Effect of a 3-month L-carnitine supplementation and resistance training program on circulating markers and bone mineral density in postmenopausal women: a randomized controlled trial.

BACKGROUND: Higher circulating levels of trimethylamine N-oxide (TMAO), which is a metabolite that can be produced by the gut microbiota from L-carnitine (LC), have been associated with bone mineral density (BMD). Because LC supplementation can improve bone density and microstructural properties in animal models, this study aimed to examine the effects of 12 weeks of LC supplementation on BMD and selected blood markers involved in bone metabolism of postmenopausal women participating in a resistance training (RT) program. METHODS: Twenty-seven postmenopausal women, who had not been treated for osteoporosis, with a total T-score above - 3.0 and no diet differences completed 12 weeks of RT. The participants' diets were supplemented with either 1 g of LC-L-tartrate and 3 g of leucine per day (LC group) or 4 g of leucine per day as a placebo (PLA group), in a double-blind fashion. RESULTS: After the intervention in the LC group, plasma total carnitine and serum decorin levels were higher than the corresponding preintervention values (p = 0.040 and p = 0.042, respectively). Moreover, plasma TMAO and serum SPARC levels were higher in the LC group than the corresponding postintervention values in the PLA group (p < 0.001 and p = 0.030, respectively). No changes in the BMD were observed after 3 months of the intervention. CONCLUSIONS: Twelve weeks of LC supplementation during RT program increased plasma TMAO levels and appeared to affect signaling molecules, as indicated by the increase in the resting SPARC and decorin levels, with no significant modification in the BMD. TRIAL REGISTRATION: Retrospectively registered at the ClinicalTrials.gov (NCT05120011).

[Effect of acupotomy intervention on the expressions of proteoglycans in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration].

OBJECTIVE: To observe the effect of acupotomy intervention on the expressions of biglycan(BGN), decorin(DCN) and Caspase-3 in lumbar intervertebral disc of rabbits with lumbar intervertebral disc degeneration (LIDD), so as to explore its possible mechanism in relieving LIDD. METHODS: Thirty male Japanese white rabbits were randomly divided into normal, model and acupotomy groups, with 10 rabbits in each group. The LIDD model was established by axial compression method, and magnetic resonance imaging (MRI) was used to judge whether the model was successful or not. After modeling, the acupotomy was applied to lumbar (L)4-L5 spinous process space and bilateral transverse processes for loosening, twice a week for 4 weeks. The structural changes of L4-L5 intervertebral disc were observed by MRI. The morphological changes of lumbar spine were observed by HE staining. The expression of Caspase-3 in nucleus pulposus was observed by immunohistochemistry, and the protein expressions of DCN and BGN in intervertebral disc were detected by Western blot, separatively. RESULTS: After mode-ling, the rabbits showed slow movement, stiff back muscles with cords or nodules, the fibrous ring structure of lumbar intervertebral disc was disordered, the number of nucleus pulposus cells was reduced, and the signal intensity of L4-L5 intervertebral disc was decreased in the model group relevant to the normal group. At the same time, the expression of Caspase-3 in nucleus pulposus was increased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were decreased significantly (P<0.05). After acupotomy treatment, the modeling induced slow movement, stiff back muscles and disordered structure of lumbar intervertebral disc were significantly improved. The number of nucleus pulposus cells was increased, the signal intensity of L4-L5 intervertebral disc was enhanced, the expression of Caspase-3 in nucleus pulposus was decreased significantly (P<0.05), and the expression levels of DCN and BGN in intervertebral disc were increased significantly (P<0.05) compared with the model group. CONCLUSION: Acupotomy intervention can inhibit cell apoptosis, reduce the degradation of extracellular matrix in nucleus pulposus of intervertebral disc, and restore the normal force balance and dynamic balance of lumbar spine, which may be one of its mechanisms underlying improving LIDD.

L-Carnitine Combined with Leucine Supplementation Does Not Improve the Effectiveness of Progressive Resistance Training in Healthy Aged Women.

OBJECTIVES: To evaluate the effect of L-carnitine (LC) in combination with leucine supplementation on muscle strength and muscle hypertrophy in aged women participating in a resistance exercise training (RET) program. DESIGN/SETTING/PARTICIPANTS: Thirty-seven out of sixty (38.3% dropout) healthy women aged 60-75 years (mean 67.6 ± 0.7 years) completed the intervention in one of three groups. One of the supplemented groups received 1 g of L-carnitine-L-tartrate in combination with 3 g of L-leucine per day (LC+L group; n = 12), and the second supplemented group received 4 g of L-leucine per day (L group; n = 13). The control group (CON group; n = 12) received no supplementation. INTERVENTION: All three groups completed the same RET protocol involving exercise sessions twice per week for 24 weeks. MEASUREMENTS: Before and after the experiment, participants performed isometric and isokinetic muscle strength testing on the Biodex dynamometer. The cross-sectional areas of the major knee extensors and total thigh muscles were assessed using magnetic resonance imaging. Fasting serum levels of insulin-like growth factor-1 (IGF-1), myostatin and decorin, and plasma levels of total carnitine (TC) and trimethylamine-N-oxide (TMAO) levels were measured. RESULTS: The 24-week RET significantly increased muscle strength and muscle volume, but the group and time interactions were not significant for the muscle variables analyzed. Plasma total carnitine increased only in the LC+L group (p = 0.009). LC supplementation also caused a significant increase in plasma TMAO, which was higher after the intervention in the LC+L group than in the L (p < 0.001), and CON (p = 0.005) groups. The intervention did not change plasma TMAO concentration in the L (p = 0.959) and CON (p = 0.866) groups. After the intervention serum decorin level was higher than before in both supplemented groups combined (p = 0.012), still not significantly different to post intervention CON (p = 0.231). No changes in serum IGF-1 and myostatin concentrations and no links between the changes in blood markers and muscle function or muscle volume were observed. CONCLUSIONS: LC combined with leucine or leucine alone does not appear to improve the effectiveness of RET.

ECM-regulation of autophagy: The yin and the yang of autophagy during wound healing.

Wound healing is a complex sequence of tissue protection, replacement, and reorganization leading to regenerated tissue. Disruption of any of these steps results in the process being incomplete as an ulcer or over-exuberant as a hypertrophic scar. Over the past decade, it has become evident that the extracellular matrix and associated components orchestrate this process. However, the cellular events that are induced by the extracellular matrix to accomplish wound healing remain to be defined. Herein we propose that matrix-regulated cellular macro-autophagy is key to both the tissue replacement and resolution stages of healing by directing cellular function or apoptosis. Further, disruptions in matrix turnover alter autophagic function leading to chronic wounds or scarring. While the literature that directly investigates autophagy during wound healing is sparse, the emerging picture supports our proposing a model of the centrality of the matrix-autophagy modulation as central to physiologic and pathologic healing.

Expression and localization of the small proteoglycans decorin and biglycan in articular cartilage of Kashin-Beck disease and rats induced by T-2 toxin and selenium deficiency.

Kashin-Beck disease (KBD) is an endemic degenerative osteoarthropathy of uncertain etiology. Our study sought to identify a correlation between small proteoglycans decorin and biglycan expression and Kashin-Beck Disease. Immunohistochemistry was used to assess the decorin and biglycan levels in cartilage specimens from both child KBD patients, and rats fed with T-2 toxin under a selenium-deficient condition. Real-time PCR and Western blot were used to assess mRNA and protein levels of decorin and biglycan in rat cartilages, as well as in C28/I2 chondrocytes stimulated by T-2 toxin and selenium in vitro. The result showed that decorin was reduced in all zones of KBD articular cartilage, while the expression of biglycan was prominently increased in KBD cartilage samples. Increased expression of biglycan and reduced expression of decorin were observed at mRNA and protein levels in the cartilage of rats fed with T-2 toxin and selenium- deficiency plus T-2 toxin diet, when compared with the normal diet group. Moreover, In vitro stimulation of C28/I2 cells with T-2 toxin resulted in an upregulation of biglycan and downregulation of decorin, T-2 toxin induction of biglycan and decorin levels were partly rescued by selenium supplement. This study highlights the focal nature of the degenerative changes that occur in KBD cartilage and may suggest that the altered expression pattern of decorin and biglycan have an important role in the onset and pathogenesis of KBD.

Low-level laser and adipose-derived stem cells altered remodelling genes expression and improved collagen reorganization during tendon repair.

OBJECTIVES: The cellular therapy using adipose-derived mesenchymal stem cells (ASCs) aims to improve tendon healing, considering that repaired tendons often result in a less resistant tissue. Our objective was to evaluate the effects of the ASCs combination with a low-level laser (LLL), an effective photobiostimulation for the healing processes. MATERIALS AND METHODS: Rats calcaneal tendons were divided into five groups: normal (NT), transected (T), transected and ASCs (SC) or LLL (L), or with ASCs and LLL (SCL). RESULTS: All treated groups presented higher expression of Dcn and greater organization of collagen fibres. In comparison with T, LLL also up-regulated Gdf5 gene expression, ASCs up-regulated the expression of Tnmd, and the association of LLL and ASCs down-regulated the expression of Scx. No differences were observed for the expression of Il1b, Timp2, Tgfb1, Lox, Mmp2, Mmp8 and Mmp9, neither in the quantification of hydroxyproline, TNF-α, PCNA and in the protein level of Tnmd. A higher amount of IL-10 was detected in SC, L and SCL compared to T, and higher amount of collagen I and III was observed in SC compared to SCL. CONCLUSIONS: Transplanted ASCs migrated to the transected region, and all treatments altered the remodelling genes expression. The LLL was the most effective in the collagen reorganization, followed by its combination with ASCs. Further investigations are needed to elucidate the molecular mechanisms involved in the LLL and ASCs combination during initial phases of tendon repair.