Oxidative Fibers Research Articles

Celecoxib Enhances Oxidative Muscle Fibre Formation and Improves Muscle Functions Through Prokr1 Activation in Mice.

Muscle diseases are serious challenges to human health. Prokineticin receptor 1 (PROKR1) has emerged as a potential target to improve muscle function through increasing oxidative muscle fibres, but there are no clinically applicable synthetic PROKR1 agonists. Drugs with biological properties of prokineticin 2 (PK2) were discovered through connectivity map (CMap) analysis. Their effects on PROKR1 were evaluated using molecular docking, PROKR1 signalling and competitive binding assays. Pregnant dams were fed diets containing varying celecoxib concentrations (0, 500, 1000 and 1500 ppm) from gestation day 5 through weaning. Offspring were given high-fat diets (HFD) from weaning until 20 weeks old, and body composition, insulin resistance, energy expenditure, exercise performance and histological analysis of muscle tissues were evaluated. Celecoxib, with a connectivity score of 64.19 to PK2 and a docking score of -9.0 to PROKR1, selectively activated Gs signalling at 4 μM of EC50 and increased NR4A2 protein levels by 1.6-fold (p < 0.01) in PROKR1-overexpressing cells. It competitively inhibited PK2 binding to PROKR1 and reduced cAMP accumulation. In murine and human myotubes, celecoxib increased Prokr1 protein levels by 1.8-fold (p < 0.05), pCreb by 1.5-fold (p < 0.05) and Nr4a2 by 1.3-fold (p < 0.05). It also elevated Myh7 index by 2.2-fold (p < 0.0001), mitochondrial content by 1.6-fold (p < 0.001) and fatty acid oxidation (FAO) activity by 4.1-fold (p < 0.05). Offspring exposed to celecoxib during pre- and postnatal muscle development exhibited activated Prokr1 signalling, enhanced oxidative muscle fibre formation and improved muscle phenotype despite HFD. At weaning, both male and female offspring showed dose-dependent increases in lean mass (> 9.35%, p < 0.001) and grip strength (< 18.0%, p < 0.01). At 12 weeks old, mice displayed a dose-dependent decrease in weight loss (> 13.3%, p < 0.05), increased lean mass (> 16.2%, p < 0.05), improved insulin resistance (> 70.4%, p < 0.0001), energy expenditure (> 173%, p < 0.0001) and grip strength (> 23.5%, p < 0.001). Celecoxib also increased Myh7-positive muscle fibre composition (> 10.8%, p < 0.05) and mitochondrial mass (> 32.8%, p < 0.05) in the gastrocnemius and soleus muscles, accompanied by significant Prokr1 signalling activation. These effects persisted in both male and female mice at 20 weeks old. Celecoxib shows promise as a PROKR1 agonist and clinically applicable exercise mimetic for the treatment of muscular disorders.

Melatonin induces fiber switching by improvement of mitochondrial oxidative capacity and function via NRF2/RCAN/MEF2 in the vastus lateralis muscle from both sex Zücker diabetic fatty rats.

The positive role of melatonin in obesity control and skeletal muscle (SKM) preservation is well known. We recently showed that melatonin improves vastus lateralis muscle (VL) fiber oxidative phenotype. However, fiber type characterization, mitochondrial function, and molecular mechanisms that underlie VL fiber switching by melatonin are still undefined. Our study aims to investigate whether melatonin induces fiber switching by NRF2/RCAN/MEF2 pathway activation and mitochondrial oxidative metabolism modulation in the VL of both sex Zücker diabetic fatty (ZDF) rats. 5-Weeks-old male and female ZDF rats (N=16) and their age-matched lean littermates (ZL) were subdivided into two subgroups: control (C) and orally treated with melatonin (M) (10mg/kg/day) for 12 weeks. Interestingly, melatonin increased oxidative fibers amounts (Types I and IIa) counteracting the decreased levels found in the VL of obese-diabetic rats, and upregulated NRF2, calcineurin and MEF2 expression. Melatonin also restored the mitochondrial oxidative capacity increasing the respiratory control ratio (RCR) in both sex and phenotype rats through the reduction of the proton leak component of respiration (state 4). Melatonin also improved the VL mitochondrial phosphorylation coefficient and modulated the total oxygen consumption by enhancing complex I, III and IV activity, and fatty acid oxidation (FAO) in both sex obese-diabetic rats, decreasing in male and increasing in female the complex II oxygen consumption. These findings suggest that melatonin treatment induces fiber switching in SKM improving mitochondrial functionality by NRF2/RCAN/MEF2 pathway activation.

The AMPK allosteric activator MK-8722 improves thehistology and spliceopathy in myotonic dystrophy type1(DM1) skeletal muscle.

Multiple signaling pathways have been reported to be altered in Myotonic Dystrophy type 1 (DM1) skeletal muscle, contributing to pathogenicity. In particular, previous work established that AMPK signaling, a key sensor of energy metabolism, is repressed in DM1 mouse muscle and that activating AMPK through exercise and/or with pharmacological activators is beneficial for the DM1 muscle phenotype. Here, we explored the effects of a newer, more specific allosteric AMPK activator acting directly on AMPK. We treated male and female HSALR mice for 1 and 4 weeks with a daily injection of the allosteric activator MK-8722, the AMP mimetic AICAR, or vehicle. Our results show that 1 and 4 weeks of treatment with MK-8722 improves alternative splicing toward wild-type levels in male and female HSALR muscle. However, the effects of MK-8722 were more modest compared to AICAR. In contrast, 4 weeks of treatment with MK-8722 improved muscle histology to a greater extent than AICAR. As expected with AMPK activation, 4 weeks of treatment with MK-8722 and AICAR promoted the expression of slower, more oxidative fibers. Finally, acute injections of MK-8722 and AICAR triggered the rapid and transient increase in phospho-AMPK in muscle. However, the peak of AMPK phosphorylation was lower with MK-8722 compared to AICAR, thereby explaining the more modest effects of AMPK allosteric activation. Altogether, our data demonstrate that chronic activation of AMPK with specific pharmacological activators is beneficial for the DM1 muscle. They further indicate that at least a portion of the beneficial effects seen following the administration of these drugs occurs through AMPK.

Molecular pathways involved in the control of contractile and metabolic properties of skeletal muscle fibers as potential therapeutic targets for Duchenne muscular dystrophy

Duchenne muscular dystrophy (DMD) is caused by mutations in the gene encoding dystrophin, a subsarcolemmal protein whose absence results in increased susceptibility of the muscle fiber membrane to contraction-induced injury. This results in increased calcium influx, oxidative stress, and mitochondrial dysfunction, leading to chronic inflammation, myofiber degeneration, and reduced muscle regenerative capacity. Fast glycolytic muscle fibers have been shown to be more vulnerable to mechanical stress than slow oxidative fibers in both DMD patients and DMD mouse models. Therefore, remodeling skeletal muscle toward a slower, more oxidative phenotype may represent a relevant therapeutic approach to protect dystrophic muscles from deterioration and improve the effectiveness of gene and cell-based therapies. The resistance of slow, oxidative myofibers to DMD pathology is attributed, in part, to their higher expression of Utrophin; there are, however, other characteristics of slow, oxidative fibers that might contribute to their enhanced resistance to injury, including reduced contractile speed, resistance to fatigue, increased capillary density, higher mitochondrial activity, decreased cellular energy requirements. This review focuses on signaling pathways and regulatory factors whose genetic or pharmacologic modulation has been shown to ameliorate the dystrophic pathology in preclinical models of DMD while promoting skeletal muscle fiber transition towards a slower more oxidative phenotype.

An investigation on the electromagnetic wave absorbing performance and corrosion resistance of carbonyl iron powder/epoxy coatings modified by ferrosoferric oxide and basalt fibers.

With the development of science and technology, there is a great demand for electromagnetic wave absorbing materials for both military and civilian purposes. Among them, carbonyl iron powder (CIP) has attracted a lot of attention due to its mature production system and good electromagnetic wave loss capability. However, the application of CIP is limited due to poor impedance matching, poor corrosion resistance, and poor oxidation resistance. Based on this, in this work, CIP and basalt fibers (BF) were used and flower-like ferrosoferric oxide (Fe3O4) was generated in situ on their surfaces by hydrothermal method. The results showed that the generation of Fe3O4 with the addition of BF greatly optimized the impedance matching of the CIP. The modified CIP had a minimum reflection loss of -51.09GHz, corresponding to an effective absorption bandwidth (<-10dB) of 6.16GHz, fully covering the Ku-band with just a 1.5mm coating thickness. Thanks to the protective effect of Fe3O4, the oxidation weight gain temperature of the modified CIP powder in air was increased from 240°C to 500°C, showing good thermal stability and oxidation resistance. In addition, the corrosion resistance of the coating was tested and analyzed using electrochemical impedance spectroscopy (EIS). The results showed that the impedance modulus of the coating at 0.01Hz was enhanced by one order of magnitude from 106Ω·cm2 to 107Ω·cm2. Finally, the radar cross section (RCS) of the material was simulated using CTS software to further evaluate the wave absorption properties.

Effect of matrix microstructure on micro- and macro- mechanical properties of 2.5D woven oxide fiber reinforced oxide matrix composites

A comprehensive learning of the mechanical behavior change mechanism of oxide/oxide composites is of great significance as a guide for their industrial applications. This study focused on examining how matrix microstructure impacted the micro- and macro- mechanical properties of the composites mainly by nanoindentation tests, macro-mechanical tests and x-ray computed tomography. The results showed that the sintering phenomenon of matrix sintered at 1200 ºC was more obvious, and there were visible transverse and longitudinal cracks. The in-situ modulus of matrix and interfacial shear modulus of the composite increased by 61.1% and 36.4%, respectively, with the increase of matrix sintering densification. Combined with these micro-mechanical parameters of the composites, the He-Hutchinson model predicted the same crack propagation modes as those obtained from fracture toughness tests. Moreover, more matrix cracks directly led to a 45.4% reduction in the flexural strength of the composites sintered at 1200 ºC compared to that sintered at 1100 ºC. In addition, a comparison analysis was conducted on the evolution of microstructure, micro- and macro- mechanical properties of 2.5D and 2D composites with the same preparation parameters.

Highly Conductive Deformation-Free Reduced Graphene Oxide Fibers : Towards High-Performance Wearable Supercapacitors

Solution-processed graphene fiber has been introduced by a wet spinning process of liquid crystal (LC) graphene oxide because of its strong hydrogen bonding and self-assembled layered structures with nematic phases. Substantially, graphene oxide (GO) solidified with layered structures in a coagulation bath. The LC-spun GO fibers generally have highly stacked and layered structures and are uneven along the fiber axis. However, due to the insulating properties of GO fiber, a reduction process should be introduced for a practical approach. Following the chemical reduction process, the LC-spun GO fiber has abundant and irregular structural deformation on the core and shell in fiber due to significant volume shrinkage. It has poor electrical conductivity, low specific surface area, and weak mechanical properties for applying high-performance supercapacitors.Herein, we introduce deformation-free graphene fiber by extruding reduced graphene oxide (rGO) and GO hybridization. This is also used in the conventional wet spinning processes. The rGO-GO hybrid dope is a possible candidate for applying porous graphene fiber with high electrical conductivity, effective surface area, and proper mechanical strength. In addition, the rGO has high electrical conductivity with low defect sites. The fabrication method is based on modified Brodie method which generates quasi-defect-free reduced graphene oxide as introduced previous work. In particular, against LC-spun GO spinning, high-quality rGO-GO dope reveals that the rGO minimizes the self-assembly of GO and adjusts the imbibition ratio simultaneously for rapid dope solvent-coagulation exchange on extruding the graphene fiber. In addition, chemically stable rGO plays a role in a frame for supporting the fiber structure after the reduction process without the deformation of core and shell structures. Despite porous rGO-GO fiber, the significantly high circularity and effective porosity could enhance electrical conductivity (~654 S/cm, after drawing) and capacitance of supercapacitors. The graphene fiber can be applicable for wearable energy storage devices with high performance.

Muscle type-specific effects of bilateral abobotulinumtoxinA injection on muscle growth and contractile function in spastic mice.

Intramuscular injection of botulinum neurotoxin type A (BoNT-A) is commonly used to improve or maintain the joint range of motion in young children with spasticity. However, the effectiveness of BoNT-A treatment is variable and movement limitations are recurrent. Here we show long-term effects of a single, bilateral abobotulinumtoxinA (aboBoNT-A) injection in the gastrocnemius medialis and soleus muscles of wild-type and spastic (B6.Cg-Glrbspa/J with a mutation in the glycine receptor) mice at a young age (6-7 days). Specifically, we evaluated the impact of aboBoNT-A-A on gait, physical performance, and spontaneous physical behavior, as well as on contractile force characteristics, morphology, and histological phenotype of soleus and gastrocnemius muscles by comparing their results to those of saline-injected controls up to 9 weeks after the injection. The detailed time course of the study specifies the timing of the aboBoNT-A injection at 1 week, the period of behavioral studies from 4-9 weeks, and the age of the mice (10 weeks) at the time of contractile force characteristics and histology assessments. In spastic mice, aboBoNT-A injection had a minor and very specific effect on physical performance, by only modestly increasing stride length as a function of age. aboBoNT-A injection caused a reduction in the force-generating capacity and a slightly smaller physiological cross-sectional area in gastrocnemius medialis, but not in soleus. Reduced physiological cross-sectional area in aboBoNT-A-injected muscles was due to a lower number of muscle fibers, rather than reduced muscle fiber cross-sectional area. The percentage of slow-type muscle fibers and mitochondrial succinate dehydrogenase activity were increased, which was associated with an improved muscle endurance capacity. In conclusion, aboBoNT-A injection reduced the number of muscle fibers, causing muscle hypertrophy in remaining fibers and a shift towards more oxidative fibers, resulting in an improved endurance capacity and gait. This study proposed potential cellular mechanisms for the therapeutic efficacy of aboBoNT-A in spasticity.

Longissimus from Berkshire pigs in a small-scale supply chain have increased oxidative metabolism, tenderness and water-holding capacity, compared with Large White × Landrace pigs in a modern commercial supply chain

Context Selection for leanness in the modern Australian pig has resulted in inconsistent quality, including a lack of pork tenderisation during ageing. Inconsistent quality is potentially a result of differences in supply chain and breed as well as the variation in muscle fibre-type proportion in pork longissimus. Aim The aim was to investigate differences in fibre-type proportion and pork quality between Large White-Landrace pigs in a large supply chain and Berkshire pigs processed in a small supply chain. Methods Pigs (n = 22) from two suppliers with different breeds (Supplier 1, Large White × Landrace, SC1-LWLR, n = 12, modern commercial pigs; Supplier 2, Berkshire, SC2-Berk, n = 10, heritage pigs) were slaughtered and samples from the longissimus were extracted at 3, 24, and 48 h postmortem for enzyme and pH analyses. Longissimus samples were subjected to ageing for either 2 or 16 days postmortem (Day 2, Day 16), assessed for colour, muscle fibre-type proportion (%), muscle fibre diameter (μm), water-holding capacity (purge, % and cook loss, %), Warner–Bratzler peak shear force (WBSF, N), and protein denaturation temperature using differential scanning calorimetry (DSC, peak temperature, °C). Key results SC1-LWLR had higher purge than SC2-Berk (2.85% and 1.83% respectively; standard error of the difference (SED) = 0.33; P = 0.003), higher cook loss on Day 16 (24.63% and 16.79% respectively; SED = 1.62; P = 0.017) and higher WBSF on Day 2 and Day 16 (Day 2, 30.9 N and 26.7 N respectively; Day 16, 28.6 N and 22.0 N respectively; SED = 0.98, interaction P = 0.003). SC1-LWLR had a lower proportion of Type I (10.1% vs 16.0%; SED = 0.51) and Type IIA (14.0% vs 22.0%; SED = 0.77) and a higher proportion of Type IIB (75.9% vs 62.0%; SED = 0.74) (P &lt; 0.001 for all) fibres. SC1-LWLR had lower DSC temperatures for two peaks. SC2-Berk had higher citrate synthase activity (P = 0.003) and glycolytic potential (P &lt; 0.001) than SC1-LWLR. Conclusions SC2-Berk longissimus had improved quality compared with SC1-LWLR pork, most likely owing, in part, to higher proportion of oxidative and intermediate fibres in the Berkshires. However, effects of differences in environmental conditions and/or processing conditions cannot be ruled out. Implications The experiment increased our understanding of how variation in supply chains and muscle fibre-type proportion can impact the production of consistently high-quality pork.

Multi-sensing yarns for continuous wireless sweat lactate monitoring

Textile integrated sensors based on conductive, electrochemically active microfibers can enable inexpensive, nearly invisible distributed sensing of sweat in clothing. Reduced graphene oxide fibers are mechanically robust, conductive, and can be easily functionalized to form a variety of sensors with properties comparable to planar fabricated sensors, given their ability to work both as electrical interconnections and as a base electrode. Here, we present an electrochemical yarn based on modified dry-spun reduced graphene oxide fibers. This braided format contains reference, counter electrode, a lactate-responsive fiber functionalized with lactate oxidase, and a pH-sensing fiber for calibration in a single, robust, weavable format. This electrochemical yarn was integrated into a demonstrator wearable textile-patch capable of continuous data collection and wireless data transmitted to an ad-hoc app. The yarns perform comparably to traditional probes in a format of broad utility for standalone or integrated monitoring of physiological parameters.

The sodium/ascorbic acid co-transporter SVCT2 distributes in a striated membrane-enriched domain at the M-band level in slow-twitch skeletal muscle fibers

BackgroundVitamin C plays key roles in cellular homeostasis, functioning as a potent antioxidant and a positive regulator of cell differentiation. In skeletal muscle, the vitamin C/sodium co-transporter SVCT2 is preferentially expressed in oxidative slow fibers. SVCT2 is up-regulated during the early fusion of primary myoblasts and decreases during initial myotube growth, indicating the relevance of vitamin C uptake via SVCT2 for early skeletal muscle differentiation and fiber-type definition. However, our understanding of SVCT2 expression and function in adult skeletal muscles is still limited.ResultsIn this study, we demonstrate that SVCT2 exhibits an intracellular distribution in chicken slow skeletal muscles, following a highly organized striated pattern. A similar distribution was observed in human muscle samples, chicken cultured myotubes, and isolated mouse myofibers. Immunohistochemical analyses, combined with biochemical cell fractionation experiments, reveal a strong co-localization of SVCT2 with intracellular detergent-soluble membrane fractions at the central sarcomeric M-band, where it co-solubilizes with sarcoplasmic reticulum proteins. Remarkably, electrical stimulation of cultured myofibers induces the redistribution of SVCT2 into a vesicular pattern.ConclusionsOur results provide novel insights into the dynamic roles of SVCT2 in different intracellular compartments in response to functional demands.

Rapid prediction of electrohydrodynamically printed polyethylene oxide (PEO) fiber width by using response surface methodology

Rapid prediction of electrohydrodynamically printed polyethylene oxide (PEO) fiber width by using response surface methodology

Sodium danshensu modulates skeletal muscle fiber type formation and metabolism by inhibiting pyruvate kinase M1.

Sodium Danshensu (SDSS) is extracted from Salvia miltiorrhiza and has many pharmacological effects. However, little is known about its effects on muscle fiber formation and metabolism. Here, we aimed to investigated the role and molecular mechanisms of SDSS in modulating the formation of skeletal muscle fiber. C2C12 cells were incubated in differentiation medium with or without SDSS for 4days. C57BL/6 mice were orally administered SDSS by gavage once a day for 8weeks. Grip strength, treadmill, muscle weight, western blotting, qPCR, immunofluorescence staining and H&E staining were performed. SDSS target proteins were searched through drug affinity responsive target stability (DARTS) and mass spectrometry analysis. Furthermore, molecular docking was carried out for Pyruvate kinase M1 (PKM1). The effect of PKM1 on myosin heavy chain (MyHCs) gene expression was verified by knockdown of PKM1 experiment. SDSS induced oxidative muscle fiber-related gene expression, and inhibited glycolytic fiber-related gene expression in C2C12 cells. Muscle mass, the percentage of slow oxidative fibers, succinic dehydrogenase activity, muscle endurance, glucose tolerance, and the expression of the MyHC1 and MyHC2a genes increased while MyHC2b expression, lactate dehydrogenase activity, and the percentage of glycolytic muscle fibers decreased in SDSS-treated mice. Mechanistically, SDSS bound to the pyruvate kinase PKM1 and significantly repressed its activity. PKM1 inhibited MyHC1 and MyHC2a expression but promoted MyHC2b expression. SDSS also significantly attenuated the effects of PKM1 on muscle fiber-related gene expression in C2C12 cells. Our findings indicate that SDSS promotes muscle fiber transformation from the glycolytic type to the oxidative type by inhibiting PKM1 activity, which provide a new idea for treating muscle atrophy, muscle metabolism diseases and improving animal meat production.

Sol-gel synthesized flexible Na2Ti6O13–aluminium oxide fibres for photocatalytic degradation of Acid red 1

Sodium titanate (Na2Ti6O13; NTO) was loaded onto aluminium oxide fibres (AFs) using the sol–gel method to synthesize NTO/AF fibres. The surface roughness of NTO/AF-n fibres increased with increasing number of dip-coating cycles (n = 1–3). The Fourier transform infrared spectra and X-ray photoelectron spectroscopy spectra of NTO/AF-n demonstrated the loading of NTO onto AF. The bandgap energies of NTO/AF-1, NTO/AF-2, NTO/AF-3 and NTO were determined to be 3.08, 3.12, 3.38 and 3.45 eV, respectively. The production of hydroxyl radicals by fibres under irradiation decreased in the order of NTO, NTO/AF-1, NTO/AF-2 and NTO/AF-3. NTO/AF-n fibres were designed for convenient separation from water, with NTO/AF-1 exhibiting the highest activity among the NTO/AF-n samples. The photocatalytic degradation efficiencies of NTO/AF-1, NTO/AF-2 and NTO/AF-3 after 30 min of reaction were determined to be 61.4 %, 51.7 % and 44.3 %, respectively. Complete removal of Acid Red 1 from the solution was achieved through a photocatalytic reaction using NTO/AF-n. The activity of NTO/AF-n samples remained stable over five reaction cycles, indicating their application potential for large-scale water treatment.

Pork quality and histological properties of longissimus muscle from boars and early and late immunocastrated pigs

Immunocastration has been introduced in pig production to reduce boar taint. However, there is not much information on how different schedule of immunocastration affects meat quality, especially muscle histological properties. In this study, carcass and meat quality characteristics, histological properties of the longissimus dorsi muscle, sensory characteristics and fatty acid composition of meat and fat from entire males (EM), late immunocastrated (LIC, first dose 8 weeks before slaughter, second dose 4 weeks before slaughter) and early immunocastrated pigs (EIC, first dose 13 weeks before slaughter, second dose 8 weeks before slaughter) were compared. Fat thickness was greater in EIC than in LIC and EM. Meat quality parameters differed mainly between EIC and EM, as EIC had a higher pH 45, lower electrical conductivity, lighter and more yellowish loins and lower drip loss than EM. EM had a higher protein and moisture content and a lower fat content than EIC and LIC. No major effect on histological properties was observed, however, the percentage of fast-twitch oxidative fibres tended to be lower in both LIC and EIC animals compared to EM. Pork from EM had higher boar taint and lower pork odour and flavour scores and higher pig and boar taint flavour scores. The results of this study show that the immunocastration schedule influences some carcass, meat and fat quality traits and, because of that, it can be modified to obtain the desired final product.

Fine-Grain High-Performance Densified Oxide Fibers Produced by Open Ultrafast High-Temperature Sintering.

The considerable grain growth occurring during the long-term high-temperature sintering of polycrystalline oxide fibers negatively affects their mechanical properties, which highlights the need for alternative sintering methods. Herein, open ultrafast high-temperature sintering (OUHS) in air, characterized by rapid heating/cooling (>10000 K min-1) and a short high-temperature holding time (<10 s), is used to produce 3 mol% yttria-stabilized zirconia continuous fibers with coherent boundaries forming robust connections between fine grains. The tensile strength of these fibers (2.33GPa on average, sintering temperature = 1673 K) notably exceeds that of their counterparts produced by traditional sintering (1.17GPa). The effects of pores on fiber mechanicalproperties are analyzed using experimental and theoretical methods. For a versatility demonstration, OUHS is applied to several types of polycrystalline oxide fibers (HfO2, Al2O3, TiO2, Y2O3, and La2Zr2O7), considerably improving their mechanical properties and enabling crystalline phase control, which demonstrates the suitability of this procedure for the development of high-performance materials.

Copper(II) succinate: electrochemical synthesis, characterization and application as a precursor for micron-sized copper(II) oxide fibers

A coordination compound of copper(II) with succinic acid was obtained by electrochemical synthesis in media of various compositions. The samples were characterized by methods of quantitative analysis, ESR and IR spectroscopy, synchronous thermal analysis. The vibrational frequencies of copper(II) succinate were calculated by using DFT and the experimental IR spectra were interpreted on the basis of the results. Micro-sized copper(II) oxide fibers were obtained by thermal decomposition of synthesized samples. It was shown that the use of the water–dimethyl sulfoxide system with a volume ratio 1:1 is optimal to achieve the formation of moderately aggregated particles with a distinct filamentous morphology.

Inhibition of CILP2 Improves Glucose Metabolism and Mitochondrial Dysfunction in Sarcopenia via the Wnt Signalling Pathway.

Skeletal muscle is the primary organ involved in insulin-mediated glucose metabolism. Elevated levels of CILP2 are a significant indicator of impaired glucose tolerance and are predominantly expressed in skeletal muscle. It remains unclear whether CILP2 contributes to age-related muscle atrophy through regulating the glucose homeostasis and insulin sensitivity. Initially, the expression levels of CILP2 were assessed in elderly mice and patients with sarcopenia. Lentiviral vectors were used to induce either silencing or overexpression of CILP2 in C2C12 myoblast cells. The effects of CILP2 on proliferation, myogenic differentiation, insulin sensitivity and glucose uptake were evaluated using immunofluorescence, western blotting, real-time quantitative polymerase chain reaction, RNA sequencing, glucose uptake experiments, dual-luciferase reporter assays and co-immunoprecipitation (CO-IP). An adeno-associated virus-9 containing a muscle-specific promoter was injected into SAMP8 senile mice to observe the efficacy of CILP2 knockout. We found that there was more CLIP2 expressed in the skeletal muscle of ageing mice (+1.1-fold, p < 0.01) and in patients with sarcopenia (+2.5-fold, p < 0.01) compared to the control group. Following the overexpression of CILP2, Ki67 (-65%, p < 0.01), PCNA (-32%, p < 0.05), MyoD1 (-89%, p < 0.001), MyoG (-31%, p < 0.05) and MyHC (-85%, p < 0.001), which indicate proliferation and differentiation potential, were significantly reduced. In contrast, MuRF-1 (+59%, p < 0.05), atrogin-1 (+43%, p < 0.05) and myostatin (+31%, p < 0.05), the markers of muscular atrophy, were significantly increased. Overexpression of CILP2 decreased insulin sensitivity, glucose uptake (-18%, p < 0.001), GLUT4 translocation to the membrane and the maximum respiratory capacity of mitochondria. Canonical Wnt signalling was identified through RNA sequencing as a potential pathway for CILP2 regulation in C2C12, and Wnt3a was confirmed as an interacting protein of CILP2 in the CO-IP assay. The addition of recombinant Wnt3a protein reversed the inhibitory effects on myogenesis and glucose metabolism caused by CILP2 overexpression. Conversely, CILP2 knockdown promoted myogenesis and glucose metabolism. CILP2 knockdown improved muscle atrophy in mice, characterized by significant increases in time to exhaustion (+42%, p < 0.001), grip strength (+19%, p < 0.01), muscle mass (+15%, p < 0.001) and mean muscle cross-sectional area (+37%, p < 0.01). CILP2 knockdown enhanced glycogen synthesis (+83%, p < 0.001) and the regeneration of oxidative and glycolytic muscle fibres in SAMP8 ageing mice via the Wnt/β-catenin signalling pathway. Our results indicate that CILP2 interacts with Wnt3a to suppress the Wnt/β-catenin signalling pathway and its downstream cascade, leading to impaired insulin sensitivity and glucose metabolism in skeletal muscle. Targeting CILP2 inhibition could offer potential therapeutic benefits for sarcopenia.

A biodegradable bi‐layer nano fibrous membrane fabricated by centrifugal spinning for active food packaging

AbstractTo solve the problem of cytotoxicity for most antimicrobial agents loaded in packaging materials, we developed a novel bi‐layer fibrous membrane by using centrifugal spinning, which of the outer layer was submicron native potato starch/polyvinyl alcohol (ST/PVA) composite fibers loaded with ZnO nanoparticles (ZnO NPs) for providing high antibacterial activity. The inner layer was nano‐based calcium alginate/polyethylene oxide (CA/PEO) fiber for providing excellent biocompatibility. The addition of ZnO caused the semicrystalline structures of ST/PVA fibers, while the CA/PEO fibers were shown semicrystalline structures due to the PEO. Fourier transform infrared indicated that posttreatment had not effect on the structures of ST/PVA/ZnO fiber, but the structure of CA/PEO fibers were affected by interaction between COO groups of alginate and Ca2+ ions. The results of mechanical property demonstrated that CA/PEO fibers showed highest stress of 3.83 ± 0.25 MPa and helpful for improving the stress of bi‐layer fibrous membrane. The obtained fibrous membrane had excellent antibacterial property with diameters of bacteriostatic zone against E. coli and S. aureus of 20.5 and 21.5 mm, respectively. On this basis, the shelf life of strawberry was improved up to 6th day by inhibit the growth of microorganisms, which indicated that the obtained fibrous membrane showed great potential for food packaging.

Cell transplantation-mediated dystrophin supplementation efficacy in Duchenne muscular dystrophy mouse motor function improvement demonstrated by enhanced skeletal muscle fatigue tolerance

BackgroundDuchenne muscular dystrophy (DMD) is an incurable neuromuscular disease leading to progressive skeletal muscle weakness and fatigue. Cell transplantation in murine models has shown promise in supplementing the lack of the dystrophin protein in DMD muscles. However, the establishment of novel, long-term, relevant methods is needed to assess its efficiency on the DMD motor function. By applying newly developed methods, this study aimed to evaluate the functional and molecular effects of cell therapy-mediated dystrophin supplementation on DMD muscles.MethodsDystrophin was supplemented in the gastrocnemius of a 5-week-old immunodeficient DMD mouse model (Dmd-null/NSG) by intramuscular xenotransplantation of healthy human immortalized myoblasts (Hu5/KD3). A long-term time-course comparative study was conducted between wild-type, untreated DMD, and dystrophin supplemented-DMD mouse muscle functions and histology. A novel GO-ATeam2 transgenic DMD mouse model was also generated to assess in vivo real-time ATP levels in gastrocnemius muscles during repeated contractions.ResultsWe found that 10.6% dystrophin supplementation in DMD muscles was sufficient to prevent low values of gastrocnemius maximal isometric contraction torque (MCT) at rest, while muscle fatigue tolerance, assessed by MCT decline after treadmill running, was fully ameliorated in 21-week-old transplanted mice. None of the dystrophin-supplemented fibers were positive for muscle damage markers after treadmill running, with 85.4% demonstrating the utilization of oxidative metabolism. Furthermore, ATP levels in response to repeated muscle contractions tended to improve, and mitochondrial activity was significantly enhanced in dystrophin supplemented-fibers.ConclusionsCell therapy-mediated dystrophin supplementation efficiently improved DMD muscle functions, as evaluated using newly developed evaluation methods. The enhanced muscle fatigue tolerance in 21-week-old mice was associated with the preferential regeneration of damage-resistant and oxidative fibers, highlighting increased mitochondrial activity, after cell transplantation. These findings significantly contribute to a more in-depth understanding of DMD pathogenesis.