Does the sequence of plyometric and dynamic stretching exercises influence subsequent sprint performance? A randomized crossover intervention study.

The objectives of this study were to evaluate the acute effects of the sequence order of drop jumps (DJ) and dynamic stretching (DS) on sprinting performances in competitive athletes and to investigate the relationships between post-activation performance enhancement (PAPE) in sprint performance and lower limb power. Thirteen male jumpers and sprinters participated in this study (19 ± 2 years; 177 ± 7 cm; 71.7 ± 5.6 kg). Through a randomized crossover design, the athletes were exposed to three different conditions after a standardized warm-up: DS+DJ, DJ+DS, and control. Sprinting performance over 40 m was analysed with consideration of initial (0 to 20 m) and final acceleration (20 to 40 m) phases. The effect of intervention was examined by two-way repeated-measures of ANOVA. Pearson's correlation test was used to determine the association between PAPE during sprinting and jump performance. There was no effect of any factor on 40-m sprint performance. Meanwhile, the performance at 20-40 m was higher after the DS+DJ condition when compared to baseline (8.79 ± 0.43 vs. 8.91 ± 0.35 m/s; p = 0.015). However, the initial acceleration was worsened in the DJ+DS condition when compared to baseline (6.26 ± 0.25 vs. 6.22 ± 0.26 m/s; p = 0.002). There was a negative correlation between CMJ height and the improvement in final acceleration (r = -0.741; p = 0.004). The use of DS prior to DJ is an effective strategy to improve performance in the final acceleration phase (20-40 m). The athletes with lower levels of lower limb power benefited the most from this PAPE strategy.

Cell Plasticity in a Mouse Model of Benign Prostate Hyperplasia Drives Amplification of Androgen-Independent Epithelial Cell Populations Sensitive to Antioxidant Therapy.

Benign prostate hyperplasia (BPH) is caused by the nonmalignant enlargement of the transition zone of the prostate gland, leading to lower urinary tract symptoms. Although current medical treatments are unsatisfactory in many patients, the limited understanding of the mechanisms driving disease progression prevents the development of alternative therapeutic strategies. The probasin-prolactin (Pb-PRL) transgenic mouse recapitulates many histopathological features of human BPH. Herein, these alterations parallel urodynamic disturbance reminiscent of lower urinary tract symptoms. Single-cell RNA-sequencing analysis of Pb-PRL mouse prostates revealed that their epithelium mainly includes low-androgen signaling cell populations analogous to Club/Hillock cells enriched in the aged human prostate. These intermediate cells are predicted to result from the reprogramming of androgen-dependent luminal cells. Pb-PRL mouse prostates exhibited increased vulnerability to oxidative stress due to reduction of antioxidant enzyme expression. One-month treatment of Pb-PRL mice with anethole trithione (ATT), a specific inhibitor of mitochondrial ROS production, reduced prostate weight and voiding frequency. In human BPH-1 epithelial cells, ATT decreased mitochondrial metabolism, cell proliferation, and stemness features. ATT prevented the growth of organoids generated by sorted Pb-PRL basal and LSCmed cells, the two major BPH-associated, androgen-independent epithelial cell compartments. Taken together, these results support cell plasticity as a driver of BPH progression and therapeutic resistance to androgen signaling inhibition, and identify antioxidant therapy as a promising treatment of BPH.

Post-activation performance enhancement effect of drop jump on long jump performance during competition.

Drop jump is widely used in training sessions, aiming for chronic effects on long jump performance. However, the acute effect of drop jump on long jump performance through its use as a Conditioning Activity (CA) has not been explored. The objective of this study was to verify the Post-activation Performance Enhancement (PAPE) responses induced by successive Drop Jumps (DJ) on competitive long jump performance. Eleven male jumpers (19.0 ± 2.0 years; 178.0 ± 9.0 cm; 73.1 ± 8.9 kg; and personal record 5.78 ± 0.44 m) volunteered for participation. The athletes performed 5 drop jumps 2 min (1'45-2'15 min) before the second, and fourth attempt during official competition of state level, the attempts without the use of CA were considered controls. The performance of the second (5.63 ± 0.43 m), third (5.65 ± 0.46, g = 0.24) and fourth (5.71 ± 0.34 m) jumps performed after activation were higher than the first (5.54 ± 0.45 m) in the control condition, p = 0.02, and p = 0.01 respectively. Differences were also found in the take-off vertical velocity of the jump between the fourth (1.55 ± 0.21) and the first jump (1.30 ± 0.40), p = 0.006. Jump performance showed positive correlation with approach velocity, r = 0.731, vertical take-off velocity, r = 0.412, and take-off duration, r = 0.508. The mean performance in jumping post-activation (5.67 ± 0.38 m) was higher than that without the use of previous CA (5.59 ± 0.44 m), p = 0.02, g = 0.19. The use of DJs as a CA prior to the long jump promotes improvements in the performance of the jump, which can be explained by the increase in the take-off vertical velocity in the athletes.

Acute effects of transcranial direct current stimulation (tDCS) on peak torque and 5000 m running performance: a randomized controlled trial.

The benefits of transcranial direct current stimulation (tDCS) on brain function, cognitive response, and motor ability are well described in scientific literature. Nevertheless, the effects of tDCS on athletes' performance remain unclear. To compare the acute effects of tDCS on the running performance of 5000 m (m) runners. Eighteen athletes were randomized into Anodal (n = 9) groups that received tDCS for 20 min and 2 mA, and Sham (n = 9), in the motor cortex region (M1). Running time in 5000 m, speed, perceived exertion (RPE), internal load and peak torque (Pt) were evaluated. The Shapiro-Wilk test followed by a paired Student's t-test was used to compare Pt and total time to complete the run between the groups. The running time and speed of the Anodal group (p = 0.02; 95% CI 0.11-2.32; d = 1.24) was lower than the Sham group (p = 0.02, 95% CI 0.05-2.20; d = 1.15). However, no difference was found in Pt (p = 0.70; 95% CI - 0.75 to 1.11; d = 0.18), RPE (p = 0.23; 95% CI - 1.55 to 0.39; d = 0.60) and internal charge (p = 0.73; 95% CI - 0.77 to 1.09; d = 0.17). Our data indicate that tDCS can acutely optimize the time and speed of 5000 m runners. However, no alterations were found for Pt and RPE.

Transcriptomic Signature and Growth Factor Regulation of Castration-Tolerant Prostate Luminal Progenitor Cells.

Background: The molecular and cellular mechanisms that drive castration-resistant prostate cancer (CRPC) remain poorly understood. LSCmed cells defines an FACS-enriched population of castration-tolerant luminal progenitor cells that has been proposed to promote tumorigenesis and CRPC in Pten-deficient mice. The goals of this study were to assess the relevance of LSCmed cells through the analysis of their molecular proximity with luminal progenitor-like cell clusters identified by single-cell (sc)RNA-seq analyses of mouse and human prostates, and to investigate their regulation by in silico-predicted growth factors present in the prostatic microenvironment. Methods: Several bioinformatic pipelines were used for pan-transcriptomic analyses. LSCmed cells isolated by cell sorting from healthy and malignant mouse prostates were characterized using RT-qPCR, immunofluorescence and organoid assays. Results: LSCmed cells match (i) mouse luminal progenitor cell clusters identified in scRNA-seq analyses for which we provide a common 15-gene signature including the previously identified LSCmed marker Krt4, and (ii) Club/Hillock cells of the human prostate. This transcriptional overlap was maintained in cancer contexts. EGFR/ERBB4, IGF-1R and MET pathways were identified as autocrine/paracrine regulators of progenitor, proliferation and differentiation properties of LSCmed cells. The functional redundancy of these signaling pathways allows them to bypass the effect of receptor-targeted pharmacological inhibitors. Conclusions: Based on transcriptomic profile and pharmacological resistance to monotherapies that failed in CRPC patients, this study supports LSCmed cells as a relevant model to investigate the role of castration-tolerant progenitor cells in human prostate cancer progression.

Research of Rickettsia spp. and Borrelia spp. in dogs in Southeast Brazil.

Dogs are important in the epidemiology of tick-borne diseases, playing a significant role mainly in endemic areas of rickettsiosis and borreliosis, and serving as sentinels in epidemiological surveys. We analyzed the distribution of Rickettsia and Borrelia spp. in dogs and their ticks in the municipalities of Guaxupé, Minas Gerais, and Tapiratiba, São Paulo, Brazil, two areas non-endemic for Baggio-Yoshinari Syndrome (BYS) and rickettsiosis. Serum from 242 dogs of different ages (>12 months) and breeds were tested by the Indirect Immunofluorescence Assay (IFA) using specific antigens for Rickettsia rickettsii, Rickettsia parkeri, Rickettsia amblyommatis, Rickettsia rhipicephali, and Rickettsia bellii, and by an indirect Enzyme Linked Immunosorbent Assay (ELISA) for the detection of homologous IgG antibodies against Borrelia burgdorferi American strain G39/40. Ticks were collected from the animals and subjected to PCR and nested PCR for detection of Rickettsia spp. (synthase citrate gene) and Borrelia spp. (flagellin gene). Serological data showed that 7.85% (19/242) of the analyzed dogs were seropositive for at least one of the five Rickettsia antigens tested; one (0.41%) was considered seropositive for R. parkeri (1:64) and one (0.41%) for R. rickettsii (1:256). Nine (3.72%) were considered seropositive for R. bellii and one (0.41%) for R. amblyommatis; a seroprevalence of 13.64% (33/242) for IgG class immunoreactive antibodies against B. burgdorferi was observed. A total of 148 ticks were collected from the dogs; among these 3.40% were identified as larvae of the genus Rhipicephalus and 0.70% of the genus Amblyomma; 89.8% were identified as Rhipicephalus sanguineus, 4.70% Amblyomma sculptum and 1.40% Amblyomma ovale; all negative for PCR of Rickettsia spp. and nested PCR for Borrelia spp.. The serological findings of this study suggest the circulation of Rickettsiae associated with the spotted fever group and vector ticks, just like Borrelia spp. in a non-endemic Brazilian area, drawing attention to the possibility of a zoonotic cycle in the region.

Ferroptosis: Cancer Stem Cells Rely on Iron until "to Die for" It.

Cancer stem cells (CSCs) are a distinct subpopulation of tumor cells with stem cell-like features. Able to initiate and sustain tumor growth and mostly resistant to anti-cancer therapies, they are thought responsible for tumor recurrence and metastasis. Recent accumulated evidence supports that iron metabolism with the recent discovery of ferroptosis constitutes a promising new lead in the field of anti-CSC therapeutic strategies. Indeed, iron uptake, efflux, storage and regulation pathways are all over-engaged in the tumor microenvironment suggesting that the reprogramming of iron metabolism is a crucial occurrence in tumor cell survival. In particular, recent studies have highlighted the importance of iron metabolism in the maintenance of CSCs. Furthermore, the high concentration of iron found in CSCs, as compared to non-CSCs, underlines their iron addiction. In line with this, if iron is an essential macronutrient that is nevertheless highly reactive, it represents their Achilles' heel by inducing ferroptosis cell death and therefore providing opportunities to target CSCs. In this review, we first summarize our current understanding of iron metabolism and its regulation in CSCs. Then, we provide an overview of the current knowledge of ferroptosis and discuss the role of autophagy in the (regulation of) ferroptotic pathways. Finally, we discuss the potential therapeutic strategies that could be used for inducing ferroptosis in CSCs to treat cancer.

Intrauterine Malnutrition Reduced Long Leptin Receptor Isoform Expression and Proinflammatory Cytokine Production in Male Rat Pulmonary Endothelial Cells Stimulated by Lipopolysaccharide.

BACKGROUND/AIMS: We have previously shown that low birth weight (LBW) rats exposed to intrauterine malnutrition have an impaired lung inflammatory response and reduced levels of inflammatory mediators; however, circulating leptin levels were not increased. We evaluated long leptin receptor isoform (ObRb) expression in lung endothelial cells from low birth weight rats and examined its role in the production of lipid mediators and cytokines. METHODS: Lung endothelial cells were obtained from normal birth weight (NBW) rats or LBW rats subjected to intrauterine malnutrition. These cells were stimulated with leptin (10 ng/mL), LPS (lipopolysaccharide, 1 µg/mL), or leptin plus LPS. Six hours after stimulation, the production of inflammatory mediators (PGE2, LTB4, IL-1ß, and IL-6) was evaluated using commercial ELISA kits, and Western blotting was performed to investigate p38MAPK, NF-κB, and ObRb expression. RESULTS: Leptin increased IL-1ß levels in only cells from the NBW group, whereas LPS increased PGE2 and LTB4 levels in cells from both groups; leptin addition potentiated lipid mediator production induced by LPS in the NBW group. LPS enhanced the production of IL-1ß and IL-6 in only endothelial cells from NBW rats. Leptin receptor expression was decreased (63%) in endothelial cells from LBW rats. None of the stimuli increased NF-κB or p38 signaling pathway expression in cells from LBW rats. CONCLUSION: These results suggest that intrauterine malnutrition compromises leptin receptor expression and cytokine production in pulmonary endothelial cells stimulated by LPS; these effects seem to involve the NF-κB and p38MAPK signaling pathways.

A promising new approach to cancer therapy: Targeting iron metabolism in cancer stem cells.

Iron is an essential nutrient that facilitates cell proliferation and growth. Iron can be detrimental, however. The ability of iron to cycle between oxidized and reduced forms contributes to the formation of free radicals. An excess of free radicals leads to lipid peroxidation, more reactive oxygen species and oxidative stress, damage to DNA and other biomolecules, and, if potentially, tumorigenesis. Iron also has a role in the maintenance of the tumor microenvironment and in metastasis. Pathways of iron acquisition, efflux, storage, and regulation are all perturbed in cancer, suggesting that reprogramming of iron metabolism is a central aspect of tumor cell survival. Recent studies have shed light on the role of iron metabolism in cancer stem cells (CSC) and suggest that specific targeting of iron metabolism in CSCs may improve the efficacy of cancer therapy. In this review, we first summarize briefly our current understanding of the intracellular processes involving iron, the effect of dietary iron, and its relation to cancer. We emphasize the importance of modifier "iron genes" in cancer and the possibility that these genes may encode biomarkers that may be used clinically. We then provide an update on the role of iron in metabolic reprogramming, the epithelial-mesenchymal transition, and the regulation of epigenetic marks essential for CSC maintenance and plasticity. Finally, we discuss the potential of targeting a recently discovered form of iron-regulated cell death, ferroptosis, in CSCs for treatment of cancer.