Hepatic noradrenergic innervation acts via CREB/CRTC2 to activate gluconeogenesis during cold.

BACKGROUND AND AIM: Although it is well established that hormones like glucagon stimulates gluconeogenesis via the PKA-mediated phosphorylation of CREB and dephosphorylation of the cAMP-regulated CREB coactivators CRTC2, the role of neural signals in the regulation of gluconeogenesis remains uncertain. METHODS AND RESULTS: Here, we characterize the noradrenergic bundle architecture in mouse liver; we show that the sympathoexcitation induced by acute cold exposure promotes hyperglycemia and upregulation of gluconeogenesis via triggering of the CREB/CRTC2 pathway. Following its induction by dephosphorylation, CRTC2 translocates to the nucleus and drives the transcription of key gluconeogenic genes. Rodents submitted to different models of sympathectomy or knockout of CRTC2 do not activate gluconeogenesis in response to cold. Norepinephrine directly acts in hepatocytes mainly through a Ca2+-dependent pathway that stimulates CREB/CRTC2, leading to activation of the gluconeogenic program. CONCLUSION: Our data demonstrate the importance of the CREB/CRTC2 pathway in mediating effects of hepatic sympathetic inputs on glucose homeostasis, providing new insights into the role of norepinephrine in health and disease.

Central angiotensin-(1-7) attenuates hypoglycemia in sepsis-like conditions via reducing systemic and hepatic inflammation.

Sepsis is understood as the result of initiating systemic inflammation derived from an inadequate host response against pathogens. In its acute phase, sepsis is marked by an exacerbated reaction to infection, tissue damage, organ failure, and metabolic dysfunction. Among these, hypoglycemia, characterized by disorders of the gluconeogenesis pathway, is related to one of the leading causes of mortality in septic patients. Recent research has investigated the involvement of sympathetic efferent neuroimmune pathways during systemic inflammation. These pathways can be stimulated by several centrally administered drugs, including Angiotensin-(1-7) (Ang-(1-7)). Therefore, the present study aims to evaluate the effects of central treatment with Ang-(1-7) on hypoglycemia during endotoxemia. For this, male Wistar Hannover rats underwent stereotaxic surgery for intracerebroventricular (i.c.v.) administration of Ang-(1-7) and cannulation of the jugular vein for lipopolysaccharide (LPS) injection. Our results demonstrate that LPS was capable of inducing hypoglycemia and that prior central treatment with Ang-(1-7) attenuated this effect. Our data also show that Ang-(1-7) reduced plasma concentrations of TNF-α, IL-1ß, IL-6, and nitric oxide, in addition to the decrease and increase of hepatic IL-6 and IL-10 respectively, in animals subjected to systemic inflammation by LPS, resulting in the reduction of systemic and hepatic inflammation, thus attenuating the deleterious effects of LPS on phosphoenolpyruvate carboxykinase protein content. In summary, the data suggest that central treatment with Ang-(1-7) attenuates hypoglycemia induced by endotoxemia, probably through anti-inflammatory action, leading to reestablishing hepatic gluconeogenesis.

Maternal Vitamin D Deficiency Impairs the Development of ß Cells in Offspring Rats in a Sex-Dependent Manner.

Recent studies have shown that maternal vitamin D deficiency (VDD) causes long-term metabolic changes in offspring. However, little is known about the impact of maternal VDD on offspring endocrine pancreas development and insulin secretion in the adult life of male and female animals. Female rats (Wistar Hannover) were fed either control (1000 IU Vitamin D3/kg), VDD (0 IU Vitamin D3/kg), or a Ca2+-enriched VDD diet (0 IU Vitamin D3/kg + Ca2+ and P/kg) for 6 weeks and during gestation and lactation. At weaning, VDD status was confirmed based on low serum calcidiol levels in dams and pups. Next, male and female offspring were randomly separated and fed a standard diet for up to 90 days. At this age, serum calcidiol levels were restored to normal levels in all groups, but serum insulin levels were decreased in VDD males without affecting glucagon levels, glycemia, or glucose tolerance. Islets isolated from VDD males showed lower insulin secretion in response to different glucose concentrations, but this effect was not observed in VDD females. Furthermore, VDD males, but not females, showed a smaller total pancreatic islet area and lower ß cell mass, an effect that was accompanied by reduced gene expression of Ins1, Ins2, Pdx1, and SLC2A2. The decrease in Pdx1 expression was not related to the methylation profile of the promoter region of this gene. Most of these effects were observed in the male VDD+Ca2+ group, indicating that the effects were not due to alterations in Ca2+ metabolism. These data show that maternal VDD selectively impairs the morphology and function of ß cells in adult male offspring rats and that female offspring are fully protected from these deleterious effects.

Comparative study of the bacterial community of organic and conventional cow's milk.

Agricultural practises such as conventional and organic farming can potentially affect the microbial communities in milk. In the present study, the bacterial diversity of milk was investigated using high-throughput sequencing on ten organic and ten conventional farms in the Azores, a region where milk production is largely based on year-round grazing systems. The microbiota of milk from both production systems was dominated by Bacillota, Pseudomonadota, Actinomycetota and Bacteroidota. The organic milk showed greater heterogeneity between farms, as reflected in the dispersion of diversity indices and the large variation in the relative abundances of the dominant genera. In contrast, conventionally produced milk showed a high degree of similarity within each season. In the conventional production system, the season also had a strong influence on the bacterial community, but this effect was not observed in the organic milk. The LEfSe analysis identified the genus Iamia as significantly (p < 0.05) more abundant in organic milk, but depending on the season, several other genera were identified that distinguished organic milk from conventionally produced milk. Of these, Bacillus, Iamia and Nocardioides were associated with the soil microbiota in organic farming.

Creatine supplementation increases postnatal growth and strength and prevents overexpression of pro-inflammatory interleukin 6 in the hippocampus in an experimental model of cerebral palsy.

ABSTRACTObjectives: The aim of this study was thus to evaluate the effect of Cr supplementation on morphological changes and expression of pro-inflammatory cytokines in the hippocampus and on developmental parameters. Methods: Male Wistar rat pups were submitted to an experimental model of CP. Cr was administered via gavage from the 21st to the 28th postnatal day, and in water after the 28th, until the end of the experiment. Body weight (BW), food consumption (FC), muscle strength, and locomotion were evaluated. Expression of interleukin-1ß (IL-1ß), interleukin-6 (IL-6), and tumor necrosis factor α (TNF-α) were assessed in the hippocampus by quantitative real-time polymerase chain reaction. Iba1 immunoreactivity was assessed by immunocytochemistry in the hippocampal hilus. Results: Experimental CP caused increased density and activation of microglial cells, and overexpression of IL-6. The rats with CP also presented abnormal BW development and impairment of strength and locomotion. Cr supplementation was able to reverse the overexpression of IL-6 in the hippocampus and mitigate the impairments observed in BW, strength, and locomotion. Discussion: Future studies should evaluate other neurobiological characteristics, including changes in neural precursor cells and other cytokines, both pro- and anti-inflammatory.

Duplex ultrasound for surveillance of lower limb revascularisation.

BACKGROUND: Lower extremity atherosclerotic disease (LEAD) - also known as peripheral arterial disease - refers to the obstruction or narrowing of the large arteries of the lower limbs, most commonly caused by atheromatous plaque. Although in many cases of less severe disease patients can be asymptomatic, the major clinical manifestations of LEAD are intermittent claudication (IC) and critical limb ischaemia, also known as chronic limb-threatening ischaemia (CLTI). Revascularisation procedures including angioplasty, stenting, and bypass grafting may be required for those in whom the disease is severe or does not improve with non-surgical interventions. Maintaining vessel patency after revascularisation remains a challenge for vascular surgeons, since approximately 30% of vein grafts may present with restenosis in the first year due to myointimal hyperplasia. Restenosis can also occur after angioplasty and stenting. Restenosis and occlusions that occur more than two years after the procedure are generally related to progression of the atherosclerosis. Surveillance programmes with duplex ultrasound (DUS) scanning as part of postoperative care may facilitate early diagnosis of restenosis and help avoid amputation in people who have undergone revascularisation. OBJECTIVES: To assess the effects of DUS versus pulse palpation, arterial pressure index, angiography, or any combination of these, for surveillance of lower limb revascularisation in people with LEAD. SEARCH METHODS: The Cochrane Vascular Information Specialist searched the Cochrane Vascular Specialised Register, CENTRAL, MEDLINE, Embase, CINAHL, and LILACS databases and World Health Organization International Clinical Trials Registry Platform and ClinicalTrials.gov trials registers to 1 February 2022. SELECTION CRITERIA: We included randomised controlled trials (RCTs) and quasi-RCTs that compared DUS surveillance after lower limb revascularisation versus clinical surveillance characterised by medical examination with pulse palpation, with or without any other objective test, such as arterial pressure index measures (e.g. ankle-brachial index (ABI) or toe brachial index (TBI)). Our primary outcomes were limb salvage rate, vessel or graft secondary patency, and adverse events resulting from DUS surveillance. Secondary outcomes were all-cause mortality, functional walking ability assessed by walking distance, clinical severity scales, quality of life (QoL), re-intervention rates, and functional walking ability assessed by any validated walking impairment questionnaire. We presented the outcomes at two time points: two years or less after the original revascularisation (short term) and more than two years after the original revascularisation (long term). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methodological procedures. We used the Cochrane RoB 1 tool to assess the risk of bias for RCTs and GRADE to assess the certainty of evidence. We performed meta-analysis when appropriate. MAIN RESULTS: We included three studies (1092 participants) that compared DUS plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation and arterial pressure index (ABI or TBI) for surveillance of lower limb revascularisation with bypass. One study each was conducted in Sweden and Finland, and the third study was conducted in the UK and Europe. The studies did not report adverse events resulting from DUS surveillance, functional walking ability, or clinical severity scales. No study assessed surveillance with DUS scanning after angioplasty or stenting, or both. We downgraded the certainty of evidence for risk of bias and imprecision. Duplex ultrasound plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation plus arterial pressure index (ABI or TBI) (short-term time point) In the short term, DUS surveillance may lead to little or no difference in limb salvage rate (risk ratio (RR) 0.84, 95% confidence interval (CI) 0.49 to 1.45; I² = 93%; 2 studies, 936 participants; low-certainty evidence) and vein graft secondary patency (RR 0.92, 95% CI 0.67 to 1.26; I² = 57%; 3 studies, 1092 participants; low-certainty evidence). DUS may lead to little or no difference in all-cause mortality (RR 1.11, 95% CI 0.70 to 1.74; 1 study, 594 participants; low-certainty evidence). There was no clear difference in QoL as assessed by the 36-item Short Form Health Survey (SF-36) physical score (mean difference (MD) 2 higher, 95% CI 2.59 lower to 6.59 higher; 1 study, 594 participants; low-certainty evidence); the SF-36 mental score (MD 3 higher, 95% CI 0.38 lower to 6.38 higher; 1 study, 594 participants; low-certainty evidence); or the EQ-5D utility score (MD 0.02 higher, 95% CI 0.03 lower to 0.07 higher; 1 study, 594 participants; low-certainty evidence). DUS may increase re-intervention rates when considered any therapeutic intervention (RR 1.38, 95% CI 1.05 to 1.81; 3 studies, 1092 participants; low-certainty evidence) or angiogram procedures (RR 1.53, 95% CI 1.12 to 2.08; 3 studies, 1092 participants; low-certainty evidence). Duplex ultrasound plus pulse palpation and arterial pressure index (ABI or TBI) versus pulse palpation plus arterial pressure index (ABI or TBI) (long-term time point) One study reported data after two years, but provided only vessel or graft secondary patency data. DUS may lead to little or no difference in vessel or graft secondary patency (RR 0.83, 95% CI 0.19 to 3.51; 1 study, 156 participants; low-certainty evidence). Other outcomes of interest were not reported at the long-term time point. AUTHORS' CONCLUSIONS: Based on low certainty evidence, we found no clear difference between DUS and standard surveillance in preventing limb amputation, morbidity, and mortality after lower limb revascularisation. We found no studies on DUS surveillance after angioplasty or stenting (or both), only studies on bypass grafting. High-quality RCTs should be performed to better inform the best medical surveillance of lower limb revascularisation that may reduce the burden of peripheral arterial disease.

Treatment of Elephantiasis with Physiological Retraction of the Skin to Clinical Standards of Normality.

Stage III lymphedema, also known as elephantiasis, is the most advanced stage and involves the occurrence of large deformities. This article reports the case of a 30-year-old woman with bilateral stage III lymphedema who weighed 109 kg. The largest circumference measurements below the knee were 97 cm on the right leg and 76 cm on the left leg. Intensive treatment was performed, involving 8 hour per day of mechanical lymphatic therapy with the RAGodoy® device, which performs passive plantar flexion and extension, 15 min of cervical lymphatic therapy per day, and the use of non-elastic laced compression stockings. Treatment resulted in a considerable loss of edema as well as the occurrence of folds of excess skin, which were resolved by continuing treatment in a slower, non-intensive manner. Folds of excess skin are common during the treatment of large lymphedemas until reaching standards of normality or near normality but can be resolved with further clinical treatment.

Isolation, Identification, and Characterization of Phosphate-Solubilizing Bacteria from Tunisian Soils.

Soil microorganisms play an important role in maintaining natural ecological balance through active participation in carbon, nitrogen, sulfur, and phosphorous cycles. Phosphate-solubilizing bacteria (PSB) are of high importance in the rhizosphere, enhancing the solubilization of inorganic phosphorus complexes into soluble forms available for plant nutrition. The investigation of this species of bacteria is of major interest in agriculture, as they can be used as biofertilizers for crops. In the present study, 28 isolates of PSB were obtained after the phosphate enrichment of soil samples from five Tunisian regions. Five PSB species were identified by 16S rRNA gene sequencing including Pseudomonas fluorescens, P. putida, and P. taiwanensis, Stenotrophomonas maltophilia, and Pantoea agglomerans. Solid and liquid Pikovskaya's (PVK) and National Botanical Research Institute's (NBRIP) media containing insoluble tricalcium phosphate were used for the evaluation of the phosphate solubilization ability of the bacterial isolates by two methods: visual evaluation of the solubilization zone around colonies (halo) and determination of solubilized phosphates in liquid medium by the colorimetric method of the vanado-molybdate yellow. Based on the results of the halo method, the isolate of each species that showed the higher phosphate solubilization index was selected for evaluation of phosphate solubilization by the colorimetric method. In the liquid media, the bacterial isolates showed phosphate solubilization ranging from 535.70 to 618.57 µg mL-1 in the NBRIP medium, and 374.20 to 544.28 µg mL-1 in the PVK medium, with the highest values produced by P. fluorescens. The best phosphate solubilization ability and higher reduction in broth pH, which indicates higher organic acid production, were achieved in NBRIP broth for most of the PSB. Strong correlations were observed between the average capability of PSB to solubilize phosphates and both the pH and total phosphorous content in the soil. The production of the hormone indole acetic acid (IAA), which can promote plant growth, was observed for all five PSB species. Among them, P. fluorescens obtained from the forest soil of northern Tunisia showed the highest production of IAA (50.4 ± 0.9 µg mL-1).

A Longitudinal Study with a Laser Methane Detector (LMD) Highlighting Lactation Cycle-Related Differences in Methane Emissions from Dairy Cows.

Reversing climate change requires broad, cohesive, and strategic plans for the mitigation of greenhouse gas emissions from animal farming. The implementation and evaluation of such plans demand accurate and accessible methods for monitoring on-field CH4 concentration in eructating breath. Therefore, this paper describes a longitudinal study over six months, aiming to test a protocol using a laser methane detector (LMD) to monitor CH4 emissions in semi-extensive dairy farm systems. Over 10 time points, CH4 measurements were performed in dry (late gestation) and lactating cows at an Azorean dairy farm. Methane traits including CH4 concentration related to eructation (E_CH4) and respiration (R_CH4), and eructation events, were automatically computed from CH4 measured values using algorithms created for peak detection and analysis. Daily CH4 emission was estimated from each profile's mean CH4 concentration (MEAN_CH4). Data were analyzed using a linear mixed model, including breed, lactation stage, and parity as fixed effects, and cow (subject) and time point as random effects. The results showed that Holsteins had higher E_CH4 than Jersey cows (p < 0.001). Although a breed-related trend was found in daily CH4 emission (p = 0.060), it was not significant when normalized to daily milk yield (p > 0.05). Methane emissions were lower in dry than in lactation cows (p < 0.05) and increased with the advancement of the lactation, even when normalizing it to daily milk yield (p < 0.05). Primiparous cows had lower daily CH4 emissions related to R_ CH4 compared to multiparous (p < 0.001). This allowed the identification of periods of higher CH4 emissions within the milk production cycle of dairy cows, and thus, the opportunity to tailor mitigation strategies accordingly.

Creatine supplementation to improve the peripheral and central inflammatory profile in cerebral palsy.

This opinion paper presents a brief review on the potential use of Creatine (Cr) to improve the inflammatory profile in individuals with Cerebral Palsy (CP). CP is a condition that causes muscle atrophy followed by reduced strength and altered muscle tone. The prevalence of chronic diseases is higher in people with CP due to this, which are often associated with peripheral inflammation, but there are no studies that have evaluated central inflammation in this condition. Nevertheless, the anti-inflammatory action of Cr has already been observed in different types of studies. Thus, the use of experimental models of CP to evaluate the expression of the inflammatory markers, especially in the brain, as well as approaches to reduce the impairments already observed becomes essential. Results obtained in these preclinical studies may contribute to the quality of therapeutic strategies offered to children suffering from CP, the most common cause of chronic motor disability in childhood.

Androgens and low density lipoprotein-cholesterol interplay in modulating prostate cancer cell fate and metabolism.

BACKGROUND: Androgens, the known drivers of prostate cancer (PCa), have been indicated as important metabolic regulators with a relevant role in stimulating lipid metabolism. Also, the relationship between obesity and the aggressiveness of PCa has been established. However, it is unknown if the androgenic hormonal environment may alter the response of PCa cells to lipid availability. PURPOSE: The present study evaluated the effect of 5α-dihydrotestosterone (DHT) in regulating lipid metabolism, and the interplay between this hormone and low-density lipoprotein (LDL)-cholesterol in modulating PCa cells fate. METHODS: Non-neoplastic and neoplastic PCa cells were treated with 10 nM DHT, and the expression of fatty acids transporter, fatty acid synthase (FASN), and carnitine palmitoyltransferase 1A (CPT1A) evaluated. PCa cells were also exposed to LDL (100 µg/ml) in the presence or absence of DHT. RESULTS: Treatment with DHT upregulated the expression of FASN and CPT1A in androgen-sensitive PCa cells. In contrast, LDL supplementation suppressed FASN expression regardless of the presence of DHT, whereas augmenting CPT1A levels. Our results also showed that LDL-cholesterol increased PCa cells viability, proliferation, and migration dependently on the presence of DHT. Moreover, LDL and DHT synergistically enhanced the accumulation of lipid droplets in PCa cells. CONCLUSIONS: The obtained results show that androgens deregulate lipid metabolism and enhance the effects of LDL increasing PCa cells viability, proliferation and migration. The present findings support clinical data linking obesity with PCa and first implicate androgens in this relationship. Also, they sustain the application of pharmacological approaches targeting cholesterol availability and androgens signaling simultaneously.

Effects of the Treatment with Flavonoids on Metabolic Syndrome Components in Humans: A Systematic Review Focusing on Mechanisms of Action.

Diets high in bioactive compounds, such as polyphenols, have been used to mitigate metabolic syndrome (MetS). Polyphenols are a large group of naturally occurring bioactive compounds, classified into two main classes: non-flavonoids and flavonoids. Flavonoids are distributed in foods, such as fruits, vegetables, tea, red wine, and cocoa. Studies have already demonstrated the benefits of flavonoids on the cardiovascular and nervous systems, as well as cancer cells. The present review summarizes the results of clinical studies that evaluated the effects of flavonoids on the components of the MetS and associated complications when offered as supplements over the long term. The results show that flavonoids can significantly modulate several metabolic parameters, such as lipid profile, blood pressure, and blood glucose. Only theaflavin and catechin were unable to affect metabolic parameters. Moreover, only body weight and body mass index were unaltered. Thus, the evidence presented in this systematic review offers bases in support of a flavonoid supplementation, held for at least 3 weeks, as a strategy to improve several metabolic parameters and, consequently, reduce the risk of diseases associated with MetS. This fact becomes stronger due to the rare side effects reported with flavonoids.

Maternal vitamin D deficiency affects the morphology and function of glycolytic muscle in adult offspring rats.

BACKGROUND: Fetal stage is a critical developmental window for the skeletal muscle, but little information is available about the impact of maternal vitamin D (Vit. D) deficiency (VDD) on offspring lean mass development in the adult life of male and female animals. METHODS: Female rats (Wistar Hannover) were fed either a control (1000 IU Vit. D3/kg) or a VDD diet (0 IU Vit. D3/kg) for 6 weeks and during gestation and lactation. At weaning, male and female offspring were randomly separated and received a standard diet up to 180 days old. RESULTS: Vitamin D deficiency induced muscle atrophy in the male (M-VDD) offspring at the end of weaning, an effect that was reverted along the time. Following 180 days, fast-twitch skeletal muscles [extensor digitorum longus (EDL)] from the M-VDD showed a decrease (20%; P < 0.05) in the number of total fibres but an increase in the cross-sectional area of IIB (17%; P < 0.05), IIA (19%; P < 0.05) and IIAX (21%; P < 0.05) fibres. The fibre hypertrophy was associated with the higher protein levels of MyoD (73%; P < 0.05) and myogenin (55% %; P < 0.05) and in the number of satellite cells (128.8 ± 14 vs. 91 ± 7.6 nuclei Pax7 + in the M-CTRL; P < 0.05). M-VDD increased time to fatigue during ex vivo contractions of EDL muscles and showed an increase in the phosphorylation levels of IGF-1/insulin receptor and their downstream targets related to anabolic processes and myogenic activation, including Ser 473 Akt and Ser 21/9 GSK-3ß. In such muscles, maternal VDD induced a compensatory increase in the content of calcitriol (two-fold; P < 0.05) and CYP27B1 (58%; P < 0.05), a metabolizing enzyme that converts calcidiol to calcitriol. Interestingly, most morphological and biochemical changes found in EDL were not observed in slow-twitch skeletal muscles (soleus) from the M-VDD group as well as in both EDL and soleus muscles from the female offspring. CONCLUSIONS: These data show that maternal VDD selectively affects the development of type-II muscle fibres in male offspring rats but not in female offspring rats and suggest that the enhancement of their size and fatigue resistance in fast-twitch skeletal muscle (EDL) is probably due to a compensatory increase in the muscle content of Vit. D in the adult age.

Factors affecting executive function performance of Brazilian elderly in the Stroop test.

Aging is related to a decrease in physiological abilities, especially cognitive functions. To unravel further evidence of age-related cognitive decline, we analyzed which physical and functional variables are predictors of cognitive performance in a sample of 498 Brazilian elderly (67.26% women). To do so, we used the Stroop test as a tool to evaluate executive functions and the General functional fitness index (GFFI) to evaluate the functional fitness of the participants. A linear regression analysis revealed that female sex (ß=-0.097; t=-2.286; P=0.023), younger age (ß=0.205; t=4.606; P<0.0001), more years of education (ß=-0.280; t=-6.358; P<0.0001), and higher GFFI (ß=-0.101; t=-2.347; P<0.02) were predictors of better cognitive performance. Body mass index (kg/m2) and nutritional status (underweight, eutrophic, overweight, or obese) were not predictors of cognitive performance. Interestingly, among the GFFI tasks, muscle strength influenced the test execution time, both in upper and lower limbs (elbow flexion: ß=-0.201; t=-4.672; P<0.0001; sit-to-stand: ß=-0.125; t=-2.580; P<0.01). Our findings showed that: 1) women performed the Stroop test faster than men; 2) the older the person, the lower was the cognitive performance; 3) the higher the education, the better the test execution time; and 4) higher scores in the GFFI were associated with a better performance in the Stroop test. Therefore, gender, age, education, and functional fitness and capacity were predictors of cognitive performance in the elderly.

Effects of ocean acidification and warming on the development and biochemical responses of juvenile shrimp Palaemon elegans (Rathke, 1837).

Anthropogenic CO2 emissions have led to the warming and acidification of the oceans. Although, there is a growing of evidence showing that simultaneous occurrence of ocean acidification and ocean warming are threats to marine organisms, information on their combined effect on coastal shrimp species remains scarce. The purpose of this study was to estimate the combined effects of seawater acidification and warming on growth-related traits and biochemical responses of P. elegans juveniles. In this work, shrimp were exposed for 65 days at 4 experimental conditions: pH 8.10 * 18 °C, pH 7.80 * 18 °C, pH 8.10 * 22 °C, pH 7.80 * 22 °C. The results showed that low pH decreases the lipid content by ∼13% (p < 0.05). Higher temperature reduced the condition factor by ∼11%, the protein content by ∼20%, the PUFA by ∼8,6% and shortened moulting events by 5 days (p > 0.05) while the SFA increased ∼9.4%. The decrease in condition factor and protein was however more prominent in organisms exposed to the combination of pH and temperature with a decrease of ∼13% and ∼21%, respectively. Furthermore, essential fatty acids as EPA and DHA also decreased by ∼20% and ∼6.6% in low pH and higher temperature condition. Despite this study suggest that warming may have a greater impact than acidification, it has been shown that their combined effect can exacerbate these impacts with consequences for the shrimp's body size and biochemical profile.

Factors affecting executive function performance of Brazilian elderly in the Stroop test

Aging is related to a decrease in physiological abilities, especially cognitive functions. To unravel further evidence of age-related cognitive decline, we analyzed which physical and functional variables are predictors of cognitive performance in a sample of 498 Brazilian elderly (67.26% women). To do so, we used the Stroop test as a tool to evaluate executive functions and the General functional fitness index (GFFI) to evaluate the functional fitness of the participants. A linear regression analysis revealed that female sex (β=-0.097; t=-2.286; P=0.023), younger age (β=0.205; t=4.606; P<0.0001), more years of education (β=-0.280; t=-6.358; P<0.0001), and higher GFFI (β=-0.101; t=-2.347; P<0.02) were predictors of better cognitive performance. Body mass index (kg/m2) and nutritional status (underweight, eutrophic, overweight, or obese) were not predictors of cognitive performance. Interestingly, among the GFFI tasks, muscle strength influenced the test execution time, both in upper and lower limbs (elbow flexion: β=-0.201; t=-4.672; P<0.0001; sit-to-stand: β=-0.125; t=-2.580; P<0.01). Our findings showed that: 1) women performed the Stroop test faster than men; 2) the older the person, the lower was the cognitive performance; 3) the higher the education, the better the test execution time; and 4) higher scores in the GFFI were associated with a better performance in the Stroop test. Therefore, gender, age, education, and functional fitness and capacity were predictors of cognitive performance in the elderly.

Molecular basis of Period 1 regulation by adrenergic signaling in the heart.

The cardiac circadian clock is responsible for the modulation of different myocardial processes, and its dysregulation has been linked to disease development. How this clock machinery is regulated in the heart remains an open question. Because noradrenaline (NE) can act as a zeitgeber in cardiomyocytes, we tested the hypothesis that adrenergic signaling resets cardiac clock gene expression in vivo. In its anti-phase with Clock and Bmal1, cardiac Per1 abundance increased during the dark phase, concurrent with the rise in heart rate and preceded by an increase in NE levels. Sympathetic denervation altered Bmal1 and Clock amplitude, while Per1 was affected in both amplitude and oscillatory pattern. We next treated mice with a ß-adrenergic receptor (ß-AR) blocker. Strikingly, the ß-AR blockade during the day suppressed the nocturnal increase in Per1 mRNA, without altering Clock or Bmal1. In contrast, activating ß-AR with isoproterenol (ISO) promoted an increase in Per1 expression, demonstrating its responsiveness to adrenergic input. Inhibitors of ERK1/2 and CREB attenuated ISO-induced Per1 expression. Upstream of ERK1/2, PI3Kγ mediated ISO induction of Per1 transcription, while activation of ß2-AR, but not ß1-AR induced increases in ERK1/2 phosphorylation and Per1 expression. Consistent with the ß2-induction of Per1 mRNA, ISO failed to activate ERK1/2 and elevate Per1 in the heart of ß2-AR-/- mice, whereas a ß2-AR antagonist attenuated the nocturnal rise in Per1 expression. Our study established a link between NE/ß2-AR signaling and Per1 oscillation via the PI3Ky-ERK1/2-CREB pathway, providing a new framework for understanding the physiological mechanism involved in resetting cardiac clock genes.

Sweet Cherries as Anti-Cancer Agents: From Bioactive Compounds to Function.

Sweet cherries (Prunus avium L.) are among the most appreciated fruits worldwide because of their organoleptic properties and nutritional value. The accurate phytochemical composition and nutritional value of sweet cherries depends on the climatic region, cultivar, and bioaccessibility and bioavailability of specific compounds. Nevertheless, sweet cherry extracts are highly enriched in several phenolic compounds with relevant bioactivity. Over the years, technological advances in chemical analysis and fields as varied as proteomics, genomics and bioinformatics, have allowed the detailed characterization of the sweet cherry bioactive phytonutrients and their biological function. In this context, the effect of sweet cherries on suppressing important events in the carcinogenic process, such as oxidative stress and inflammation, was widely documented. Interestingly, results from our research group and others have widened the action of sweet cherries to many hallmarks of cancer, namely metabolic reprogramming. The present review discusses the anticarcinogenic potential of sweet cherries by addressing their phytochemical composition, the bioaccessibility and bioavailability of specific bioactive compounds, and the existing knowledge concerning the effects against oxidative stress, chronic inflammation, deregulated cell proliferation and apoptosis, invasion and metastization, and metabolic alterations. Globally, this review highlights the prospective use of sweet cherries as a dietary supplement or in cancer treatment.

Effects of varying sources of Cu, Zn, and Mn on mineral status and preferential intake of salt-based supplements by beef cows and calves and rainfall-induced metal loss.

Three studies were completed to evaluate the effects of Cu, Zn, and Mn source on preferential intake, trace mineral status, and rainfall-induced metal loss of salt-based mineral supplements. Mineral supplements were formulated to contain 2,500, 5,500, and 4,000 mg/kg of Cu, Zn, and Mn, respectively. Supplements differed only by source of Cu, Zn, and Mn, which were hydroxychloride, organic, or sulfate sources. In Exp. 1, the three formulations were offered simultaneously for 18 wk to preweaned beef calves (four pastures; 17 calves per pasture) within separate containers inside covered cow-exclusion areas. Consumption averaged 21 ± 2.4 g/calf daily (sum of all three sources), with a greater (P < 0.001) percentage of the total intake coming from the hydroxychloride vs. organic or sulfate sources of Cu, Zn, and Mn. In Exp. 2, the same sulfate and hydroxychloride formulations were randomly assigned to pastures (n = 4 pastures per treatment) containing 18 to 20 cow-calf pairs/pasture. Treatments were offered for 20 wk within covered areas designed to assess cow and calf intake separately. At weaning, liver biopsies were collected from four cow-calf pairs/pasture (n = 16 cows and calves per treatment). Source of Cu, Zn, and Mn had no effect on voluntary mineral intake among calves (P = 0.44) and cows (P = 0.14). Calves consuming mineral containing hydroxychloride sources of Cu, Zn, and Mn tended (P = 0.06) to have greater average daily gain over the 20-wk period compared with calves consuming sulfate sources of the same elements (1.09 vs. 1.06 kg/d; SEM = 0.013). Mineral status of cows and calves was not affected (P ≥ 0.17) by source of Cu, Zn, and Mn. In Exp. 3, each of the mineral formulations from Exp. 1 was exposed to a 10.2-cm precipitation event delivered in three equal 3.4-cm applications within a week. To accomplish this, 750 g of mineral was placed into Buchner funnels (177 cm2) on 20- to 25-µm pore filter paper. Deionized water (pH adjusted to 5.6) was poured over the mineral. Total leaching losses of Cu, Zn, and Mn were less (P < 0.001) for formulations containing hydroxychloride vs. organic and sulfate sources. These results imply that, when offered a choice, calves preferentially consume mineral supplements formulated with hydroxychloride vs. sulfate or organic sources of Cu, Zn, and Mn. In addition, hydroxychloride sources of Cu, Zn, and Mn are less susceptible to rainfall-induced leaching losses compared with sulfate and organic sources.

Glutaminolysis is a metabolic route essential for survival and growth of prostate cancer cells and a target of 5α-dihydrotestosterone regulation.

PURPOSE: Resistance to androgen-deprivation therapies and progression to so-called castrate-resistant prostate cancer (CRPC) remain challenges in prostate cancer (PCa) management and treatment. Among other alterations, CRPC has been associated with metabolic reprogramming driven by androgens. Here, we investigated the role of androgens in regulating glutaminolysis in PCa cells and determined the relevance of this metabolic route in controlling the survival and growth of androgen-sensitive (LNCaP) and CRPC (DU145 and PC3) cells. METHODS: PCa cells (LNCaP, DU145 and PC3) and 3-month old rats were treated with 5α-dihydrotestosterone (DHT). Alternatively, LNCaP cells were exposed to the glutaminase inhibitor BPTES, alone or in combination with the anti-androgen bicalutamide. Biochemical, Western blot and extracellular flux assays were used to evaluate the viability, proliferation, migration and metabolism of PCa cells in response to DHT treatment or glutaminase inhibition. RESULTS: We found that DHT up-regulated the expression of the glutamine transporter ASCT2 and glutaminase, both in vitro in LNCaP cells and in vivo in rat prostate cells. BPTES diminished the viability and migration of PCa cells, while increasing caspase-3 activity. CRPC cells were found to be more dependent on glutamine and more sensitive to glutaminase inhibition. BPTES and bicalutamide co-treatment had an additive effect on suppressing LNCaP cell viability. Finally, we found that inhibition of glutaminolysis differentially affected glycolysis and lipid metabolism in both androgen-sensitive and CRPC cells. CONCLUSION: Our data reveal glutaminolysis as a central metabolic route controlling PCa cell fate and highlight the relevance of targeting glutaminase for CRPC treatment.