Yu Zhou

Disuse muscle atrophy (DMA) is a significant healthcare challenge characterized by progressive loss of muscle mass and function resulting from prolonged inactivity. The development of effective strategies for muscle recovery is essential. In this study, we established a DMA mouse model through hindlimb suspension to evaluate the therapeutic potential of lactate in alleviating the detrimental effects on the gastrocnemius muscle. Using NMR-based metabolomic analysis, we investigated the metabolic changes in DMA-injured gastrocnemius muscles compared to controls and evaluated the beneficial effects of lactate treatment. Our results show that lactate significantly reduced muscle mass loss and improved muscle function by downregulating Murf1 expression, decreasing protein ubiquitination and hydrolysis, and increasing myosin heavy chain levels. Crucially, lactate corrected perturbations in four key metabolic pathways in the DMA gastrocnemius: the biosynthesis of phenylalanine, tyrosine, and tryptophan; phenylalanine metabolism; histidine metabolism; and arginine and proline metabolism. In addition to phenylalanine-related pathways, lactate also plays a role in regulating branched-chain amino acid metabolism and energy metabolism. Notably, lactate treatment normalized the levels of eight essential metabolites in DMA mice, underscoring its potential as a therapeutic agent against the consequences of prolonged inactivity and muscle wasting. This study not only advances our understanding of the therapeutic benefits of lactate but also provides a foundation for novel treatment approaches aimed at metabolic restoration and muscle recovery in conditions of muscle wasting.

Trimethylamine N-oxide (TMAO) has attracted interest because of its association with cardiovascular disease and diabetes, and evidence for the beneficial effects of TMAO is accumulating. This study investigates the role of TMAO in improving exercise performance and elucidates the underlying molecular mechanisms. Using C2C12 cells, we established an oxidative stress model and administered TMAO treatment. Our results indicate that TMAO significantly protects myoblasts from oxidative stress-induced damage by increasing the expression of Nrf2, heme oxygenase-1 (HO-1), NAD(P)H dehydrogenase (NQO1), and catalase (CAT). In particular, suppression of Nrf2 resulted in a loss of the protective effects of TMAO and a significant decrease in the expression levels of Nrf2, HO-1, and NQO1. In addition, we evaluated the effects of TMAO in an exhaustive swimming test in mice. TMAO treatment significantly prolonged swimming endurance, increased glutathione and taurine levels, enhanced glutathione peroxidase activity, and increased the expression of Nrf2 and its downstream antioxidant genes, including HO-1, NQO1, and CAT, in skeletal muscle. These findings underscore the potential of TMAO to counteract exercise-induced oxidative stress. This research provides new insights into the ability of TMAO to alleviate exercise-induced oxidative stress via the Nrf2 signaling pathway, providing a valuable framework for the development of sports nutrition supplements aimed at mitigating oxidative stress.

Lactate is a general compound fuel serving as the fulcrum of metabolism, which is produced from glycolysis and shuttles between different cells, tissues and organs. Lactate is usually accumulated abundantly in muscles during exercise. It remains unclear whether lactate plays an important role in the metabolism of muscle cells. In this research, we assessed the effects of lactate on myoblasts and clarified the underlying metabolic mechanisms through NMR-based metabonomic profiling. Lactate treatment promoted the proliferation and differentiation of myoblasts, as indicated by significantly enhanced expression levels of the proteins related to cellular proliferation and differentiation, including p-AKT, p-ERK, MyoD and myogenin. Moreover, lactate treatment profoundly regulated metabolisms in myoblasts by promoting the intake and intracellular utilization of lactate, activating the TCA cycle, and thereby increasing energy production. For the first time, we found that lactate treatment evidently promotes AMPK signaling as reflected by the elevated expression levels of p-AMPK and p-ACC. Our results showed that lactate as a metabolic regulator activates AMPK, remodeling the cellular metabolic profile, and thereby promoting the proliferation and differentiation of myoblasts. This study elucidates molecular mechanisms underlying the effects of lactate on skeletal muscle in vitro and may be of benefit to the exploration of lactate acting as a metabolic regulator.

From unstable crystals to relatively stable monohydrate crystals, many researchers have been working on S-nitrosocaptopril for more than two decades. S-nitrosocaptopril monohydrate (Cap-NO·H₂O) is a novel crystal form of S-nitrosocaptopril (Cap-NO), and is not only a nitric oxide (NO) donor, but also an angiotensin-converting enzyme inhibitor (ACEI). Yet, a method for long-term storage has never been reported. In order to determine the optimal storage conditions, Plackett–Burman (PB) design was performed to confirm the critical factors. Response surface methodology (RSM) was employed to determine the optimal Cap-NO·H₂O storage condition, based on the rough interval determined by the path of steepest ascent experiment. The optimized storage condition was denoted as nitrogen purity of 97%, temperature of −10 °C and 1.20 g deoxidizer. In this case, a final preservation rate of 97.91 ± 0.59% could be obtained. In specific storage conditions, Cap-NO·H₂O was found to be stable for at least 6 months in individual PE package, procreating a potentially applicable avenue.