Niacin supplementation attenuates the regression of three-dimensional capillary architecture in unloaded female rat skeletal muscle.

Inactivity can lead to muscle atrophy and capillary regression in skeletal muscle. Niacin (NA), known for inducing hypermetabolism, may help prevent this capillary regression. In this study involving adult female Sprague-Dawley rats, the animals were randomly assigned to one of four groups: control (CON), hindlimb unloading (HU), NA, and HU with NA supplementation (HU + NA). For a period of 2 weeks, the rats in the HU and HU + NA groups underwent HU, while those in the NA and HU + NA groups received NA (750 mg/kg) twice daily through oral administration. The results demonstrated that HU lowered capillary number, luminal diameter, and capillary volume, as well as decreased succinate dehydrogenase activity, slow fiber composition, and PGC-1α expression within the soleus muscle. However, NA supplementation prevented these alterations in capillary structure due to unloading by stimulating PGC-1α factors and inhibiting mitochondrial dysfunction. Therefore, NA supplementation could serve as a potential therapeutic approach for preserving the capillary network and mitochondrial metabolism of muscle fibers during periods of inactivity.

Effects of interleukin-15 on autophagy regulation in the skeletal muscle of mice.

This study aimed to evaluate the role of skeletal muscle-derived interleukin (IL)-15 in the regulation of skeletal muscle autophagy using IL-15 knockout (KO) and transgenic (TG) mice. Male C57BL/6 wild-type (WT), IL-15 KO, and IL-15 TG mice were used in this study. Changes in muscle mass, forelimb grip strength, succinate dehydrogenase (SDH) activity, gene and protein expression levels of major regulators and indicators of autophagy, comprehensive gene expression, and DNA methylation in the gastrocnemius muscle were analyzed. Enrichment pathway analyses revealed that the pathology of IL-15 gene deficiency was related to the autophagosome pathway. Moreover, although IL-15 KO mice maintained gastrocnemius muscle mass, they exhibited a decrease in autophagy induction. IL-15 TG mice exhibited a decrease in gastrocnemius muscle mass and an increase in forelimb grip strength and SDH activity in skeletal muscle. In the gastrocnemius muscle, the ratio of phosphorylated adenosine monophosphate-activated protein kinase α (AMPKα) to total AMPKα and unc-51-like autophagy activating kinase 1 and Beclin1 protein expression were higher in the IL-15 TG group than in the WT group. IL-15 gene deficiency induces a decrease in autophagy induction. In contrast, IL-15 overexpression could improve muscle quality by activating autophagy induction while decreasing muscle mass. The regulation of IL-15 in autophagy in skeletal muscles may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.NEW & NOTEWORTHY IL-15 gene deficiency can decrease autophagy induction. However, although IL-15 overexpression induced a decrease in muscle mass, it led to an improvement in muscle quality. Based on these results, understanding the role of IL-15 in regulating autophagy pathways within skeletal muscle may lead to the development of therapies for the autophagy-induced regulation of skeletal muscle mass and cellular quality control.

Alternating current electromagnetic field exposure lessens intramyocellular lipid accumulation due to high-fat feeding via enhanced lipid metabolism in mice.

Long-term high-fat feeding results in intramyocellular lipid accumulation, leading to insulin resistance. Intramyocellular lipid accumulation is related to an energy imbalance between excess fat intake and fatty acid consumption. Alternating current electromagnetic field exposure has been shown to enhance mitochondrial metabolism in the liver and sperm. Therefore, we hypothesized that alternating current electromagnetic field exposure would ameliorate high-fat diet-induced intramyocellular lipid accumulation via activation of fatty acid consumption. C57BL/6J mice were either fed a normal diet (ND), a normal diet and exposed to an alternating current electromagnetic field (ND+EMF), a high-fat diet (HFD), or a high-fat diet and exposed to an alternating current electromagnetic field (HFD+EMF). Electromagnetic field exposure was administered 8 hrs/day for 16 weeks using an alternating current electromagnetic field device (max.180 mT, Hokoen, Utatsu, Japan). Tibialis anterior muscles were collected for measurement of intramyocellular lipids, AMPK phosphorylation, FAT/CD-36, and carnitine palmitoyltransferase (CPT)-1b protein expression levels. Intramyocellular lipid levels were lower in the HFD + EMF than in the HFD group. The levels of AMPK phosphorylation, FAT/CD-36, and CPT-1b protein levels were higher in the HFD + EMF than in the HFD group. These results indicate that alternating current electromagnetic field exposure decreases intramyocellular lipid accumulation via increased fat consumption.

A Three-Dimensional Anterior and Middle Cranial Fossa Model for Skull Base Surgical Training with Two Layers of the Colored Dura Mater.

BACKGROUND: Adequate epidural procedures and anatomical knowledge are essential for the technical success of skull base surgery. We evaluated the usefulness of our three-dimensional (3D) model of the anterior and middle cranial fossa as a learning tool in improving knowledge of anatomy and surgical approaches, including skull base drilling and dura matter peeling techniques. METHODS: Using a 3D printer, a bone model of the anterior and middle cranial fossa was created based on multi-detector row computed tomography data, incorporating artificial cranial nerves, blood vessels, and dura mater. The artificial dura mater was painted using different colors, with 2 pieces glued together to allow for the simulation of peeling the temporal dura propria from the lateral wall of the cavernous sinus. Two experts in skull base surgery and 1 trainee surgeon operated on this model and 12 expert skull base surgeons watched the operation video to evaluate this model subtlety on a scale of 1 to 5. RESULTS: A total of 15 neurosurgeons, 14 of whom were skull base surgery expert, evaluated, scoring 4 or higher on most of the items. The experience of dural dissection and 3D positioning of important structures, including cranial nerves and blood vessels, was similar to that in actual surgery. CONCLUSIONS: This model was designed to facilitate teaching anatomical knowledge and essential epidural procedure-related skills. It was shown to be useful for teaching essential elements of skull-base surgery.

Mild Hyperbaric Oxygen Exposure Enhances Peripheral Circulatory Natural Killer Cells in Healthy Young Women.

Mild hyperbaric oxygen (HBO) enhances oxygen absorption in blood, relieving fatigue without causing oxidative stress. The benefits of mild HBO have been recognized in the treatment of lifestyle-related diseases and hypertension, but no research has been conducted on its effects on immunity. The aim of the present study is to investigate the effect of mild HBO on natural killer (NK) cells and cytokines in healthy young women. This crossover randomized control trial was conducted with 16 healthy young women. Participants were randomly exposed to normobaric oxygen (NBO; 1.0 atmospheres absolute (ATA), 20.8% oxygen) and mild HBO conditions (1.4 ATA, 35-40% oxygen, injected 18L oxygen per minute) in a hyperbaric oxygen chamber for 70 min. Heart rate, parasympathetic activity, NK cell count, interleukin (IL)-6, IL-12p70 and derivatives of reactive oxygen metabolites (d-ROMs) were measured before and after both exposures. In the NBO condition, parasympathetic activity remained unchanged, whereas after mild HBO exposure, parasympathetic activity was significantly increased. NK cells remained unchanged after NBO exposure, while NK cells were increased after exposure to mild HBO. Exposure to mild HBO did not increase d-ROM values, IL-6 and IL-12p70 protein levels. These findings suggest that exposure to mild HBO can be a useful protocol to increase NK cells by regulating parasympathetic activity via increasing oxygen delivery.

High Concentrations of Nucleotides Prevent Capillary Regression during Hindlimb Unloading by Inhibiting Oxidative Stress and Enhancing Mitochondrial Metabolism of Soleus Muscles in Rats.

Prolonged inactivity in skeletal muscles decreases muscle capillary development because of an imbalance between pro- and antiangiogenic signals, mitochondrial metabolism disorders, and increased oxidative stress. Nucleotides have been shown to exert a dose-dependent effect on disuse-induced muscle atrophy. However, the dose-dependent effect on capillary regression in disused muscles remains unclear. Therefore, this study investigated the dose-dependent effect of nucleotides on capillary regression due to disuse. For this purpose, Wistar rats were divided into five groups as follows: control rats fed nucleotide-free diets (CON), hindlimb-unloaded rats fed nucleotide-free diets (HU), and hindlimb-unloaded rats fed 1.0%, 2.5%, and 5.0% nucleotide diets, (HU + 1.0% NT), (HU + 2.5% NT), and (HU + 5.0% NT), respectively. Unloading increased reactive oxygen species (ROS) production and decreased mitochondrial enzyme activity, thereby decreasing the number of muscle capillaries. In contrast, 5.0% nucleotide-containing diet prevented increases in ROS production and reductions in the expression levels of NAMPT, PGC-1α, and CPT-1b proteins. Moreover, 5.0% nucleotide-containing diet prevented mitochondrial enzyme activity (such as citrate synthase and beta-hydroxy acyl-CoA dehydrogenase activity) via NAMPT or following PGC-1α upregulation, thereby preventing capillary regression. Therefore, 5.0% nucleotide-containing diet is likely to prevent capillary regression by decreasing oxidative stress and increasing mitochondrial metabolism.

'Hook' Shape Lister Tubercle Is Associated with a Greater Incidence of Extensor Pollicis Longus Tendon Rupture after Distal Radius Fracture.

Background: A rupture of the extensor pollicis longus (EPL) tendon located close to the Lister tubercle is an uncommon complication of distal radius fractures. This study aimed to determine whether the size and shape of Lister tubercle in patients with EPL rupture differs from a matched group of patients with distal radius fractures without EPL rupture. Methods: We identified 15 patients with EPL rupture (3.5%) out of 426 with distal radius fractures treated conservatively at our hospital over 4 years. Out of the remaining 411 patients with distal radius fractures without EPL rupture, we selected patients using simple random sampling and pseudo-randomised them such that their age, sex and fracture type were matched with patients exhibiting EPL rupture. The size and shape of the Lister tubercle and the size of the EPL groove were measured in both groups using computed tomographic scans and compared. Results: There was no difference in the size of the Lister tubercle or the EPL groove between both groups. A 'hook'-shaped Lister tubercle was noted in 8 out of 15 patients with EPL rupture but in only 1 out of 15 matched patients without EPL rupture. Conclusions: A 'hook'-shaped Lister tubercle was seen more often in patients with EPL rupture following distal radius fracture. Level of Evidence: Level III (Therapeutic).

Beneficial effects of mild hyperbaric oxygen exposure on microcirculation in peripheral tissues in healthy subjects: a pilot study.

BACKGROUND: Exposure to mild hyperbaric oxygen (HBO) increases blood oxygenation by dissolving oxygen into blood plasma and increased oxygen bound to hemoglobin in red blood cells. This research is an attempt to provide insight into the responses of exposure to mild HBO on microcirculation in peripheral tissues. METHODS: Fifteen healthy individuals were exposed to normobaric oxygen (1.00 ATA, 20.9% oxygen, NBO) and mild HBO (1.4 ATA, 35-39.5% oxygen) in a mild HBO chamber for 70 minutes under each condition. Peripheral oxygen saturation (SpO2), heart rate, blood flow in skin, and hemodynamics in capillaries of finger nailfold were measured under both exposures. RESULTS: The value of SpO2 was increased from 98% to 100% after mild HBO exposure although that of SpO2 under NBO was unaltered (P=0.000; P=0.818). Heart rate was decreased after exposure to the mild HBO although that unchanged under the NBO (P=0.000; P=0.706). The mean value of high frequency power in heart rate variability increased after exposure to the mild HBO (P=0.045). Average blood velocity and flow rate in capillaries of finger nailfold were not increased under to NBO whereas those were significantly increased from 92 µm/s to 126 µm/s (P=0.040, P=0.000), and 12247 µm/s to 20926 µm/s after exposure to mild HBO (P<0.05), (P=0.002, P=0.875), respectively. CONCLUSIONS: These results indicate that exposure to mild HBO increases blood flow in the capillaries of peripheral tissues by regulating parasympathetic nerve activities through increasing oxygen delivery, oxygen bound to hemoglobin in red blood cells and dissolved oxygen content in plasma.

Protective effects of chlorogenic acid on capillary regression caused by disuse muscle atrophy.

Inactivity causes muscle atrophy and capillary regression in skeletal muscle. Chlorogenic acid has an antioxidant capacity and may prevent capillary regression. Therefore, the protective effects of chlorogenic acid on inactivity-induced capillary regression in rat soleus muscle were investigated. Twenty male Wistar rats were randomly divided into four groups: control (CON), chlorogenic acid supplementation (CGA), 2-week hindlimb unloading (HU), 2-week hindlimb unloading plus chlorogenic acid supplementation (HU+CGA). The rats in CGA and HU+CGA groups were orally administrated chlorogenic acid (850 mg/kg/day). Unloading resulted in a decrease in capillary number, oxidative capacity, and an increase in oxidative stress of the soleus muscle, whereas chlorogenic acid supplementation prevented capillary and metabolic changes resulting from unloading by reducing oxidative stress. In conclusion, chlorogenic acid supplementation may qualify as an effective treatment to reduce capillary regression in skeletal muscle caused by disuse muscle atrophy.

Protective effects of Enterococcus faecium strain R30 supplementation on decreased muscle endurance under disuse in rats.

NEW FINDINGS: What is the central question of this study? Does Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch by altering the autonomic nervous system in atrophied skeletal muscles? What is the main finding and its importance? R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres by upregulating peroxisome proliferator-activated receptor-γ coactivator-1α and activating the calcineurin-nuclear factor of activated T-cells signalling pathway, thus ameliorating the decrease in muscle endurance associated with disuse. ABSTRACT: Enterococcus faecium strain R30 (R30), a new lactic acid bacterial strain for supplementation, was hypothesized to attenuate shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres in atrophied skeletal muscles. We further postulated that the prevention of slow-to-fast fibre shifts would suppress the decreased muscle endurance associated with atrophy. To evaluate the protective effects of R30, we analysed slow-to-fast fibre shifts and disuse-associated reduced muscle endurance. R30 was administered to rats with an acclimation period of 7 days before hindlimb unloading (HU) for 2 weeks. The composition ratio of the fibre type and the expression levels of peroxisome proliferator-activated receptor-γ coactivator-1α (PGC-1α), calcineurin and nuclear factor of activated T-cells (NFAT) were measured. Muscle endurance was evaluated at the end of the 2-week HU period in an in situ environment. R30 supplementation suppressed the slow-to-fast fibre switch and decreased the HU-induced expression of PGC-1α proteins and the deactivation of the calcineurin-NFAT pathway. Furthermore, R30 prevented a decrease in HU-associated muscle endurance in calf muscles. These results indicate that R30 supplementation may attenuate the shifts in the typology of whole muscle fibres from slow- to fast-twitch fibres via the upregulation of PGC-1α and the activation of the calcineurin-NFAT signalling pathway, thereby ameliorating the decrease in muscle endurance associated with disuse.

Reduced metabolic capacity in fast and slow skeletal muscle via oxidative stress and the energy-sensing of AMPK/SIRT1 in malnutrition.

The effects of malnutrition on skeletal muscle result in not only the loss of muscle mass but also fatigue intolerance. It remains unknown whether the metabolic capacity is related to the fiber type composition of skeletal muscle under malnourished condition although malnutrition resulted in preferential atrophy in fast muscle. The purpose of the present study was to investigate the effects of metabolic capacity in fast and slow muscles via the energy-sensing of AMPK and SIRT1 in malnutrition. Wistar rats were randomly divided into control and malnutrition groups. The rats in the malnutrition group were provided with a low-protein diet, and daily food intake was limited to 50% for 12 weeks. Malnutrition with hypoalbuminemia decreased the body weight and induced the loss of plantaris muscle mass, but there was little change in the soleus muscle. An increase in the superoxide level in the plasma and a decrease in SOD-2 protein expression in both muscles were observed in the malnutrition group. In addition, the expression level of AMPK in the malnutrition group increased in both muscles. Conversely, the expression level of SIRT1 decreased in both muscles of the malnutrition group. In addition, malnutrition resulted in a decrease in the expression levels of PGC-1α and PINK protein, and induced a decrease in the levels of two key mitochondrial enzymes (succinate dehydrogenase and citrate synthase) and COX IV protein expression in both muscles. These results indicate that malnutrition impaired the metabolic capacity in both fast and slow muscles via AMPK-independent SIRT1 inhibition induced by increased oxidative stress.

Preventive effects of low-intensity endurance exercise for severe hyperglycemia-induced capillary regression in non-obese type 2 diabetes rat skeletal muscle.

Although endurance exercise is effective for reducing diabetes-related capillary regression, it is difficult to prescribe high-intensity endurance exercise due to the potential worsening of complications in patients with severe hyperglycemia. Therefore, this study aimed to examine whether chronic low-intensity exercise training may prevent severe hyperglycemia-induced capillary regression of skeletal muscle in non-obese type 2 diabetes. Non-diabetic Sprague Dawley rats were assigned to a control (Con) group and an exercise (Ex) group. Likewise, spontaneously diabetic Torii rats were assigned to a diabetic sedentary (DM) group or a diabetic exercise (DMEx) group. Rats in the Ex and DMEx groups were placed on a motor-driven treadmill running at low speed (15 m/min) for 60 min/day, 5 days/week, for 14 weeks. Serum glucose levels were significantly increased in the DM group, but not in the DMEx group. Although the capillary-to-fiber ratio in the plantaris muscle was significantly lower in the DM group compared to the control group, the ratio in the DMEx group was significantly higher compared to the DM group. Moreover, the succinate dehydrogenase activity and expression levels of vascular endothelial growth factor and peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α) were reduced in the plantaris muscle of the DM group. However, those in the DMEx group were significantly higher than those in the DM group. These results indicate that low-intensity chronic endurance exercise training has the potential to prevent the progression of capillary regression in the skeletal muscles of non-obese type 2 diabetes patients with severe hyperglycemia.

Differential effects of pre-exercise on cancer cachexia-induced muscle atrophy in fast- and slow-twitch muscles.

We hypothesized that pre-exercise may effectively prevent cancer cachexia-induced muscle atrophy in both fast- and slow-twitch muscle types. Additionally, the fast-twitch muscle may be more affected by cancer cachexia than slow-twitch muscle. This study aimed to evaluate the effects of pre-exercise on cancer cachexia-induced atrophy and on atrophy in fast- and slow-twitch muscles. Twelve male Wistar rats were randomly divided into sedentary and exercise groups, and another 24 rats were randomly divided into control, pre-exercise, cancer cachexia induced by intraperitoneal injections of ascites hepatoma AH130 cells, and pre-exercise plus cancer cachexia groups. We analyzed changes in muscle mass and in gene and protein expression levels of major regulators and indicators of muscle protein degradation and synthesis pathways, angiogenic factors, and mitochondrial function in both the plantaris and soleus muscles. Pre-exercise inhibited muscle mass loss, rescued protein synthesis, prevented capillary regression, and suppressed hypoxia in the plantaris and soleus muscles. Pre-exercise inhibited mitochondrial dysfunction differently in fast- and slow-twitch muscles. These results suggested that pre-exercise has the potential to inhibit cancer-cachexia-induced muscle atrophy in both fast- and slow-twitch muscles. Furthermore, the different progressions of cancer-cachexia-induced muscle atrophy in fast- and slow-twitch muscles are related to differences in mitochondrial function.

Preventive effects of medium-chain triglycerides supplementation on the oxidative capacity in skeletal muscle under cachectic condition.

Cachexia is a multifactorial condition characterized by muscle mass loss and induces metabolic dysfunction of the skeletal muscles. The preventive effects of medium-chain triglycerides (MCT) supplementation on the oxidative capacity in skeletal muscle under cachectic condition were investigated in the present study. ICR mice were randomly divided into four groups; control, lipopolysaccharide (LPS), LPS plus long-chain triglycerides (LCT) and LPS plus MCT supplementation. LCT and MCT oil were administered to the LPS + LCT and LPS + MCT groups orally (5.0 g/kg body weight/day) by a catheter for one week. Cachexia was induced in the LPS, LPS + LCT, and LPS + MCT groups via LPS injection (7.5 mg/kg body weight, i.p.) after the supplementation. LPS induced a reduction of ketone bodies concentration in blood plasma. LPS also induced a decrease in succinate dehydrogenase activity and PGC-1α expression level in tibialis anterior muscles. Meanwhile, MCT supplementation suppressed a decrease in ketone bodies concentration and succinate dehydrogenase activity. In addition, MCT supplementation increased the level of citrate synthase activity in the muscles. These results suggested the preventive effect of MCT supplementation on oxidative capacity in skeletal muscle and the involvements of ketone bodies regulation under cachectic condition.

Acute effects of lactic acid-fermented and enzyme-digested soybean on protein synthesis via mTOR signaling in the skeletal muscle.

Protein-containing nutrients result in the efficient hypertrophy of muscles by increasing muscle protein synthesis. Soybean is often ingested by athletes or individuals who exercise; however, it takes very long to be absorbed. Lactic acid-fermented and enzyme-digested (LFED) soybean is absorbed faster than untreated soybean. This study aims at determining muscle protein synthesis after ingesting a single bolus of soybean or LFED soybean produced by lactic acid bacteria and protease digestion. Eight-week-old overnight-fasted ICR mice were administered powdered or LFED soybean. Mice were euthanized at 7, 15, 30, 60, 90, and 120 min after soybean intake. We have demonstrated that LFED soybean administration was quicker in stimulating muscle protein synthesis by activating mammalian target of rapamycin (mTOR) signaling than orally ingesting untreated soybean in the gastrocnemius muscle. These results suggested that LFED soybean is a more efficient source of nutrition for muscle hypertrophy than untreated soybean.

Transcutaneous carbon dioxide attenuates impaired oxidative capacity in skeletal muscle in hyperglycemia model.

Hyperglycemia impairs oxidative capacity in skeletal muscle. Muscle oxidative capacity is regulated by peroxisome proliferator-activated receptor-γ co-activator-1α (PGC-1α). Transcutaneous carbon dioxide (CO2) enhances PGC-1α expression in skeletal muscle. Therefore, the aim of this study was to clarify the effects of CO2 therapy on muscle oxidative capacity impaired by streptozotocin (STZ)-induced hyperglycemia. Eight-week-old male Wistar rats were randomly divided into 4 groups: control, CO2 treatment, STZ-induced hyperglycemia, and STZ-induced hyperglycemia treated with CO2. STZ-induced hyperglycemia resulted in a decrease of muscle oxidative capacity and decreased PGC-1α and cytochrome c oxidase subunit 4 (COX-4) expression levels; while, application of transcutaneous CO2 attenuated this effect, and enhanced the expression levels of endothelial nitric oxide synthesis (eNOS). These results indicate that transcutaneous CO2 improves impaired muscle oxidative capacity via enhancement of eNOS and PGC-1α-related signaling in the skeletal muscle of rats with hyperglycemia.

Nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy mimicking rapid-onset Guillain-Barré syndrome: a case report.

Nivolumab, an anti-programmed death-1-specific monoclonal antibody, has demonstrated a durable response and effect on overall survival and has become one of the standard treatments for patients with advanced melanoma. Reported herein is a case of nivolumab-induced chronic inflammatory demyelinating polyradiculoneuropathy, in which an 85-year-old woman with stage IV melanoma developed grade 1 paresthesia 2 weeks after the initial dose of nivolumab was administered. With continued treatment, the neurological deficiency deteriorated rapidly, mimicking Guillain-Barré syndrome, causing such a dramatic decrease in her activities of daily living that she could no longer function in daily life. Thus, nivolumab treatment was discontinued. A course of intravenous immunoglobulin infusion yielded a dramatic clinical improvement; in particular, improved motor control was observed within a few days. Her initial presentation was suggestive of acute inflammatory demyelinating polyradiculoneuropathy, a subtype of Guillain-Barré syndrome; however, the good response to steroids and exacerbation 8 weeks after the onset were suggestive of chronic inflammatory demyelinating polyradiculoneuropathy induced by nivolumab. This is the first case of Guillain-Barré syndrome-like autoimmune polyradiculoneuropathy induced by programmed death-1/programmed death-ligand 1 inhibitors. Although neurological adverse events related to nivolumab are rare, they can become severe, requiring early diagnosis and intervention. Intravenous immunoglobulin may be considered as an effective initial treatment for patients who develop acute autoimmune nervous system disorders due to nivolumab.