Search Results (6)

Hypoxia, a condition of low oxygenation frequently found in triple-negative breast tumors (TNBC), promotes extracellular vesicle (EV) secretion and favors cell invasion, a complex process in which cell morphology is altered, dynamic focal adhesion spots are created, and ECM is remodeled. Here, we investigated the invasive properties triggered by TNBC-derived hypoxic small EV (SEVh) in vitro in cells cultured under hypoxic (1% O₂) and normoxic (20% O₂) conditions, using phenotypical and proteomic approaches. SEVh characterization demonstrated increased protein abundance and diversity over normoxic SEV (SEVn), with enrichment in pro-invasive pathways. In normoxic cells, SEVh promotes invasive behavior through pro-migratory morphology, invadopodia development, ECM degradation, and matrix metalloprotease (MMP) secretion. The proteome profiling of 20% O₂-cultured cells exposed to SEVh determined enrichment in metabolic processes and cell cycles, modulating cell health to escape apoptotic pathways. In hypoxia, SEVh was responsible for proteolytic and catabolic pathway inducement, interfering with integrin availability and gelatinase expression. Overall, our results demonstrate the importance of hypoxic signaling via SEV in tumors for the early establishment of metastasis. Full article

A deficit of estrogen is associated with energy substrate imbalance, raising the risk of metabolic diseases. Physical training (PT) is a potent metabolic regulator through oxidation and storage of substrates transported by GLUT4 and FAT CD36 in skeletal muscle. However, little is known about the effects of PT on these carriers in an estrogen-deficit scenario. Thus, the aim of this study was to determine the influence of 12 weeks of PT on metabolic variables and GLUT4 and FAT CD36 expression in the skeletal muscle of animals energetically impaired by ovariectomy (OVX). The trained animals swam 30 min/day, 5 days/week, at 80% of the critical load intensity. Spontaneous physical activity was measured biweekly. After training, FAT CD36 and GLUT4 expressions were quantified by immunofluorescence in the soleus, as well as muscular glycogen and triglyceride of the soleus, gluteus maximus and gastrocnemius. OVX significantly reduced FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01), while PT significantly increased FAT CD36, GLUT4 and spontaneous physical activity (p < 0.01). PT increased soleus glycogen, and OVX decreased muscular triglyceride of gluteus maximus. Therefore, OVX can cause energy disarray through reduction in GLUT4 and FAT CD36 and their muscle substrates and PT prevented these metabolic consequences, masking ovarian estrogen’s absence. Full article

Background: Skeletal muscle adaptations are affected by resistance training (RT)-induced acute and chronic transcriptional responses. An under-explored gene target involved in mechanotransduction is the expression of the G protein-coupled receptor 56 (GPR56). However, studies investigating the acute and chronic effects of RT manipulations on GPR56 mRNA are scarce. Methods: Twenty subjects had each leg randomly assigned to a standard ((CON) no specific manipulation) or a variable RT (manipulations in load, volume, muscle action, and pause in a session-by-session fashion (VAR)). GPR56 mRNA expression was assessed before and after 16 training sessions (chronic effect) and 24 h after a 17th session (acute effect). Results: Acute GPR56 mRNA expression increased at 24 h (p < 0.01) without differences between CON and VAR (p > 0.05). No differences were found in GPR56 mRNA expression when comparing each VAR condition (load vs. sets vs. eccentric actions vs. pause) nor with CON at 24 h (p > 0.05). Chronic GPR56 mRNA expression increased at Post compared with Pre (p < 0.02) for VAR only, with a tendency (p = 0.058) toward higher expression for VAR as compared with CON. Conclusion: GPR56 mRNA expression is acutely and chronically modulated by RT. Additionally, chronic GPR56 mRNA expression is modulated by RT variable manipulations. Full article

Several side effects of anabolic-androgenic steroid (AAS) administration associated with training are reported in the biomechanical properties of the calcaneal tendon (CT) of rats. Thus, the aim of the present study is to evaluate the effects of the detraining and discontinuation of AAS administration on the CT morphology of rats submitted to exercise in water. Animals were divided into two groups (20/group): (1) Immediately after training (IA), and (2) Six weeks of detraining and AAS discontinuation (6W). The IA group included four subgroups: Sedentary (S), Trained (T), Sedentary with AAS administration (SAAS), and trained with AAS administration (TAAS). The 6W group included four subgroups: Sedentary (6W-S), six weeks of detrained (6W-T), six weeks of sedentary with AAS discontinuation (6W-SAAS), and six weeks of detrained with AAS discontinuation (6W-TAAS). Data show significant reduction in adipose cells volume density (Vv%) in the distal CT in 6W-TAAS group, indicating that training can exert a positive effect on the tendon. The 6W-SAAS group exhibited increased adipose cells Vv% in the distal region, compared with the W6-S and W6-T groups. A decrease in tendon proper cells Vv% and in peritendinous sheath cells Vv% of proximal and distal regions was also observed. In 6W-TAAS group showed increase in adipose cells, blood vessels, peritendinous sheath cells, and tendon proper cells Vv% in the distal region of the CT. The vertical jumps in water were not able to protect CT regions from the negative effects of AAS discontinuation for six weeks. However, after detraining and AAS discontinuation, many protective factors of the mechanical load in the long-term could be observed. Full article

Exercise training (ET), anabolic androgenic steroids (AAS), and aging are potential factors that affect tendon homeostasis, particularly extracellular matrix (ECM) remodeling. The goal of this review is to aggregate findings regarding the effects of resistance training (RT), AAS, and aging on tendon homeostasis. Data were gathered from our studies regarding the impact of RT, AAS, and aging on the calcaneal tendon (CT) of rats. We demonstrated a series of detrimental effects of AAS and aging on functional and biomechanical parameters, including the volume density of blood vessel cells, adipose tissue cells, tendon calcification, collagen content, the regulation of the major proteins related to the metabolic/development processes of tendons, and ECM remodeling. Conversely, RT seems to mitigate age-related tendon dysfunction. Our results suggest that AAS combined with high-intensity RT exert harmful effects on ECM remodeling, and also instigate molecular and biomechanical adaptations in the CT. Moreover, we provide further information regarding the harmful effects of AAS on tendons at a transcriptional level, and demonstrate the beneficial effects of RT against the age-induced tendon adaptations of rats. Our studies might contribute in terms of clinical approaches in favor of the benefits of ET against tendinopathy conditions, and provide a warning on the harmful effects of the misuse of AAS on tendon development. Full article

Alternagin-C (ALT-C) is a disintegrin-like protein isolated from Rhinocerophis alternatus snake venom, which induces endothelial cell proliferation and angiogenesis. The aim of this study was to evaluate the systemic effects of a single dose of alternagin-C (0.5 mg·kg⁻¹, via intra-arterial) on oxidative stress biomarkers, histological alterations, vascular endothelial growth factor (VEGF) production, and the degree of vascularization in the liver of the freshwater fish traíra, Hoplias malabaricus, seven days after the initiation of therapy. ALT-C treatment increased VEGF levels and hepatic angiogenesis. ALT-C also enhanced hepatic antioxidant enzymes activities such as superoxide dismutase, catalase, glutathione peroxidase, and glutathione reductase, decreasing the basal oxidative damage to lipids and proteins in the fish liver. These results indicate that ALT-C improved hepatic tissue and may play a crucial role in tissue regeneration mechanisms. Full article