A MEMS affinity glucose sensor using a biocompatible glucose-responsive polymer

We present a MEMS affinity sensor that can potentially allow long-term continuous monitoring of glucose in subcutaneous tissue for diabetes management. The sensing principle is based on detection of viscosity changes due to affinity binding between glucose and poly(acrylamide-ran-3-acrylamidophenylboronic acid) (PAA-ran-PAAPBA), a biocompatible, glucose-specific polymer. The device uses a magnetically driven vibrating microcantilever as a sensing element, which is fabricated from Parylene and situated in a microchamber. A solution of PAA-ran-PAAPBA fills the microchamber, which is separated from the surroundings by a semi-permeable membrane. Glucose permeates through the membrane and binds reversibly to the phenylboronic acid moiety of the polymer. This results in a viscosity change of the sensing solution, which is obtained by measuring the damped cantilever vibration using an optical lever setup, allowing determination of the glucose concentration. Experimental results demonstrate that the device is capable of detecting glucose at physiologically relevant concentrations from 27 mg/dL to 324 mg/dL. The glucose response time constant of the sensor is approximately 3 min, which can be further improved with device design optimization. Excellent reversibility and stability are observed in sensor responses, as highly desired for long-term, stable continuous glucose monitoring.     

A new computer-assisted three-dimensional reconstruction method provides accurate measurement of glomerular mesangial volume

Many glomerulopathies are characterized by progressive mesangial (interstitial) expansion which can be quantitated by morphometric analysis. The purpose of this study was to analyze mesangial and glomerular volumes using a new computer-assisted reconstruction (CAR) method. CAR was compared to two standard planar methods, point-counting and linear integration, for accuracy and time efficiency. In Phase I of the study, a computer-based model of the mesangial space was created by placing spherical and ellipsoidal objects of known volume into an enclosing volume mimicking the glomerulus. The simulated mesangium occupied approximately 10 percent of the glomerular volume. The model glomerulus was sectioned serially into ten sections of equal thickness and the three morphometric methods applied to determine the mesangial/glomerular volume. The complexity of the mesangial model was varied by increasing the number of mesangial regions from one to ten to 100. The CAR method estimated the model mesangial volume more accurately (1–9 percent error) through each level of complexity compared to point-counting (3–17 percent error) and linear integration (3–18 percent error). The point-counting method consistently overestimated (P < 0.05) the fractional mesangial volume for the ten- and 100-region mesangium models. In Phase II of the study, a normal rat glomerulus was sectioned serially (215 sections) and a transmission electron micrograph (TEM) of every fifth section (n = 43) was obtained. Each TEM image (2% of glomerular surface) was digitized for analysis by CAR. Point-counting and linear integration were also performed on the whole glomerular TEMs (n = 10, randomly chosen). The estimated relative mesangial/glomerular volume was 6.6 ± 0.1 percent by CAR (x? ± SD), 9.7 ± 1.5 by linear integration, and 14.9 ± 3.4 by point-counting. The point-counting method was most efficient, requiring 40 ± 8 sec/section, followed by CAR at 85 ± 24 sec/section. Linear integration was least efficient (93 ± 23 sec/section). We conclude that CAR is the most accurate morphometric method of the three compared for estimating mesangial and glomerular methods, although it is more time consuming than the point-counting method and requires more complex instrumentation. CAR is the only method that will analyze the shape and three-dimensional complexity of glomerular structures using TEMs.     

4,4-二甲基甾醇生物活性研究进展

旨在为4,4-二甲基甾醇在功能食品、保健品和药品等领域的开发应用提供科学的理论参考,概述了4,4-二甲基甾醇的来源、提取与分离纯化方法、鉴定方法及吸收与代谢,在此基础上对4,4-二甲基甾醇的降血糖、抗炎、减肥降脂、抑菌、抗肿瘤及抗阿尔茨海默病等方面表现的潜在生物活性进行了归纳总结,并对目前存在的问题提出相应的对策。4,4-二甲基甾醇是一种重要的植物甾醇,具有多种生物活性,表现出较大的潜在应用价值。     

Impact of Sulfated Hyaluronan on Bone Metabolism in Diabetic Charcot Neuroarthropathy and Degenerative Arthritis

Bone in diabetes mellitus is characterized by an altered microarchitecture caused by abnormal metabolism of bone cells. Together with diabetic neuropathy, this is associated with serious complications including impaired bone healing culminating in complicated fractures and dislocations, especially in the lower extremities, so-called Charcot neuroarthropathy (CN). The underlying mechanisms are not yet fully understood, and treatment of CN is challenging. Several in vitro and in vivo investigations have suggested positive effects on bone regeneration by modifying biomaterials with sulfated glycosaminoglycans (sGAG). Recent findings described a beneficial effect of sGAG for bone healing in diabetic animal models compared to healthy animals. We therefore aimed at studying the effects of low- and high-sulfated hyaluronan derivatives on osteoclast markers as well as gene expression patterns of osteoclasts and osteoblasts from patients with diabetic CN compared to non-diabetic patients with arthritis at the foot and ankle. Exposure to sulfated hyaluronan (sHA) derivatives reduced the exaggerated calcium phosphate resorption as well as the expression of genes associated with bone resorption in both groups, but more pronounced in patients with CN. Moreover, sHA derivatives reduced the release of pro-inflammatory cytokines in osteoclasts of patients with CN. The effects of sHA on osteoblasts differed only marginally between patients with CN and non-diabetic patients with arthritis. These results suggest balancing effects of sHA on osteoclastic bone resorption parameters in diabetes.     

Organokines,Sarcopenia, and Metabolic Repercussions: The Vicious Cycle and the Interplay with Exercise

Sarcopenia is a disease that becomes more prevalent as the population ages, since it is directly linked to the process of senility, which courses with muscle atrophy and loss of muscle strength. Over time, sarcopenia is linked to obesity, being known as sarcopenic obesity, and leads to other metabolic changes. At the molecular level, organokines act on different tissues and can improve or harm sarcopenia. It all depends on their production process, which is associated with factors such as physical exercise, the aging process, and metabolic diseases. Because of the seriousness of these repercussions, the aim of this literature review is to conduct a review on the relationship between organokines, sarcopenia, diabetes, and other metabolic repercussions, as well the role of physical exercise. To build this review, PubMed-Medline, Embase, and COCHRANE databases were searched, and only studies written in English were included. It was observed that myokines, adipokines, hepatokines, and osteokines had direct impacts on the pathophysiology of sarcopenia and its metabolic repercussions. Therefore, knowing how organokines act is very important to know their impacts on age, disease prevention, and how they can be related to the prevention of muscle loss.     

Insights into the Genetics and Signaling Pathways in Maturity-Onset Diabetes of the Young

Diabetes Mellitus (DM) is a complex disease with a significant impact in today’s world. Studies have emphasized the crucial role of genetics in DM, unraveling the distinction of monogenic diabetes from the most common types that have been recognized over the years, such as type 1 diabetes (T1DM) and type 2 diabetes (T2DM). A literature search was carried out to scrutinize the subtypes of maturity-onset diabetes of the young (MODY), as well as the connection between the recognized genetic and molecular mechanisms responsible for such phenotypes. Thus far, 14 subtypes of MODY have been identified. Here, the authors review the pathophysiological and molecular pathways in which monogenic diabetes genes are involved. Despite being estimated to affect approximately 2% of all T2DM patients in Europe, the exact prevalence of MODY is still unknown, enhancing the need for research focused on biomarkers. Due to its impact in personalized medicine, a follow-up of associated complications, and genetic implications for siblings and offspring of affected individuals, it is imperative to diagnose the monogenic forms of DM accurately. Currently, advances in the genetics field has allowed for the recognition of new DM subtypes, which until now were considered to be slight variations of the typical forms. New molecular insights can define therapeutic strategies, aiming for the prevention, correction, or at least delay of β-cell dysfunction. Thus, it is imperative to act in the close interaction between genetics and clinical manifestations to improve diagnosis and individualize treatment.     

Accuracy of FIB-4 to Detect Elevated Liver Stiffness Measurements in Patients with Non-Alcoholic Fatty Liver Disease: A Cross-Sectional Study in Referral Centers

The identification of advanced fibrosis by applying noninvasive tests is still a key component of the diagnostic algorithm of NAFLD. The aim of this study is to assess the concordance between the FIB-4 and liver stiffness measurement (LSM) in patients referred to two liver centers for the ultrasound-based diagnosis of NAFLD. Fibrosis 4 Index for Liver Fibrosis (FIB-4) and LSM were assessed in 1338 patients. A total of 428 (32%) had an LSM ≥ 8 kPa, whereas 699 (52%) and 113 (9%) patients had an FIB-4 < 1.3 and >3.25, respectively. Among 699 patients with an FIB-4 < 1.3, 118 (17%) had an LSM ≥ 8 kPa (false-negative FIB-4). This proportion was higher in patients ≥60 years, with diabetes mellitus (DM), arterial hypertension or a body mass index (BMI) ≥ 27 kg/m². In multiple adjusted models, age ≥ 60 years (odds ratio (OR) = 1.96, 95% confidence interval (CI) 1.19–3.23)), DM (OR = 2.59, 95% CI 1.63–4.13), body mass index (BMI) ≥ 27 kg/m² (OR = 2.17, 95% CI 1.33–3.56) and gamma-glutamyltransferase ≥ 25 UI/L (OR = 2.68, 95% CI 1.49–4.84) were associated with false-negative FIB-4. The proportion of false-negative FIB-4 was 6% in patients with none or one of these risk factors and increased to 16, 31 and 46% among those with two, three and four concomitant risk factors, respectively. FIB-4 is suboptimal to identify patients to refer to liver centers, because about one-fifth may be false negative at FIB-4, having instead an LSM ≥ 8 KPa.     

Pleiotropic Effects of APOB Variants on Lipid Profiles,Metabolic Syndrome,and the Risk of Diabetes Mellitus

Apolipoprotein B (ApoB) plays a crucial role in lipid and lipoprotein metabolism. The effects of APOB locus variants on lipid profiles, metabolic syndrome, and the risk of diabetes mellitus (DM) in Asian populations are unclear. We included 1478 Taiwan Biobank participants with whole-genome sequence (WGS) data and 115,088 TWB participants with Axiom genome-wide CHB array data and subjected them to genotype–phenotype analyses using APOB locus variants. Five APOB nonsynonymous mutations, including Asian-specific rs144467873 and rs13306194 variants, were selected from participants with the WGS data. Using a combination of regional association studies, a linkage disequilibrium map, and multivariate analysis, we revealed that the APOB locus variants rs144467873, rs13306194, and rs1367117 were independently associated with total, low-density lipoprotein (LDL), and non-high-density lipoprotein (non-HDL) cholesterol levels; rs1318006 was associated with HDL cholesterol levels; rs13306194 and rs35131127 were associated with serum triglyceride levels; rs144467873, rs13306194, rs56213756, and rs679899 were associated with remnant cholesterol levels; and rs144467873 and rs4665709 were associated with metabolic syndrome. Mendelian randomization (MR) analyses conducted using weighted genetic risk scores from three or two LDL-cholesterol-level-associated APOB variants revealed significant association with prevalent DM (p = 0.0029 and 8.2 × 10⁻⁵, respectively), which became insignificant after adjustment for LDL-C levels. In conclusion, these results indicate that common and rare APOB variants are independently associated with various lipid levels and metabolic syndrome in Taiwanese individuals. MR analyses supported APOB variants associated with the risk of DM through their associations with LDL cholesterol levels.     

Daily Treatment of Mice with Type 2 Diabetes with Adropin for Four Weeks Improves Glucolipid Profile,Reduces Hepatic Lipid Content and Restores Elevated Hepatic Enzymes in Serum

Adropin is a peptide hormone encoded by Energy Homeostasis Associated gene. Adropin modulates energy homeostasis and metabolism of lipids and carbohydrates. There is growing evidence demonstrating that adropin enhances insulin sensitivity and lowers hyperlipidemia in obese mice. The aim of this study was to investigate the effects of daily administration of adropin for four weeks in mice with experimentally induced type 2 diabetes (T2D). Adropin improved glucose control without modulating insulin sensitivity. Adropin reduced body weight, size of adipocytes, blood levels of triacylglycerol and cholesterol in T2D mice. T2D mice treated with adropin had lower liver mass, reduced hepatic content of triacylglycerol and cholesterol. Furthermore, adropin attenuated elevated blood levels of hepatic enzymes (ALT, AST, GGT and ALP) in T2D mice. In T2D mice, adropin increased the circulating adiponectin level. Adropin had no effects on circulating insulin and glucagon levels and did not alter pancreatic islets morphology. These results suggest that adropin improves glucose control, lipid metabolism and liver functions in T2D. In conjunction with reduced lipid content in hepatocytes, these results render adropin as an interesting candidate in therapy of T2D.     

Effects of Probiotic Supplementation during Pregnancy on the Future Maternal Risk of Metabolic Syndrome

Probiotics are live microorganisms that induce health benefits in the host. Taking probiotics is generally safe and well tolerated by pregnant women and their children. Consumption of probiotics can result in both prophylactic and therapeutic effects. In healthy adult humans, the gut microbiome is stable at the level of the dominant taxa: Bacteroidetes, Firmicutes and Actinobacteria, and has a higher presence of Verrucomicrobia. During pregnancy, an increase in the number of Proteobacteria and Actinobacteria phyla and a decrease in the beneficial species Roseburia intestinalis and Faecalibacterium prausnitzii are observed. Pregnancy is a “window” to the mother’s future health. The aim of this paper is to review studies assessing the potentially beneficial effects of probiotics in preventing the development of diseases that appear during pregnancy, which are currently considered as risk factors for the development of metabolic syndrome, and consequently, reducing the risk of developing maternal metabolic syndrome in the future. The use of probiotics in gestational diabetes mellitus, preeclampsia and excessive gestational weight gain is reviewed. Probiotics are a relatively new intervention that can prevent the development of these disorders during pregnancy, and thus, would reduce the risk of metabolic syndrome resulting from these disorders in the mother’s future.