Ischemia-reperfusion injury leads to severe muscular damage. Even if prompt revascularization is the treatment of choice, muscular alterations can lead to severe sequalae as mitochondrial dysfunction. Accordingly, adjunctive strategies are needed to overcome the muscular damage. Mitochondrial transplantation has shown beneficial effects in cardiac ischemia-reperfusion, but its role in peripheral muscle is not well established. In this study, we found that mitochondrial transplantation partially restored muscular function when submitted to ischemia reperfusion.

Aim: We aimed to evaluate an innovative dose–response approach to assess the metaboreflex with control of intramuscular metabolic perturbation (concept of metaboreflex gain). We also investigated potential sex differences in the metaboreflex using this new approach. Methods: Thirty participants (15 females) completed one familiarization and two experimental visits to evaluate the method and assess its reproducibility. Each visit involved four consecutive bouts of sustained isometric knee extension at 20% of maximal voluntary force interspersed with 2 min of post‐exercise circulatory occlusion (PECO). Intramuscular metabolic perturbation was quantified indirectly via changes in quadriceps twitch force evoked by electrical stimulation of the femoral nerve (∆Q _TW ). Metaboreflex gain was calculated as the ratio of ∆mean arterial pressure (∆MAP) during PECO to ∆Q _TW . Results: We found a gradual increase in ∆MAP ( p < 0.0001) that was linearly correlated with the gradual decrease in ∆Q _TW ( p < 0.0001) during the exercise bouts ( r ² = 0.93; p = 0.037). Bland–Altman analysis showed a mean bias of 0.3 ± 0.5 for metaboreflex gain. Males exhibited greater metaboreflex to PECO than females when assessed “classically” with no control of ∆Q _TW (∆MAP; 49.1% ± 17.9% vs. 36.5% ± 8.7%; p = 0.020), whereas there was no sex difference when assessed using the metaboreflex gain (∆MAP/∆Q _TW ; 1.3 ± 0.6 vs. 1.8 ± 1.3; p = 0.325). The metaboreflex gain was not consistent across exercise bouts, showing that contrasting conclusions might emerge between two single assessments performed at different levels of metaboreflex activation. Conclusion: This study highlights the critical need for using a dose–response relationship while accounting for neuromuscular fatigue as a proxy for the metabolic stimulus when assessing the muscle metaboreflex in humans. Trial Registration: Clinical trials registration number: NCT06775119

By combining acute and chronic muscle biopsies from patients with breast cancer with complementary in vitro experiments, we determined that breast cancer chemotherapy triggers a rapid skeletal muscle atrophy driven by NF-κB activation and subsequent upregulation of the ubiquitin-proteasome system. Importantly, sulfasalazine fully prevented muscle atrophy by mitigating the imbalance in protein turnover, offering promising perspectives for clinical translation and improving patient prognosis.

Standard chemotherapy regimens for patients with breast cancer are based on epirubicin–cyclophosphamide (EC) and paclitaxel (TAX) administrations. While it has been shown that first EC administration impairs mitochondrial homeostasis, the isolated effects of TAX have not been studied without previous chemotherapy exposure. We conducted a prospective clinical study including five patients with breast cancer who underwent two vastus lateralis muscle biopsies before and 4 days after the first TAX administration, without any prior chemotherapy exposure. Mitochondrial respiratory capacity, reactive oxygen species production, mitochondrial dynamics and ultrastructure, and apoptosis were assessed using high‐resolution respirometry, western blotting, transmission electron microscopy, and TUNEL assay, respectively. Post‐TAX, the number of intermyofibrillar mitochondria decreased (−18%; P = 0.049), while the proportion of damaged mitochondria increased (+34%; P = 0.012). Mitochondrial area, perimeter and major/minor axis lengths increased ( P  < 0.05) while intermyofibrillar cristae area decreased (4.29% pre‐TAX vs. 2.60% post‐TAX; P = 0.044). Despite these morphological changes, oxidative phosphorylation capacity and respiratory control ratio remained unchanged, whereas complex I‐linked substrate respiration decreased (−29%; P = 0.046). MFN2 (−43%; P = 0.040) and Fis1 (−46%; P = 0.046) protein levels decreased post‐TAX while mitophagy markers were unchanged. Apoptosis was increased, as documented by increased Bax (+58%; P = 0.045) and TUNEL‐positive nuclei (+395%; P = 0.041). In only 4 days, the first TAX administration induced severe skeletal muscle mitochondrial remodelling in patients with breast cancer, characterized by impaired mitochondrial dynamics that resulted in swollen and damaged organelles. These findings demonstrate that mitochondrial toxicity, classically documented at the end of treatment, occurs acutely and after only one chemotherapy administration.

AMITO is an open-access, standalone application for mitochondrial analysis from TEM images that combines automated and manual workflows within a single user-friendly interface. Validated against conventional FIJI analysis, AMITO demonstrated excellent reproducibility while substantially reducing analysis time and experimenter-dependent variability. By integrating morphology and ultrastructure quantification without requiring programming expertise, AMITO provides a reliable and accessible solution to improve robustness, efficiency, and reproducibility in mitochondrial research.

Breast cancer treatment impairs aerobic and neuromuscular capacities, leading to a decrease in quality of life. Exercise may counteract these effects if it is individualized to patient characteristics. This study aimed to assess the feasibility and potential effects of combined concentric and eccentric cycling training on exercise capacity. Twenty‐one patients with breast cancer (59 ± 9 years; 164 ± 5 cm; and 72 ± 13 kg) were assessed before and after exercise training twice a week for six weeks. Assessments included a test to determine power output at ventilatory threshold (P _VT ), a 6‐min walking test (6‐MWT), and a measure of quadriceps muscle force and architecture. Exercise training adherence, attendance and rate of perceived exertion (RPE) were also measured. The exercise training included two concentric cycling bouts (7 × 1 min at 130%P _VT and 5 × 2 min at 110%P _VT ) and one eccentric cycling bout (7 × 1 min at 130%P _VT ). The exercise training protocol was associated with high attendance (90%) and adherence (98%) rates and was well tolerated (3.5/10 of RPE). From pre‐ to postexercise training, we documented an increase in aerobic capacity, characterized by increased oxygen consumption (+11.1% and p = 0.001) and power output (+10.9% and p = 0.004) at VT. These changes were accompanied by neuromuscular adaptations, with greater muscle force (+18.3% and p < 0.001), vastus lateralis thickness (+5.0% and p = 0.031), fascicle length (+11.9% and p < 0.001), pennation angle (+11.3% and p = 0.001), and rectus femoris cross‐sectional area (+11.6% and p = 0.020). These adaptations led to increased 6‐MWT distance (+4.4% and p = 0.005). Thanks to an individualized exercise training with high adherence and attendance, aerobic and neuromuscular parameters were improved, leading to greater exercise capacity in breast cancer.