Rat Skeletal Muscle Research Articles

Photobiomodulation and Physical Exercise Modulate of Cell Survival Proteins in the Skeletal Muscle of Rats with Heart Failure and Diabetes Mellitus.

Introduction: Heart failure (HF) and type 2 diabetes mellitus (DM2) are global health problems that often lead to muscle atrophy. These conditions are associated with increased autophagy and apoptosis in the muscle cells, resulting in decreased muscle mass. Physical exercise associated with photobiomodulation (PBM) seems promising to attenuate the skeletal muscle changes caused by HF and DM2, due to its direct effects on mitochondria, which may result in an increase in antioxidant capacity. Objective: To verify the influence of physical exercise and the association with PBM on autophagy, apoptosis, and cell survival signaling pathways in myocytes from rats with HF and DM2. Materials and Methods: Male rats were assigned to one of four groups: control (CT), HF+DM (disease model), exercise+HF+DM (EX+HF+DM), and EX+HF+DM+PBM (EX+HF+DM+PBM). To induce DM2, we administered streptozotocin (STZ) (0.25 mL/kg, intraperitoneally). HF was induced by coronary ligation. One week post-induction, an 8-week aerobic exercise and PBM protocol was initiated. Western blot analysis was used to measure the expression of apoptosis-related proteins and autophagy. Results: The EX+HF+DM+PBM group showed a substantial increase in Nrf2, p-AKT, and LC3-I levels compared to the HF+DM group. Conclusions: These findings suggest that physical exercise combined with PBM can upregulate proteins that promote myocyte survival in rats with HF and DM2.

The Effect of “Carvacrol” on Ischemia-Reperfusion Injury in the Skeletal Muscles of Rats

The Effect of “Carvacrol” on Ischemia-Reperfusion Injury in the Skeletal Muscles of Rats

Chemical synthesis of NiO nanoparticles from Solanum trilobatum leaf extract for antibacterial and cytotoxic properties

The chemical precipitation approach was employed to synthesize Nickel oxide nanoparticles (NiONPs) using Solanum trilobatum leaf extract as the stimulant and Nickel nitrate as the precursor. The Nickel oxide is examined using a range of characterization methods including X-ray diffraction, Fourier Transform Infrared spectroscopy, High-Resolution Transmission Electron Microscopy, High-Resolution Scanning Electron Microscopy, X-ray photoelectron spectroscopy, Thermo gravimetric Analysis/Derivative Thermo gravimetric Analysis, Diffuse Reflectance Spectroscopy, cytotoxicity and antimicrobial investigations The X-ray diffraction examination determined that the average size of the crystals increases as the quantities of leaf extract in the NiO2 composites rise. The decrease in line broadening (β) value and the increase in leaf extract concentrations may be the cause of this phenomenon. The FTIR spectrum confirms that the as-synthesized NiO-NPs are of great purity and match well with the XRD pattern. The thermal stability of the synthesized samples was determined using TGA/DTG analysis. The analysis was conducted in an air atmosphere, with the temperature increasing at a rate of 10°C per minute. The temperature range for the analysis was from room temperature to 750°C. The optical properties are determined by the use of Diffuse Reflectance Spectroscopy, which examines the coordinated movement of electrons in the conduction band when exposed to electromagnetic waves. Rat skeletal muscle cell line and SKMEL cancer cells were cultured on 96-well plates and incubated at 37°C and 5 % CO2 for 24 hours to allow them to adapt to the culture conditions. An investigation was conducted to assess the antibacterial properties of synthesized nanocomposites against two types of bacteria: gram-positive Staphylococcus aureus (MTCC No: 87) and gram-negative Escherichia coli (MTCC No: 443), in order to explore their potential for biological applications.

Effect of diabetes on microvascular morphology and permeability of rat skeletal muscle: in vivo imaging using two-photon laser scanning microscopy.

This investigation evaluated the microvascular permeability and ultrastructure of skeletal muscle capillaries in the skeletal muscle of diabetic (DIA) rats using two-photon laser scanning microscopy (TPLSM) and transmission electron microscopy (TEM). Microvascular permeability was assessed in the tibialis anterior muscle of control (CON) and DIA (streptozocin) male Wistar rats (n = 20, 10-14 wk) by in vivo imaging using TPLSM after fluorescent dye intravenous infusion. Fluorescent dye leakage was quantified to determine microvascular permeability. The ultrastructure was imaged by TEM ex vivo to calculate the size and number of intercellular clefts between capillary endothelial cells and also intracellular vesicles. Compared with control, the volumetrically determined interstitial fluorescent dye leakage, the endothelial cell thickness, and the number of intercellular clefts per capillary perimeter were significantly higher, and the cleft width was significantly narrower in tibialis anterior (TA) of DIA (interstitial fluorescent dye leakage, 2.88 ± 1.40 vs. 10.95 ± 1.41 µm3 × min × 106; endothelial thickness, 0.28 ± 0.02 vs. 0.45 ± 0.03 µm; number of intercellular clefts per capillary perimeter, 6.3 ± 0.80 vs. 13.6 ± 1.7/100 µm; cleft width, 11.92 ± 0.95 vs. 8.40 ± 1.03 nm, CON vs. DIA, respectively, all P < 0.05). The size of intracellular vesicles in the vascular endothelium showed an increased proportion of large vesicles in the DIA group compared with the CON group (P < 0.05). Diabetes mellitus enhances the microvascular permeability of skeletal muscle microvessels due, in part, to a higher density and narrowing of the endothelial intercellular clefts, and larger intracellular vesicles.NEW & NOTEWORTHY Microvascular permeability in diabetic muscle was investigated using our original two-photon scanning laser microscopy method. Compared with controls, the leakage volume was increased in diabetic muscle, which was atrophic with smaller capillary diameter, endothelial cell thickening, and the appearance of more endothelial intercellular gaps or clefts, and large vesicles. Hyperpermeability was closely related to ultrafine structural changes of the capillary endothelial cell junctions.

Impacts of endurance training and crocin supplementation on the apoptotic pathways in rat skeletal muscle following doxorubicin administration

Background and aims: Doxorubicin (DOX), in addition to its anti-cancer properties, causes toxicity and increases the apoptosis of healthy tissues. The objective of the current research was to explore the concurrent influence of an eight-week aerobic training regimen combined with crocin supplementation on the apoptosis induced by DOX within the soleus muscle tissue of male rodents. Methods: In this study, a cohort of 40 male Wistar rats, each weighing between 200 and 220 g and approximately 8 weeks old, were systematically distributed into five distinct experimental clusters, including a healthy control (normal saline) and a patient control (intraperitoneal injection of 2 mg/kg of DOX ). The other clusters were DOX-exercise (intraperitoneal injection of 2 mg/kg of DOX with eight weeks of treadmill/5 days a week), DOX-crocin (intraperitoneal injection of 2 mg/kg) 2 kg of DOX along with 10 mg/kg of crocin extract/8 weeks), and DOX-exercise-crocin. Results: The administration of DOX was associated with a notable elevation in Bax and a reduction in Bcl-2 expression (P=0.001 and P=0.001). In contrast, engaging in eight weeks of aerobic exercise, ingesting crocin, or a synergistic approach combining both interventions resulted in a marked upregulation of Bcl-2 expression (P=0.001). This combined treatment also led to a significant diminution in the Bax mRNA (P=0.006) and a decrease in the Bax/Bcl-2 ratio (P=0.001) within the soleus muscle tissue of male rodents subjected to DOX exposure. Conclusion: Aerobic exercise with crocin supplementation could inhibit apoptosis caused by DOX in the soleus muscle of male rats.

Age-induced changes in skeletal muscle mitochondrial DNA synthesis, quantity, and quality in genetically unique rats

AbstractMitochondrial genomic integrity is a key element of physiological processes and health. Changes in the half-life of the mitochondrial genome are implicated in the generation and accumulation of age-induced mitochondrial DNA (mtDNA) mutations, which are implicated in skeletal muscle aging and sarcopenia. There are conflicting data on the half-life of mtDNA, and there is limited information on how aging affects half-life in skeletal muscle. We hypothesized that skeletal muscle mtDNA synthesis rates would decrease with age in both female and male rats concomitant with changes in mtDNA integrity reflected in mtDNA copy number and mutation frequency. We measured mitochondrial genome half-life using stable isotope labeling over a period of 14 days and assessed mtDNA copy number and deletion mutation frequency using digital PCR in the quadriceps muscle of 9-month-old and 26-month-old male and female OKC-HET rats. We found a significant age-related increase in mtDNA half-life, from 132 days at 9 months to 216 days at 26 months of age in OKC-HET quadriceps. Concomitant with the increase in mtDNA half-life, we found an age-related increase in mtDNA deletion mutation frequency in both male and female rats. Notably, 26-month-old female rats had a lower mutation frequency than male rats, and there were no changes in mtDNA copy number with sex, age, or mitochondrial genotype. These data reveal several key findings: (1) mtDNA turnover in rat skeletal muscle decreases with age, (2) mtDNA half-lives in skeletal muscle are approximately an order of magnitude longer than what is reported for other tissues, and (3) muscle mtDNA turnover differs significantly from the turnover of other mitochondrial macromolecules including components of the mitochondrial nucleoid. These findings provide insight into the factors driving age-induced mtDNA mutation accumulation, which contribute to losses of mitochondrial genomic integrity and may play a role in skeletal muscle dysfunction.

Resistance training suppresses accumulation of senescent fibro-adipogenic progenitors and senescence-associated secretory phenotype in aging rat skeletal muscle

AbstractAccumulation of senescent cells in tissues contributes to multiple aging-related pathologies. Senescent fibro-adipogenic progenitors (FAPs) contribute to aging-related muscle atrophy. Resistance training can help to maintain skeletal muscle mass, improve mobility, and reduce certain health risks commonly associated with aging. We investigated, using rat model, the impact of resistance training on FAPs in aging skeletal muscle, which remains unclear. Twenty-two-month-old female rats were divided into sedentary and training groups. The training group rodents were trained to climb a ladder while bearing a load for 20 training sessions over 2 months, after which, the flexor hallucis longus muscles were collected and analyzed. Senescent cells were identified using a senescence-associated β-galactosidase stain and p21 immunohistochemistry (IHC), and FAPs were identified using platelet-derived growth factor receptor alpha IHC. The results indicate that resistance training in rats prevented aging-associated skeletal muscle atrophy and suppressed M2 polarization of macrophages. The number of senescent cells was significantly reduced in the 24-month-old training group, with most of them being FAPs. Conversely, the number of senescent FAPs increased significantly in the 24-month-old sedentary group compared with that in the 18-month-old sedentary group. The number of senescent FAPs in the 24-month-old training group decreased significantly. Resistance training also suppressed the senescence-associated secretory phenotype (SASP). The killer T cell-specific marker, CD8α, was elevated in the skeletal muscles of the aging rats following resistance training, indicating upregulation of recognition and elimination of senescent cells. Overall, resistance training suppressed the accumulation of senescent FAPs and acquisition of SASP in aging skeletal muscles.

CaMKII protein expression and phosphorylation in human skeletal muscle by immunoblotting: Isoform specificity

Calcium (Ca2+)/calmodulin-dependent protein kinase II (CaMKII) is activated during exercise by reactive oxygen species (ROS) and Ca2+ transients initiating muscle contraction. CaMKII modulates antioxidant, inflammatory, metabolic and autophagy signalling pathways. CaMKII is coded by four homologous genes (α, β, γ, and δ). In rat skeletal muscle, δD, δA, γD, γB and βM have been described while different characterisations of human skeletal muscle CaMKII isoforms have been documented. Precisely discerning between the various isoforms is pivotal for understanding their distinctive functions and regulatory mechanisms in response to exercise and other stimuli. This study aimed to optimize the detection of the different CaMKII isoforms by western blotting using eight different CaMKII commercial antibodies in human skeletal muscle. Exercise-induced posttranslational modifications, i.e. phosphorylation and oxidations, allowed the identification of specific bands by multitargeting them with different antibodies after stripping and reprobing. The methodology proposed has confirmed the molecular weight of βM CaMKII and allows distinguishing between γ/δ and δD CaMKII isoforms. The corresponding molecular weight for the CaMKII isoforms resolved were: δD, at 54.2 ± 2.1 kDa; γ/δ, at 59.0 ± 1.2 kDa and 61.6 ± 1.3 kDa; and βM isoform, at 76.0 ± 1.8 kDa. Some tested antibodies showed high specificity for the δD, the most responsive isoform to ROS and intracellular Ca2+ transients in human skeletal muscle, while others, despite the commercial claims, failed to show such specificity.

Impact of Eccentric Exercise Interventions with Small and Large Ranges of Motion on Rat Skeletal Muscle Tissue and Muscle Force Production.

Eccentric training induces greater hypertrophy while causing more muscle damage than concentric training. This study examined the effects of small-range eccentric contractions (SR-ECCs) and large-range eccentric contractions (LR-ECCs) on muscle morphology, contractility, and damage in rats. Thirty male Fischer 344 rats were divided into five groups: small-range ECC single-bout (SR-ECCSB, n = 4), large-range ECC single-bout (LR-ECCSB, n = 4), SR-ECC intervention (SR-ECCIntv, n = 7), LR-ECC intervention (LR-ECCIntv, n = 8), and control (Cont, n = 7). These groups underwent transcutaneous electrical stimulation involving 80 ECCs twice a week for four weeks. The results indicated that the LR-ECCSB group had more Evans blue dye-positive fibers than other groups. The SR-ECCIntv group showed no increase in the mean myofiber cross-sectional area. However, Pax7+ and Ki67+ cells significantly increased in both ECCIntv groups compared to the Cont group, and the connective tissue area was significantly greater in the LR-ECCIntv than in others. Muscle force was lower in both ECCIntv groups compared to the Cont group. These findings suggest that SR-ECC intervention may induce a smaller increase in the number of fibers with a large myofiber cross-sectional area and satellite cell proliferation with less muscle damage and myofibrosis compared to LR-ECCs.

Lymphatic Capillarization in Different Fiber Types of Rat Skeletal Muscles With Growth and Age.

To clarify the effect of growth and advancing age on lymphatic capillarization in rat skeletal muscles, we examined the histological and biochemical changes of lymphatic capillaries in different fiber types of skeletal muscles across juvenile, young, and middle-aged generations. We collected the tibialis anterior (TA), extensor digitorum longus (EDL), and soleus (SOL) muscles. Immunohistochemical staining using LYVE-1 and CD31 markers was used for lymphatic and blood capillaries, respectively. Real-time PCR was used to analyze mRNA expression of lymphangiogenic factors. The density of LYVE-1-positive lymphatic capillaries in the muscles peaked during the juvenile period and subsequently decreased with increasing age. In contrast to blood capillaries, fast-twitch dominant muscles (i.e., TA and EDL) exhibited an age-related decrease in lymphatic capillaries. Similar to blood capillaries, lymphatic capillaries were abundant in SOL, a slow-twitch dominant muscle, which showed less susceptibility to age-related lymphatic decline. The mRNA expression of lymphangiogenic factors was significantly upregulated in SOL and decreased in all muscles of middle-aged rats. The age-related decrease of lymphatic capillaries in fast-twitch muscles might be associated with age-related muscle atrophy.

Trimetazidine improves angiogenesis and tissue perfusion in ischemic rat skeletal muscle.

Introduction: Peripheral artery disease (PAD) is an increasingly common disease, causing significant complications for patients. Trimetazidine (TMZ) not only improves clinical symptoms in PAD patients but also facilitates angiogenesis in ischemic hind limbs. Our aim was to find the function of TMZ in promoting angiogenesis and tissue perfusion in ischemic rat skeletal muscle. Methods: The rats underwent femoral artery ligation (FAL) and then treated with TMZ and saline. Hematoxylin-eosin and Masson's trichrome stain in the ischemic gastrocnemius muscle to analyze muscle morphology and atrophy. To identify angiogenesis and the tissue perfusion, CD31 immunohistochemical staining and laser speckle contrast imaging was conducted. Additionally, hind limb motor ability was measured. Finally, qRT-PCR and Western blotting were used to statistically analyze the expression levels of HIF-1α and VEGF. Results: Our study demonstrated significant enhancement in angiogenesis and tissue perfusion after FAL when treated with TMZ compared to the saline group. Histologically, it mitigates ischemia-induced muscle atrophy and inflammation, as well as reduces fibrosis progression in the TMZ group. Additionally, hind limb motor ability improved in rats treated with TMZ during motor experiments. Discussion: It suggests that TMZ can promote angiogenesis and improve tissue perfusion in ischemic skeletal muscle of rats by activating the HIF-1α/VEGF signaling pathway. Additionally, it leads to significant improvement in ischemia-induced motor limitations in the hind limbs of rats.

Changes in contractile characteristics of rat skeletal muscles associated with P2-receptor activation after spinal cord transection

Introduction. Traumatic spinal cord and peripheral-nerve injury is associated with release of proinflammatory cytokines and chemokines, which may stimulate neuronal activity. Adenosine triphosphoric acid (ATP) is an important pain mediator involved in the acute and chronic neuropathic pain development. Its excessive release from primary injured tissue leads to activation of P2-receptors, which may further start secondary injury mechanisms. Although the effects of ATP on the peripheral nervous system are relatively well studied, the pathophysiological role of purinergic signaling after spinalization remains unclear. The study was aimed at assessing the post-spinalization effects of P2-receptors on the contractile characteristics of rat skeleton muscles. Materials and methods. The objects of the study were the soleus muscle, the extensor digitorum longus (EDL) muscle, and diaphragm in intact rats and spinalized rats. Seven days after laminectomy followed by spinal cord transection, animals were anesthetized, exsanguinated, and their muscles with nerve stumps were isolated. Contractile response parameters were recorded using mechanomyography (MMG). To study effects of ATP on ligand binding, ATP was added to a bath and mechanical responses in the rat muscles were assessed 7 min after. After washing with Krebs–Henseleit solution, the preparations were incubated with suramin solution for 20 min with subsequent ATP application. Then the mechanical responses in the muscles were again recorded. Statistical significance was assessed using Student's t-test for independent (unpaired) and paired samples. Results. We found a significant (p 0.05) decrease in the modulating activity of ATP, as the main endogenous signaling agent, in the cholinergic synapse of the soleus muscle from 32.4 to 5.8% and from 13.7 to 5.6% for the EDL muscle after the spinalization (spinal cord injury at the Th6–Th7 level) compared with intact animals. No such dramatic changes were observed in the diaphragm. Conclusions. Abnormal ATP-mediated modulation of neuromuscular transmission demonstrated in this study supports the involvement of purinergic signaling in the neurotrophic control and functioning of various motor units.

Reactivation by novel pyridinium oximes of rat serum and skeletal muscle acetylcholinesterase inhibited by organophosphates.

The treatment of organophosphate (OP) anticholinesterases currently lacks an effective oxime reactivator of OP-inhibited acetylcholinesterase (AChE) which can penetrate the blood-brain barrier (BBB). Our laboratories have synthesized novel substituted phenoxyalkyl pyridinium oximes and tested them for their ability to promote survival of rats challenged with lethal doses of nerve agent surrogates. These previous studies demonstrated the ability of some of these oximes to promote 24-h survival to rats challenged with a lethal level of highly relevant surrogates for sarin and VX. The reactivation of OP-inhibited AChE in peripheral tissues was likely to be a major contributor to their efficacy in survival of lethal OP challenges. In the present study, twenty of these novel oximes were screened in vitro for reactivation ability for AChE in rat skeletal muscle and serum using two nerve agent surrogates: phthalimidyl isopropyl methylphosphonate (PIMP, a sarin surrogate) and 4-nitrophenyl ethyl methylphosphonate (NEMP, a VX surrogate). The oximes demonstrated a range of 23%-102% reactivation of AChE in vitro across both tissue types. Some of the novel oximes tested in the present study demonstrated the ability to more effectively reactivate AChE in serum than the currently approved oxime, 2-PAM. Therefore, some of these novel oximes have the potential to reverse AChE inhibition in peripheral target tissues and contribute to survival efficacy.

Impact of Hyperhomocysteinemia on Cytokine and Matrix Metalloproteinases Contents in Rat Skeletal Muscle

Abstract Background: High levels of homocysteine (Hcy) in the blood (hyperhomocysteinemia [HHcy]) are associated with many pathologies, including atherosclerosis, coronary heart disease, stroke, neurological disorders, and a decrease in muscle mass and strength. The present study aimed to evaluate the levels of pro- and anti-inflammatory cytokines and matrix metalloproteinases (MMPs) in skeletal muscle of rats with experimental HHcy. Methods: HHcy in rats of two age groups was induced by intragastric administration of D, L-thiolactone Hcy for 8 weeks. The criterion for the development of pathological conditions was a blood Hcy level above 15 mmol L−1. Cytokine and MMP levels in muscle homogenate were determined by enzyme-linked immunosorbent assay. Results: The findings of the study on the content of pro-inflammatory cytokines in skeletal muscles of rats with hyperhomocysteinemia indicated the following. For immature rats, the greatest reduction in tumor necrosis factor-α and interleukin-8 (IL-8) content was observed, whereas, for mature individuals, the most pronounced decline in IL-1b was evident in skeletal muscle tissue under the pathology state. The content of anti-inflammatory interferon-γ was also reduced in the muscles of both age groups by 30% compared to the control, besides a decrease in the content of collagenase MMP-1 was also observed. Conclusions: The presence of HHcy is associated with metabolic changes in skeletal muscles, which can result in a depletion of cytokines and a slowing down of proteolytic remodeling. This, in turn, can lead to the development of muscular abnormalities, including dysfunction, weakness, and muscle degeneration.

RETRACTION: Melatonin Inhibits the Expression of the Inducible Isoform of Nitric Oxide Synthase and Nuclear Factor Kappa B Activation in Rat Skeletal Muscle.

Alonso M, Collado PS, González-Gallego J. Melatonin inhibits the expression of the inducible isoform of nitric oxide synthase and nuclear factor kappa B activation in rat skeletal muscle. J Pineal Res 2006;41:8-14. https://doi.org/10.1111/j.1600-079X.2006.00323.x The above article, published online on 28 June 2006 in Wiley Online Library (wileyonlinelibrary.com), has been retracted by agreement between the journal Editor-in-Chief, Gianluca Tosini, and John Wiley and Sons Ltd. Following publication, concerns were raised by third parties regarding Figure 1. The authors could not provide the original data for this figure, and were unable to provide a satisfactory explanation to resolve the concerns. The retraction has been agreed because of concerns that portions of the figure were duplicated, affecting the interpretation of the data and results presented. The authors disagree with this decision.

Unveiling the Threat of Maternal Advanced Glycation End Products to Fetal Muscle: Palmitoleic Acid to the Rescue.

Advanced glycation end products (AGEs) accumulate in the plasma of pregnant women with hyperglycemia, potentially inducing oxidative stress and fetal developmental abnormalities. Although intrauterine hyperglycemia has been implicated in excessive fetal growth, the effects of maternal AGEs on fetal development remain unclear. We evaluated the differentiation regulators and cellular signaling in the skeletal muscles of infants born to control mothers (ICM), diabetic mothers (IDM), and diabetic mothers supplemented with either cis-palmitoleic acid (CPA) or trans-palmitoleic acid (TPA). Cell viability, reactive oxygen species levels, and myotube formation were assessed in AGE-exposed C2C12 cells to explore potential mitigation by CPA and TPA. Elevated receptors for AGE expression and decreased Akt and AMPK phosphorylation were evident in rat skeletal muscles in IDM. Maternal palmitoleic acid supplementation alleviated insulin resistance by downregulating RAGE expression and enhancing Akt phosphorylation. The exposure of the C2C12 cells to AGEs reduced cell viability and myotube formation and elevated reactive oxygen species levels, which were attenuated by CPA or TPA supplementation. This suggests that maternal hyperglycemia and plasma AGEs may contribute to skeletal muscle disorders in offspring, which are mitigated by palmitoleic acid supplementation. Hence, the maternal intake of palmitoleic acid during pregnancy may have implications for fetal health.

Investigating the Impact of Resistance Training on Myokines Gene Expression in the Skeletal Muscle of Rats

Introduction: Myokines are produced in response to contractions and mechanical stress caused by exercise and plays a key role in muscle regeneration or control of some diseases. The role of resistance training in the secretion of myokines has been less investigated. The purpose of this study was to investigate the effect of 4 weeks of resistance training on the expression of musclin, apelin and decorin genes in the soleus muscle of male Wistar rats. Methods: The present study was experimental. Sixteen 8-week-old male Wistar rats with an average weight of 223±16.99 grams were randomly divided into 2 groups of control (n=8) and resistance training (n=8). After familiarizing the animals with the laboratory environment and resistance training on the ladder, the rats in the resistance training group trained on the ladder for 4 weeks, 3 days per week. Expression values of musclin, apelin and decorin genes of soleus muscle were measured by RT-PCR method. To analyze the data, independent t test was used at the level of p&lt;0.05 using SPSS version 16 statistical software. Results: The results of this study showed that performing 4 weeks of resistance training on a regular basis can significantly increase musclin (p=0.0004), apelin (p&lt;0.0001) and decorin (p=0.0078) in the slow-twitch soleus muscle compared to the control group. Conclusion: It seems that doing resistance exercises regularly in a short period of time can significantly increase some myokines in slow-twitch muscles, which can have beneficial and preventive effects against lifestyle-related diseases.

Transcriptomics reveals transient and dynamic muscle fibrosis and atrophy differences following spinal cord injury in rats.

The rate and magnitude of skeletal muscle wasting after severe spinal cord injury (SCI) exceeds most other disuse conditions. Assessing the time course of molecular changes can provide insight into the progression of muscle wasting post-SCI. The goals of this study were (1) to identify potential targets that may prevent the pathologic features of SCI in soleus muscles and (2) to establish therapeutic windows for treating these pathologic changes. Four-month-old Sprague-Dawley male rats received T9 laminectomy (SHAM surgery) or severe contusion SCI. Hindlimb locomotor function was assessed weekly, with soleus muscles obtained 1week, 2weeks, 1month and 3months post-surgery (n=6-7 per group per timepoint). RNA was extracted from muscles for bulk RNA-sequencing analysis (n=3-5 per group per timepoint). Differentially expressed genes (DEGs) were evaluated between age-matched SHAM and SCI animals. Myofiber size, muscle fibre type and fibrosis were assessed on contralateral muscles. SCI produced immediate and persistent hindlimb paralysis, with Basso-Beattie-Bresnahan locomotor scores remaining below 7 throughout the study, contributing to a progressive 25-50% lower soleus mass and myofiber atrophy versus SHAM (P<0.05 at all timepoints). Transcriptional comparisons of SCI versus SHAM resulted in 184 DEGs (1week), 436 DEGs (2weeks), 133 DEGs (1month) and 1200 DEGs (3months). Upregulated atrophy-related genes included those associated with cell senescence, nuclear factor kappa B, ubiquitin proteasome and unfolded protein response pathways, along with upregulated genes that negatively influence muscle growth through the transforming growth factor beta pathway and inhibition of insulin-like growth factor-I/Akt/mechanistic target of rapamycin and p38/mitogen-activated protein kinase signalling. Genes associated with extracellular matrix (ECM), including collagens, collagen crosslinkers, proteoglycans and those regulating ECM integrity, were enriched within upregulated DEGs at 1week but subsequently downregulated at 2weeks and 3months and were accompanied by >50% higher ECM areas and hydroxyproline levels in SCI muscles (P<0.05). Myofiber remodelling genes were enriched in upregulated DEGs at 2weeks and 1month and were downregulated at 3months. Genes that regulate neuromuscular junction remodelling were evident in muscles post-SCI, along with slow-to-fast fibre-type shifts: 1 week and 2 weeks SCI muscles were composed of 90% myosin heavy chain (MHC) type I fibres, which decreased to only 16% at 3months and were accompanied by 50% fibres containing MHC IIX (P<0.05). Metabolism genes were enriched in upregulated DEGs at 1month and were further enriched at 3months. Our results substantiate many known pathologic features of SCI-induced wasting in rat skeletal muscle and identify a progressive and dynamic transcriptional landscape within the post-SCI soleus. Future studies are warranted to consider these therapeutic treatment windows when countering SCI muscle pathology.

SIRT1/AMPK-mediated pathway: Ferulic acid from sugar beet pulp mitigating obesity-induced diabetes-linked complications and improving metabolic health

Obesity-induced type 2 diabetes (T2D) increases the risk of metabolic syndrome due to the high calorie intake. The role of sugar beet pulp (SBP) in T2D and the mechanism of its action remain unclear, though it is abundant in phenolics and has antioxidant activity. In this study, we isolated and purified ferulic acid from SBP, referred to as SBP-E, and studied the underlying molecular mechanisms in the regulation of glucose and lipid metabolism developing high glucose/high fat diet-induced diabetic models in vitro and in vivo. SBP-E showed no cytotoxicity and reduced the oxidative stress by increasing glutathione (GSH) in human liver (HepG2) and rat skeletal muscle (L6) cells. It also decreased body weight gain, food intake, fasting blood glucose levels (FBGL), glucose intolerance, hepatic steatosis, and lipid accumulation. Additionally, SBP-E decreased the oxidative stress and improved the antioxidant enzyme levels in high-fat diet (HFD)-induced T2D mice. Further, SBP-E reduced plasma and liver advanced glycation end products (AGEs), malondialdehyde (MDA), and pro-inflammatory cytokines, and increased anti-inflammatory cytokines in HFD-fed mice. Importantly, SBP-E significantly elevated AMPK, glucose transporter, SIRT1 activity, and Nrf2 expression and decreased ACC activity and SREBP1 levels in diabetic models. Collectively, our study results suggest that SBP-E treatment can improve obesity-induced T2D by regulating glucose and lipid metabolism via SIRT1/AMPK signalling and the AMPK/SREBP1/ACC1 pathway.

The Effect of "Proanthocyanidin" on Ischemia-Reperfusion Injury in Skeletal Muscles of Rats.

Background and Objectives: Lower limb skeletal muscle ischemia-reperfusion (IR) injury is associated with increased morbidity and mortality, and it is common in several clinical situations such as aortic aneurysms repairment, peripheral arterial surgery, vascular injury repairment, and shock. Although it is generally accepted that oxidative stress mediators have a significant role in IR injury, its precise mechanism is still unknown. Anecdotally, it is sustained not only by structural and functional changes in the organ it affects but also by damage to distant organs. The purpose of this report is to illustrate the effect of proanthocyanidin on IR injury. Materials and Methods: In our study, 18 male Wistar albino rats were used. The subjects were divided into three groups containing six mice each (control, C; ischemia-reperfusion, IR; ischemia-reperfusion and proanthocyanidin; IR-PRO). Intraperitoneal proanthocyanidin was given to the IR and proanthocyanidin groups 30 min before laparotomy, and 1 h ischemia led to these two groups. After one hour, reperfusion started. Muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, muscle oval-central nucleus ratio, leukocyte cell infiltration, catalase enzyme activity, and TBARS were all examined in lower-limb muscle samples after one hour of reperfusion. Results: When skeletal muscle samples were evaluated histopathologically, it was discovered that muscle atrophy-hypertrophy, muscle degeneration-congestion, fragmentation-hyalinization, and leukocyte cell infiltration with oval-central nucleus standardization were significantly higher in the IR group than in the C and IR-P groups. Oval-central nucleus standardization was significantly higher in the IR and IR-PRO groups than in the control group. TBARS levels were significantly higher in the IR group than in the control and IR-PRO groups, while catalase enzyme activity was found to be significantly lower in the IR group than in the control and IR-PRO groups. Conclusions: As a consequence of our research, we discovered that proanthocyanidins administered before IR have a protective impact on skeletal muscle in rats. Further research in this area is required.