Assessing Sex-Specific Circadian, Metabolic, and Cognitive Phenotypes in the AβPP/PS1 and APPNL - F/NL - F Models of Alzheimer’s Disease

Background: Circadian disruption has long been recognized as a symptom of Alzheimer’s disease (AD); however, emerging data suggests that circadian dysfunction occurs early on in disease development, potentially preceding any noticeable cognitive deficits. Objective: This study compares the onset of AD in male and female wild type (C57BL6/J), transgenic (AβPP/PS1), and knock-in (APPNL - F/NL - F) AD mouse models from the period of plaque initiation (6 months) through 12 months. Methods: Rhythmic daily activity patterns, glucose sensitivity, cognitive function (Morris water maze, MWM), and AD pathology (plaques formation) were assessed. A comparison was made across sexes. Results: Sex-dependent hyperactivity in AβPP/PS1 mice was observed. In comparison to C57BL/6J animals, 6-month-old male AβPP/PS1 demonstrated nighttime hyperactivity, as did 12-month-old females. Female AβPP/PS1 animals performed significantly worse on a MWM task than AβPP/PS1 males at 12 months and trended toward increased plaque pathology. APPNL - F/NL - F 12-month-old males performed significantly worse on the MWM task compared to 12-month-old females. Significantly greater plaque pathology occurred in AβPP/PS1 animals as compared to APPNL - F/NL - F animals. Female AβPP/PS1 animals performed significantly worse than APPNL - F/NL - F animals in spatial learning and memory tasks, though this was reversed in males. Conclusion: Taken together, this study provides novel insights into baseline sex differences, as well as characterizes baseline diurnal activity variations, in the AβPP/PS1 and APPNL - F/NL - F AD mouse models.

Dependence of field-effect biosensor sensitivity on photo-induced processes in Si and its conductivity type

The effect of photoelectron processes in n-Si and p-Si on the glucose sensitivity of a capacitive field-effect biosensor based on electrolyte/oxide/semiconductor structure was investigated. We obtained that illumination of n-Si/SiO2/PEI structure during the GOx adsorption increases the glucose sensitivity by three times compare to GOx adsorption in the dark. In contrast, p-Si illumination during the GOx adsorption led to a decrease in sensor sensitivity from 2.9 mV/mM to 2.2 mV/mM. The result is explained by a change in the density of immobilized GOx molecules due to a change in the electrostatic forces of attraction under illumination and stabilization of the photo-generated charge on the surface electronic states of the Si/SiO2 and SiO2/PEI interfaces after illumination.

Hydrothermally synthesized Nickel cobalt oxide for bifunctional electrochemical supercapacitor and nonenzymatic glucose biosensor

Herein, various nickel cobalt oxide nanostructures with different Ni concentrations are prepared via hydrothermal route and then calcination process for electrochemical supercapacitor as well as nonenzymatic glucose biosensor. The electrode synthesized on carbon cloth using Ni0.9Co2.1O4 nanosheet-like morphology showed a maximum 516.51 F g−1 specific capacitance at 10 mV s−1 scan rate and the cyclic stability of 87.7% over 2000 GCD cycles. The electrode prepared with Ni0.3Co2.7O4 on CC offered a linear response from 0 to 0.3 mM glucose concentration and exhibited a maximum of 759.5 µA mM−1 cm−2 glucose sensitivity.

Momordica charantia nanoparticles promote mitochondria biogenesis in the pancreas of diabetic-induced rats: gene expression study

Background Mitochondria dysfunction is one of the clinical features of diabetes mellitus (DM), which is a hallmark of insulin resistance (IR). This study investigates the therapeutic effect of Momordica charantia nanoparticles on mitochondria biogenesis in diabetic-induced rats. Forty-two adult wistar rats (average weight of 189 ± 10.32) were grouped as follows: STZ (65 mg/kg), control group, STZ + silver nitrate (10 mg/kg), STZ + M. charantia silver nanoparticles (50 mg/kg), STZ + metformin (100 mg/kg), and STZ + M. charantia aqueous extract (100 mg/kg). DM was induced intraperitoneal using freshly prepared solution of STZ (65 mg/kg), and rats with fasting blood sugar (FBS) above 250 mg/dl after 72 h of induction were considered diabetic. Treatment started after the third day of induction and lasted for 11 days. Effect of M. charantia nanoparticles on glucose level and pancreatic expression of genes involved in mitochondria biogenesis (PGC-1α, AMPK, GSK-3β, PPARϒ), inflammation (IL-1B, TNFα) and glucose sensitivity (PI3K, AKT, PTEN Insulin and Glut2) were quantified using reverse-transcriptase polymerase chain reaction (RT-PCR). Results The results showed that M. charantia nanoparticles promote mitochondria biogenesis, glucose sensitivity and reverse inflammation in the pancreas of diabetes rat model through upregulation of PGC-1α, AMPK, PPARϒ, AKT, Insulin and Glut2 mRNA expression and downregulation of GSK-3β, PI3K, IL-1B and TNFα mRNA expression in the pancreas of diabetic rats. Conclusion This study thus concludes that M. charantia nanoparticles may provide effective therapeutics against mitochondria dysfunction in the pancreas of diabetic model.

Skeletal Muscle O-GlcNAc Transferase Action on Global Metabolism Is Partially Mediated Through Interleukin-15

Besides its roles in locomotion and thermogenesis, skeletal muscle plays a significant role in global glucose metabolism and insulin sensitivity through complex nutrient sensing networks. Our previous work showed that the muscle-specific ablation of O-GlcNAc transferase (OGT) led to a lean phenotype through enhanced interleukin-15 (IL-15) expression. We also showed OGT epigenetically modified and repressed the Il15 promoter. However, whether there is a causal relationship between OGT ablation-induced IL-15 secretion and the lean phenotype remains unknown. To address this question, we generated muscle specific OGT and interleukin-15 receptor alpha subunit (IL-15rα) double knockout mice (mDKO). Deletion of IL-15rα in skeletal muscle impaired IL-15 secretion. When fed with a high-fat diet, mDKO mice were no longer protected against HFD-induced obesity compared to wild-type mice. After 22 weeks of HFD feeding, mDKO mice had an intermediate body weight and glucose sensitivity compared to wild-type and OGT knockout mice. Taken together, these data suggest that OGT action is partially mediated by muscle IL-15 production and provides some clarity into how disrupting the O-GlcNAc nutrient signaling pathway leads to a lean phenotype. Further, our work suggests that interfering with the OGT-IL15 nutrient sensing axis may provide a new avenue for combating obesity and metabolic disorders.

Respiratory Parameters for the Classification of Dysfunctional Insulin Secretion by Pancreatic Islets

The development of obesity and type 2 diabetes (T2D) has been associated with impaired mitochondrial function. In pancreatic beta (β) cells, mitochondrial energy metabolism plays a central role in triggering and controlling glucose-stimulated insulin secretion (GSIS). Here, we have explored whether mitochondrial bioenergetic parameters assessed with Seahorse extracellular flux technology can quantitatively predict insulin secretion. We metabolically stressed male C57BL/6 mice by high-fat feeding (HFD) and measured the glucose sensitivity of islet respiration and insulin secretion. The diet-induced obese (DIO) mice developed hyperinsulinemia, but no pathological secretory differences were apparent between isolated DIO and chow islets. Real-time extracellular flux analysis, however, revealed a lower respiratory sensitivity to glucose in DIO islets. Correlation of insulin secretion with respiratory parameters uncovers compromised insulin secretion in DIO islets by oxidative power. Normalization to increased insulin contents during DIO improves the quantitative relation between GSIS and respiration, allowing to classify dysfunctional properties of pancreatic insulin secretion, and thereby serving as valuable biomarker for pancreatic islet glucose responsiveness and health.

Ethylene reduces glucose sensitivity and reverses photosynthetic repression through optimization of glutathione production in salt-stressed wheat (Triticum aestivum L.)

Ethylene plays a crucial role throughout the life cycle of plants under optimal and stressful environments. The present study reports the involvement of exogenously sourced ethylene (as ethephon; 2-chloroethyl phosphonic acid) in the protection of the photosynthetic activity from glucose (Glu) sensitivity through its influence on the antioxidant system for adaptation of wheat (Triticum aestivum L.) plants under salt stress. Ten-day-old plants were subjected to control and 100 mM NaCl and treated with 200 µl L−1 ethephon on foliage at 20 days after seed sowing individually or in combination with 6% Glu. Plants receiving ethylene exhibited higher growth and photosynthesis through reduced Glu sensitivity in the presence of salt stress. Moreover, ethylene-induced reduced glutathione (GSH) production resulted in increased psbA and psbB expression to protect PSII activity and photosynthesis under salt stress. The use of buthionine sulfoximine (BSO), GSH biosynthesis inhibitor, substantiated the involvement of ethylene-induced GSH in the reversal of Glu-mediated photosynthetic repression in salt-stressed plants. It was suggested that ethylene increased the utilization of Glu under salt stress through its influence on photosynthetic potential and sink strength and reduced the Glu-mediated repression of photosynthesis.

Nanoparticles Prepared From Pterostilbene (PTE): A New Strategy for Reducing Blood Glucose and Improving Diabetic Complications

Aim: New envisions are put forward on the cross application of plant extracts and biomaterials, especially new conjectures are put forward on glucose lowering nanodrug delivery systems.Study design and methods: In this study, pterostilbene (PTE) was esterified with acryloyl chloride firstly, and then 3-acrylamidophenyl boric acid (AAPBA) and PTE esterified by acryloyl chloride were copolymerized into p(AAPBA-b-PTE). The characterization and structure of its polymer were examined. Additionally, p(AAPBA-b-PTE) nanoparticles and insulin loaded p(AAPBA-b-PTE) nanoparticles were prepared. The properties of pH, temperature and glucose sensitivity were investigated. And tested the drug loading and release of NPs. The nanoparticle toxicity was observed through cell and animal experiments, and the nanoparticle biodegradation process under physiological conditions was also observed. Finally, the effects of NPs on reducing blood sugar, antioxidation and improving micro inflammation were investigated in vivo.Results: Based on PTE, we successfully synthesized p(AAPBA-b-PTE) NPs. The NPs were basically round in shape with sizes between 150 and 250 nm. It has good pH and glucose sensitivity. The entrapment efficiency (EE) of insulin loaded NPs is about 56%, and the drug loading (LC) is about 13%. The highest release of insulin was 70%, and the highest release of PTE was 85%. Meanwhile, the insulin could undergo self-regulation according to the change of glucose concentration, thus achieving an effective and sustained release. Both in vivo and in vitro experiments showed that the NPs were safe and nontoxic. Under physiological conditions, it can be completely degraded within 40 days. Fourteen days after the mice were injected with p(AAPBA-b-PTE) NPs, there were no obvious abnormalities in the heart, liver, spleen, lung, and kidney. Moreover, the NPs can effectively reduce blood glucose, improve the antioxidant capacity and improve the micro inflammation status in mice.Conclusions: Using PTE as raw material, p(AAPBA-b-PTE) NPs were successfully prepared, which can effectively reduce blood glucose, improve antioxidant capacity, and reduce inflammatory response. It provided a new way for the combination of plant extracts and biomaterials to regulate and treat diseases through NPs or other dosage forms.