symptom severity and functional status were asses­sed by visual analog scale (VAS) and the Boston Carpal Tunnel Syndrome Questionnaire (BCTQ) scores for treatment effectiveness. Randomized wrists were administered PCIT or 5%PDIT accompanied by ultrasound guidance. VAS, BCTQ scores and the electro­physiological study repeated before and after treatment at the 1st and 6th months after perineural injection therapies (PITs) were recorded.

Compared with baseline data, within groups there was significant improvement in VAS, BCTQ severity and function scores at 1st and 6th months follow-up (all p < 0.001). Considerable advance were detected in the median sensory nerve conduction velocity (SNCV) when pretreatment values were compared with posttreatment first month in both groups (p = 0.01; p < 0.001, respectively). No significant change occurred in median distal motor latency (DML) values between the 1st and 6th months in the groups (p = 0.095; p = 0.113, respectively). No significant difference was observed bet­ween 5%PDIT and PCIT groups.

Clinical and electrophysiologic improvement in CTS began from 1st month after PCIT and 5%PDIT. At the 6th month follow-up of the patients, 5%PDIT and PCIT had similar therapeutic effects. As a result, we can consider the replacement of PCIT with 5%PDIT in mild-to-moderate CTS patients especially in those who are hesitant because of the corticosteroid’s adverse effects.

[Deep eutectic solvents synergistic with carboxymethyl -ß-cyclodextrin on the improvement of chiral separation of metoprolol by capillary electrophoresis].

The physical and chemical properties of chiral drugs are very similar. However, their pharmacological and toxicological effects vary significantly. For example, one enantiomer may have favorable properties whereas the other may be ineffective or even have toxic side effects. Hence, exploring innovative strategies to improve enantiomeric resolution is of great importance. Metoprolol (MET) is a ß-receptor blocker used to treat hypertension, stable angina pectoris, and supraventricular tachyarrhythmia. Establishing chiral separation and analysis methods of MET enantiomers is important for enhancing the quality of chiral drugs. Capillary electrophoresis (CE) has the advantages of a small sample size, simple operation, high separation efficiency, and many alternative modes; therefore it is widely used in the field of chiral drug separation. The chiral selectors commonly used for CE-based chiral separation include cyclodextrin (CD) and its derivatives, polysaccharides, proteins, and macrocyclic antibiotics. CD is one of the most commonly used and effective chiral selectors for CE. The relatively hydrophobic structure inside the cavity and the relatively hydrophilic structure outside the cavity of CD enable it and chiral molecules to form inclusion compounds with different binding constants, thus achieving chiral separation. However, the use of CD alone as a chiral selector does not always yield satisfactory separation results. Hence, the addition of other additives, such as ionic liquids and deep eutectic solvents (DESs) to assist CD-based chiral separation systems has received extensive attention. Previous studies on the enantiomeric separation of MET by CE have focused on the addition of CD and its derivatives alone for separation. Few studies have been conducted on the synergistic addition of auxiliary additives to CD to improve the enantiomeric resolution of MET. In this study, three DESs, namely, choline chloride-D-glucose, choline chloride-D-fructose, and lactate-D-glucose, were used for the CE-based chiral separation of MET for the first time, and the synergistic effect of the DESs on the separation of MET enantiomers by CD-based capillary zone electrophoresis was speculated. For this purpose, an uncoated fused silica capillary with inner diameter of 50 µm, total length of 50 cm and effective length of 41.5 cm was used as the separation column. First, the effects of CD type, CD concentration, buffer pH, and buffer concentration on MET separation were investigated, and the optimal conditions (15 mmol/L carboxymethyl-ß-cyclodextrin (CM-ß-CD), pH=3.0, and 40 mmol/L phosphate buffer) were obtained. Other CE conditions were as follows: UV detection at 230 nm, applied voltage of 25 kV. All operations were carried out at 20 ℃. Next, three types of DESs were prepared as auxiliary additives via a mixed-heating method. The DESs were mixed in a 50 mL round-bottomed flask at a certain molar ratio and then heated in a water bath at 80 ℃ for 3 h until a clear and transparent liquid was obtained. The effects of different DESs and their mass fraction on chiral separation were subsequently studied. The optimal choline chloride-D-fructose mass fraction was ultimately determined to be 1.5%. The resolution of MET increased from 1.30 without DES to 2.61 with 1.5% choline chloride-D-fructose, thereby achieving baseline separation. Finally, the separation effect and mechanism were speculated. The MET chiral separation method established in this study is of great significance for improving the quality of chiral compounds and ensuring the safety and effectiveness of clinical drugs. Furthermore, it may be useful in the research and development of CE-based chiral separation techniques using CD derivatives with DESs.

Analysis and dynamical structure of glucose insulin glucagon system with Mittage-Leffler kernel for type I diabetes mellitus.

In this paper, we propose a fractional-order mathematical model to explain the role of glucagon in maintaining the glucose level in the human body by using a generalised form of a fractal fractional operator. The existence, boundedness, and positivity of the results are constructed by fixed point theory and the Lipschitz condition for the biological feasibility of the system. Also, global stability analysis with Lyapunov's first derivative functions is treated. Numerical simulations for fractional-order systems are derived with the help of Lagrange interpolation under the Mittage-Leffler kernel. Results are derived for normal and type 1 diabetes at different initial conditions, which support the theoretical observations. These results play an important role in the glucose-insulin-glucagon system in the sense of a closed-loop design, which is helpful for the development of artificial pancreas to control diabetes in society.

Leveraging continuous glucose monitoring for personalized modeling of insulin-regulated glucose metabolism.

Continuous glucose monitoring (CGM) is a promising, minimally invasive alternative to plasma glucose measurements for calibrating physiology-based mathematical models of insulin-regulated glucose metabolism, reducing the reliance on in-clinic measurements. However, the use of CGM glucose, particularly in combination with insulin measurements, to develop personalized models of glucose regulation remains unexplored. Here, we simultaneously measured interstitial glucose concentrations using CGM as well as plasma glucose and insulin concentrations during an oral glucose tolerance test (OGTT) in individuals with overweight or obesity to calibrate personalized models of glucose-insulin dynamics. We compared the use of interstitial glucose with plasma glucose in model calibration, and evaluated the effects on model fit, identifiability, and model parameters' association with clinically relevant metabolic indicators. Models calibrated on both plasma and interstitial glucose resulted in good model fit, and the parameter estimates associated with metabolic indicators such as insulin sensitivity measures in both cases. Moreover, practical identifiability of model parameters was improved in models estimated on CGM glucose compared to plasma glucose. Together these results suggest that CGM glucose may be considered as a minimally invasive alternative to plasma glucose measurements in model calibration to quantify the dynamics of glucose regulation.