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Regenerative Therapy Jun 2024Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury...
BACKGROUND
Skeletal muscle injury (SMI) is often treated conservatively, although it can lead to scar tissue formation, which impedes muscle function and increases muscle re-injury risk. However, effective interventions for SMIs are yet to be established.
HYPOTHESIS
The administration of Silk Elastin® (SE), a novel artificial protein, to the SMI site can suppress scar formation and promote tissue repair.
STUDY DESIGN
A controlled laboratory study.
METHODS
: Fibroblast migration ability was assessed using a scratch assay. SE solution was added to the culture medium, and the fibroblast migration ability was compared across different concentrations. : An SMI model was established with Sprague-Dawley rats, which were assigned to three groups based on the material injected to the SMI site: SE gel (SE group; n = 8), atelocollagen gel (Atelo group; n = 8), and phosphate buffer saline (PBS group; n = 8). Histological evaluations were performed at weeks 1 and 4 following the SMI induction. In the 1-week model, we detected the expression of transforming growth factor (TGF)-β1 in the stroma using immunohistological evaluation and real-time polymerase chain reaction analysis. In the 4-week model, we measured tibialis anterior muscle strength upon peroneal nerve stimulation as a functional assessment.
RESULTS
: The fibroblast migration ability was suppressed by SE added at a concentration of 10⁴ μg/mL in the culture medium. : In the 1-week model, the SE group exhibited significantly lower TGFβ -1 expression than the PBS group. In the 4-week model, the SE group had a significantly larger regenerated muscle fiber diameter and smaller scar formation area ratio than the other two groups. Moreover, the SE group was superior to the other two groups in terms of regenerative muscle strength.
CONCLUSION
Injection of SE gel to the SMI site may inhibit tissue scarring by reducing excessive fibroblast migration, thereby enhancing tissue repair.
CLINICAL RELEVANCE
The findings of this study may contribute to the development of an early intervention method for SMIs.
PubMed: 38948131
DOI: 10.1016/j.reth.2024.05.012 -
World Journal of Stem Cells Jun 2024Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe... (Clinical Trial)
Clinical Trial
BACKGROUND
Traumatic brain injury (TBI) is characterized by a disruption in the normal function of the brain due to an injury following a trauma, which can potentially cause severe physical, cognitive, and emotional impairment. Stem cell transplantation has evolved as a novel treatment modality in the management of TBI, as it has the potential to arrest the degeneration and promote regeneration of new cells in the brain. Wharton's Jelly-derived mesenchymal stem cells (WJ-MSCs) have recently shown beneficial effects in the functional recovery of neurological deficits.
AIM
To evaluate the safety and efficiency of MSC therapy in TBI.
METHODS
We present 6 patients, 4 male and 2 female aged between 21 and 27 years who suffered a TBI. These 6 patients underwent 6 doses of intrathecal, intramuscular (i.m.) and intravenous transplantation of WJ-MSCs at a target dose of 1 × 10/kg for each application route. Spasticity was assessed using the Modified Ashworth scale (MAS), motor function according to the Medical Research Council Muscle Strength Scale, quality of life was assessed by the Functional Independence Measure (FIM) scale and Karnofsky Performance Status scale.
RESULTS
Our patients showed only early, transient complications, such as subfebrile fever, mild headache, and muscle pain due to i.m. injection, which resolved within 24 h. During the one year follow-up, no other safety issues or adverse events were reported. These 6 patients showed improvements in their cognitive abilities, muscle spasticity, muscle strength, performance scores and fine motor skills when compared before and after the intervention. MAS values, which we used to assess spasticity, were observed to statistically significantly decrease for both left and right sides ( < 0.001). The FIM scale includes both motor scores ( < 0.05) and cognitive scores ( < 0.001) and showed a significant increase in pretest posttest analyses. The difference observed in the participants' Karnofsky Performance Scale values pre and post the intervention was statistically significant ( < 0.001).
CONCLUSION
This study showed that cell transplantation has a safe, effective and promising future in the management of TBI.
PubMed: 38948099
DOI: 10.4252/wjsc.v16.i6.641 -
Frontiers in Physiology 2024The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems.
UNLABELLED
The purpose of this study was to compare acute responses between manual and automated blood flow restriction (BFR) systems.
METHODS
A total of 33 individuals completed this study. On visit 1, arterial occlusion pressure (AOP, mm Hg), cardiovascular responses, and discomfort (RPE-D) were measured with each BFR system at rest. On visit 2, unilateral bicep curls were completed [30% one-repetition maximum; 50% AOP] with one system per arm. Muscle thickness (MT, cm) and maximal force (N) were assessed before (pre), immediately (post-0), 5 min (post-5), and 10 min (post-10) post-exercise. Ratings of perceived exertion (RPE-E) and ratings of perceived discomfort (RPE-D) were assessed throughout the exercise. AOP and repetitions were compared with Bayesian paired t-tests. Other outcomes were compared with Bayesian RMANOVAs. BF represents the likelihood of the best model vs. the null. The results are presented as mean ± SD.
RESULTS
Supine cardiovascular responses and RPE-D were similar for manual and automated (all BF ≤ 0.2). Supine AOP for manual (157 ± 20) was higher than that of automated (142 ± 17; BF = 44496.0), but similar while standing (manual: 141 ± 17; automated: 141 ± 22; BF = 0.2). MT (time, BF = 6.047e + 40) increased from Pre (3.9 ± 0.7) to Post-0 (4.4 ± 0.8; BF = 2.969e + 28), with Post-0 higher than Post-5 (4.3 ± 0.8) and Post-10 (4.3 ± 0.8; both BF ≥ 275.2). Force (time, BF = 1.246e + 29) decreased from Pre (234.5 ± 79.2) to Post-0 (149.8 ± 52.3; BF = 2.720e + 22) and increased from Post-0 to Post-5 (193.3 ± 72.7; BF = 1.744e + 13), with Post-5 to Post-10 (194.0 ± 70.6; BF = 0.2) being similar. RPE-E increased over sets. RPE-D was lower for manual than automated. Repetitions per set were higher for manual (Set 1: 37 ± 18; Set 4: 9 ± 5) than automated (Set 1: 30 ± 7; Set 4: 7 ± 3; all BF ≥ 9.7).
CONCLUSION
Under the same relative pressure, responses are mostly similar between BFR systems, although a manual system led to lower exercise discomfort and more repetitions.
PubMed: 38948082
DOI: 10.3389/fphys.2024.1409702 -
Cureus May 2024Multiple fractures are frequently encountered in adults following road traffic accidents. A 32-year-old male presented with multiple fractures in his right lower...
Multiple fractures are frequently encountered in adults following road traffic accidents. A 32-year-old male presented with multiple fractures in his right lower extremity, including a femoral shaft fracture, distal third fractures of the tibia and fibula, as well as a calcaneal fracture. The patient provided a history indicative of a road traffic accident. X-rays were performed on both hip joints, both knee joints, and the ankle joints. Treatment involved open reduction and internal fixation (ORIF) with interlocking nailing for the femur, tibia, and fibula, alongside ORIF with plating using a screw-out set (SOS) and cannulated cancellous (CC) screw fixation for the calcaneal fracture. Additionally, the Ilizarov procedure was conducted following debridement over the right foot. Post-surgery, the patient experienced primary symptoms of hip joint pain and restricted hip joint movement. Physiotherapy was initiated to address these issues. Evaluation of outcome measures indicated a reduction in joint pain, significant enhancement in joint mobility, and an increase in muscle strength.
PubMed: 38947633
DOI: 10.7759/cureus.61427 -
Journal of Pain Research 2024Chronic musculoskeletal pain (CMP), defined as persistent discomfort in musculoskeletal tissues persisting for over 3 months, afflicts an estimated 1.71 billion people... (Review)
Review
Chronic musculoskeletal pain (CMP), defined as persistent discomfort in musculoskeletal tissues persisting for over 3 months, afflicts an estimated 1.71 billion people globally, leading to significant functional impairments and psychological distress, thereby detrimentally affecting individuals' quality of life. The objective of this narrative review is to elucidate the complex relationship among dietary habits, sarcopenia, and gut microbiota composition, with an eye toward enhancing patient management and outcomes. Given the burgeoning interest in the influence of diet on CMP, a detailed examination of the current literature is warranted. Nutritional intake is a critical determinant of the gut microbiota profile, which, in turn, is linked to musculature integrity and performance, potentially leading to sarcopenia. The development of sarcopenia can aggravate CMP owing to diminished muscular strength and functionality. Additionally, disruptions in the gut microbiota may directly modulate nociception, intensifying CMP manifestations. Thus, nutritional optimization emerges as a viable approach to CMP management. Emphasizing a diet conducive to a healthy gut microbiome could forestall or mitigate sarcopenia, thereby attenuating CMP intensity. Nevertheless, the domain calls for further empirical exploration to unravel the nuances of these interactions and to forge efficacious dietary strategies for individuals with CMP. Beyond mere analgesia, comprehensive patient care for CMP requires acknowledgment of the complex and multifactorial nature of pain and its foundational elements. Embracing an integrative treatment model allows healthcare practitioners to promise better patient prognoses, enriched life quality, and a decrease in the sustained healthcare costs associated with CMP.
PubMed: 38947129
DOI: 10.2147/JPR.S456202 -
MedRxiv : the Preprint Server For... Jun 2024Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined....
BACKGROUND
Inclusion body myositis (IBM) is the most prevalent muscle disease in adults for which no current treatment exists. The pathogenesis of IBM remains poorly defined. Inflammation and mitochondrial dysfunction are the most common histopathological findings. In this study, we aimed to explore the interplay between inflammation and mitochondrial dysfunction in IBM patients, highlighting sex differences.
METHODS
We included 38 IBM patients and 22 age- and sex-matched controls without myopathy. Bulk RNA sequencing, Meso Scale Discovery ELISA, western blotting, histochemistry and immunohistochemistry were performed on frozen muscle samples from the study participants.
RESULTS
We demonstrated activation of the NLRP3 inflammasome in IBM muscle samples, with the NLRP3 inflammasome pathway being the most upregulated. On muscle histopathology, there is increased NRLP3 immunoreactivity in both inflammatory cells and muscle fibers. Mitophagy is critical for removing damaged mitochondria and preventing the formation of a vicious cycle of mitochondrial dysfunction-NLRP3 activation. In the IBM muscle samples, we showed altered mitophagy, most significantly in males, with elevated levels of p-S65-Ubiquitin, a mitophagy marker. Furthermore, p-S65-Ubiquitin aggregates accumulated in muscle fibers that were mostly type 2 and devoid of cytochrome-c-oxidase reactivity. Type 2 muscle fibers are known to be more prone to mitochondrial dysfunction. levels correlated with p-S65-Ubiquitin levels in both sexes but with loss of in muscle strength only in males. Finally, we identified sex-specific molecular pathways in IBM, with females having activation of pathways that could offset some of the pathomechanisms of IBM.
CONCLUSIONS
NLRP3 inflammasome is activated in IBM, along with altered mitophagy particularly in males, which is of potential therapeutic significance. These findings suggest sex-specific mechanisms in IBM that warrant further investigation.
PubMed: 38947067
DOI: 10.1101/2024.06.15.24308845 -
MedRxiv : the Preprint Server For... Jun 2024Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and...
BACKGROUND
Weekly Steroids in Muscular Dystrophy (WSiMD) was a pilot study to evaluate once weekly prednisone in patients with Limb Girdle and Becker muscular dystrophy (LGMD and BMD, respectively). At study endpoint, there were trends towards increased lean mass, reduced fat mass, reduced creatine kinase and improved motor function. The investigation was motivated by studies in mouse muscular dystrophy models in which once weekly glucocorticoid exposure enhanced muscle strength and reduced fibrosis.
METHODS
WSiMD participants provided blood samples for aptamer serum profiling at baseline and after 6 months of weekly steroids. A subset completed magnetic resonance (MR) evaluation of muscle at study onset and endpoint.
RESULTS/CONCLUSIONS
At baseline compared to age and sex-matched healthy controls, the aggregate serum protein profile in the WSiMD cohort was dominated by muscle proteins, reflecting leak of muscle proteins into serum. Disease status produced more proteins differentially present in serum compared to steroid-treatment effect. Nonetheless, a response to prednisone was discernable in the WSiMD cohort, even at this low dose. Glucocorticoids downregulated muscle proteins and upregulated certain immune process- and matrix-associated proteins. Muscle MR fat fraction showed trends with functional status. The prednisone-responsive markers could be used in larger trial of prednisone efficacy.
PubMed: 38947030
DOI: 10.1101/2024.06.14.24308858 -
Diabetes, Metabolic Syndrome and... 2024Growing evidence indicates that there is a close relationship between type 2 diabetes mellitus (T2DM) and sarcopenia, and T2DM patients are often accompanied by obesity....
Importance of Assessing Sarcopenia in Patients with Type 2 Diabetes Mellitus Based on Body Fat Percentage Measured by Dual-Energy X-Ray Absorptiometry in Different Genders.
BACKGROUND
Growing evidence indicates that there is a close relationship between type 2 diabetes mellitus (T2DM) and sarcopenia, and T2DM patients are often accompanied by obesity. However, research exploring the connection between body fat percentage (BFP) and sarcopenia is currently limited.
METHODS
This was a cross-sectional study that included 676 patients with T2DM over 50 years old. The appendicular skeletal muscle mass index (ASMI), handgrip strength, and 5-time chair stand test (5-TCST) were measured, and sarcopenia was diagnosed according to the Asian Working Group on Sarcopenia (AWGS). Spearman's coefficient was used to evaluate the correlation of BFP and body mass index (BMI) with the diagnostic elements of sarcopenia, and BFP and other relevant covariates were included in the binary logistic regression model. The subgroup performed an interaction test for statistically significant population baseline information.
RESULTS
The prevalence of sarcopenia was 18.0% in males and 11.6% in females. Spearman correlation analysis showed that BFP was positively correlated with ASMI in women (=0.107, =0.029), but not in men. BFP was negatively correlated with grip strength (male: = -0.187, =0.003; female: =-0.108, =0.029). There was a positive correlation between BFP and 5-TCST (male: =0.199, =0.001; female: =0.144, =0.003). After adjusting for confounding factors, BFP was an independent risk factor for sarcopenia (men, OR: 1.33, 95% CI: 1.15-1.54; women, OR: 1.26, 95% CI: 1.13-1.41). This correlation was generally consistent, as demonstrated in further subgroup analyses.
CONCLUSION
High BFP was significantly associated with sarcopenia risk, and this association was independent of gender, age, and BMI.
PubMed: 38946913
DOI: 10.2147/DMSO.S461748 -
Frontiers in Cell and Developmental... 2024Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed...
BACKGROUND
Osteoarthritis (OA) knee patients have limited ability in physical function, or difficulties with physical tasks and activities may develop disability. This study aimed to observe the predictors of self-reported and performance-based physical function in patients with knee OA by analyzing the impacts of demographic, pathological, and muscle impairment factors.
METHODS
135 knee OA patients participated in this study to complete self-reported questionnaires using Knee Injury and Osteoarthritis Outcome Score (KOOS). When measuring performance-based physical function, a 6-meter gait speed (6MGS) test was measured to evaluate their mobility, and a 5-time Sit-to-Stand test (5STS) was assessed to evaluate their balance. Pain intensity, knee extensor and flexor muscle strength, age, body mass index (BMI), durations of symptoms, and radiographic severity were also collected. Spearman correlation and stepwise multiple linear regression were used to explore the association and predictors in self-reported and performance-based physical function.
RESULTS
BMI and durations of symptoms did not indicate any significant correlation with either self-reported or performance-based physical function. Age is significantly negatively associated with 6MGS ( = -0.383, < 0.01), while knee extensor muscle strength has a moderate correlation with 5STS ( = -0.528, < 0.01). In the stepwise multiple linear regression models, pain intensity (β = 0.712, < 0.001), knee flexor muscle strength (β = 0.112, = 0.042) were significantly associated with self-reported physical function in daily activities and contributed to 55.0% of the variance in KOOS-PF score. Knee muscle strength, including knee extensor (5STS: β = -0.428, < 0.001) and flexor muscle strength (6MGS: β = 0.367, < 0.001), were the main predictors with performance-based physical function.
CONCLUSION
Pain intensity was the leading risk factor of self-reported physical function, and knee flexor muscle strength contributed as well. The severity of knee OA, durations of symptoms and BMI did not contribute to physical function. However, knee extensor and flexor muscle strength were the main predictors of performance-based performance. Our results show that strengthening of weak knee muscles in both quadriceps and hamstring muscle strength should be considered a priory consideration in knee OA no matter if people are in the early or end-stage of knee OA.
PubMed: 38946798
DOI: 10.3389/fcell.2024.1406830 -
Osteoarthritis and Cartilage Open Sep 2024Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes... (Review)
Review
OBJECTIVE
Osteoarthritis prevalence differs between women and men; whether this is the result of differences in pre-morbid articular or peri-articular anatomical morphotypes remains enigmatic. Albeit sex within humans cannot be reduced to female/male, this review focusses to the sexual dimorphism of peri-articular tissues, given lack of literature on non-binary subjects.
METHODS
Based on a Pubmed search and input from experts, we selected relevant articles based on the authors' judgement of relevance, interest, and quality; no "hard" bibliometric measures were used to evaluate the quality or importance of the work. Emphasis was on clinical studies, with most (imaging) data being available for the knee and thigh.
RESULTS
The literature on sexual dimorphism of peri-articular tissues is reviewed: 1) bone size/shape, 2) subchondral/subarticular bone, 3) synovial membrane and infra-patellar fad-pad (IPFP), 4) muscle/adipose tissue, and 5) peri-articular tissue response to treatment.
CONCLUSIONS
Relevant sex-specific differences exist for 3D bone shape and IPFP size, even after normalization to body weight. Presence of effusion- and Hoffa-synovitis is associated with greater risk of incident knee osteoarthritis in overweight women, but not in men. When normalized to bone size, men exhibit greater muscle, and women greater adipose tissue measures relative to the opposite sex. Reduced thigh muscle specific strength is associated with incident knee osteoarthritis and knee replacement in women, but not in men. These observations may explain why women with muscle strength deficits have a poorer prognosis than men with similar deficits. A "one size/sex fits all" approach must be urgently abandoned in osteoarthritis research.
PubMed: 38946793
DOI: 10.1016/j.ocarto.2024.100485