Integrated aerobic exercise with LDE-docetaxel treatment: a novel approach to combat prostate cancer progression.

The variability in response to conventional prostate cancer (PC) therapies, coupled with the emergent issue of drug resistance, underscores the critical need for innovative treatment strategies. Aerobic physical exercise reduced incidence of several cancers, but the mechanism underlying these effects associated the nanoemulsion not fully understood. The application of a lipid nanoemulsion (LDE) delivery system for docetaxel (DTX), showing marked enhancement in therapeutic efficacy when combined with aerobic physical exercise. This novel intervention potentiates the antitumor activity of LDE-delivered DTX by augmenting nanoparticle internalization and inducing cell cycle arrest. Our findings reveal that this synergistic treatment not only significantly reduces prostate weight and mitigates adenocarcinoma proliferation but also attenuates anti-apoptotic BCL-2 protein expression. Concurrently, it elevates pro-apoptotic proteins and diminishes inflammatory markers. Metabolic profiling of the combined therapy group disclosed additional benefits, such as reduced lipid and plasma glucose levels. Collectively, our data illuminate the profound impact of integrating LDE-mediated DTX delivery with structured physical exercise, which together spearhead a dual-front assault on PC. This multimodal approach heralds a new paradigm in PC management, accentuating the promise of combined pharmacological and non-pharmacological interventions to elevate tumor suppressor protein activity and refine patient outcomes.

Different nutritional systems influence the tenderness and lipid oxidation of ewe lamb meat without altering gene expression.

Feeding is a determining factor in the various characteristics of sheep meat and animal performance, the objectives were to evaluate the effect of supplementation of ewe lambs finished in different nutritional planes on the gene expression of CASP3, CAPN1, CAPN2 and CAST and its possible association with meat quality. Samples of the Longissimus lumborum muscle of 24 ewe lambs were used, distributed in 3 groups (n=8): P (pasture), PS (pasture and supplement) and F (feedlot). Physicochemical analyses were performed for centesimal analysis, pH, lipid oxidation, Warner-Bratzler shear force and RT-qPCR for the analysis of relative gene expression of the following genes: CASP3, CAPN1, CAPN2 and CAST. There is an increase in daily weight gain and ethereal extract values in the meat of confined animals, due to the greater energy intake in the nutrition of these animals. Animals kept only on pasture have lower lipid oxidation in meat than other treatments because of the lower percentage of lipids. The Warner-Bratzler shear force is considerably higher in the meat of animals kept only on pasture but is still considered tender. The different nutritional systems do not interfere with the gene expression of CASP3, CAPN1, CAPN2 and CAST in ewe lambs.

In vitro maturation in synthetic oviductal fluid increases gene expression associated with quality and lipid metabolism in bovine oocytes.

Traditionally, in vitro oocyte and embryo culture progresses through a series of varying culture medium. To investigate simplifying the in vitro production of bovine cumulus-oocyte complexes (COCs), this study used synthetic oviductal fluid (SOF) supplemented with conjugated linoleic acid (CLA). Special interest was placed on gene expression linked to lipid metabolism and oocyte maturation. COCs were matured in different media: Medium 199 (M199 group), M199 with 100 µM CLA (M199 + CLA group), SOF (SOF group), and SOF with 100 µM CLA (SOF + CLA group). COCs matured with SOF showed a higher relative abundance of mRNA of quality indicators gremlin 1 (GREM1) and prostaglandin-endoperoxide synthase 2 (PTGS2) in oocytes, and GREM1 in cumulus cells compared with in the M199 group. SOF medium COCs had a higher relative abundance of fatty acid desaturase 2 (FADS2) compared with the M199 group, which is essential for lipid metabolism in oocytes. Furthermore, the abundance of stearoyl-coenzyme A desaturase 1 (SCD1) in oocytes matured with SOF was not influenced by the addition of CLA, whereas the relative abundance of SCD1 was reduced in M199 medium with CLA. We concluded that maturation in SOF medium results in a greater abundance of genes linked to quality and lipidic metabolism in oocytes, regardless of the addition of CLA.

Aerobic physical exercise modifies the prostate tumoral environment.

Exercise is recognized for its potential role in reducing the risk of certain cancers. However, the molecular mechanisms behind this risk reduction are not fully understood. Here, we hypothesized that aerobic physical exercise induces cancer attenuating effects through the modulation of oxidative stress and inflammation. To test this hypothesis, twenty male Sprague Dawley rats with chemically induced prostate tumors were divided into two groups: Prostate cancer (PC) in the absence and presence of exercise (PC + Ex). Rats in the PC + Ex group performed exercises on a treadmill for 8 weeks, 5 sessions per week, at an intensity of 60 % of maximum capacity. Weight and feed efficiency, Ki-67, apoptosis, prostatic inflammation, and markers of oxidative stress were analyzed. We found that aerobic physical exercise significantly decreased prostate cell proliferation (p < 0.05) across modulation, tumor size, and prostate weight. The PC + Ex group also significantly reduced anti-apoptosis protein expression (p < 0.05) and increased pro-apoptotic protein expression. Furthermore, physical exercise increased enzymatic antioxidant defenses in the prostate, plasma, and whole blood. Moreover, PC + Ex reduced lipid peroxidation and protein carbonyl levels (p < 0.05). In the prostate, there was an increase in anti-inflammatory cytokines (IL-10), and a reduction in pro-inflammatory cytokines (IL-6, TNF-α, and NF-κB) after 8 weeks of physical exercise. In conclusion, we found that aerobic physical exercise is a functional, beneficial, and applicable approach to control PC progression, because it modifies the systemic environment, including the regulation of glucose and circulating lipids. This modification of the cancer cells environment has anti-inflammatory and antioxidant effects that attenuate tumor growth.

The high-intensity interval training mitigates the cardiac remodeling in spontaneously hypertensive rats.

AIM: To evaluate the influence of high-intensity interval training (HIIT) on cardiac structural and functional characteristics and myocardial mitogen-activated protein kinase (MAPK) signaling in hypertensive rats. METHODS: Male rats (12 months old) were divided into three groups: Wistar Kyoto rats (WKY, n = 8); sedentary spontaneously hypertensive rats (SED-SHR, n = 10), and trained spontaneously hypertensive rats (HIIT-SHR, n = 10). Systolic blood pressure (SBP), functional capacity, echocardiography, isolated papillary muscle, and gene expression of MAPK gene-encoding proteins associated with Elk1, cJun, ATF2, MEF2 were analyzed. KEY FINDINGS: HIIT decreased SBP and increased functional capacity, left ventricular diastolic diameter, posterior wall thickness-left ventricle, relative wall thickness-left ventricle, and resting tension of the papillary muscle. In hypertensive rats, we observed a decrease in the gene-encoding ATF2 protein; this decrease was reversed by HIIT. SIGNIFICANCE: The influence of HIIT in the SHR model in the compensated hypertension phase generated an increase in cardiac hypertrophy, attenuated myocardial diastolic dysfunction, lowered blood pressure, improved functional capacity, and reversed the alteration in gene-encoding ATF2 protein.

An approach to uncover the relationship between 17b-estradiol and ESR1/ESR2 ratio in the regulation of canine corpus luteum.

The canine corpus luteum (CL) is able to synthetise, activate and deactivate 17b-estradiol (E2) and also expresses nuclear estrogen receptors in a time-dependent manner during diestrus. Nevertheless, we are still missing a better comprehension of E2 functions in the canine CL, especially regarding the specific roles of estrogen receptor alpha (ERa) and ERb, encoded by ESR1 and 2, respectively. For that purpose, we analyzed transcriptomic data of canine non-pregnant CL collected on days 10, 20, 30, 40, 50 and 60 of diestrus and searched for differentially expressed genes (DEG) containing predicted transcription factor binding sites (TFBS) for ESR1 or ESR2. Based on biological functions of DEG presenting TFBS, expression of select transcripts and corresponding proteins was assessed. Additionally, luteal cells were collected across specific time points during diestrus and specificity of E2 responses was tested using ERa and/or ERb inhibitors. Bioinformatic analyses revealed 517 DEGs containing TFBS, from which 67 for both receptors. In general, abundance of predicted ESR1 targets was greater in the beginning, while abundance of ESR2 targets was greater in the end of diestrus. ESR1/ESR2 ratio shifted from an increasing to a decreasing pattern from day 30 to 40 post ovulation. Specific receptor inhibition suggested an ERa-mediated positive regulation of CL function at the beginning of diestrus and an ERb-mediated effect contributing to luteal regression. In conclusion, our data points toward a broad spectrum of action of E2 and its nuclear receptors, which can also act as transcription factors for other genes regulating canine CL function.

High-intensity interval training attenuates the effects caused by arterial hypertension in the ventral prostate.

BACKGROUND: The prostatic effects induced by arterial hypertension is very controversial and its mechanism is unclear. High-intensity interval training (HIIT) is an exercise considered to be hypotensive. The objective of this work was to investigate the molecular, biochemical, and morphological effects of 8 weeks of HIIT in the prostatic tissue of spontaneously hypertensive rats (SHR). METHODS: Twenty male SHR rats, 51.4 weeks old, were used. The SHR animals were divided into two groups: spontaneously sedentary hypertensive and spontaneously hypertensive submitted to HIIT. We analyze androgens receptor and glucocorticoid receptors in the prostate. Still, we verify effects of the hypertension and HIIT on the physiopathology prostatic, for immunohistochemistry investigated BCL-2, BAX, IGF-1, FAS/CD95, data's inflammatory tumour necrosis factor α, nuclear factor kappa B and interleukin (IL)-6, anti-inflammatory IL-10. The echocardiographic evaluation was performed at the baseline and after the training period. RESULTS: Arterial hypertension promote high prostatic intraepithelial neoplasia incidence in the prostate, increases IGF-1, BCL-2 (p < 0.05), and inflammatory proteins (p < 0.05). Eight weeks of HIIT training reduced the arterial pressure and increase the concentration of tissue collagen and intracellular glycogen and showed a higher expression of BAX, FAS/CD95, and IL-10 proteins (p < 0.05), coinciding with a lower incidence of lesions and lower prostate weight (p < 0.05) and reduction of the BCL-2 and IGF-1. CONCLUSION: Our data suggested that arterial hypertension suppressed apoptosis and increased damage prostatic. On other hand, HIIT promotes morphology and function improves in the prostatic environment, inhibited inflammation, and increased apoptosis.

Insulin induces steroidogenesis in canine luteal cells via PI3K-MEK-MAPK.

Glucose uptake increases in canine luteal cells under insulin treatment. We hypothesize that insulin also increases luteal cell steroidogenesis. Dogs underwent elective ovariohysterectomy from days 10-60 post ovulation and their corpora lutea (CL) and blood samples were collected. Deep RNA sequencing determined differentially expressed genes in CL; those related to insulin signaling and steroidogenesis were validated in vivo by qPCR and their respective proteins by Western blotting and immunofluorescence. Next, luteal cell cultures were stimulated with insulin with or without inhibition of MAPK14, MAP2K1 and PI3K. Studied proteins except P450 aromatase showed the same expression pattern of coding genes in vivo. The expression of HSD3B and CYP19A1 was higher in insulin-treated cells (P < 0.005). Following respective pathway blockades, the culture medium had decreased concentrations of progesterone (P4) and 17b-estradiol (E2) (P < 0.01). Our results indicate that insulin increases HSD3B and CYP19A1 expression via MAPK and PI3K, and contributes to the regulation of P4 and E2 production in canine luteal cells.

Prebiotics mannan-oligosaccharides accelerate sexual maturity in rats: A randomized preclinical study.

BACKGROUND AND AIM: The prebiotics, mannan-oligosaccharides (MOS), demonstrate the ability to increase probiotic microorganisms and fixation and removal of pathogens associated with chronic systemic inflammation in the digestive system. Inflammatory processes play an important role in modulating the brain-intestinal axis, including maintaining male reproductive function and spermatogenesis and regulating stress. The aim of the present study was to evaluate the action of MOS on testosterone and corticosterone concentrations and the reproductive system development of rats in the growth phase as an animal model. MATERIALS AND METHODS: In total, 128 male rats were used, randomly divided into four experimental groups (n=32): Control; MOS 1; MOS 2; and MOS 3. From each group, eight animals were sacrificed in four experimental moments (14, 28, 42, and 56 days, respectively, moments 1, 2, 3, and 4) and hormonal measurements and histological evaluations were performed. RESULTS: The results revealed the effect of diet, MOS, and timing on testicle weight (p<0.05). At moments 3 and 4, the groups supplemented with MOS showed higher concentrations of testosterone and decreased corticosterone levels throughout the experimental period. Groups supplemented with MOS showed an increase in the frequency of relative sperm and sperm scores. The radii of the seminiferous tubules presented a significant statistical effect of the diet, moments, and diet + moment interaction. CONCLUSION: It was concluded that the three different MOS prebiotics brought forward sexual maturity.

Hormônio do crescimento versus treinamento de força: alterações nas estruturas colágenas, lipídicas e glicídicas / Growth hormone (gh) versus strength training: changes in collagen, lipid and glucidic structures

O objetivo deste estudo foi avaliar o efeito da aplicação de hormônio do crescimento (Growth Hormone - GH) e treinamento de força (TF) na composição do tecido ósseo de ratos Wistar a partir da Espectroscopia Raman. 40 ratos machos foram distribuídos de forma aleatória em quatro grupos: controle (C [n=10]), controle a aplicação de GH (GHC [n=10]), treinamento de força (T [n=10]) e treinamento de força e aplicação de GH (GHT [n=10]). O treinamento foi composto por quatro séries de 10 saltos aquáticos, realizados três vezes por semana, com sobrecarga correspondente a 50% do peso corpóreo e duração de quatro semanas. O GH foi aplicado na dose de 0,2 UI/Kg em cada animal, três vezes por semana e em dias alternados. Ao final do experimento, os animais foram eutanasiados e coletados os fêmures direitos para realização da análise da composição óssea. A espectroscopia Raman (ER) foi utilizada para observar os seguintes compostos a partir de suas respectivas bandas: colágeno e fosfolipídio (1445 cm-1), colesterol (548 cm-1), glicerol (607 cm-1), glicose (913 cm-1), Pico de carboidrato (931 cm-1 ) e prolina (918 cm-1 ). Para a análise estatística, foram realizados os testes de normalidade de Shapiro-Wilk e análise de variâncias ANOVA one-way, seguida pelo pós-teste de Tukey. Os resultados revelaram aumento nas concentrações de colágeno e fosfolipidio, colesterol, glicerol, glicose, pico de carboidrato e prolina em todos os grupos experimentais, associados ou não à realização do ST e/ou aplicação de GH. Porém, somente o grupo T diferiu significativamente do grupo C (p<0,05). Conclui-se que todas intervenções puderam promover ganho no tecido ósseo, porém, somente o grupo T demonstrou diferença significativa nos compostos minerais analisados. (AU)

The objective of this study was to evaluate the effect of the application of growth hormone (GH) and strength training (TF) on the bone tissue composition of Wistar rats using Raman Spectroscopy. 40 male rats were randomly assigned to four groups: control (C [n = 10]), control the application of GH (GHC [n = 10]), strength training (T [n = 10]) and training of strength and application of GH (GHT [n = 10]). The training consisted of four series of 10 water jumps, performed three times a week, with an overload corresponding to 50% of body weight and lasting four weeks. GH was applied at a dose of 0.2 IU / kg to each animal, three times a week and on alternate days. After four weeks, the animals were euthanized and the right femurs were collected to carry out the analysis of the bone composition. Raman spectroscopy (ER) was used to observe the following compounds from their respective bands: collagen and phospholipid (1445 cm-1), cholesterol (548 cm-1), glycerol (607 cm-1), glucose (913 cm-1), Peak carbohydrate (931 cm-1), proline (918 cm-1). For statistical analysis, the Shapiro-Wilk normality tests and ANOVA One-Way analysis of variances were performed, followed by the Tukey post-test. The results revealed an increase in the concentrations of collagen and phospholipid, cholesterol, glycerol, glucose, peak carbohydrate and proline in all experimental groups, associated or not with the performance of ST and / or application of GH. However, only group T differed significantly from group C (p <0.05). It was concluded that all intervention could promote gain in bone tissue, however, only the T group showed a significant difference in the analyzed mineral compounds. (AU)