Effect of the kinesio taping application method for the activation and strength of gastrocnemius muscles in healthy adults

The objective of this study was to verify the effect of kinesio-taping (KT) application of the origin for muscle insertion (O>I) and insertion for muscle origin (I>O) in healthy participants, through surface electromyography and peak torque of gastrocnemius muscles. A total of 69 participants with an average age of 22.9±5.2 years were evaluated, 41 women with an average age of 22.0±5.1 years, BMI 25.1±4.6 kg/m2, and 28 men with an average age of 22.0±5.1 years, BMI 23.1±3.3 kg/m2, randomized under three conditions: O>I, I>O and no KT (control), repeated three times with five-minute rest between sessions. The peak torque of the gastrocnemius lateral (GML) and medial (GMM) muscles was evaluated at speeds 30º/s 60º/s 120º/s and muscle activity through surface electromyography. Repeated-measurement ANOVA showed effect only on the variable speed (F=767,1; p<0.001) and the variables condition (F=0.010; p=0.990) and interaction (F=0.199; p=0.892) were not significant. In electromyography, Root mean Square (RMS) did not differ in the conditions evaluated, presenting standard behavior without significant differences. The KT application regardless of being O>I or I>O muscular, did not alter the muscle recruitment or contribute to the increase in peak torque performance during the three speeds.

Ablation of the FACIT collagen XII disturbs musculoskeletal ECM organization and causes patella dislocation and myopathy

Collagen XII, belonging to the fibril-associated collagens with interrupted triple helix (FACIT) family, assembles from three identical α-chains encoded by the COL12A1 gene. The trimeric molecule consists of three N-terminal noncollagenous NC3 domains joined by disulfide bonds followed by a short interrupted collagen triple helix at the C-terminus. Collagen XII is expressed widely in the musculoskeletal system and mutations in the COL12A1 gene cause an Ehlers-Danlos/myopathy overlap syndrome, which is associated with skeletal abnormalities and muscle weakness. Our study defines the role of collagen XII in patella development using the Col12a1-/- mouse model. Deficiency in Col12a1 expression causes malformed facies patellaris femoris grooves at an early stage, which leads to patella subluxation and growth retardation. Due to the patella subluxation, more muscle fibers with centralized nuclei occur in the quadriceps than in the gastrocnemius muscles indicating a local effect. To further understand the role of collagen XII in the skeletal tissues single cell RNAseq (scRNA-seq) was performed. Comparison of the gene expression in the tenocyte cell sub-population of wild type and Col12a1-/- mice showed that several matrix genes are altered. Finally, we reinvestigated collagen XII deficient patients and observed a patella instability.

Stevioside Attenuates Insulin Resistance in Skeletal Muscle by Facilitating IR/IRS-1/Akt/GLUT 4 Signaling Pathways: An In Vivo and In Silico Approach

Type-2 diabetes mellitus (T2DM), the leading global health burden of this century majorly develops due to obesity and hyperglycemia-induced oxidative stress in skeletal muscles. Hence, developing novel drugs that ameliorate these pathological events is an immediate priority. The study was designed to analyze the possible role of Stevioside, a characteristic sugar from leaves of Stevia rebaudiana (Bertoni) on insulin signaling molecules in gastrocnemius muscle of obesity and hyperglycemia-induced T2DM rats. Adult male Wistar rats rendered diabetic by administration of high fat diet (HFD) and sucrose for 60 days were orally administered with SIT (20 mg/kg/day) for 45 days. Various parameters were estimated including fasting blood glucose (FBG), serum lipid profile, oxidative stress markers, antioxidant enzymes and expression of insulin signaling molecules in diabetic gastrocnemius muscle. Stevioside treatment improved glucose and insulin tolerances in diabetic rats and restored their elevated levels of FBG, serum insulin and lipid profile to normalcy. In diabetic gastrocnemius muscles, Setvioside normalized the altered levels of lipid peroxidase (LPO), hydrogen peroxide (H2O2) and hydroxyl radical (OH*), antioxidant enzymes (CAT, SOD, GPx and GSH) and molecules of insulin signaling including insulin receptor (IR), insulin receptor substrate-1 (IRS-1) and Akt mRNA levels. Furthermore, Stevioside enhanced glucose uptake (GU) and oxidation in diabetic muscles by augmenting glucose transporter 4 (GLUT 4) synthesis very effectively in a similar way to metformin. Results of molecular docking analysis evidenced the higher binding affinity with IRS-1 and GLUT 4. Stevioside effectively inhibits oxidative stress and promotes glucose uptake in diabetic gastrocnemius muscles by activating IR/IRS-1/Akt/GLUT 4 pathway. The results of the in silico investigation matched those of the in vivo study. Hence, Stevioside could be considered as a promising phytomedicine to treat T2DM.

The Histone H3 K4me3, K27me3, and K27ac Genome-Wide Distributions Are Differently Influenced by Sex in Brain Cortexes and Gastrocnemius of the Alzheimer’s Disease PSAPP Mouse Model

Background: Women represent the majority of Alzheimer’s disease patients and show typical symptoms. Genetic, hormonal, and behavioral mechanisms have been proposed to explain sex differences in dementia prevalence. However, whether sex differences exist in the epigenetic landscape of neuronal tissue during the progression of the disease is still unknown. Methods: To investigate the differences of histone H3 modifications involved in transcription, we determined the genome-wide profiles of H3K4me3, H3K27ac, and H3K27me3 in brain cortexes of an Alzheimer mouse model (PSAPP). Gastrocnemius muscles were also tested since they are known to be different in the two sexes and are affected during the disease progression. Results: Correlation analysis distinguished the samples based on sex for H3K4me3 and H3K27me3 but not for H3K27ac. The analysis of transcription starting sites (TSS) signal distribution, and analysis of bounding sites revealed that gastrocnemius is more influenced than brain by sex for the three histone modifications considered, exception made for H3K27me3 distribution on the X chromosome which showed sex-related differences in promoters belonging to behavior and cellular or neuronal spheres in mice cortexes. Conclusions: H3K4me3, H3K27ac, and H3K27me3 signals are slightly affected by sex in brain, with the exception of H3K27me3, while a higher number of differences can be found in gastrocnemius.

Effects of dihydropyridine receptor signal on sarcoplasmic reticulum Ca2+ leakage after muscle contractions in rats

The purpose of this study is to investigate the mechanism underlying sarcoplasmic reticulum (SR) Ca2+ leakage at recovery phase after in vivo contractions. Rat gastrocnemius muscles were electrically stimulated in vivo, and then mechanically skinned fibers were prepared from the muscles excised 30 min after repeated high-intensity contractions. SR Ca2+ leakage was increased in the skinned fibers from stimulated muscles. Thereafter, SR Ca2+ leakage in skinned fibers was measured (1) under a continuously depolarized condition and (2) in the presence of nifedipine in the sealed transverse tubular system. In either of the two conditions, SR Ca2+ leakage in the rested fibers reached a level similar to that in the stimulated fibers. Furthermore, 1 mM tetracaine (Tet) treatment, but not 3 mM Mg2+ (3 Mg) treatment, lessened SR Ca2+ leakage in stimulated fibers. Depolarization-induced force in skinned fibers was more greatly decreased by Tet treatment than by 3 Mg treatment (92% reduction in Tet versus 31% reduction in 3 Mg), whereas caffeine-induced force in skinned fibers was similarly decreased by either treatment (73% reduction in Tet versus 75% reduction in 3 Mg). This difference indicates that Tet exerts a greater inhibitory effect on the dihydropyridine receptor (DHPR) signal to ryanodine receptor (RYR) than 3 Mg, although their inhibitory effects on RYR are almost similar. These results suggest that the increased Ca2+ leakage after muscle contractions is mainly caused by the orthograde signal of DHPRs to RYRs.

Ameliorating Effects of Coriander on Gastrocnemius Muscles Undergoing Precachexia in a Rat Model of Rheumatoid Arthritis: A Proteomics Analysis

Coriander is a commonly used vegetable, spice, and folk medicine, possessing both nutritional and medicinal properties. Up to two-thirds of patients with rheumatoid arthritis (RA) exhibit loss of body mass, predominately skeletal muscle mass, a process called rheumatoid cachexia, and this has major effects of the quality of life of patients. Owing to a lack of effective treatments, the initial stage of cachexia has been proposed as an important period for prevention and decreasing pathogenesis. In the current study, we found that cachexia-like molecular disorders and muscle weight loss were in progress in gastrocnemius muscle after only 5 days of RA induction in rats, although rheumatoid cachexia symptoms have been reported occurring approximately 45 days after RA induction. Oral administration of coriander slightly restored muscle loss. Moreover, iTRAQ-based quantitative proteomics revealed that coriander treatment could partially restore the molecular derangements induced by RA, including impaired carbon metabolism, deteriorated mitochondrial function (tricarboxylic acid cycle and oxidative phosphorylation), and myofiber-type alterations. Therefore, coriander could be a promising functional food and/or complementary therapy for patients with RA against cachexia.

Ezrin Prompted Myoblast Differentiation and Muscle Fiber Specialization and Gastrocnemius Muscle Repair in Peroneal Nerve Injury Model through PKA-NFATs Signaling Pathway

Background: Muscular dystrophy is a destructive neuromuscular disease characterized by progressive muscle weakness and muscle atrophy. The role of Ezrin in myoblast differentiation/fusion and muscle atrophy is still unknown.Method: Gastrocnemius muscle atrophy model were prepared by mechanical clamp of peroneal nerve. Differentiating C2C12 cells treated with Ad-Ezrin or Ad-shEzrin were detected by gene chip, Q-PCR, immunofluorescence staining and Western blot.Results: Ezrin was expressed in MyHC I/II myofibers in vivo, and time-dependently increased during myoblast differentiation/fusion characterized by MyoG+/MEF2c nuclei and MyHC+ myotubes in vitro. Overexpression of Ezrin promoted myoblast differentiation/fusion in time-dependent manner, inducing the increased MyHC-I+ and MyHC-II+ muscle fiber specialization, the specific effects could be abolished by addition of Ad-Periaxin. Ad-Ezrin did not alter PKA and PKAreg II α levels, but PKAreg I α/β. The PKA inhibitor, H-89, remarkably abolished the over-expression effects by Ezrin on an increased myoblast differentiation/fusion. By contrast, Knockdown of Ezrin by shRNA significantly delayed myoblast differentiation/fusion accompanied by the decreased PKA reg I/II ratio, the inhibitory effects could be eliminated by PKAreg I activator N6-Bz-cAMP. Meanwhile, Ad-Ezrin enhanced type I muscle fiber specialization, accompanied by the increased levels of NFATc1/c2.Furthermore, Ad-NFATc2 or Ad-NFATc4 reversed the inhibitory effects of Ad-shEzrin on myoblast differentiation/fusion. Importantly, in vivo transfection of Ad-Ezrin into gastrocnemius muscles in peroneal nerve injury model increased the numbers of MyHC-I+ and MyHC-II+ myofibers, reducing muscle atrophy and fibrosis.Conclusions: Ezrin activated PKA-NFAT-MyoD/MyoG/MEF2C signaling pathway, triggering myoblast differentiation/fusion and muscle fiber specialization in periaxin-depentdent manner, contributing to gastrocnemius muscles repair.

Impact of C57BL/6J and SV-129 Mouse Strain Differences on Ischemia-Induced Postnatal Angiogenesis and the Associated Leukocyte Infiltration in a Murine Hindlimb Model of Ischemia

Strain-related differences in arteriogenesis in inbred mouse strains have already been studied excessively. However, these analyses missed evaluating the mouse strain-related differences in ischemia-induced angiogenic capacities. With the present study, we wanted to shed light on the different angiogenic potentials and the associated leukocyte infiltration of C57BL/6J and SV-129 mice to facilitate the comparison of angiogenesis-related analyses between these strains. For the induction of angiogenesis, we ligated the femoral artery in 8–12-week-old male C57BL/6J and SV-129 mice and performed (immuno-) histological analyses on the ischemic gastrocnemius muscles collected 24 h or 7 days after ligation. As evidenced by hematoxylin and eosin staining, C57BL/6J mice showed reduced tissue damage but displayed an increased capillary-to-muscle fiber ratio and an elevated number of proliferating capillaries (CD31+/BrdU+ cells) compared to SV-129 mice, thus showing improved angiogenesis. Regarding the associated leukocyte infiltration, we found increased numbers of neutrophils (MPO+ cells), NETs (MPO+/CitH3+/DAPI+), and macrophages (CD68+ cells) in SV-129 mice, whereas macrophage polarization (MRC1- vs. MRC1+) and total leukocyte infiltration (CD45+ cells) did not differ between the mouse strains. In summary, we show increased ischemia-induced angiogenic capacities in C57BL/6J mice compared to SV-129 mice, with the latter showing aggravated tissue damage, inflammation, and impaired angiogenesis.

Effects of vigorous isometric muscle contraction on titin stiffness-related contractile properties in rat fast-twitch muscles

This study was conducted to examine the effects of an acute bout of vigorous isometric contractions on titin stiffness-related contractile properties in rat fast-twitch skeletal muscles. Intact gastrocnemius muscles were electrically stimulated in situ until the force was reduced to ~50% of the initial force. Immediately after cessation of the stimulation, the superficial regions of the muscles were dissected and subjected to biochemical and skinned fiber analyses. The stimulation resulted in a decrease in the titin-based passive force. The amounts of fragmented titin were unchanged by the stimulation. Protein kinase Cα-treatment increased the passive force in stimulated fibers to resting levels. The stimulation had no effect on the maximum Ca2+-activated force (max Ca2+ force) at a sarcomere length (SL) of 2.4 μm and decreased myofibrillar (my)-Ca2+ sensitivity at 2.6-μm SL. Stretching the SL to 3.0 μm led to the augmentation of the max Ca2+ force and my-Ca2+ sensitivity in both rested and stimulated fibers. For the max Ca2+ force, the extent of the increase was smaller in stimulated than in rested fibers, whereas for my-Ca2+ sensitivity, it was higher in stimulated than in rested fibers. These results suggest that vigorous isometric contractions decrease the titin-based passive force, possibly because of a reduction in phosphorylation by protein kinase Cα, and that the decreased titin stiffness may contribute, at least in part, to muscle fatigue.

Urine miRNAs as potential biomarkers for systemic reactions induced by exposure to embedded metal

Aim: Explore the potential of urine microRNAs as biomarkers that may reflect the biological responses to pure metals embedded in skeletal muscle over time. Materials & methods: We tested a panel of military-relevant metals embedded in the gastrocnemius muscles of 3-month-old, male, Sprague–Dawley rats (n = 8/group) for a duration of 1, 3, 6 and 12 months, and performed small RNA-sequencing on the urine samples. Results: Results provide potential tissue targets affected by metal exposure and a list of unique or common urine microRNA biomarkers indicative of exposure to various metals, highlighting a complex systemic response. Conclusion: We have identified a panel of miRNAs as potential urine biomarkers to reflect the complex systemic response to embedded metal exposure.