A Comparative Study of Structural and Metabolic Brain Networks in Patients With Mild Cognitive Impairment

Background: Changes in the metabolic and structural brain networks in mild cognitive impairment (MCI) have been widely researched. However, few studies have compared the differences in the topological properties of the metabolic and structural brain networks in patients with MCI.Methods: We analyzedmagnetic resonance imaging (MRI) and fluoro-deoxyglucose positron emission tomography (FDG-PET) data of 137 patients with MCI and 80 healthy controls (HCs). The HC group data comes from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. The permutation test was used to compare the network parameters (characteristic path length, clustering coefficient, local efficiency, and global efficiency) between the two groups. Partial Pearson’s correlation analysis was used to calculate the correlations of the changes in gray matter volume and glucose intake in the key brain regions in MCI with the Alzheimer’s Disease Assessment Scale-Cognitive (ADAS-cog) sub-item scores.Results: Significant changes in the brain network parameters (longer characteristic path length, larger clustering coefficient, and lower local efficiency and global efficiency) were greater in the structural network than in the metabolic network (longer characteristic path length) in MCI patients than in HCs. We obtained the key brain regions (left globus pallidus, right calcarine fissure and its surrounding cortex, left lingual gyrus) by scanning the hubs. The volume of gray matter atrophy in the left globus pallidus was significantly positively correlated with comprehension of spoken language (p = 0.024) and word-finding difficulty in spontaneous speech item scores (p = 0.007) in the ADAS-cog. Glucose intake in the three key brain regions was significantly negatively correlated with remembering test instructions items in ADAS-cog (p = 0.020, p = 0.014, and p = 0.008, respectively).Conclusion: Structural brain networks showed more changes than metabolic brain networks in patients with MCI. Some brain regions with significant changes in betweenness centrality in both structural and metabolic networks were associated with MCI.

Effects of calorie intake and sampling time on thyroid stimulating hormone concentration

BackgroundThis study aimed to investigate the effects of blood collected after calorie intake on the level of thyroid stimulating hormone (TSH), comparing with the blood collected in fasting state.MethodsThis study was a prospective, randomized, controlled study. Subjects from the outpatients in the department of endocrinology without evident of thyroid diseases were included and then randomized into the fasting group, diet intake group, and glucose intake group, respectively. Fasting blood was collected from all the subjects at 7:00 am for the measurement of TSH and free thyroxine (FT4). Afterward, the subjects were maintained at fasting state (fasting group), had an intake of the mixed diet with the calories of 400 Kcal (diet intake group), and had an intake of 75 g glucose (glucose intake group), respectively, and blood was acquired again 2 h later (9:00 am on the same day) for TSH and FT4 measurement. The levels between 7:00 am and 9:00 am were compared.ResultsOf the 150 subjects, 146 met the inclusion criteria, of which 48, 48, and 50 were in the diet intake group, glucose intake group, and fasting group, respectively. The TSH in the diet intake group was significantly lower at 9:00 am (TSH9am) than the level at 2h before (TSH7am) (P<0.001), of which the median variation was -0.71 mU/L, and the median variation rate was -32.4%. In the glucose intake group, the TSH9am was also significantly lower than TSH7am (P<0.001), of which the median variation was -0.73 mU/L, and median variation rate was -31.5%. While in the fasting group, the TSH9am decreased slightly but statistically significantly lower than TSH7am (P<0.001), of which the median variation was -0.1 mU/L, and the median variation rate was -5.2%. According to TSH7am, 9 subjects in total (3 subjects in each group) met the diagnostic criteria of subclinical hypothyroidism. However, according toTSH9am, only 2 patients in the fasting group still met the diagnostic criteria of subclinical hypothyroidism.ConclusionComparing with the fasting state, the TSH level at 2h after the calorie intake was decreased by about 30%, which could influence the diagnosis of subclinical hypothyroidism.Trial registrationChiCTR2100047454.

The Effect of High Glucose Intake on Weight Gain in Very Low Birth Weight Neonates: A Randomized Controlled Trial

This study aims at evaluating the effect of high glucose intake as a component of total parenteral nutrition on birth weight (BW) regain in very low birth weight neonates. Ninety newborns with BW <1500 g were randomized to control or experimental groups. Both groups received the same total parenteral nutrition regimens except glucose intake provided by dextrose water (DW) serum: 7 to 15 g/kg/d (10% DW) in the former versus 8.75 to 18.75 g/kg/d (12.5% DW) in the latter. Body weight as the primary outcome was monitored until the BW was regained. Results revealed that neonates who received 12.5% DW regained BW significantly faster (10.98 ± 2.46 vs 13.24 ± 4.03 days, P = .024) and needed lesser duration of respiratory support (5.34 ± 2.11 vs 7.17 ± 3.19 days, P = .003). As the proposed intervention can reduce neonatal intensive care unit admission duration, it mitigates risks of health care−associated infections, while favorably affecting the health economy.

The Effect of Aerobic Exercise Training Frequency on Arterial Stiffness in a Hyperglycemic State in Middle-Aged and Elderly Females

The frequency of aerobic exercise training in reducing the increase in arterial stiffness during acute hyperglycemia, a risk factor for cardiovascular disease, is unknown. The aim of the study was to determine the aerobic exercise training frequency on arterial stiffness in a hyperglycemic state in middle-aged and elderly females. Twenty healthy elderly people were randomly assigned to a two-times-a-week (T2, n = 10) and four-times-a-week (T4, n = 10) exercise group. All participants exercised for 35 min per session, which consisted of jogging exercises with a heart rate intensity of 65%. Brachial-ankle (ba), and heart-brachial (hb) pulse wave velocity (PWV) were measured before, 4 and 8 weeks after intervention; before the oral ingestion of 75-g of glucose; and 30, 60, and 90 min after ingestion. The baPWV before and 4 weeks after the intervention increased in both groups (p < 0.05), but only increased 8 weeks after intervention in the T2 group. hbPWV was unchanged before, 4 and 8 weeks after intervention in both groups. These findings show that frequent aerobic exercise suppresses the increase in arterial stiffness following glucose intake. The results of this study can be used to support the implementation of exercise programs for middle-aged and elderly patients.

THE CARBON MONOXIDE DONOR, TOPIRAMATE, AND BLOCKERS OF AQUAPORINE RECEPTORS DECREASE MYOCARDIAL ISCHEMIA-REPERFUSION INJIRY

We investigated the metabolism of mouse isolated heart under the influence of tricarbonyldichlorothenium (II)- dimer (CORM-2 and 2,3-4,5-bis-O-isopropylidene-βD-fructopyranose sulfamate (topiramate) as potential blockers of aquaporine channel (AQP3) of cardiac myocytes. The results were compared with those obtained from the group receiving anti-AQP3 monoclonal antibodies. A decrease in coronary flow was found during the period preceding ischemia (topiramate did not cause this effect). However, at the end of reperfusion, CORM-2 was responsible for its stabilization. This compound did not affect glucose intake (topiramate increased it only at the end of reperfusion), decreased Ca2+ deposition in cardiac muscle (AQP3-IgG antibodies and topiramate had similar effect), decreased creatinine release, AST (especially at the end of reperfusion). The action of CORM-2 increased the amplitude of the R waveform before ischemia and during reperfusion. At the end of reperfusion the R-wave amplitude decreased. The effect of topiramate caused an increase in amplitude only at the beginning of reperfusion. Administration of CORM-2, topiramate and antibodies resulted in prolongation of the interval before and during ischemia. At the same time, the effect of these drugs and antibodies reduced the development of ischemic damage. The results indicate that the released CO from CORM-2 has effects similar to those of anti-AQP3 antibodies. The action of topiramate had signs of calcium channel blocking.

Dynamic alterations in the central glutamatergic status following food and glucose intake: in vivo multimodal assessments in humans and animal models

Fluctuations of neuronal activities in the brain may underlie relatively slow components of neurofunctional alterations, which can be modulated by food intake and related systemic metabolic statuses. Glutamatergic neurotransmission plays a major role in the regulation of excitatory tones in the central nervous system, although just how dietary elements contribute to the tuning of this system remains elusive. Here, we provide the first demonstration by bimodal positron emission tomography (PET) and magnetic resonance spectroscopy (MRS) that metabotropic glutamate receptor subtype 5 (mGluR5) ligand binding and glutamate levels in human brains are dynamically altered in a manner dependent on food intake and consequent changes in plasma glucose levels. The brain-wide modulations of central mGluR5 ligand binding and glutamate levels and profound neuronal activations following systemic glucose administration were further proven by PET, MRS, and intravital two-photon microscopy, respectively, in living rodents. The present findings consistently support the notion that food-associated glucose intake is mechanistically linked to glutamatergic tones in the brain, which are translationally accessible in vivo by bimodal PET and MRS measurements in both clinical and non-clinical settings.

Exosomal microRNA-503-3p derived from macrophages represses glycolysis and promotes mitochondrial oxidative phosphorylation in breast cancer cells by elevating DACT2

MicroRNAs (miRNAs) are emerging drivers in tumor progression, while the role of miR-503-3p in breast cancer (BC) remains largely unknown. We aimed to explore the impact of macrophage-derived exosomal miR-503-3p in the development of BC by regulating disheveled-associated binding antagonist of beta-catenin 2 (DACT2). miR-503-3p and DACT2 expression in BC tissues and cells was assessed, and the expression of Wnt/β-catenin signaling pathway-related proteins in BC cells was also evaluated. Macrophages were induced and exosomes were extracted. The screened BC cell lines were, respectively, treated with exosomes, miR-503-3p inhibitor/mimic or upregulated/inhibited DACT2, and then the phenotypes, glucose intake, oxygen consumption rate, and adenosine-triphosphate (ATP) level of BC cells were determined. Cell growth in vivo was also observed. MiR-503-3p was elevated, DACT2 was reduced, and Wnt/β-catenin signaling pathway was activated in BC cells. Macrophage-derived exosomes, upregulated miR-503-3p or inhibited DACT2 promoted malignant behaviors of BC cells, glucose intake, and activity of the Wnt/β-catenin signaling pathway, while repressed oxygen consumption rate and ATP level in BC cells. Reversely, reduced miR-503-3p or upregulated DACT2 exerted opposite effects. This study revealed that reduction of macrophage-derived exosomal miR-503-3p repressed glycolysis and promoted mitochondrial oxidative phosphorylation in BC by elevating DACT2 and inactivating Wnt/β-catenin signaling pathway. Our research may provide novel targets for BC treatment.

A Handheld Metabolic Device (Lumen) to Measure Fuel Utilization in Healthy Young Adults: Device Validation Study

Background Metabolic carts measure the carbon dioxide (CO2) produced and oxygen consumed by an individual when breathing to assess metabolic fuel usage (carbohydrates versus fats). However, these systems are expensive, time-consuming, and only available in health care laboratory settings. A small handheld device capable of determining metabolic fuel usage via CO2 from exhaled air has been developed. Objective The aim of this study is to evaluate the validity of a novel handheld device (Lumen) for measuring metabolic fuel utilization in healthy young adults. Methods Metabolic fuel usage was assessed in healthy participants (n=33; mean age 23.1 years, SD 3.9 years) via respiratory exchange ratio (RER) values obtained from a metabolic cart as well as % CO2 from the Lumen device. Measurements were performed at rest in two conditions: fasting, and after consuming 150 grams of glucose, in order to determine changes in metabolic fuel usage. Reduced major axis regression and simple linear regression were performed to test for agreement between RER and Lumen % CO2. Results Both RER and Lumen % CO2 significantly increased after glucose intake (P<.001 for both) compared with fasting conditions, by 0.089 and 0.28, respectively. Regression analyses revealed an agreement between the two measurements (F1,63=18.54; P<.001). Conclusions This study shows the validity of Lumen for detecting changes in metabolic fuel utilization in a comparable manner with a laboratory standard metabolic cart, providing the ability for real-time metabolic information for users under any circumstances.

Effect of Sucrose on Cisplatin-induced Fatigue-like Behavior in Mice: Comparison With Fructose and Glucose

Background/Aim: Fatigue is the most common symptom in patients with cancer undergoing radiation therapy or cancer chemotherapy. However, cancer-related fatigue remains undertreated and poorly understood. Materials and Methods: Mice were administered a single dose of cisplatin (10 mg/kg, intraperitoneally) or saline (as a control) and then treated with sucrose, fructose, glucose (each at 500 or 5,000 mg/kg, orally), or saline (control) daily for 4 days. cisplatin-induced fatigue-like behavior was investigated by assessment of running activity on a treadmill. The influence of glucose intake on tumor growth was also examined in Lewis lung carcinoma (LLC)-bearing mice. Results: Administration of sucrose and glucose improved cisplatin-induced fatigue-like behavior in mice, whereas administration of fructose showed only slight antifatigue effects. Although glucose-fed mice showed increased tumor growth, this was balanced out by the powerful cytotoxicity of cisplatin. Conclusion: Sucrose, and especially glucose, may improve patient quality of life during treatment with anticancer agents by preventing fatigue without interfering with the antitumor effects of cisplatin.