With this study we investigated the role of nonsteroidal anti‐inflammatory drugs (NSAIDs) in human skeletal muscle regeneration. Young men ingested NSAID [1200 mg/d ibuprofen (IBU)] or placebo (PLA) daily for 2 wk before and 4 wk after an electrical stimulation‐induced injury to the leg extensor muscles of one leg. Muscle biopsies were collected from the vastus lateralis muscles before and after stimulation (2.5 h and 2,7, and 30 d) and were assessed for satellite cells and regeneration by immunohistochemistry and real‐time RT‐PCR, and we also measured telomere length. After injury, and compared with PLA, IBU was found to augment the proportion of ActiveNotch1 ⁺ satellite cells at 2 d [IBU, 29 ± 3% vs. PLA, 19 ± 2% (means ± sem )], satellite cell content at 7 d [IBU, 0.16 ± 0.01 vs. PLA, 0.12 ± 0.01 (Pax7 ⁺ cells/fiber)], and to expedite muscle repair at 30 d. The PLA group displayed a greater proportion of embryonic myosin ⁺ fibers and a residual ~2‐fold increase in mRNA levels of matrix proteins (all P < 0.05). Endomysial collagen was also elevated with PLA at 30 d. Minimum telomere length shortening was not observed. In conclusion, ingestion of NSAID has a potentiating effect on Notch activation of satellite cells and muscle remodeling during large‐scale regeneration of injured human skeletal muscle.—Mackey, A. L., Rasmussen, L. K., Kadi, F., Schjerling, P., Helmark, I. C., Ponsot, E., Aagaard, P., Durigan, J. L. Q., Kjaer, M. Activation of satellite cells and the regeneration of human skeletal muscle are expedited by ingestion of nonsteroidal anti‐inflammatory medication. FASEB J. 30, 2266–2281 (2016). www.fasebj.org

The application of cryotherapy is widely used in sports medicine today. Cooling could minimize secondary hypoxic injury through the reduction of cellular metabolism and injury area. Conflicting results have also suggested cryotherapy could delay and impair the regeneration process. There are no definitive findings about the effects of cryotherapy on the process of muscle regeneration. The aim of the present study was to evaluate the effects of a clinical-like cryotherapy on inflammation, regeneration and extracellular matrix (ECM) remodeling on the Tibialis anterior (TA) muscle of rats 3, 7 and 14 days post-injury. It was observed that the intermittent application of cryotherapy (three 30-minute sessions, every 2 h) in the first 48 h post-injury decreased inflammatory processes (mRNA levels of TNF-α, NF-κB, TGF-β and MMP-9 and macrophage percentage). Cryotherapy did not alter regeneration markers such as injury area, desmin and Myod expression. Despite regulating Collagen I and III and their growth factors, cryotherapy did not alter collagen deposition. In summary, clinical-like cryotherapy reduces the inflammatory process through the decrease of macrophage infiltration and the accumulation of the inflammatory key markers without influencing muscle injury area and ECM remodeling.

This study investigated the effects of 5 and 15°C cold-water immersion on recovery from exercise resulting in exercise-induced muscle damage. 42 college-aged men performed 5×20 drop-jumps and were randomly allocated into one of 3 groups: (1) 5°C; (2) 15°C; or (3) control. After exercise, individuals from the cold-water immersion groups had their lower limbs immerged in iced water for 20 min. Isometric knee extensor torque, countermovement jump, muscle soreness, and creatine kinase were measured before, immediately after, 24, 48, 72, 96 and 168 h post-exercise. There was no between-group difference in isometric strength recovery (p=0.73). However, countermovement jump recovered quicker in cold-water immersion groups compared to control group (p<0.05). Countermovement jump returned to baseline after 72 h in 15°C, 5°C group recovered after 96 h and control did not recovered at any time point measured. Also, creatine kinase returned to baseline at 72 h and remained stable for all remaining measurements for 15°C group, whereas remained elevated past 168 h in both 5°C and control groups. There was a trend toward lower muscle soreness (p=0.06) in 15°C group compared to control at 24 h post-exercise. The result suggests that cold-water immersion promote recovery of stretch-shortening cycle performance, but not influence the recovery of maximal contractile force. Immersion at warmer temperature may be more effective than colder temperatures promoting recovery from strenuous exercise.

In elderly persons, weak tendons contribute to functional limitations, injuries, and disability, but re‐sistance training can attenuate this age‐related decline. We evaluated the effects of resistance training on the extracellular matrix (ECM) of the calcaneal tendon (CT) in young and old rats and its effect on tendon remodeling. Wistar rats aged 3 mo (young, n = 30) and 20 mo (old, n = 30) were divided into 4 groups: young sedentary, young trained, old sedentary (OS), and old trained (OT). The training sessions were conducted over a 12‐wk period. Aging in sedentary rats showed down‐regulation in key genes that regulated ECM remodeling. Moreover, the OS group showed a calcification focus in the distal region of the CT, with reduced blood vessel volume density. In contrast, resistance training was effective in up‐regulating connective tissue growth factor, VEGF, and decorin gene expression in old rats. Resistance training also increased proteoglycan content in young and old rats in special small leucine‐rich proteoglycans and blood vessels and prevented calcification in OT rats. These findings confirm that resistance training is a potential mechanism in the prevention of aging‐related loss in ECM and that it attenuates the detrimental effects of aging in tendons, such as ruptures and tendinopathies.—Marqueti, R. C., Durigan, J. L. Q., Oliveira, A. J. S., Mekaro, M. S., Guzzoni, V., Aro, A. A., Pimentel, E. R., Selistre‐de‐Araujo, H. S. Effects of aging and resistance training in rat tendon remodeling. FASEB J. 32,353‐368 (2018). www.fasebj.org

The extracellular matrix (ECM) is a 3-dimensional network of molecules that play a central role in differentiation, migration, and survival for maintaining normal homeostasis. It seems that ECM remodeling is required for adipose tissue expansion. Despite evidence indicating that ECM is an essential component of tissue physiology, adipose tissue ECM has received limited attention. Hence, there is great interest in approaches to neutralize the harmful effects of ECM enlargement. This review compiles and discusses the current literature on adipose tissue ECM remodeling in response to different dietary patterns and exercise training. High-calorie diets result in substantial adipose tissue ECM remodeling, which in turn could lead to fibrosis (excess deposition of collagens, elastin, and fibronectin), inflammation, and the onset of metabolic dysfunction. However, combining a nutritionally balanced diet with exercise is a remarkable potential strategy for lipolytic activity, preventing rapid ECM expansion in different adipose tissue depots. Despite the distinct exercise modalities (aerobic or resistance exercise) reversing adipose tissue fibrosis in animal models, the beneficial effect on humans remains controversial. Defining molecular pathways and specific mechanisms that mediate the positive effects on adipose tissue, ECM is essential in developing optimized interventions to improve health and clinical outcomes.