bims-musmir 2026-05-24 papers

J Physiol. 2026 May 21.

Restoration of neuromuscular function by mitochondrial transplantation in injured mouse skeletal muscle.

Stephen E Alway, Peter J Ferrandi, Hector G Paez, Christopher R Pitzer, Junaith S Mohamed, Michael R Deschenes, James A Carson.

Rehabilitative activity can improve injury repair, but it risks additional damage and reduces the functional recovery of regenerating muscle. This study tested the hypothesis that moderate electrically evoked contractions would slow restoration of neuromuscular function after cardiotoxin-induced injury; however exogenous mitochondrial transplantation (MT) would enhance recovery of contractile function after injury. Cardiotoxin was injected into the tibialis anterior of C57BL/6 mice (10-12 weeks of age) to induce muscle necrosis. Exogenous mitochondria or phosphate-buffered saline (PBS) were injected into the mouse tail vein after cardiotoxin injury. Injured muscles were either rested or given 40 Hz submaximal electrically evoked contractions to cardiotoxin-injured muscles during the recovery period. Relative to intra-animal non-damaged control muscles restoration of peak tetanic torque after both rested and evoked contractions during recovery and twitch torque was greater, and the difference between control and injured muscle twitch one-half relaxation time was lower in injured muscles that were rested for 10 days after injury and received MT compared to PBS-treated muscles. Neuromuscular junction efficiency in cardiotoxin-injured muscles was ∼70% of control undamaged muscles, but MT improved the recovery of neuromuscular junction efficiency to produce torque by 14 days after cardiotoxin injury in muscles that received additional damage induced by evoked contractions during the recovery period. These data suggest that MT enhances the recovery of neuromuscular function when the muscle is rested after injury, but it provides limited improvement in muscle function when the muscle is challenged with electrically evoked contractions in the recovery period after injury. KEY POINTS: Mitochondrial transplantation by systemically infusing healthy donor mitochondria into injured mice improved the recovery of maximal torque production of injured muscles when evoked contractions were provided to the regenerating muscle during the recovery period after injury. Mitochondrial transplantation improved the restoration of neuromuscular junction efficiency after muscle injury. The recovery of maximal torque capabilities function following cardiotoxin-induced tibialis anterior muscle injury was attenuated by electrically evoked muscle contractions conducted every other day during the recovery period in young adult mice.

Keywords: mitochondria; muscle contractile properties; muscle injury; neuromuscular junction; regeneration

DOI: https://doi.org/10.1113/JP290801

Cell Rep. 2026 May 21. pii: S2211-1247(26)00440-7. [Epub ahead of print]45(6): 117362

Cachexia-induced alterations of miR-27a-3p drive cell-type specific effects in FAPs and tumor cells that coincide with muscle wasting.

Ashok Narasimhan, Chun Wai Cheung, Nasim Kajabadi, Bruce Lin, Lin Wei Tung, Chihkai Chang, Fabio M V Rossi.

The contribution of muscle-resident stromal cells to cancer-associated muscle wasting is poorly understood. We characterized the role of fibroadipogenic progenitors (FAPs) in pancreatic cancer-associated cachexia and investigated how dysregulated microRNAs in the tumor and FAPs drive muscle wasting. In cancer-bearing mice, FAPs engage in a chronic pro-inflammatory and pro-adipogenic program coinciding with muscle wasting. Additionally, in vitro and in vivo findings suggest that FAPs from cachectic mice cause muscle wasting, indicating that they may release pro-atrophic factors. Cancer-induced downregulation of miR-27a-3p in FAPs increased adipogenesis, whereas its upregulation in cancer cells increased proliferation and migration, highlighting the challenges of targeting pleiotropic molecules therapeutically. Knocking down miR-27a in the tumor improved both the micro- and macroenvironment of the muscle in vivo. Overall, we demonstrate that miR-27a-3p contributes to tumor progression and the dysregulation of FAPs, cooperatively driving muscle wasting. Our findings underscore the importance of tissue-specific targeting of microRNAs in cancer.

Keywords: CP: metabolism; CP: molecular biology; PDAC; cachexia; fibroadipogenic progenitors; lipid metabolism; miR-27a-3p; miRNAs; muscle wasting; pancreatic cancer

DOI: https://doi.org/10.1016/j.celrep.2026.117362

Methods Mol Biol. 2026 ;3010 123-130

MicroRNA Quantification on Fast and Slow-Twitch Skeletal Muscles of Mouse.

Magally Ramírez-Ramírez, María Luisa Benítez-Hess, Estela G García-González, J Manuel Hernández-Hernández.

microRNAs (miRNAs) are noncoding RNAs of approximately 24 nucleotides long that are expressed in multiple tissues and organs. miRNAs regulate the expression of specific target genes, and their expression profile can provide insight into the cell biology altered by diseases or drug treatments. Research has demonstrated that several miRNAs regulate muscle differentiation and the specification of fiber type. Hence, an established tool to routinely quantify miRNA abundance is of the utmost importance. The stem-loop quantitative reverse transcription PCR (RT-qPCR) is a methodology that allows the analysis of a specific miRNA with high sensitivity. Upon hybridization with a structured stem-loop oligonucleotide to the 3' end of the target miRNA, a retro-transcription is possible for further qPCR quantification. In this chapter, we describe a protocol to quantify miRNAs in dissected mouse fast and slow-twitch muscle.

Keywords: Fast-twitch fiber; MicroRNA; RNA isolation; Skeletal muscle; Slow-twitch fiber; Stem–loop PCR; miRNAs isolation

DOI: https://doi.org/10.1007/978-1-0716-5126-1_13

FEBS J. 2026 May 18.

The epigenetic landscape of skeletal muscle in response to exercise and aging.

Sabrina Champsi, David A Hood.

Skeletal muscle exhibits a remarkable level of plasticity that enables it to adapt to exercise training, as well as the deleterious effects of aging. Fundamental to this malleability are epigenetic processes, which collectively enhance chromatin remodeling and subsequently alter DNA availability for gene expression. A growing body of evidence has demonstrated that acute exercise is a powerful inducer of epigenetic remodeling, capable of stimulating gene-specific alterations, which transcriptionally activate exercise-responsive genes. These epigenetic processes, including DNA methylation and various histone modifications, are highly responsive to exercise-induced signaling cascades and mitochondrially-related metabolites, together indicating that exercise can modulate the nuclear and mitochondrial epigenome as a mechanism to regulate gene expression. However, aging is characterized by a unique epigenetic signature, which likely supports the alterations in gene expression observed with age. Yet, the effects of exercise on epigenetic regulation with age remain underexplored. To investigate the intersectionality of these two phenotypes and highlight significant gaps within the literature, this review aimed to discuss the different types of epigenetic modifications that have been reported within skeletal muscle and how they are altered with acute and chronic exercise. Furthermore, we aimed to analyze mitochondrial epigenetics and their role in mediating alterations in mitochondrial-nuclear crosstalk observed with exercise and age. Elucidating age-dependent adaptations in the epigenome and the differential effects of exercise in these populations will help uncover the complexity of gene regulation with age, and importantly, reveal how exercise can regulate many of these processes to improve muscle health.

Keywords: aging; epigenetics; exercise; mitochondria; skeletal muscle

DOI: https://doi.org/10.1111/febs.70591

Mol Biol Rep. 2026 May 22. pii: 797. [Epub ahead of print]53(1):

Upregulation of ANRIL and H19 lncRNAs in bipolar disorder: a putative role for miR-339-5p in molecular pathogenesis.

Fatemeh Shahnemati, Mohammad Javad Mokhtari, Iman Jamhiri.

BACKGROUNDS: Bipolar disorder (BD) is a highly heterogeneous and multifactorial condition that imposes substantial burdens on both individuals and society. Despite advances in understanding the neurobiology of BD, its precise etiology remains unclear. Long non-coding RNAs (lncRNAs), particularly H19 and ANRIL, have recently emerged as key regulators of inflammatory pathways and may contribute to the dysregulated immune responses observed in BD.
AIMS: This study investigated the expression levels of H19 and ANRIL lncRNAs in individuals with BD and explored their potential role as biomarkers for the disorder.
MATERIALS AND METHODS: We measured the expression levels of H19 and ANRIL in the peripheral blood of 90 patients with BD and 90 healthy controls using real-time PCR. Furthermore, receiver operating characteristic (ROC) curve analysis and correlation analysis were conducted to evaluate the association between gene expression and specific clinical features of BD. A computational study was conducted to investigate the binding sites of miRNAs on the H19 and ANRIL lncRNAs.
RESULTS: The expression levels of H19 and ANRIL were significantly higher in patients with BD compared to healthy controls. The area under the curve (AUC) values for H19 and ANRIL were 0.60 and 0.74, respectively. A computational study revealed that miR-339-5p is a common microRNA that may regulate H19 and ANRIL lncRNAs.
CONCLUSIONS: Given the role of miR-339-5p in inhibiting inflammation, the upregulation of H19 and ANRIL may contribute to the pathology of BD through the regulation of miR-339-5p. Moreover, peripheral expression levels of the lncRNA ANRIL may serve as potential biomarkers for BD. Importantly, these findings underscore the therapeutic promise of small RNA-based strategies-such as miRNA mimics or siRNA approaches-to restore immune balance and provide novel treatment options for BD.

Keywords: Biomarkers; In silico; Inflammation; Starbase; microRNAs

DOI: https://doi.org/10.1007/s11033-026-11995-5