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Kidney & Blood Pressure Research May 2024Background Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle... (Review)
Review
Background Chronic kidney disease (CKD) is a progressive systemic condition characterized by numerous complications. Among these, alterations in skeletal muscle physiology, such as sarcopenia, are particularly significant, as they are associated with poor outcomes and reduced quality of life. Summary Various interventions, including pharmacological approaches and lifestyle modifications have been investigated to slow CKD progression and prevent or treat its complications. Physical exercise, in particular, has emerged as a promising intervention with multiple beneficial effects. These include improvements in physical functioning, increased muscle mass, modulation of metabolic abnormalities, and reduced cardiovascular risk. However, the pathophysiology of physical exercise in patients with kidney disease is complex and remains only partially understood. A crucial advancement in understanding this phenomenon has been the identification of myokines-molecules expressed and released by skeletal muscle in response to physical activity. These myokines can exert both paracrine and systemic effects, influencing not only skeletal muscle physiology but also other processes such as energy metabolism and lipid regulation. Key Messages The interplay among skeletal muscle, physical activity, and myokines may act as a pivotal regulator in various physiological processes, including aging, as well as in pathological conditions like cachexia and sarcopenia, frequently observed in CKD patients at different stages, including patients on dialysis. Despite the potential importance of this relationship, only a limited number of studies have explored the relationship between exercise and myokine, and the effect of this interaction on experimental models or individuals with kidney disease. In the following sections, we review and discuss this topic.
PubMed: 38815556
DOI: 10.1159/000539489 -
Redox Biology May 2024Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to...
Cysteine, the rate-controlling amino acid in cellular glutathione synthesis is imported as cystine, by the cystine/glutamate antiporter, xCT, and subsequently reduced to cysteine. As glutathione redox is important in muscle regeneration in aging, we hypothesized that xCT exerts upstream control over skeletal muscle glutathione redox, metabolism and regeneration. Bioinformatic analyses of publicly available datasets revealed that expression levels of xCT and GSH-related genes are inversely correlated with myogenic differentiation genes. Muscle satellite cells (MuSCs) isolated from Slc7a11 mice, which harbour a mutation in the Slc7a11 gene encoding xCT, required media supplementation with 2-mercaptoethanol to support cell proliferation but not myotube differentiation, despite persistently lower GSH. Slc7a11 primary myotubes were larger compared to WT myotubes, and also exhibited higher glucose uptake and cellular oxidative capacities. Immunostaining of myogenic markers (Pax7, MyoD, and myogenin) in cardiotoxin-damaged tibialis anterior muscle fibres revealed greater MuSC activation and commitment to differentiation in Slc7a11 muscle compared to WT mice, culminating in larger myofiber cross-sectional areas at 21 days post-injury. Slc7a11 mice subjected to a 5-week exercise training protocol demonstrated enhanced insulin tolerance compared to WT mice, but blunted muscle mitochondrial biogenesis and respiration in response to exercise training. Our results demonstrate that the absence of xCT inhibits cell proliferation but promotes myotube differentiation by regulating cellular metabolism and glutathione redox. Altogether, these results support the notion that myogenesis is a redox-regulated process and may help inform novel therapeutic approaches for muscle wasting and dysfunction in aging and disease.
PubMed: 38815331
DOI: 10.1016/j.redox.2024.103213 -
Arteriosclerosis, Thrombosis, and... May 2024Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging...
BACKGROUND
Pulmonary hypertension (PH) represents an important phenotype in heart failure with preserved ejection fraction (HFpEF). However, management of PH-HFpEF is challenging because mechanisms involved in the regulation of PH-HFpEF remain unclear.
METHODS
We used a mass spectrometry-based comparative plasma proteomics approach as a sensitive and comprehensive hypothesis-generating discovery technique to profile proteins in patients with PH-HFpEF and control subjects. We then validated and investigated the role of one of the identified proteins using in vitro cell cultures, in vivo animal models, and independent cohort of human samples.
RESULTS
Plasma proteomics identified high protein abundance levels of B2M (β2-microglobulin) in patients with PH-HFpEF. Interestingly, both circulating and skeletal muscle levels of B2M were increased in mice with skeletal muscle SIRT3 (sirtuin-3) deficiency or high-fat diet-induced PH-HFpEF. Plasma and muscle biopsies from a validation cohort of PH-HFpEF patients were found to have increased B2M levels, which positively correlated with disease severity, especially pulmonary capillary wedge pressure and right atrial pressure at rest. Not only did the administration of exogenous B2M promote migration/proliferation in pulmonary arterial vascular endothelial cells but it also increased PCNA (proliferating cell nuclear antigen) expression and cell proliferation in pulmonary arterial vascular smooth muscle cells. Finally, deletion improved glucose intolerance, reduced pulmonary vascular remodeling, lowered PH, and attenuated RV hypertrophy in mice with high-fat diet-induced PH-HFpEF.
CONCLUSIONS
Patients with PH-HFpEF display higher circulating and skeletal muscle expression levels of B2M, the magnitude of which correlates with disease severity. Our findings also reveal a previously unknown pathogenic role of B2M in the regulation of pulmonary vascular proliferative remodeling and PH-HFpEF. These data suggest that circulating and skeletal muscle B2M can be promising targets for the management of PH-HFpEF.
PubMed: 38813697
DOI: 10.1161/ATVBAHA.123.320270 -
Current Developments in Nutrition Jun 2024Glutamine in milk is believed to play an important role in neonatal intestinal maturation and immune function. For lactating mothers, glutamine utilization is increased...
BACKGROUND
Glutamine in milk is believed to play an important role in neonatal intestinal maturation and immune function. For lactating mothers, glutamine utilization is increased to meet the demands of the enlarged intestine and milk production. However, the source of such glutamine during lactation has not been studied.
OBJECTIVES
We aimed to assess the effects of lactation on the expression of glutamine synthetase (GS) in the mammary gland and other tissues of lactating mice.
METHODS
Mouse tissues were sampled at 4 time points: 8-wk-old (virgin, control), post-delivery day 5 (PD5, early lactation), PD15 (peak lactation), and involution (4 days after weaning at PD21). We examined the gene expression and protein concentrations of GS and the first 2 enzymes of branched-chain amino acid catabolism: branched-chain aminotransferase 2 (BCAT2) and branched-chain ketoacid dehydrogenase subunit E1α (BCKDHA).
RESULTS
The messenger RNA (mRNA) expression and protein concentrations of GS in mammary glands were significantly lower at PD5 and PD15 compared with the control but were restored at involution. Within the mammary gland, GS protein was only detected in adipocytes with no evidence of presence in mammary epithelial cells. Compared with the control, mRNA and protein concentrations of BCAT2 and BCKDHA in mammary glands significantly decreased during lactation and involution. No changes in GS protein concentrations during lactation were found in the liver, skeletal muscle, and lung. In non-mammary adipose tissue, GS protein abundance was higher during lactation compared with the virgin.
CONCLUSIONS
This work shows that, within the mouse mammary gland, GS is only expressed in adipocytes and that the relative GS abundance in mammary gland sections is lower during lactation. This suggests that mammary adipocytes may be a site of glutamine synthesis in the lactating mouse. Identifying the sources of glutamine production during lactation is important for optimizing milk glutamine concentration to enhance neonatal and maternal health.
PubMed: 38813479
DOI: 10.1016/j.cdnut.2024.102168 -
Frontiers in Medicine 2024Prior research underscores the significance of paraspinal muscles in maintaining spinal stability. This study aims to investigate the predictive value of paraspinal...
OBJECTIVE
Prior research underscores the significance of paraspinal muscles in maintaining spinal stability. This study aims to investigate the predictive value of paraspinal muscle parameters for the occurrence of new vertebral compression fractures (NVCF) following percutaneous vertebroplasty (PVP) or percutaneous kyphoplasty (PKP) in patients with osteoporotic vertebral compression fractures (OVCF).
METHODS
Retrospectively collected data from October 2019 to February 2021 (internal validation, = 235) and March 2021 to November 2021 (external validation, = 105) for patients with OVCF treated with PVP/PKP at our institution. They were randomly divided into training (188 cases) and validation groups (47 cases) at an 8:2 ratio. Lasso regression and multivariable logistic regression identified independent risk factors in the training set, and a Nomogram model was developed. Accuracy was assessed using receiver operating characteristic curves (ROC), calibration was evaluated with calibration curves and the Hosmer-Lemeshow test, and clinical utility was analyzed using decision curve analysis (DCA) and clinical impact curve (CIC).
RESULTS
Surgical approach, spinal computed tomography (CT) values, and multifidus skeletal muscle index (SMI) are independent predictors of postoperative NVCF in OVCF patients. A Nomogram model, based on the identified predictors, was developed and uploaded online. Internal validation results showed area under the curve (AUC) values of 0.801, 0.664, and 0.832 for the training set, validation set, and external validation, respectively. Hosmer-Lemeshow goodness-of-fit tests ( = 7.311-14.474, = 0.070-0.504) and calibration curves indicated good consistency between observed and predicted values. DCA and CIC demonstrated clinical net benefit within risk thresholds of 0.06-0.84, 0.12-0.23, and 0.01-0.27. At specificity 1.00-0.80, the partial AUC (0.106) exceeded that at sensitivity 1.00-0.80 (0.062).
CONCLUSION
Compared to the spinal CT value, the multifidus SMI has certain potential in predicting the occurrence of NVCF. Additionally, the Nomogram model of this study has a greater negative predictive value.
PubMed: 38813387
DOI: 10.3389/fmed.2024.1379078 -
World Journal of Gastroenterology May 2024Cirrhosis is frequently associated with sarcopenia, with reported rates of over 80% in patients with decompensated alcohol-related liver disease. Sarcopenia negatively...
Cirrhosis is frequently associated with sarcopenia, with reported rates of over 80% in patients with decompensated alcohol-related liver disease. Sarcopenia negatively impacts the prognosis of cirrhotic patients and affects the response to treatment of patients with hepatocellular carcinoma (HCC). For these reasons, identifying an easy-to-perform method to assess sarcopenia in is a key element in the optimization of care in this patient population. Assessment of muscle mass by computed tomography is considered the standard of care for the diagnosis of sarcopenia, but exposure to radiation and high costs limit its application in this setting, especially for repeated assessments. We believe that ultrasound, a cheap and harmless technique also used for HCC screening in cirrhotic patients, could have an expanding role in the diagnosis and follow-up of sarcopenia in these patients.
Topics: Sarcopenia; Humans; Ultrasonography; Liver Cirrhosis; Carcinoma, Hepatocellular; Tomography, X-Ray Computed; Prognosis; Liver Neoplasms; Muscle, Skeletal
PubMed: 38813055
DOI: 10.3748/wjg.v30.i17.2287 -
Turkish Journal of Medical Sciences 2023The firing rate of the mirror neuron system in monkeys decreases systematically with more repetitions. The aim of this study is to investigate whether the activity of...
BACKGROUND/AIM
The firing rate of the mirror neuron system in monkeys decreases systematically with more repetitions. The aim of this study is to investigate whether the activity of the mirror neuron system varies based on the observed movement and the contents of the action, as well as whether there is inhibition in the mirror neuron system when humans observe repeated actions. If inhibition is present, the second question of the study is whether it is related to the organization of the observed action.
MATERIALS AND METHODS
Fourteen healthy volunteers participated in the study. Transcranial magnetic stimulation was applied to the left primary motor cortex and motor evoked potentials (MEPs) were recorded from the right first dorsal interosseous and abductor pollicis brevis muscles while the participants were watching videos specially prepared for the study.
RESULTS
There were no significant changes in MEP amplitudes compared to baseline MEPs while observing aimless action. However, while participants watched the repeated action video, the mean MEP amplitude increased at the beginning of the movement, but neither facilitation nor inhibition was detected when the participants watched the phase of grasping the object of the action compared to the baseline MEP amplitude. On the other hand, while participants were watching different activities, an increased MEP amplitude was observed at the beginning of the movement and in the grasping of the object of the action. Additionally, there was no significant reduction in MEP amplitude during any movement stages while observing the repeated action video.
CONCLUSION
The findings of this study suggest that the activation of the mirror neuron system in humans depends on the content and stages of the observed movement. Additionally, there was no inhibition or systematic reduction in MEP amplitudes while watching a repeated action.
Topics: Humans; Mirror Neurons; Transcranial Magnetic Stimulation; Male; Evoked Potentials, Motor; Female; Adult; Motor Cortex; Young Adult; Muscle, Skeletal; Movement; Electromyography
PubMed: 38813024
DOI: 10.55730/1300-0144.5710 -
Turkish Journal of Medical Sciences 2023The aim was to investigate the effect of thoracic mobilization exercises on hamstring flexibility. (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND AND AIM
The aim was to investigate the effect of thoracic mobilization exercises on hamstring flexibility.
MATERIALS AND METHODS
One hundred twenty individuals with hamstring tightness were included in the study. The participants were randomized into two groups: the experimental group (EG) (n = 60) or the control group (CG) (n = 60). The EG performed a home-based thoracic mobilization exercise program comprising 2 sets with 10 repetitions, once a day, 3 days a week, for 4 weeks. The CG performed active-assisted stretching of the hamstring comprising 3 sets with 10 repetitions for 15 seconds. The active knee extension (AKE) test was used to measure hamstring flexibility, and self-reported hamstring pain intensity was evaluated with a visual analog scale (VAS). All evaluations were conducted at the beginning and end of the intervention.
RESULTS
Both groups showed significant improvement in AKE (p<0.05). Pain intensity during the stretching exercises was significantly decreased only in the EG. The improvements in AKE and VAS score were greater in the EG than in the CG (p < 0.05). Between-group effect sizes were large for AKE (d = 1.075) and VAS score (d = 1.077).
CONCLUSION
The current study showed that thoracic mobilization exercises may increase hamstring flexibility and reduce pain intensity during hamstring stretch exercises.
Topics: Humans; Male; Hamstring Muscles; Female; Adult; Range of Motion, Articular; Muscle Stretching Exercises; Exercise Therapy; Young Adult; Middle Aged; Pain Measurement
PubMed: 38813012
DOI: 10.55730/1300-0144.5695 -
Turkish Journal of Medical Sciences 2023It is known that the correlation of pulmonary function tests (PFT) with muscle dysfunction is insufficient. Here, we aimed to evaluate the diaphragm functions in...
BACKGROUND/AIM
It is known that the correlation of pulmonary function tests (PFT) with muscle dysfunction is insufficient. Here, we aimed to evaluate the diaphragm functions in individuals with Friedreich's ataxia (FRDA) and to examine its relationship with respiratory parameters and disease severity.
MATERIALS AND METHODS
This prospective study, conducted between November and December 2022, at Erciyes University, included 14 individuals with genetically confirmed FRDA and an age- and gender-matched healthy control group of eight individuals. We examined pulmonary functions with spirometric methods and evaluated diaphragm excursion, and diaphragm thickness-expiratory (Tde) and - end of inspiration (Tdi) with ultrasonography during calm breathing. Thickening fraction (TF) calculated. Also, we examined PaCO2 at rest. The neurological status of individuals was assessed using the Scale for the Assessment and Rating of Ataxia (SARA).
RESULTS
The mean values of FEV1(lt), FEV1(%), FVC (lt), and FVC (%) were higher in the control group (p; <0.001, 0.013, <0.001, and 0.009, respectively). Also, mean Tdi, Tde, excursion and TF were lower in the FRDA group compared to the control group (p = 0.005, 0.294,0.005, and 0.019, respectively). The mean excursion value was 1.13 ± 0.54cm in the FRDA group and 1.71 ± 0.49cm in the control group. There is a strong, negative, and statistically significant correlation between SARA total score with excursion and TF (r = -0.7432, p = 0.002; r = -0.697, p = 0.008). There is no statistically significant relationship between excursion and BMI, standing-to-supine decrease in FVC, FEV1, and PaCO2. Also, the relationship between maximal inspiratory pressure (PImax) and excursion was moderate.
CONCLUSION
Diaphragm ultrasound may reveal respiratory dysfunction better than PFT. Diaphragm excursion and TF are associated with disease scores in individuals with FDRA. Further studies are needed regarding the detection of alveolar hypoventilation.
Topics: Humans; Friedreich Ataxia; Diaphragm; Male; Female; Ultrasonography; Prospective Studies; Adult; Respiratory Function Tests; Young Adult; Spirometry; Case-Control Studies
PubMed: 38812999
DOI: 10.55730/1300-0144.5696 -
Turkish Journal of Medical Sciences 2023Children with cerebral palsy (CP), even those who have very mild impairment, have lower muscle strength than their typically developing peers. The ankle dorsiflexors... (Randomized Controlled Trial)
Randomized Controlled Trial
BACKGROUND/AIM
Children with cerebral palsy (CP), even those who have very mild impairment, have lower muscle strength than their typically developing peers. The ankle dorsiflexors (DFs) and plantarflexors (PFs) of children with CP are especially weak. Weakness in the ankle muscles causes problems in functional skills, mobility, and balance in spastic CP (SCP). The aim of this study was to investigate the effects of progressive functional exercises (PFEs) on the DF, PF, or dorsi-plantar flexor (DPF) muscles in children with SCP, specifically, the functional mobility, balance, and maximum voluntary contraction (MVC), and compare the effects of strengthening these muscles individually or combined.
MATERIALS AND METHODS
This randomized trial was conducted between December 1st, 2018, and May 15th, 2019, at Gazi University, Department of Physiotherapy and Rehabilitation. Randomly assigned into groups were 27 independently ambulant patients with unilateral/bilateral SCP, where PFEs were applied to the DF, PF, or DPF muscles. Muscle tone, balance, and functional mobility were assessed. The MVC was evaluated by surface electromyography. PFEs were performed 4 times a week, for 6 weeks.
RESULTS
The spasticity of the PF muscles decreased in all of the groups. PFE of the DF muscles led to an increase in ankle joint range of motion (ROM) and improved functional mobility (p < 0.05). PFE of the PF muscles resulted in improvements in balance and functional mobility (p < 0.05). PFE of the DPF muscles brought about improvements in balance but not in functional mobility (p < 0.05). No significant difference in the MVC was observed in any of the groups (p > 0.05).
CONCLUSION
Gains are obtained according to the function of a muscle group. By training the DF muscles, it is possible to improve function and ROM. Furthermore, training the PF muscles led to improvements in balance and functional mobility, indicating that it is possible to bring about positive changes in spastic muscles. This study showed that muscle groups must be exercised according to the intended goal.
Topics: Humans; Cerebral Palsy; Male; Female; Child; Exercise Therapy; Muscle Spasticity; Muscle, Skeletal; Ankle Joint; Range of Motion, Articular; Ankle; Electromyography; Muscle Strength; Adolescent
PubMed: 38812998
DOI: 10.55730/1300-0144.5682