Celecoxib attenuates hindlimb unloading-induced muscle atrophy via suppressing inflammation, oxidative stress and ER stress by inhibiting STAT3.

Improving inflammation may serve as useful therapeutic interventions for the hindlimb unloading-induced disuse muscle atrophy. Celecoxib is a selective non-steroidal anti-inflammatory drug. We aimed to determine the role and mechanism of celecoxib in hindlimb unloading-induced disuse muscle atrophy. Celecoxib significantly attenuated the decrease in soleus muscle mass, hindlimb muscle function and the shift from slow- to fast-twitch muscle fibers caused by hindlimb unloading in rats. Importantly, celecoxib inhibited the increased expression of inflammatory factors, macrophage infiltration in damaged soleus muscle. Mechanistically, Celecoxib could significantly reduce oxidative stress and endoplasmic reticulum stress in soleus muscle of unloaded rats. Furthermore, celecoxib inhibited muscle proteolysis by reducing the levels of MAFbx, MuRF1, and autophagy related proteins maybe by inhibiting the activation of pro-inflammatory STAT3 pathway in vivo and in vitro. This study is the first to demonstrate that celecoxib can attenuate disuse muscle atrophy caused by hindlimb unloading via suppressing inflammation, oxidative stress and endoplasmic reticulum stress probably, improving target muscle function and reversing the shift of muscle fiber types by inhibiting STAT3 pathways-mediated inflammatory cascade. This study not only enriches the potential molecular regulatory mechanisms, but also provides new potential therapeutic targets for disuse muscle atrophy.

MuSCs and IPCs: roles in skeletal muscle homeostasis, aging and injury.

Skeletal muscle is a highly specialized tissue composed of myofibres that performs crucial functions in movement and metabolism. In response to external stimuli and injuries, a range of stem/progenitor cells, with muscle stem cells or satellite cells (MuSCs) being the predominant cell type, are rapidly activated to repair and regenerate skeletal muscle within weeks. Under normal conditions, MuSCs remain in a quiescent state, but become proliferative and differentiate into new myofibres in response to injury. In addition to MuSCs, some interstitial progenitor cells (IPCs) such as fibro-adipogenic progenitors (FAPs), pericytes, interstitial stem cells expressing PW1 and negative for Pax7 (PICs), muscle side population cells (SPCs), CD133-positive cells and Twist2-positive cells have been identified as playing direct or indirect roles in regenerating muscle tissue. Here, we highlight the heterogeneity, molecular markers, and functional properties of these interstitial progenitor cells, and explore the role of muscle stem/progenitor cells in skeletal muscle homeostasis, aging, and muscle-related diseases. This review provides critical insights for future stem cell therapies aimed at treating muscle-related diseases.

Transcriptome sequencing promotes insights on the molecular mechanism of SKP-SC-EVs mitigating denervation-induced muscle atrophy.

BACKGROUND: Complex pathophysiological changes accompany denervation-induced skeletal muscle atrophy, but no effective treatment strategies exist. Our previous study indicated that extracellular vesicles derived from skin-derived precursors-derived Schwann cells (SKP-SC-EVs) can effectively mitigate denervation-induced muscle atrophy. However, the specific molecular mechanism remains unclear. METHODS AND RESULTS: In this study, we used bioinformatics methods to scrutinize the impact of SKP-SC-EVs on gene expression in denervation-induced skeletal muscle atrophy. We found that SKP-SC-EVs altered the expression of 358 genes in denervated skeletal muscles. The differentially expressed genes were predominantly participated in biological processes, including cell cycle, inflammation, immunity, and adhesion, and signaling pathways, such as FoxO and PI3K.Using the Molecular Complex Detection (MCODE) plugin, we identified the two clusters with the highest score: cluster 1 comprised 37 genes, and Cluster 2 consisted of 24 genes. Then, fifty hub genes were identified using CytoHubba. The intersection of Hub genes and genes obtained by MCODE showed that all 23 genes related to the cell cycle in Cluster 1 were hub genes, and 5 genes in Cluster 2 were hub genes and associated with inflammation. CONCLUSIONS: Overall, the differentially expressed genes in denervated skeletal muscle following SKP-SC-EVs treatment are primarily linked to the cell cycle and inflammation. Consequently, promoting proliferation and inhibiting inflammation may be the critical process in which SKP-SC-EVs delay denervation-induced muscle atrophy. Our findings contribute to a better understanding of the molecular mechanism of SKP-SC-EVs delaying denervation-induced muscle atrophy, offering a promising new avenue for muscle atrophy treatment.

Improvement in the healing of bone fractures using a cyclodextrin/Ni-MOF nanofibers network: the development of a novel substrate to increase the surface area with desirable functional properties.

In this study, a ß-cyclodextrins (ß-CDs)/Ni-based MOF (ß-CDs/Ni-based MOF) fibrous network with focus on biocompatible and biodegradable properties was used as a new material for orthopedic applications. The final products were synthesized by an efficient, rapid, and controllable electrospinning route under optimal conditions, including a flow rate of 0.3 mL g-1, applied voltage of 18 kV, and spinning distance of 20 cm. Efficient characterization by various analyzes showed that the ß-CDs/Ni-based MOF fibrous nanostructures had a thermal stability at about 320 °C and homogeneous particles with a narrow size distribution. The BET analysis results showed a specific surface area of 2140 m2 g-1 for these compounds, which facilized potential conditions needed for the application of these compounds as a new substrate to improve the healing of bone fractures. The results showed the better porosity of the ß-CDs/Ni-based MOF scaffolds as an essential property, leading to higher proliferation and nutrition and oxygen delivery, resulting in more tissue regeneration. This study proposes a novel strategy for a fibrous network substrate with distinct properties for orthopedic purposes.

Effect of Acupoint Hot Compress on Postpartum Urinary Retention After Vaginal Delivery: A Randomized Clinical Trial.

Importance: Acupoint hot compress during the early postpartum period may benefit patients after a vaginal delivery, but the evidence of this effect is limited. Objective: To assess whether acupoint hot compress involving the abdominal, lumbosacral, and plantar regions could reduce the incidence of postpartum urinary retention, relieve postpartum uterine contraction pain, prevent emotional disorders, and promote lactation. Design, Setting, and Participants: This multicenter randomized clinical trial was conducted at 12 hospitals in China. Pregnant patients were screened for eligibility (n = 13 949) and enrolled after vaginal delivery (n = 1200) between January 17 and August 15, 2021; data collection was completed on August 18, 2021. After vaginal delivery, these participants were randomized 1:1 to either the intervention group or control group. Statistical analysis was based on per-protocol population. Interventions: Participants in the control group received routine postpartum care. Participants in the intervention group received routine postpartum care plus 3 sessions of a 4-hour acupoint hot compress involving the abdominal, lumbosacral, and plantar regions within 30 minutes, 24 hours, and 48 hours after delivery. Main Outcomes and Measures: The primary outcome was the incidence of postpartum urinary retention, defined as the first urination occurring more than 6.5 hours after delivery and/or use of an indwelling catheter within 72 hours after delivery. The secondary outcomes were postpartum uterine contraction pain intensity (assessed with the visual analog scale [VAS]), depressive symptoms (assessed with the Edinburgh Postnatal Depression Scale), and lactation conditions (including lactation initiation time, breastfeeding milk volume, feeding mood and times, and newborn weight). Results: Of the 1200 participants randomized, 1085 completed the study (537 in the intervention group and 548 in the control group, with a median [IQR] age of 26.0 [24.0-29.0] years). Participants in the intervention group compared with the control group had significantly decreased incidence of postpartum urinary retention (relative risk [RR], 0.58; 95% CI, 0.35-0.98; P = .03); improved postpartum uterine contraction pain when measured at 6.5 hours (median [IQR] VAS score, 1 [1-2] vs 2 [1-2]; P < .001), 28.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [1-2]; P < .001), 52.5 hours (median [IQR] VAS score, 1 [0-1] vs 1 [0-1]; P < .001), and 76.5 hours (median [IQR] VAS score, 0 [0-1] vs 0 [0-1]; P = .01) after delivery; reduced depressive symptoms (RR, 0.73; 95% CI, 0.54-0.98; P = .01); and increased breastfeeding milk volume measured at 28.5, 52.5, and 76.5 hours after delivery. No adverse events occurred in either of the 2 groups. Conclusions and Relevance: Results of this trial showed that acupoint hot compress after vaginal delivery decreased postpartum urinary retention, uterine contraction pain, and depressive symptoms and increased breastfeeding milk volume. Acupoint hot compress may be considered as an adjunctive intervention in postnatal care that meets patient self-care needs. Trial Registration: Chinese Clinical Trial Registry Identifier: ChiCTR2000038417.