Glucose Levels Research Articles

Molecular mechanisms of Buqing granule for the treatment of diabetic retinopathy: Network pharmacology analysis and experimental validation.

Diabetic retinopathy (DR) is a common microvascular complication of diabetes mellitus. Its blindness rate is high; therefore, finding a reasonable and safe treatment plan to prevent and control DR is crucial. Currently, there are abundant and diverse research results on the treatment of DR by Chinese medicine Traditional Chinese medicine compounds are potentially advantageous for DR prevention and treatment because of its safe and effective therapeutic effects. To investigate the effects of Buqing granule (BQKL) on DR and its mechanism from a systemic perspective and at the molecular level by combining network pharmacology and in vivo experiments. This study collected information on the drug targets of BQKL and the therapeutic targets of DR for intersecting target gene analysis and protein-protein interactions (PPI), identified various biological pathways related to DR treatment by BQKL through Gene Ontology and Kyoto Encyclopedia of Genes and Genomes enrichment analyses, and preliminarily validated the screened core targets by molecular docking. Furthermore, we constructed a diabetic rat model with a high-fat and high-sugar diet and intraperitoneal streptozotocin injection, and administered the appropriate drugs for 12 weeks after the model was successfully induced. Body mass and fasting blood glucose and lipid levels were measured, and pathological changes in retinal tissue were detected by hematoxylin and eosin staining. ELISA was used to detect the oxidative stress index expression in serum and retinal tissue, and immunohistochemistry, real-time quantitative reverse transcription PCR, and western blotting were used to verify the changes in the expression of core targets. Six potential therapeutic targets of BQKL for DR treatment, including Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3, were screened using PPI. Enrichment analysis indicated that the MAPK signaling pathway might be the core target pathway of BQKL in DR treatment. Molecular docking prediction indicated that BQKL stably bound to these core targets. In vivo experiments have shown that compared with those in the Control group, rats in the Model group had statistically significant (P < 0.05) severe retinal histopathological damage; elevated blood glucose, lipid, and malondialdehyde (MDA) levels; increased Caspase-3, c-Jun, and TP53 protein expression; and reduced superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) levels, ganglion cell number, AKT1, MAPK1, and MAPK3 protein expression. Compared with the Model group, BQKL group had reduced histopathological retinal damage and the expression of blood glucose and lipids, MDA level, Caspase-3, c-Jun and TP53 proteins were reduced, while the expression of SOD, GSH-Px level, the number of ganglion cells, AKT1, MAPK1, and MAPK3 proteins were elevated. These differences were statistically significant (P < 0.05). BQKL can delay DR onset and progression by attenuating oxidative stress and inflammatory responses and regulating Caspase-3, c-Jun, TP53, AKT1, MAPK1, and MAPK3 proteins in the MAPK signaling pathway mediates these alterations.

Effects of Supplementing Different Quantities of Moringa stenopetala Leaves on Plasma Metabolite and Acylcarnitine Profile, Body Condition Score and Milk Yield Performance in Zebu (Bos indicus) Cattle.

The formulation of multi-nutrient blocks based on low-cost and locally available browse feed resources can be a valid feeding strategy in Sub-Saharan Africa, where inadequate feed supply, both in quality and quantity, is a major constraint. We evaluated the four different inclusion percentages (M-0%, M-25%, M-35% and M-45%) of Moringa stenopetala leaf powder to multi-nutrient blocks on their change on blood metabolite of dairy cows under practical, ranging conditions. Multi-nutrient blocks with four inclusion rates of M. stenopetala leaves were applied as complementary feed for free ranging dairy cows. The study was performed on 24 free ranging dairy cows reared around Arba Minch town in the Southern Ethiopian Rift Valley. Blood samples were collected from the jugular vein of dairy cows both before and after supplementation. Plasma glucose, beta hydroxy butyrate (BHB), urea, creatinine, triglycerides and nonesterified fatty acids (NEFA) concentration was quantified spectrophotometrically. Dried serum spots were subject to quantitative electrospray tandem mass spectrometry to estimate changes in nutrient metabolism based on selected carnitines. Based on these measurements, the milk yield and body condition score were increased during the period of multi-nutrient block supplementation. During the supplementation period, the cows got higher plasma glucose, triglyceride and urea concentrations and lower concentrations of BHB, NEFA and creatinine. From the metabolite profiles, a more efficient nutrient use could be concluded. Although no clear dose-response relationship was observed, the highest inclusion of the M. stenopetala leaves in the multi-nutrient blocks gave the best performance. This outcome supports the idea of implementing M. stenopetala based multi-nutrient blocks on tropical smallholder farms that are not easily accessible to conventional extension services.

Accelerated Longitudinal Glycemic Changes in Relation to Urinary Toxic/Essential Metals and Metal Mixtures Among Mexican Americans Living in Starr County, Texas.

Metal and metalloid exposures (hereafter "metals") are associated with adverse health outcomes, including type 2 diabetes; however, previous studies were largely cross- sectional or underpowered. Furthermore, underserved racial/ethnic groups are underrepresented in environmental health research despite having higher rates of type 2 diabetes and a greater risk of metal exposures. Consequently, we evaluated continuous glycemic traits in relation to baseline urinary toxic metal, essential metal, and metal mixtures in a cohort of Mexican American adults. A total of 510 participants were selected based upon self-reported diabetes status and followed over 3 years. Urinary metals were assessed at baseline. Linear mixed-effects models were used to estimate per-month changes in hemoglobin A1c, fasting plasma glucose, and postload glucose in relation to urinary metal levels. Multiple statistical approaches were used to assess the associations between glycemic traits and metal mixtures. After adjustment, higher urinary levels of arsenic, selenium, copper, molybdenum, nickel, and tin were associated with faster increases in measures of glycemia. The toxic metal mixture composed of arsenic, lead, cadmium, nickel, and tin was associated with faster increases in postload glucose. Using postload glucose criteria, highest versus lowest arsenic was predicted to accelerate conversion of normoglycemia to prediabetes and diabetes by 23 and 65 months, respectively. In this underrepresented, high-risk Mexican American population, exposure to toxic metals and alterations in essential metal homeostasis were associated with faster increases in glycemia over time that may accelerate type 2 diabetes development.

Bioassay guided isolation and compounds identification of the anti-diabetic fractions of (rosemary) Rosmarinus officinalis leaves extract

BackgroundDiabetes mellitus is a metabolic disease characterized by prolonged elevated blood glucose levels. It is a common health problem with a high mortality and morbidity to the human race. A number of medicinal plants such as rosemary (Rosmarinus officinalis) have been used for the treatment of diabetes. Most of the anti-diabetic conventional drugs have been found to have some side effects and there is therefore need to explore new sources of anti-diabetic drugs. The aim of the current study was to investigate the possibility of getting anti-diabetic compounds from R. officinalis that can be used as leads for drug discovery.MethodologyR. officinalis leaves were macerated in 50% methanol in dichloromethane and the crude extract fractionated by column chromatography. The obtained fractions were subjected to an in-vitro alpha-amylase inhibition assay. The anti-hyperglycemic potential of the fractions was evaluated in diabetic induced Wistar rats. The most potent fractions were analyzed by gas chromatography-mass spectrophotometry (GC-MS) for identification of the compounds.ResultsA total of 21 chromatographic fractions were assembled with different alpha- amylase inhibition activity. Eleven of the fractions had more than 30% alpha-amylase inhibition activity. The ethyl acetate fraction had the highest inhibition potential (LC50 of 2.8 μg/mL). The anti-diabetic assay in rats showed that fractions (F1) and (F4) had highest blood glucose reduction of 44.5 ± 0.4 and 52.8 ± 1.3%, respectively (p < 0.05). GC-MS analysis of fractions F1 and F4 showed the presence of 21 and 23 compounds in F1 and 23, respectively.ConclusionThis study has demonstrated that R. officinalis crude extract fractions obtained from 50% methanol in dichloromethane possesses alpha-amylase inhibitory and anti-hyperglycemic activities as well as secondary metabolites with varying chemical structures. The hexane and hexane/ethyl acetate (8/2) fractions showed most potent alpha-amylase inhibition with high anti-hyperglycemic activity giving hope of a possibility of obtaining lead compounds for new anti-diabetic drugs.

Rapid correction of chronic hyperglycemia and bone remodeling, warning against overdoing.

It is widely recognized that chronic hyperglycemia decreases bone quality, although little is known about the impact of the rapid correction of chronic hyperglycemia on the quality of bone remodeling. This spotlight article explores this correlation by focusing on the stages of bone remodeling linked to glucose levels.

Platelet indices as predictors of poor glucoregulation in type 2 diabetes mellitus adults at Bishoftu General Hospital, Ethiopia.

Diabetes is a chronic metabolic syndrome that has become a global public health problem with significant morbidity and mortality. It is a pro-inflammatory and pro-thrombotic condition characterized by increased platelet activation and alterations in platelet indices. However, the use of platelet indices as predictors of poor glucoregulation has not been fully evaluated in this context, and evidence for their role as predictors of poor glycemic status in diabetic patients is limited. To evaluate platelet indices and determine their prognostic significance in relation to inadequate glucoregulation among individuals diagnosed with type 2 diabetes at Bishoftu General Hospital in Ethiopia, from June 15 to August 12, 2022. A comparative cross-sectional study was conducted in 261 participants including 174 individuals with type 2 diabetes mellitus (T2DM) and 87 non-diabetic controls. The systematic random sampling technique was used to select par-ticipants. Data were collected using structured questionnaires, physical measurements, checklists, and laboratory tests. Platelet parameters and fasting blood glucose levels were determined from blood samples using Sysmex-XN550 and CobasC311 analyzers, respectively. The hematology analyzer output was checked and participants were also screened for malaria parasites using a prepared blood smear. Collected data were entered into Epi-data version 3.1 and exported to SPSS version 25 for analysis. The χ 2 test, Mann-Whitney U test, Kruskal-Wallis test, post hoc test, Spearman correlation, and receiver operating characteristic curve were used for analysis. A P value < 0.05 was considered statistically significant. The results of our study indicate that diabetic patients have significantly higher levels of platelet distribution width (PDW), mean platelet volume (MPV), platelet large cell ratio (PLCR), and plateletcrit (PCT) compared to healthy individuals (P < 0.001). Furthermore, these indices were found to be significantly elevated in individuals with poor glycemic control in T2DM compared to those with good glycemic control and healthy controls. We also observed significant correlations between these indices and various anthropometric and clinical variables. Our findings suggest that PDW, with a cut-off value of 15.75 fL and an area under the curve (AUC) of 0.803, MPV, with a cut-off value of 12.25 fL and an AUC of 0.774, PLCR, with a cut-off value of 36.3% and an AUC of 0.775, and PCT, with a cut-off value of 0.24% and an AUC of 0.761, can serve as predictors of poor glycemic control in patients with diabetes mellitus. The observed correlation between diabetic patients and a significant increase in platelet indices has highlighted their potential as predictors of poor glycemic control in diabetes. Therefore, regular screening and profiling of platelet indices is recommended as part of the follow-up process for individuals with diabetes mellitus.

Stroke Measures Analysis of pRognostic Testing-Mortality nomogram predicts long-term mortality after ischemic stroke.

Predicting long-term mortality is essential for understanding prognosis and guiding treatment decisions in patients with ischemic stroke. Therefore, this study aimed to develop and validate the method for predicting 1- and 5-year mortality after ischemic stroke. We used data from the linked dataset comprising the administrative claims database of the Health Insurance Review and Assessment Service and the Clinical Research Center for Stroke registry data for patients with acute stroke within 7 days of onset. The outcome was all-cause mortality following ischemic stroke. Clinical variables linked to long-term mortality following ischemic stroke were determined. A nomogram was constructed based on the Cox's regression analysis. The performance of the risk prediction model was evaluated using the Harrell's C-index. This study included 42,207 ischemic stroke patients, with a mean age of 66.6 years and 59.2% being male. The patients were randomly divided into training (n = 29,916) and validation (n = 12,291) groups. Variables correlated with long-term mortality in patients with ischemic stroke, including age, sex, body mass index, stroke severity, stroke mechanisms, onset-to-door time, pre-stroke dependency, history of stroke, diabetes mellitus, hypertension, coronary artery disease, chronic kidney disease, cancer, smoking, fasting glucose level, previous statin therapy, thrombolytic therapy, such as intravenous thrombolysis and endovascular recanalization therapy, medications, and discharge modified Rankin Scale were identified as predictors. We developed a predictive system named Stroke Measures Analysis of pRognostic Testing-Mortality (SMART-M) by constructing a nomogram using the identified features. The C-statistics of the nomogram in the developing and validation groups were 0.806 (95% confidence interval (CI), 0.802-0.812) and 0.803 (95% CI, 0.795-0.811), respectively. The SMART-M method demonstrated good performance in predicting long-term mortality in ischemic stroke patients. This method may help physicians and family members understand the long-term outcomes and guide the appropriate decision-making process.

The association between macrosomia and glucose, lipids and hormones levels in maternal and cord serum: a case-control study

BackgroundThe formation of macrosomia is associated with excessive nutrition and/or unable to regulate effectively. This case-control study aims to explore the relationship between macrosomia and glucose, lipids and hormones levels in maternal and cord serum.MethodsIn the case-control study, 78 pairs of mothers and newborns were recruited who received care at one hospital of Hebei, China between 2016 and 2019. According to the birth weight (BW) of newborns, participants were divided into macrosomia group (BW ≥ 4000 g, n = 39) and control group (BW between 2500 g and 3999 g, n = 39). Maternal vein blood and cord vein blood were collected and assayed. All data were compared between the two groups. Unconditional logistics regression analysis was used to test the relationship between macrosomia and glucose, lipids and hormones in maternal and cord serum.ResultsIn maternal and cord serum, the levels of leptin, leptin/adiponectin ratio (LAR), glucose and triglyceride (TG) in macrosomia group were higher than those in control group, and the levels of high-density lipoprotein cholesterol (HDL-C) were lower. The percentage of maternal glucose and lipids transfer to cord blood did not differ between the two groups. High levels of TG in maternal serum were positively correlated with macrosomia, and high levels of LAR, TG and glucose in cord serum were positively correlated with macrosomia.ConclusionIn conclusion, the results of the current study, suggest that the nutrients and metabolism-related hormones in maternal and umbilical cord are closely related to macrosomia. During pregnancy, the nutritional status of pregnant women should be paid attention to and to obtain a good birth outcome.

1-Hour Post-Load Glucose: Early Screening for High Risk of Type 2 Diabetes in Koreans with Normal Fasting Glucose.

With rising the prevalence of type 2 diabetes mellitus (T2DM) and prediabetes, the importance of 1-hour post-load plasma glucose (1-h PG) for early hyperglycemia screening is emphasized. This study investigates the utility of 1-h PG in predicting T2DM in adults with normal fasting plasma glucose (FPG) levels. 7,504 participants were categorized into three groups: normal glucose tolerance (NGT) with 1-h PG < 155 mg/dL, NGT with 1-h PG ≥ 155 mg/dL, and impaired glucose tolerance (IGT). Insulin sensitivity and secretion indices were compared between groups at baseline, and T2DM incidence was analyzed using Cox proportional hazards models. The predictive abilities of 1-h PG and 2-hour post-load plasma glucose (2-h PG) were assessed with receiver operating characteristic analysis. At baseline, the composite insulin sensitivity index in the NGT & 1-h PG ≥ 155 mg/dL group was similarly reduced as in the IGT group (P = .076). Over a mean follow-up of 7.4 years, T2DM developed in 960 patients (12.8%). The highest risk was in the IGT group (hazard ratio [HR] 5.47), followed by the NGT & 1-h PG ≥ 155 mg/dL group (HR 2.74), compared to the NGT & 1-h PG < 155 mg/dL group. The 1-h PG level had a higher area under the curve (0.772) than other glycemic parameters, including 2-h PG. Even with normal FPG, a 1-h PG ≥ 155 mg/dL indicates lower insulin sensitivity similar to IGT and increased T2DM risk, making it a more effective early screening tool than 2-h PG.

Association analysis between serum asprosin and metabolic characteristics, Complications in type 2 diabetic patients with different durations.

To investigated the association between serum asprosin and metabolic characteristics in type 2 diabetes mellitus patients with different durations. A total of 436 patients with type 2 diabetes mellitus were enrolled in this study from the community health service center in southeastern Shanxi Province. All the patients were divided into two groups according to their diabetes duration: diabetes duration ≤5 years group (n = 132) and diabetes duration ≥10 years group (n = 304). Fasting blood samples were gathered and serum asprosin was tested. Pearson/Spearman correlation analysis was carried out. Asprosin was comparable between the two groups. Asprosin was positively correlated with systolic blood pressure (SBP), triglycerides, creatinine, serum uric acid and low-density lipoprotein cholesterol in the diabetes duration ≤5 years group (P < 0.05). In the diabetes duration ≥10 years group, asprosin was independently correlated with SBP, diastolic blood pressure, body mass index, total cholesterol, triglycerides, low-density lipoprotein cholesterol, creatinine, serum uric acid, fasting plasma glucose and glycosylated hemoglobin (P < 0.05). Asprosin was associated with alanine aminotransferase and estimated glomerular filtration rate (P < 0.05). Multiple linear regression analysis found that SBP and diastolic blood pressure is an independent factor related to serum asprosin in the group with diabetes duration ≤5 years (P < 0.05). Fasting plasma glucose, SBP, total cholesterol and serum uric acid is an independent factor related to serum asprosin in the group with diabetes duration ≥10 years (P < 0.05). Serum asprosin was significantly increased in the group with diabetes duration ≥10 years, and glycosylated hemoglobin, blood pressure and estimated glomerular filtration rate were independent risk factors in long-duration type 2 diabetes mellitus.

Ensemble machine learning framework for predicting maternal health risk during pregnancy

Maternal health risks can cause a range of complications for women during pregnancy. High blood pressure, abnormal glucose levels, depression, anxiety, and other maternal health conditions can all lead to pregnancy complications. Proper identification and monitoring of risk factors can assist to reduce pregnancy complications. The primary goal of this research is to use real-world datasets to identify and predict Maternal Health Risk (MHR) factors. As a result, we developed and implemented the Quad-Ensemble Machine Learning framework to predict Maternal Health Risk Classification (QEML-MHRC). The methodology used a vacxsriety of Machine Learning (ML) models, which then integrated with four ensemble ML techniques to improve prediction. The dataset collected from various maternity hospitals and clinics subjected to nineteen training and testing tests. According to the exploratory data analysis, the most significant risk factors for pregnant women include high blood pressure, low blood pressure, and high blood sugar levels. The study proposed a novel approach to dealing with high-risk factors linked to maternal health. Dealing with class-specific performance elaborated further to properly understand the distinction between high, low, and medium risks. All tests yielded outstanding results when predicting the amount of risk during pregnancy. In terms of class performance, the dataset associated with the “HR” class outperformed the others, predicting 90% correctly. GBT with ensemble stacking outperformed and demonstrated remarkable performance for all evaluation measure (0.86) across all classes in the dataset. The key success of the models used in this work is the ability to measure model performance using a class-wise distribution. The proposed approach can help medical experts assess maternal health risks, saving lives and preventing complications throughout pregnancy. The prediction approach presented in this study can detect high-risk pregnancies early on, allowing for timely intervention and treatment. This study’s development and findings have the potential to raise public awareness of maternal health issues.

250 Effects of corn processing on growth performance, starch digestibility, and blood metabolites in receiving beef steers

Abstract Corn is the most common grain ingredient fed to feedlot cattle in the U.S. and most corn goes through some processing to increase the energy availability. This study examined the effects of a novel corn processing method on the growth performance, starch digestibility, and blood metabolites of growing steers compared with traditional corn processing methods. Angus-cross steers [n = 218; body weight (BW) = 230 ± 18.5 kg] were sorted into pens of 6 or 7 steers upon arrival and fed a common receiving diet for 2 d prior to being weighed, processed, and starting dietary treatments (n = 12 pens/treatment) on d 0. Treatments included diets with dry rolled corn (ROLL), steam flaked corn (FLAKE), and high shear dry extruded corn (EXT; High-Gel Insta-Pro International, Grimes, IA). Corn was included at 30% DM of a corn silage and SweetBran-based diet. Due to illness concerns, diets were adjusted to reduce corn in the diet to 25% on d 5; in feed antibiotic was fed d 5 to 9, and all calves were weighed and administered Draxxin (1.1 mL/45.45 kg) on d 17. Final BW were collected on d 37 and 38 and serum (glucose, insulin) and fecal samples (total tract starch digestibility) were collected from one steer per pen. Data were analyzed using the Mixed procedure of SAS 9.4 (Cary, NC) with pen as the experimental unit. Treatment did not affect midpoint (d 17) BW or average daily gain (ADG) from d 0 to 17 (P ≥ 0.31). Final BW, ADG, and dry matter intake were not different between treatments (P ≥ 0.15). Feed efficiency (gain:feed) was greatest in EXT (0.261) compared with ROLL (0.232) with FLAKE (0.259) being intermediate and not different from other treatments (P = 0.007). Total tract starch digestibility was determined using the equations from Zinn et al. (2007) and was increased in EXT and FLAKE compared with ROLL (P = 0.0002). Serum glucose and insulin on d 36 were not affected by treatment (P ≥ 0.19). Overall, a growing diet of 25% high shear dry extruded corn increased feed efficiency and total tract starch digestibility over dry rolled corn and resulted in similar performance to steers fed steam flaked corn.

22 Effects of trace mineral source and chromium propionate supplementation on rumen fermentation, growth performance, and carcass characteristics in finishing beef steers

Abstract Crossbred beef steers [n = 400; body weight (BW) = 370 ± 8 kg] were used to evaluate the effects of trace mineral (TM) source and chromium propionate (Cr) on rumen fermentation characteristics, plasma glucose and mineral concentrations, performance, and carcass characteristics in feedlot steers fed a steam-flaked corn-based finishing diet. Steers were blocked by initial BW and randomly assigned within block to 1 of 4 treatments (10 steers/pen) with 10 pens per treatment. The experimental design was a randomized complete block design with a 2 x 2 factorial arrangement of treatments. Factors included: 1) TM source [sulfate or hydroxychloride (IntelliBond] Cu, Mn, and Zn TM supplemented at 18, 40, and 90 mg/kg DM, respectively) and 2) with or without supplemental Cr (KemTRACE) at 0.0 or 0.25 mg/kg DM. Steers were individually weighed on d -1 and 0 and every 28 d throughout the experiment. Jugular blood samples and rumen contents were collected from 10 steers per treatment on d 28 and 84 of the experiment for plasma glucose and TM concentration and volatile fatty acid analysis, respectively. On d 154 of the experiment, steers were harvested at a commercial abattoir and carcass data was collected. Data were analyzed on a pen mean basis for a randomized complete block design using PROC MIXED of SAS. There was no TM source by Cr supplementation interactions for any of the response variables measured, therefore only main effects are reported. Overall ADG (P = 0.03) and gain:feed (P = 0.02) were greater in steers receiving supplemental Cr when compared with steers not supplemented with Cr. Hot carcass weight (P = 0.04), dressing percentage (P = 0.01), longissimus muscle area (P = 0.03), and USDA yield grades (P = 0.04) were greater in steers receiving hydroxychloride TM compared with steers receiving sulfate TM. Steers supplemented with Cr had a greater dressing percentage (P = 0.01) and longissimus muscle area (P = 0.04) compared with steers not supplemented with Cr. On d 28 of the experiment, ruminal acetate concentrations were lesser (P = 0.01) and ruminal propionate concentrations tended to be greater (P = 0.12) in steers receiving hydroxychloride TM compared with steers receiving sulfate TM. Steers supplemented with Cr had greater ruminal acetate concentrations (P = 0.04) and plasma glucose concentrations (P = 0.05) on d 28 of the experiment when compared with non-supplemented controls. These data indicate the Cr supplementation and TM source can influence feedlot steer performance, carcass characteristics, and rumen fermentation characteristics.

123 Effects of a Saccharomyces cerevisiae based direct-fed microbial on performance, health, and rumen bacterial community of newly weaned beef steers during a 56-d receiving period

Abstract We examined the effects of a blend of Saccharomyces cerevisiae, multiple live probiotic bacteria and their fermentation products on performance, health, and the ruminal bacterial community of newly weaned beef steers during a 56-d receiving period. Newly weaned Angus crossbred steers [n = 40; 221 ± 25.6 kg body weight (BW); 180 ± 17 d of age] were stratified by BW into four pens (10 steers per pen) such that each pen had a similar average BW at the beginning of the experiment. The pens were randomly assigned to receive a corn silage basal diet (CON; n = 20) or the basal diet supplemented with 9 g·steer⁻¹·d⁻¹of PRO feed additive (PRO; n = 20). The PRO additive is a blend of Saccharomyces cerevisiae and the fermentation products of Enterococcus faecium, Bacillus licheniformis, Bacillus subtilis, Lactobacillus animalis, Propionibacterium freudenreichii. The DMI and water consumed were monitored using the GrowSafe intake nodes and custom flow meters, respectively. Body weights were recorded weekly to calculate average daily gain (ADG). Before morning feeding, 10 mL of blood was taken from each steer on d 0 to 7, and thereafter weekly for analyses of immune cells, plasma glucose and NEFAs. On d 56, rumen fluid samples (200 mL each) were collected from all the steers for microbiome analysis. Over the 56-d receiving period, the supplemental PRO had no effects on DMI, water intake, or ADG. However, compared with CON, beef steers fed supplemental PRO tended to have greater ADG (P = 0.08) and BW (P = 0.07) during the first 14 d of the study. There was a treatment × day interaction (P ≤ 0.05) for WBC, neutrophils and monocytes over the 56 d such that beef steers fed supplemental PRO had decreased blood concentrations on certain days during the first 7 d after weaning, indicating reduced inflammation or stress response. The results of the rumen microbiome analysis revealed that the relative abundance of complex fiber degrading or obligate proton-reducing bacterial genera such as Bacteroides, Ruminococcus gauvreauii group, Desulfovibrio, Syntrophococcus, and Acetitomaculum were greater (P ≤ 0.05) in beef steers fed supplemental PRO compared with CON. This study demonstrated that dietary supplementation of PRO improved the growth performance, reduced stress or inflammatory response during the initial days after weaning and altered the ruminal bacterial community towards increased relative abundance of bacterial genera associated with improved rumen function.

Polysaccharides from Ostrea rivularis alleviate type II diabetes induced-retinopathy and VGEF165-induced angiogenesis via PI3K/AKT signaling pathway

The purpose of this study was to investigate the role of polysaccharides from Ostrea rivularis Gloud (ORPs) in the progression of diabetic retinopathy (DR) and its anti-angiogenic effect on endothelial cell. Transgenic db/db mice with DR model were used to evaluate the protective effect of ORPs on retinal damage. It was found that ORPs could down-regulated levels of random blood glucose and fasting insulin, and further ameliorate retinal structure abnormalities as well as vascular network structure. Moreover, ORPs could reduce the expression of VEGF in retinal tissue and lessen pathological angiogenesis, thus slowing the progression of DR. In vitro, the proliferation, migration and tube formation of VGEF165-induced EA.hy926 cells were inhibited with ORPs administration. Furthermore, the expression of related proteins in the PI3K/AKT pathway and angiogenesis related factors were improved after ORPs intervention. Overall, these findings suggested that ORPs could effectively control the development of DR, and inhibit VGEF165-induced EA.hy926 cells proliferation, migration and tube formation, which effects might work through blocking the activation of PI3K/AKT signaling pathway.

Palmitic acid promotes miRNA release from adipocyte exosomes by activating NF-κB/ER stress

ObjectiveThe release of adipose tissue-derived miRNAs is increased under conditions of obesity, but the exact molecular mechanisms involved have not been elucidated. This study investigated whether obesity-induced increases in palmitic acid (PA) content could activate the NF-κB/endoplasmic reticulum stress (ER stress) pathway and promote the expression and release of exosomal miRNAs in adipocytes.MethodsAbdominal adipose tissue and serum samples were collected from normal weight individuals and people with obesity to clarify the correlation of serum PA content with NF-κB/ER stress and the release of exosomal miRNAs. NF-κB and ER stress were blocked in obese mice and in vitro cultured adipocytes to demonstrate the molecular mechanisms by which PA promotes the release of exosomal miRNAs.The morphology, particle size and distribution of the exosomes were observed via transmission electron microscopy and NTA.ResultsAccompanied by increased serum PA levels, the NF-κB/ER stress pathway was activated in the adipose tissue of people with obesity and in high-fat diet (HFD)-induced obese mice; moreover, the levels of miRNAs in both adipose tissue and serum were increased. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reduced the levels of miRNAs in abdominal adipose tissue and serum, decreased blood glucose levels, and improved glucose tolerance and insulin sensitivity in obese mice. In 3T3-L1 adipocytes, high concentrations of PA activated the NF-κB/ER stress pathway and increased the expression and release of miRNAs in exosomes. P-p65 (Bay11-7082) and ER stress (TUDCA) blockers significantly reversed the increased release exosomal miRNAs cause by PA.ConclusionsObesity-induced increases in PA content increase the expression and release of miRNAs in adipocyte exosomes by activating the NF-κB/ER stress pathway.

Exploring the Feasibility of Digital Voice Assistants for Delivery of a Home-Based Exercise Intervention in Older Adults With Obesity and Type 2 Diabetes Mellitus: Randomized Controlled Trial.

Current clinical guidelines for the management of type 2 diabetes mellitus (T2DM) in older adults recommend the use of antihyperglycemic medications, monitoring of blood glucose levels, regular exercise, and a healthy diet to improve glycemic control and reduce associated comorbidities. However, adherence to traditional exercise programs is poor (<35%). Common barriers to adherence include fear of hypoglycemia and the need for blood glucose level monitoring before exercise. Digital health strategies offer great promise for managing T2DM as they facilitate patient-practitioner communication, support self-management, and improve access to health care services for underserved populations. We have developed a novel web-based software program allowing practitioners to create tailored interventions and deliver them to patients via digital voice assistants (DVAs) in their own homes. We aim to evaluate the feasibility of a 12-week, home-based, personalized lifestyle intervention delivered and monitored by DVAs for older adults with obesity and T2DM. In total, 50 older adults with obesity aged 50-75 years with oral hypoglycemic agent-treated T2DM were randomized to the intervention (DVA, n=25) or a control group (n=25). Participants allocated to the DVA group were prescribed a home-based muscle strengthening exercise program (~20- to 30-min sessions) and healthy eating intervention, delivered via DVAs (Alexa Echo Show 8; Amazon) using newly developed software ("Buddy Link"; Great Australian Pty Ltd). Control group participants received generalized physical activity information via email. Outcomes were feasibility, DVA usability (System Usability Scale), and objectively assessed physical activity and sedentary time (wrist-worn accelerometers). In total, 45 (90%) out of 50 participants completed this study. Mean adherence to prescribed exercise was 85% (SD 43%) with no intervention-related adverse events. System usability was rated above average (70.4, SD 16.9 out of 100). Compared with controls, the DVA group significantly decreased sedentary time (mean difference -67, SD 23; 95% CI -113 to -21 min/d), which was represented by a medium to large effect size (d=-0.6). A home-based lifestyle intervention delivered and monitored by health professionals using DVAs was feasible for reducing sedentary behavior and increasing moderate-intensity activity in older adults with obesity and T2DM. Australian New Zealand Clinical Trials Registry (ANZCTR) ACTRN12621000307808; https://www.anzctr.org.au/Trial/Registration/TrialReview.aspx?id=381364&isReview=true.

Metabolic health in people living with type 1 diabetes in Belgium: a repeated cross-sectional study.

Metabolic abnormalities such as central obesity, insulin resistance, dyslipidaemia and hypertension, often referred to as 'the metabolic syndrome' (or 'combined metabolic abnormalities'), are increasingly being identified in people living with type 1 diabetes, accelerating the risk for CVD. As a result, in recent years, treatment in people living with type 1 diabetes has shifted to improving overall metabolic health rather than glucose control alone. In Belgium, diabetes care for people living with type 1 diabetes is centrally organised. The Initiative for Quality Improvement and Epidemiology in Diabetes, imposed by the Belgian health insurance system, has systematically collected data from patients on intensive insulin therapy treated in all 101 diabetes clinics in Belgium since 2001. The aim of this real-world study is to describe the evolution of treatment and metabolic health, including the prevalence of obesity and combined metabolic abnormalities, in people living with type 1 diabetes over the past 20 years, and to compare the treatment and prevalence of complications between those with and without combined metabolic abnormalities. We analysed data on adults (≥16 years old) living with type 1 diabetes, who were diagnosed at age ≤45 years and who had a diabetes duration ≥1 year, collected between 2001 and 2022. The evolution of HbA1c, BMI, LDL-cholesterol, systolic BP, lipid-lowering therapy and antihypertensive therapy over time was analysed. The prevalence of individual and multiple metabolic abnormalities according to various definitions of the metabolic syndrome/combined metabolic abnormalities was analysed, and the association between combined metabolic abnormalities and metabolic health indicators, complications and treatment was investigated in the 2022 data. The final dataset consisted of 26,791 registrations of adults living with type 1 diabetes collected between 2001 and 2022. Although glycaemic and lipid control generally improved over time, the prevalence of obesity strongly increased (12.1% in 2001 vs 21.7% in 2022, p<0.0001), as did the presence of combined metabolic abnormalities (WHO criteria: 26.9% in 2001 vs 42.9% in 2022 in women, p<0.0001; 30.4% in 2001 vs 52.1% in 2022 in men, p<0.0001; WHO criteria without albuminuria: 22.3% in 2001 vs 40.6% in 2022 in women, p<0.0001; 25.1% in 2001 vs 49.2% in 2022 in men, p<0.0001; NCEP-ATPIII criteria: 39.9% in 2005 vs 57.2% in 2022 in women, p<0.0001; 40.8% in 2005 vs 60.9% in 2022 in men, p<0.0001; IDF criteria: 43.9% in 2005 vs 59.3% in 2022 in women, p<0.001; 33.7% in 2005 vs 50.0% in 2022 in men, p<0.0001). People with combined metabolic abnormalities had higher glucose levels compared to those without combined metabolic abnormalities (HbA1c >58 mmol in men: 48.9% vs 36.9%; HbA1c >58 mmol in women: 53.3% vs 41.1%, p<0.0001). People with combined metabolic abnormalities were more often treated with adjunct therapies such as metformin, sodium-glucose transport protein 2 inhibitors and glucagon-like peptide-1 receptor agonists. In both men and women, the presence of combined metabolic abnormalities was strongly related to the presence of eye complications, peripheral neuropathy, chronic kidney disease and CVD, corrected for age, diabetes duration and HbA1c. Overweight, obesity and combined metabolic abnormalities are increasingly being identified in people living with type 1 diabetes, further accelerating the risk of microvascular and macrovascular complications. Early identification of the presence of combined metabolic abnormalities should enable therapeutic interventions to be modified towards multifactorial approaches, with attention to education on avoidance of overweight (e.g. dietary counselling) in addition to strict glycaemic control and intensification of use of antihypertensive agents and statins. Use of adjunct therapies in this population as a tool should be explored more thoroughly to reduce risk of complications.

The Therapeutic Potential of Theobromine in Obesity: A Comprehensive Review.

Obesity, characterized by chronic low-grade inflammation, is a significant health concern. Phytochemicals found in plants are being explored for therapeutic use, particularly in combating obesity. Among these, theobromine, commonly found in cocoa and chocolate, shows promise. Although not as extensively studied as caffeine, theobromine exhibits positive effects on human health. It improves lipid profiles, aids in asthma treatment, lowers blood pressure, regulates gut microbiota, reduces tumor formation, moderates blood glucose levels, and acts as a neuroprotective agent. Studies demonstrate its anti-obesity effects through mechanisms such as browning of white adipose tissue, activation of brown adipose tissue, anti-inflammatory properties, and reduction of oxidative stress. This study aims to suggest theobromine as a potential therapeutic agent against obesity-related complications.

Encapsulation of telmisartan inside insulinoma-cell-derived extracellular vesicles outperformed biomimetic nanovesicles in modulating the pancreatic inflammatory microenvironment.

Diabetes mellitus (DM) is a chronic metabolic condition, characterized by hyperglycaemia, oxidative imbalance, pancreatic β-cell death, and insulin insufficiency. Angiotensin II (Ang II) increases oxidative stress, inflammation, and apoptosis, and Ang II type 1 receptor (AT1R) blockers (ARBs) can ameliorate inflammatory response and oxidative stress. However, like other small-molecule drugs, free ARBs show poor in vivo efficacy and dose-limiting toxicities. Hence, in this study, we developed nano-formulations of telmisartan (TEL), an ARB, by encapsulating it inside a murine insulinoma cell-derived extracellular vesicle (nanoTEL) and a bio-mimetic lipid nanovesicle (lipoTEL). Both nano-formulations showed spherical morphology and sustained release of TEL. In vitro, nanoTEL restored oxidative equilibrium, attenuated reactive oxygen species levels, enhanced the uptake of glucose analogue, and increased the expression of glucose transporter protein 4 better than lipoTEL. In a streptozotocin-induced murine model of diabetes, nanoTEL lowered blood glucose levels, improved glucose tolerance, and promoted insulin synthesis and secretion significantly better than lipoTEL. Moreover, nanoTEL was found superior in ameliorating the pancreatic inflammatory microenvironment by regulating NF-κBp65, HIF-1α, and PPAR-γ expression; modulating IL-1β, IL-6, tumor necrosis factor-α, IL-10, and IL-4 levels and inducing the polarization of macrophage from M1 to M2. Further, nanoTEL administration induced angiogenesis and promoted the proliferation of pancreatic cells to restore the structural integrity of the islets of Langerhans more efficiently than lipoTEL. These findings collectively suggest that nanoTEL outperforms lipoTEL in restoring the function of pancreatic β-cells by modulating the pancreatic inflammatory microenvironment and show potential for the treatment of DM.