Mitofusin 2 maintains haematopoietic stem cells with extensive lymphoid potential.

Haematopoietic stem cells (HSCs), which sustain production of all blood cell lineages, rely on glycolysis for ATP production, yet little attention has been paid to the role of mitochondria. Here we show in mice that the short isoform of a critical regulator of HSCs, Prdm16 (refs 4, 5), induces mitofusin 2 (Mfn2), a protein involved in mitochondrial fusion and in tethering of mitochondria to the endoplasmic reticulum. Overexpression and deletion studies, including single-cell transplantation assays, revealed that Mfn2 is specifically required for the maintenance of HSCs with extensive lymphoid potential, but not, or less so, for the maintenance of myeloid-dominant HSCs. Mfn2 increased buffering of intracellular Ca(2+), an effect mediated through its endoplasmic reticulum-mitochondria tethering activity, thereby negatively regulating nuclear translocation and transcriptional activity of nuclear factor of activated T cells (Nfat). Nfat inhibition rescued the effects of Mfn2 deletion in HSCs, demonstrating that negative regulation of Nfat is the prime downstream mechanism of Mfn2 in the maintenance of HSCs with extensive lymphoid potential. Mitochondria therefore have an important role in HSCs. These findings provide a mechanism underlying clonal heterogeneity among HSCs and may lead to the design of approaches to bias HSC differentiation into desired lineages after transplantation.

Caffeine intake and its influences on heart rate variability recovery in healthy active adults after exercise: A systematic review and meta-analysis.

AIMS: Results regarding the effects of caffeine (CAF) intake on the autonomic control of heart rate recovery exercise remain inconclusive. Thus far, no study has used effect measures to pool the results of different experiments. We aim to assess the acute effect of CAF intake before exercise on the recovery of heart rate variability (HRV) after exercise through a systematic review and meta-analysis. DATA SYNTHESIS: Randomized controlled clinical trials were included; sample composed of physically active or trained adults; CAF should be offered/ingested before exercise, with dosage between 100 and 400 mg or between 2 and 6 mg/kg and administration/ingestion route analogous in the protocols; studies required to present results of HRV indices before and after exercise. Bias risk analysis and meta-analysis were performed. Twelve studies were included in the qualitative synthesis and five studies were encompassed in the quantitative synthesis (meta-analysis). For the Root-mean-square standard deviation (RMSSD) index we revealed p = 0.67, Total 95% confidence interval (95% CI) ranged from -0.45 to 0.29, and 66.7% for heterogeneity between groups were reported. Concerning the High Frequency (HF) index, we observed p = 0.22, Total 95% CI that ranged from -0.34 to 0.30, and 44% for heterogeneity between groups. CONCLUSIONS: CAF intake did not affect heart rate variability recovery after exercise.

Physical exercise increases global and gene-specific (interleukin-17 and interferon-γ) DNA methylation in lymphocytes from aged women.

NEW FINDINGS: What is the central question of this study? Is lymphocyte DNA methylation differentially modulated by resistance training and aerobic exercise in older women? What is the main finding and its importance? The practice of resistance training led to an increased global DNA methylation in lymphocytes. The exercise-induced increase of inflammatory genes methylation may be associated with immune function impairment during ageing. ABSTRACT: Ageing-induced increase in inflammatory gene expression through a reduction in DNA methylation might contribute to chronic diseases. Regular physical exercise practices, in turn, are associated with a decrease in the incidence of inflammatory diseases. We herein evaluated the effects of three exercise modalities on lymphocyte global and gene-specific (interferon γ (IFN-γ) and interleukin 17A (IL-17A) DNA methylation in aged women (68 ± 7.5 years). This cross-sectional study included 86 women, divided into four groups according to the physical exercise practice: 20 were practicing resistance training (RT); 24 were practicing water aerobics exercise (W); 22 were practicing water aerobics and resistance exercise (RWT), and 20 did not practice any physical exercise (CON). We evaluated volunteer functional capability using the Timed Up and Go (TUG) test, global lymphocyte DNA methylation by enzyme-linked immunosorbent assay, IFN-γ and IL-17A methylation by qPCR and CD4+ IFN-γ+ and CD4+ IL-17+ cell percentage by flow cytometry. The three physically exercised groups performed functional capability tests in a shorter period and showed a higher global lymphocyte DNA methylation and methylated CpGs of IL-17A and IFN-γ promoter regions than the control group. The practice of resistance training (RT and RWT groups) lead to high global DNA methylation. The combination of resistance training and aerobic exercise led to the increase of lymphocyte IL-17A and IFN-γ gene methylation induced by each separately. However, the percentage of IFN-γ+ and IL-17+ cells was lower only in the RT group. The exercise-induced increase of inflammatory-gene methylation may be associated with gene expression changes and immune function impairment during ageing.

Maternal high-fat diet up-regulates type-1 cannabinoid receptor with estrogen signaling changes in a sex- and depot- specific manner in white adipose tissue of adult rat offspring.

PURPOSE: Obesity and high-fat (HF) diet are associated with over activation of the endocannabinoid system (ECS). We have demonstrated that maternal HF diet induces early obesity and modulates cannabinoid signaling in visceral (VIS) and subcutaneous (SUB) white adipose tissue (WAT) in weanling rat offspring. We hypothesized that perinatal maternal HF diet would program the expression of ECS in adipose tissue in a long-term way in parallel to alterations in epigenetic markers and sex hormone signaling. METHODS: Progenitor female rats received control diet (C, 9% fat) or isocaloric high-fat diet (HF, 28% fat) for 8 weeks before mating, gestation, and lactation. All pups were weaned to C diet and they were euthanized at 180 days old. RESULTS: Maternal HF diet induced overweight and increased SUB WAT mass of male and female adult offspring. Maternal HF diet induced hypertrophy of VIS and SUB adipocytes only in female offspring associated with increased type 1 cannabinoid receptor protein (CB1) and mRNA (Cnr1) levels. These changes were associated with increased estrogen receptor α binding to Cnr1 promoter in SUB WAT of adult female offspring, which may contribute to higher expression of Cnr1. CONCLUSION: Increased CB1 signaling in adipose tissue might contribute to higher adiposity programmed by maternal HF diet because endocannabinoids stimulate the accumulation of fat in the adipose tissue. Our findings provide molecular insights into sex-specific targets for anti-obesity therapies based on the endocannabinoid system.

Diabetes and impaired fasting glucose in a population-based sample of individuals aged 75 + years: associations with cognition, major depressive disorder, functionality and quality of life-the Pietà study.

OBJECTIVES: To investigate the rates of diabetes mellitus (DM) and impaired fasting glucose (IFG) in a population-based sample of individuals aged 75 + years old and their associations with cognitive performance, depression, functionality, and quality of life (QoL). STUDY DESIGN: Overall, 350 people participated in the study. Assessments of cognition, mood, functionality and QoL were performed using the mini-mental state examination (MMSE), clock-drawing, category fluency tests, the Mini-International Neuropsychiatric Interview, Pfeffer's Functional Activities Questionnaire, and the WHO Quality of Life-Old (WHOQOL-OLD). RESULTS: IFG (ADA criteria) was identified in 42.1% of the sample, while the DM rate was 24.1%. Lack of knowledge of the DM diagnosis and lack of treatment occurred in 27% and 39% of the sample, respectively. Rates of dementia and depression, MMSE, category fluency scores, and previous cardiovascular events did not differ between the glycaemic groups. Individuals with DM performed worse on the clock-drawing test, functionality, and WHOQOL-OLD than the other participants. Individuals with IFG presented similar QoL and functionality when compared with the group without DM. CONCLUSIONS: IFG and DM were common in this population-based sample aged 75 + years old, as were inadequate diagnoses and treatments of DM. DM individuals presented poor performance in the executive function test, functionality, and QoL. Further studies are recommended to investigate the value of an IFG diagnosis among the most elderly population.

Quality of Movement Is Associated With Cognitive Function in Physically Inactive Older Women.

The relationship between the quality of movement, considering different global and universal basic patterns of movement and cognition domains in older adults remain unclear. The current study explored this association in physically inactive older women. In total, 187 participants, aged 60-70 years (mean = 64.9, SD = 6.9 years), were recruited from a physical education program in a public university. The older adults performed the following tests: Functional Movement Screen, Montreal Cognitive Assessment, and Modified Baecke Questionnaire for the Older Adults. The regression analysis showed an association between age (ß = -0.11, 95% confidence interval, CI, [-0.10, 0.30], p = .03); visuospatial abilities (ß = 0.36, 95% CI [0.24, 1.23], p < .001); language (ß = 0.23, 95% CI [0.20, 1.08], p < .001); and orientation domains (ß = 0.13, 95% CI [0.11, 1.22], p = .016) of the Montreal Cognitive Assessment and the Functional Movement Screen. The quality of movement was related to both age and cognitive performance, such as the visuospatial abilities, language, and orientation domains, in physically inactive older women.

Identification and genome analysis of tomato chlorotic spot virus and dsRNA viruses from coinfected vegetables in the Dominican Republic by high-throughput sequencing.

The Tomato chlorotic spot virus (TCSV) was first reported in the 1980s, having its occurrence limited to Brazil and Argentina. Due to an apparent mild severity in the past, molecular studies concerning TCSV were neglected. However, TCSV has disseminated over the USA and Caribbean countries. In Dominican Republic TCSV has been recently reported on important cultivated crops such as pepper and beans. In this work, we provide the first complete genome of a TCSV isolate from symptomatic plants in Dominican Republic, which was obtained by high-throughput sequencing. In addition, three dsRNA viruses from different virus families were identified coinfecting these plants Bell pepper endornavirus (BPEV), Southern tomato virus (STV) and Pepper cryptic virus 2 (PCV-2). Phylogenetic analysis showed that the Dominican Republic TCSV isolate has a close relationship with other TCSV isolates and a reassortant isolate between TCSV and Groundnut ringspot virus (GRSV), all found in USA. BPEV, STV and PCV-2 isolates from Dominican Republic were close related to corresponding American isolates. The possible biological implications of these virus-mixed infections are discussed.

CRISPR-Cas9-modified pfmdr1 protects Plasmodium falciparum asexual blood stages and gametocytes against a class of piperazine-containing compounds but potentiates artemisinin-based combination therapy partner drugs.

Emerging resistance to first-line antimalarial combination therapies threatens malaria treatment and the global elimination campaign. Improved therapeutic strategies are required to protect existing drugs and enhance treatment efficacy. We report that the piperazine-containing compound ACT-451840 exhibits single-digit nanomolar inhibition of the Plasmodium falciparum asexual blood stages and transmissible gametocyte forms. Genome sequence analyses of in vitro-derived ACT-451840-resistant parasites revealed single nucleotide polymorphisms in pfmdr1, which encodes a digestive vacuole membrane-bound ATP-binding cassette transporter known to alter P. falciparum susceptibility to multiple first-line antimalarials. CRISPR-Cas9 based gene editing confirmed that PfMDR1 point mutations mediated ACT-451840 resistance. Resistant parasites demonstrated increased susceptibility to the clinical drugs lumefantrine, mefloquine, quinine and amodiaquine. Stage V gametocytes harboring Cas9-introduced pfmdr1 mutations also acquired ACT-451840 resistance. These findings reveal that PfMDR1 mutations can impart resistance to compounds active against asexual blood stages and mature gametocytes. Exploiting PfMDR1 resistance mechanisms provides new opportunities for developing disease-relieving and transmission-blocking antimalarials.

Altered behavior of adult obese rats by monosodium l-glutamate neonatal treatment is related to hypercorticosteronemia and activation of hypothalamic ERK1 and ERK2.

OBJECTIVES: Obesity is a metabolic and hormonal disorder with serious social and psychological impacts. There is a close relationship among obesity, neuroendocrine homeostasis and behavioral patterns. However, few data are available in the literature regarding this subject. This study assessed behavior and memory of adult obese rats by monosodium l-glutamate (MSG) neonatal treatment or highly palatable dietary treatment. METHODS: MSG obesity was induced by subcutaneous injections of MSG (4 mg/g) during the first 5 days of life (Ob-MSG); control group (C-MSG), received saline solution equimolar. Both groups were fed with commercial chow. To induce dietary obesity, 21-day-old rats were assigned to two experimental diets: highly palatable diet (Ob-Diet) and control diet (C-Diet) composed of commercial chow. Ninety-day-old animals were submitted to behavioral assessment by the open-field test and short- and long-term memory by the object recognition test. Biometric variables were obtained, the Lee index was calculated and mass of retroperitoneal and perigonadal fat pads was measured. Furthermore, an altered behavioral profile was investigated by quantification of plasmatic corticosterone, expression, and activity of hypothalamic extracellular signal-regulated kinase protein (ERK) 1 and 2. RESULTS: Increased Lee index and fat pads were observed in Ob-MSG and Ob-Diet groups. Ob-MSG presented a higher level of anxiety and impaired long-term memory compared to C-MSG, while there was no difference between Ob-Diet and C-Diet. The Ob-MSG group presented a higher level of plasmatic corticosterone and increased phosphorylation of hypothalamic ERK1 and 2. DISCUSSION: Both treatments induced obesity but only Ob-MSG showed altered behavioral parameters, which is related to increased concentration of corticosterone and hypothalamic ERK1 and 2 activation.

(+)-SJ733, a clinical candidate for malaria that acts through ATP4 to induce rapid host-mediated clearance of Plasmodium.

Drug discovery for malaria has been transformed in the last 5 years by the discovery of many new lead compounds identified by phenotypic screening. The process of developing these compounds as drug leads and studying the cellular responses they induce is revealing new targets that regulate key processes in the Plasmodium parasites that cause malaria. We disclose herein that the clinical candidate (+)-SJ733 acts upon one of these targets, ATP4. ATP4 is thought to be a cation-transporting ATPase responsible for maintaining low intracellular Na(+) levels in the parasite. Treatment of parasitized erythrocytes with (+)-SJ733 in vitro caused a rapid perturbation of Na(+) homeostasis in the parasite. This perturbation was followed by profound physical changes in the infected cells, including increased membrane rigidity and externalization of phosphatidylserine, consistent with eryptosis (erythrocyte suicide) or senescence. These changes are proposed to underpin the rapid (+)-SJ733-induced clearance of parasites seen in vivo. Plasmodium falciparum ATPase 4 (pfatp4) mutations that confer resistance to (+)-SJ733 carry a high fitness cost. The speed with which (+)-SJ733 kills parasites and the high fitness cost associated with resistance-conferring mutations appear to slow and suppress the selection of highly drug-resistant mutants in vivo. Together, our data suggest that inhibitors of PfATP4 have highly attractive features for fast-acting antimalarials to be used in the global eradication campaign.

Balancing drug resistance and growth rates via compensatory mutations in the Plasmodium falciparum chloroquine resistance transporter.

The widespread use of chloroquine to treat Plasmodium falciparum infections has resulted in the selection and dissemination of variant haplotypes of the primary resistance determinant PfCRT. These haplotypes have encountered drug pressure and within-host competition with wild-type drug-sensitive parasites. To examine these selective forces in vitro, we genetically engineered P. falciparum to express geographically diverse PfCRT haplotypes. Variant alleles from the Philippines (PH1 and PH2, which differ solely by the C72S mutation) both conferred a moderate gain of chloroquine resistance and a reduction in growth rates in vitro. Of the two, PH2 showed higher IC50 values, contrasting with reduced growth. Furthermore, a highly mutated pfcrt allele from Cambodia (Cam734) conferred moderate chloroquine resistance and enhanced growth rates, when tested against wild-type pfcrt in co-culture competition assays. These three alleles mediated cross-resistance to amodiaquine, an antimalarial drug widely used in Africa. Each allele, along with the globally prevalent Dd2 and 7G8 alleles, rendered parasites more susceptible to lumefantrine, the partner drug used in the leading first-line artemisinin-based combination therapy. These data reveal ongoing region-specific evolution of PfCRT that impacts drug susceptibility and relative fitness in settings of mixed infections, and raise important considerations about optimal agents to treat chloroquine-resistant malaria.

Subtle changes in endochin-like quinolone structure alter the site of inhibition within the cytochrome bc1 complex of Plasmodium falciparum.

The cytochrome bc1 complex (cyt bc1) is the third component of the mitochondrial electron transport chain and is the target of several potent antimalarial compounds, including the naphthoquinone atovaquone (ATV) and the 4(1H)-quinolone ELQ-300. Mechanistically, cyt bc1 facilitates the transfer of electrons from ubiquinol to cytochrome c and contains both oxidative (Qo) and reductive (Qi) catalytic sites that are amenable to small-molecule inhibition. Although many antimalarial compounds, including ATV, effectively target the Qo site, it has been challenging to design selective Qi site inhibitors with the ability to circumvent clinical ATV resistance, and little is known about how chemical structure contributes to site selectivity within cyt bc1. Here, we used the proposed Qi site inhibitor ELQ-300 to generate a drug-resistant Plasmodium falciparum clone containing an I22L mutation at the Qi region of cyt b. Using this D1 clone and the Y268S Qo mutant strain, P. falciparum Tm90-C2B, we created a structure-activity map of Qi versus Qo site selectivity for a series of endochin-like 4(1H)-quinolones (ELQs). We found that Qi site inhibition was associated with compounds containing 6-position halogens or aryl 3-position side chains, while Qo site inhibition was favored by 5,7-dihalogen groups or 7-position substituents. In addition to identifying ELQ-300 as a preferential Qi site inhibitor, our data suggest that the 4(1H)-quinolone scaffold is compatible with binding to either site of cyt bc1 and that minor chemical changes can influence Qo or Qi site inhibition by the ELQs.

Butter naturally enriched in cis-9, trans-11 CLA prevents hyperinsulinemia and increases both serum HDL cholesterol and triacylglycerol levels in rats.

BACKGROUND: Evidence from in vitro and animal studies indicates that conjugated linoleic acid (CLA) possesses anti-diabetic properties, which appear to be attributed to cis-9, trans-11 CLA, the major CLA isomer in ruminant fat. However, there is a shortage of studies addressing CLA from natural source. The present study aimed to evaluate the effects of butter naturally enriched in cis-9, trans-11 CLA on parameters related to glucose tolerance, insulin sensitivity and dyslipidemia in rats. METHODS: Forty male Wistar rats were randomly assigned to the following dietary treatments (n=10/group), for 60 days: 1) Normal fat-Soybean oil (NF-So): diet containing 4.0% soybean oil (SO); 2) High Fat-Control Butter (HF-Cb): diet containing 21.7% control butter and 2.3% SO; 3) High Fat-CLA enriched Butter (HF-CLAb): diet containing 21.7% cis-9, trans-11 CLA-enriched butter and 2.3% SO; and 4) High fat-Soybean oil (HF-So): diet containing 24.0% SO. HF-Cb and HF-CLAb diets contained 0.075% and 0.235% of cis-9, trans-11 CLA, respectively. RESULTS: HF-CLAb-fed rats had lower serum insulin levels at fasting than those fed with the HF-Cb diet, while the PPARγ protein levels in adipose tissue was increased in HF-CLAb-fed rats compared to HF-Cb-fed rats. Furthermore, R-QUICK was lower in HF-Cb than in NF-So group, while no differences in R-QUICK were observed among NF-So, HF-CLAb and HF-So groups. Serum HDL cholesterol levels were higher in HF-CLAb-fed rats than in those fed NF-So, HF-Cb and HF-So diets, as well as higher in NF-So-fed rats than in HF-Cb and HF-So-fed rats. HF-CLAb, HF-Cb and HF-So diets reduced serum LDL cholesterol levels when compared to NF-So, whereas serum triacylglycerol levels were increased in HF-CLAb. CONCLUSION: Feeding rats on a high-fat diet containing butter naturally enriched in cis-9, trans-11 CLA prevented hyperinsulinemia and increased HDL cholesterol, which could be associated with higher levels of cis-9, trans-11 CLA, vaccenic acid, oleic acid and lower levels of short and medium-chain saturated fatty acids from butter naturally modified compared to control butter. On the other hand CLA-enriched butter also increased serum triacylglycerol levels, which could be associated with concomitant increases in the content of trans-9 and trans-10 C18:1 isomers in the CLA-enriched butter.

Association of Alcohol Consumption with Cognition and Functionality in Older Adults Aged 75+ Years: The Pietà Study.

The relationship between alcohol consumption and cognition is still controversial. This is a cross-sectional population-based study conducted in Caeté (MG), Brazil, where 602 individuals aged 75+ years, 63.6% female, and with a mean education of 2.68 years, were submitted to thorough clinical assessments and categorized according to the number of alcoholic beverages consumed weekly. The prevalence rates of previous and current alcohol consumption were 34.6% and 12.3%, respectively. No association emerged between cognitive diagnoses and current/previous alcohol consumption categories. Considering current alcohol intake as a dichotomous variable, the absence of alcohol consumption was associated with dementia (OR = 2.34; 95%CI: 1.39-3.90) and worse functionality (p = 0.001). Previous consumption of cachaça (sugar cane liquor) increased the risk of dementia by 2.52 (95%CI: 1.25-5.04). The association between the consumption of cachaça and dementia diagnosis has not been described before.

14-Week exercise training modifies the DNA methylation levels at gene sites in non-Alzheimer's disease women aged 50 to 70 years.

Exercise training emerges as a key strategy in lifestyle modification, capable of reducing the risk of developing Alzheimer's disease (AD) due to risk factors such as age, family history, genetics and low level of education associated with AD. We aim to analyze the effect of a 14-week combined exercise training (CT) on the methylation of genes associated with AD in non-alzheimer's disease women. CT sessions lasted 60 min, occurring three times a week for 14 weeks. Forty non-Alzheimer's disease women aged 50 to 70 years (60.7 ± 4.1 years) with a mean height of 1.6 ± 0.1 m, mean weight of 73.12 ± 9.0 kg and a mean body mass index of 29.69 ± 3.5 kg/m2, underwent two physical assessments: pre and post the 14 weeks. DNA methylation assays utilized the EPIC Infinium Methylation BeadChip from Illumina. We observed that 14 weeks of CT led to reductions in systolic (p = 0.001) and diastolic (p = 0.017) blood pressure and improved motor skills post-intervention. Among 25 genes linked to AD, CT induced differentially methylated sites in 12 genes, predominantly showing hypomethylated sites (negative ß values). Interestingly, despite hypomethylated sites, some genes exhibited hypermethylated sites (positive ß values), such as ABCA7, BDNF, and WWOX. A 14-week CT regimen was adequate to induce differential methylation in 12 CE-related genes in healthy older women, alongside improvements in motor skills and blood pressure. In conclusion, this study suggest that combined training can be a strategy to improve physical fitness in older individuals, especially able to induce methylation alterations in genes sites related to development of AD. It is important to highlight that training should act as protective factor in older adults.

Effect of Gestational Fish Oil Supplementation on Liver Metabolism and Mitochondria of Male and Female Rat Offspring Programmed by Maternal High-Fat Diet.

SCOPE: Perinatal maternal moderately high-fat diet (mHFD) is associated with obesity and fatty liver disease in offspring, and maternal fish oil (FO: n-3 PUFA source) supplementation may attenuate these disorders. This study evaluates the effects of FO given to pregnant rats fed a mHFD on the offspring's liver at weaning. METHODS AND RESULTS: Female Wistar rats receive an isoenergetic, control (CT: 10.9% from fat) or high-fat (HF: 28.7% from fat) diet before mating, and throughout pregnancy and lactation. FO supplementation (HFFO: 2.9% of FO in the HF diet) is given to one subgroup of HF dams during pregnancy. At weaning, male and female mHFD offspring display higher body mass, adiposity, and hepatic cellular damage, steatosis, and inflammation, accompanied by increased damaged mitochondria. FO does not protect pups from systemic metabolic alterations and partially mitigates hepatic histological damage induced by mHFD only in females. However, FO reduces mRNA expression of lipogenic genes, and mitochondrial damage, and modified mitochondrial morphology suggestive of early adaptations via mitochondrial dynamics. CONCLUSIONS: Gestational FO supplementation has limited beneficial effects on the damage caused by perinatal mHFD consumption in offspring's liver at weaning. However, FO imprinting effect on lipid metabolism and mitochondria may have beneficial long-term outcomes.

Comparing Fourteen Weeks of Multicomponent Training Versus Combined Training in Physically Inactive Older Women: A Randomized Trial.

BACKGROUND: Combined (CT) and multicomponent training (MT) presents several benefits for aging individuals. However, the literature does not provide evidence on which of the two physical training models can better enhance improvements in physical capacity and health parameters in middle-aged and older women. OBJECTIVE: The aim of this study was to compare the effects of MT and CT on physical capacity, cognitive, behavioral, and psychosocial assessment, and biochemical profile of physically inactive women aged between 50 and 70 years. METHODS: Participants were randomized into two groups: MT (32 women, 64.2 ± 6.4 years) and CT (39 women, 61.4 ± 4.3 years). Both training sessions had a weekly volume of 180 min, for 14 weeks, with assessments at baseline and after the training period. RESULTS: CT showed better results when compared to MT. In the four evaluation blocks, we noticed differences in the effect size (L = large, M = moderate, S = small, and T = trivial) between the groups in 26 variables in total, highlighting the CT group (L = 11, M = 5, S = 2, and T = 8) compared to the MT group (L = 8, M = 7, S = 7, and T = 4). Our findings showed group-time differences for strength variables using the maximum dynamic repetition test in upper and lower limbs and for agility. The multicomponent training showed improvement in the functional strength of the upper limbs evaluated through the elbow flexion and extension test (p = 0.037), and HDL (p = 0.022). CONCLUSIONS: Fourteen weeks of CT showed better benefits when compared to MT.

Older postmenopausal women with lower lean mass have hypermethylated sites in the PI3K-Akt pathway.

Introduction: The decrease in lean mass is directly related to the loss of independence, muscle strength, and worse quality of life over the years. Although the genetic determinants of muscle mass were well recognized, recent literature has been uncovering new epigenetic factors affecting the state of muscular tissue. This study aimed to verify differences in the DNA methylation profile among Brazilian postmenopausal women aged 50-70 years according to the lean mass evaluation. Methods: A cross-sectional study comprised 40 women aged 50-70 years. After K-means cluster analysis the 40 participants were divided into two groups, the Lower Lean Mass group with 20 participants (61.1 ± 4.6 years) and the Higher Lean Mass group with 20 participants (60.7 ± 3.2 years). Lean mass was measured by dual-energy X-ray emission densitometry (DEXA). The participants' DNA was extracted using the Salting Out technique and subsequently, the Illumina 850k EPIC Infinium Methylation BeadChip was performed to obtain methylation data. Results: We obtained 1,913 differentially methylated sites (p ≤ 0.005 of ß > 5% and ß < -5%) in a total of 979 genes between groups (p ≤ 0.005; -5% > ß > 5%). In addition, the PI3K-Akt pathway had the greatest power of significance with an FDR of 4.6 × 10-3. Conclusion: Our results demonstrate a differentiation between specific sites of different genes, which have essential functions in body composition and energy metabolism, supporting future studies that aim to relate lean mass with epigenetics.

Fourteen weeks of multicomponent training associated with flexibility training modifies postural alignment, joint range of motion and modulates blood pressure in physically inactive older women: a randomized clinical trial.

Background: Body relaxation and pain reduction are some of the reported benefits of flexibility training (through active stretching exercises), however their effects on posture and blood circulation are uncertain. We aimed to investigate the effects of flexibility training (through active stretching exercises) in combination with multicomponent training (MT) on blood pressure (BP), and the correlation with changes in body alignment and flexibility in physically inactive women. Methods: Women aged 60-70 years were into three groups: multicomponent training group (MT), multicomponent training plus flexibility training group (FT), and control group (CG). After randomization, the resting blood pressure was measured and the participants were reallocated into subgroups according to pressure values >130/80 mmHg (This classification is according to the American Heart Association (AHA), resulting in the subgroups: flexibility training (FT); flexibility training for hypertensive patients (FTSAH); multicomponent training (MT); multicomponent training for hypertensive patients (MTSAH); control group (CG); control group of hypertensive patients (CGSAH). The interventions lasted 14 weeks. Systolic (sBP) and diastolic (dBP) BP, range of motion (flexion and extension), and postural analysis by asymmetry in the frontal plane and asymmetry in the sagittal plane, displacement and the flexibility test were collected before (Pre) and after training (Post). In total, 141 women participated in the study (without SAH: FT = 23, MT = 20, and CG = 21; with SAH: FTSAH = 28, MTSAH = 23, and CGSAH = 26). Results: Systolic blood pressure, in the pre and post moments were: FT (116 ± 6.7 vs. 114 ± 4.7); FTSAH (144 ± 16.5 vs. 121 ± 10.1); MT: (120 ± 6.8 vs. 121 ± 7.3); MTSAH: (137 ± 10.6 vs. 126 ± 13.0); CG: (122 ± 5.3 vs. 133 ± 19.2); and CGSAH: (140 ± 9.7 vs. 143 ± 26.2), presenting an F value (p-value - group x time) of 12.00 (<0.001), with improvement in the groups who trained. The diastolic blood pressure in the pre and post moments were: FT (71 ± 4.7 vs. 74 ± 6.8); FTSAH (88 ± 9.6 vs. 70 ± 12.0); MT: (74 ± 4.5 vs. 77 ± 11.7); MTSAH: (76 ± 10.4 vs. 76 ± 10.2); CG: (69 ± 7.11 vs. 82 ± 11.4); and CGSAH: (76 ± 13.4 vs. 86.6 ± 7.7), presenting an F value (p-value - group x time) of 8.00 (p < 0.001), with improvement in the groups who trained. In the Elastic Net Regression, sBP was influenced by height (ß: -0.044); hip flexion (ß: 0.071); Shoulder extension (ß: 0.104); low back flexion (ß: 0.119) and dBP (ß: 0.115). In the Elastic Net Regression, dBP was influenced by asymmetry in the sagittal plane variables (0.040); asymmetry in the frontal plane (ß: 0.007); knee flexion (ß: -0.398); BM (ß: 0.007); Shoulder flexion (ß: -0.142); Hip flexion (ß: -0.004); sBP (ß: 0.155) and Ankle Flexion (ß: -0.001). Conclusion: The displacement of the asymmetry in the frontal plane and asymmetry in the sagittal plane, and the increase in the flexion position in the hip, lumbar, head, and knee regions, influenced the highest-pressure levels. Multicomponent training associated with flexibility training promoted improvement in body alignment, COM, and joint angles, and decreased blood pressure.

Effect of chronic administration of the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on oxidative stress in different brain areas of rats.

Selenium (Se) is an essential mineral for mammals. It is a nutrient related to the complex metabolic and enzymatic functions. Although Se has important physiological functions in the cells, organic compounds of Se can be extremely toxic, and may affect the central nervous system. This study aims to investigate the effect of the chronic treatment with the vinyl chalcogenide 3-methyl-1-phenyl-2-(phenylseleno)oct-2-en-1-one on some parameters of oxidative stress in the brain of rats. Animals received the vinyl chalcogenide (125, 250 or 500 µg/kg body weight) intraperitoneally once a day during 30 days. The cerebral cortex, the hippocampus, and the cerebellum were dissected and homogenized in KCl. Afterward, thiobarbituric acid reactive substances (TBARS), carbonyl, sulfhydryl, catalase (CAT), superoxide dismutase (SOD) and glutathione peroxidase (GPx) activities were measured in the brain. Results showed that the organoselenium enhanced TBARS in the cerebral cortex of rats but the compound was not able to change carbonyl levels. Furthermore, the organoselenium reduced thiol groups measured by the sulfhydryl assay in all tissues studied. The activity of the antioxidant enzyme CAT was increased by the organochalcogen in the cerebral cortex and in the cerebellum, and the activity of SOD was increased in the hippocampus. On the other hand, the activity of the antioxidant enzyme GPx was reduced in all brain structures. Our findings indicate that this organoselenium compound induces oxidative stress in different brain regions of rats, corroborating to the fact that this tissue is a potential target for organochalcogen action.