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1.
BMC Geriatr ; 24(1): 300, 2024 Mar 29.
Artigo em Inglês | MEDLINE | ID: mdl-38553690

RESUMO

BACKGROUND AND AIMS: This study evaluated whether stored iron determines the adaptive response induced by Nordic walking (NW) training combined with 10 hours' time-restricted eating (TRE) in older adults. TRIAL DESIGN AND METHODS: Twenty-four participants underwent 12-week NW training supported by 10 h of TRE. The group was divided due to baseline ferritin concentration low < 75 ng/ml (LF) and high level ≥ 75 ng/ml (HF). Body composition, physical fitness and blood collection were assessed at baseline and post-intervention. RESULTS: NW + TRE induced a statistically significant decrease in ferritin levels in all participants (p = 0.01). Additionally, statistically significant intergroup differences in the LF vs. HF in the reduction of serum ferritin levels (p = 0.04) were observed. The procedure NW + TRE diminished HbA1c levels (p < 0.01) and glucose in all participants (p = 0.05). The range of HbA1c drop was more pronounced among those participants who experienced a greater decrease in the stored iron (p = 0.04, [Formula: see text]=0.17, F=4.59). Greater changes in body weight and percent of body fat were recorded in the HF group (for both p<0.01). CONCLUSION: Body iron stores determine the effects of a 12-week NW + TRE intervention on serum ferritin. The changes in HbA1c are more pronounced in subjects with a higher decrease in serum ferritin. TRIAL REGISTRATION: All experimental protocols were approved by the Bioethical Committee of the Regional Medical Society in Gdansk, Poland (NKBBN/330/2021) according to the Declaration of Helsinki. We confirm that all methods were carried out in accordance with relevant guidelines and regulations. The trial was registered as a clinical trial (NCT05229835, date of first registration: 14/01/2022, direct link: https://classic. CLINICALTRIALS: gov/ct2/show/NCT05229835 ). Informed consent was obtained from all subjects.


Assuntos
Ferro , Caminhada Nórdica , Humanos , Idoso , Ferro/metabolismo , Hemoglobinas Glicadas , Caminhada/fisiologia , Ferritinas
2.
Int J Mol Sci ; 24(7)2023 Apr 04.
Artigo em Inglês | MEDLINE | ID: mdl-37047706

RESUMO

The quantitative polymerase chain reaction (qRT-PCR) technique gives promising opportunities to detect and quantify RNA targets and is commonly used in many research fields. This study aimed to identify suitable reference genes for physical exercise and omega-3 fatty acids supplementation intervention. Forty healthy, physically active men were exposed to a 12-week eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA) supplementation and standardized endurance training protocol. Blood samples were collected before and after the intervention and mRNA levels of six potential reference genes were tested in the leukocytes of 18 eligible participants using the qRT-PCR method: GAPDH (Glyceraldehyde-3-phosphate dehydrogenase), ACTB (Beta actin), TUBB (Tubulin Beta Class I), RPS18 (Ribosomal Protein S18), UBE2D2 (Ubiquitin-conjugating enzyme E2 D2), and HPRT1 (Hypoxanthine Phosphoribosyltransferase 1). The raw quantification cycle (Cq) values were then analyzed using RefFinder, an online tool that incorporates four different algorithms: NormFinder, geNorm, BestKeeper, and the comparative delta-Ct method. Delta-Ct, NormFinder, BestKeeper, and RefFinder comprehensive ranking have found GAPDH to be the most stably expressed gene. geNorm has identified TUBB and HPRT as the most stable genes. All algorithms have found ACTB to be the least stably expressed gene. A combination of the three most stably expressed genes, namely GAPDH, TUBB, and HPRT, is suggested for obtaining the most reliable results.


Assuntos
Ácidos Graxos Ômega-3 , Hipoxantina Fosforribosiltransferase , Masculino , Humanos , Hipoxantina Fosforribosiltransferase/genética , Reação em Cadeia da Polimerase , Exercício Físico , Suplementos Nutricionais , Reação em Cadeia da Polimerase em Tempo Real/métodos , Perfilação da Expressão Gênica/métodos , Padrões de Referência
3.
Int J Mol Sci ; 24(20)2023 Oct 19.
Artigo em Inglês | MEDLINE | ID: mdl-37895038

RESUMO

Multiple myeloma (MM) is an incurable hematologic malignancy originating from clonal plasma cell proliferation within the bone marrow, predominantly affecting older individuals. While anemia serves as a diagnostic criterion for MM, it often ameliorates upon achieving disease remission. Iron metabolism parameters have emerged as potential prognostic indicators in MM. Notably, physical exercise has been established to influence iron metabolism. This study aimed to assess alterations in serum iron, ferritin, and transferrin concentrations, as well as leukocyte gene expression, in MM patients undergoing a six-week cycle of Nordic walking training. Thirty patients divided into an exercise group (NW, n = 15, mean age 63.1 ± 8.4 years) and a control group (CG, n = 15, mean age: 63.5 ± 3.6 years) completed the study protocol. Blood samples were collected at baseline, after three and six weeks of training, and after nine weeks. Serum ferritin, transferrin, and iron concentrations were measured, along with the leukocyte expression of genes. Additionally, serum oxidative damage marker levels were determined. Following the Nordic walking training cycle, a declining trend in serum ferritin concentrations was observed. Intracellular mRNA levels of genes associated with iron metabolism were positively influenced by the training regimen, indicating the potential impact of this physical activity on gene expression and ferritin concentrations. Although positive trends were noted, extended training periods might be requisite for significant changes. To conclude, moderate-intensity exercise induces favorable shifts in the analyzed parameters among MM patients, potentially influencing disease progression. Consequently, Nordic walking training is a safe recommendation for MM patients, though sustained training beyond six weeks could be necessary for notable effects on iron metabolism factors.


Assuntos
Mieloma Múltiplo , Caminhada , Humanos , Idoso , Pessoa de Meia-Idade , Caminhada Nórdica , Mieloma Múltiplo/terapia , Ferro/metabolismo , Ferritinas/metabolismo , Estresse Oxidativo , Biomarcadores/metabolismo , Transferrinas/metabolismo
4.
J Pediatr Hematol Oncol ; 44(1): e68-e73, 2022 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-33625078

RESUMO

The molecular mechanism that regulates iron homeostasis is based on a network of signals, which reflect on the iron requirements of the body. HFE-related hemochromatosis is characterized by excessive intestinal absorption of dietary iron, in particular cases resulting in pathologically high iron storage in tissues and organs. During childhood, HFE gene homozygosity or heterozygosity manifests exclusively in the form of biochemical abnormalities. Because of their mutual link, bioavailable iron and endogenous erythropoietin (EPO) are indispensable for effective erythropoiesis. We analyzed the impact of p.(His63Asp) polymorphism of the HFE gene on erythropoiesis taking into consideration endogenous EPO production in the developmental age. In the study we performed, we observed a significant, strong and negative correlation between the concentration of EPO, hemoglobin, and red blood cell count. A negative trend was also noted on the impact of iron concentration and transferrin saturation on EPO production. In conclusion, this preliminary study demonstrates an impaired impact of endogenous EPO on erythropoiesis in the presence of increased iron content in carriers of p.(His63Asp) (heterozygotes) variant of the HFE gene in developmental age.


Assuntos
Eritropoetina/sangue , Proteína da Hemocromatose/genética , Hemocromatose , Mutação de Sentido Incorreto , Polimorfismo Genético , Adolescente , Substituição de Aminoácidos , Eritropoetina/genética , Hemocromatose/sangue , Hemocromatose/genética , Proteína da Hemocromatose/metabolismo , Humanos , Masculino
5.
Int J Mol Sci ; 23(19)2022 Sep 29.
Artigo em Inglês | MEDLINE | ID: mdl-36232801

RESUMO

In this study, we aim to verify whether swim training can improve lactate metabolism, NAD+ and NADH levels, as well as modify the activity of glycolytic and NADH shuttle enzymes and monocarboxylate transporters (MCTs) in skeletal muscle of amyotrophic lateral sclerosis (ALS) mice. ALS mice (SOD1G93A) (n = 7 per group) were analyzed before the onset of ALS, at first disease symptoms (trained and untrained), and the last stage of disease (trained and untrained), and then compared with a wild-type (WT) group of mice. The blood lactate and the skeletal muscle concentration of lactate, NAD+ and NADH, MCT1 and MCT4 protein levels, as well as lactate dehydrogenase (LDH) and malate dehydrogenase (MDH) activities in skeletal muscle were determined by fluorometric, Western blotting, liquid chromatography-MS3 spectrometry, and spectrometric methods. In the untrained terminal ALS group, there were decreased blood lactate levels (p < 0.001) and increased skeletal muscle lactate levels (p < 0.05) as compared with a WT group of mice. The amount of nicotinamide adenine dinucleotides in the ALS groups were also significantly reduced as well as LDH activity and the level of MCT1. Swim training increased lactate levels in the blood (p < 0.05 vs. ALS TERMINAL untrained). In addition, cytosolic MDH activity and the cMDH/LDH 2.1 ratio were significantly higher in trained vs. untrained mice (p < 0.05). The data indicate significant dysfunction of lactate metabolism in ALS mice, associated with a reduction in muscle anaerobic metabolism and NADH transporting enzymes, as well as swim-induced compensation of energy demands in the ALS mice.


Assuntos
Esclerose Lateral Amiotrófica , NAD , Adenina/metabolismo , Esclerose Lateral Amiotrófica/metabolismo , Animais , Modelos Animais de Doenças , Ácido Láctico/metabolismo , Malato Desidrogenase/metabolismo , Camundongos , Transportadores de Ácidos Monocarboxílicos/metabolismo , Músculo Esquelético/metabolismo , NAD/metabolismo , Niacinamida/metabolismo
6.
Eur J Nutr ; 60(3): 1619-1631, 2021 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-32794021

RESUMO

PURPOSE: Hyperhomocysteinemia is an independent risk factor for cardiovascular diseases and also promotes neuronal death in various neurodegenerative diseases. There is evidence that iron can mediate homocysteine (Hcy) toxicity. Thus, the aim of this study was to investigate the effect of Hcy on iron metabolism in HUVEC and SH-SY5Y cells. METHODS: HUVEC and SH-SY5Y cells were treated with 3 mM Hcy for a defined time. RESULTS: We demonstrate that Hcy induced the upregulation of ferritins type L and H in HUVEC cells in a time-dependent manner and had no effect on the ferritins in SH-SY5Y cells. The change in ferritin expression was preceded by a significant decrease in the cellular level of the active form of Akt kinase in HUVEC but not in SH-SY5Y cells. An increase in ferritin L and H protein levels was observed in the Akt1, Akt2, Akt3 siRNA transfected cells, while in the cells transfected with FOXO3a siRNA, a decrease in both ferritins levels was noticed. Moreover, in the HUVEC cells treated with Hcy for 6 days, the active form of kinase Akt returned to the control level and it was accompanied by a drop in ferritin L and H protein levels. Cytotoxicity of hydrogen peroxide significantly increased in HUVEC cells pre-treated with Hcy for 24 h. CONCLUSIONS: These data indicate that Hcy induces an increase in cellular ferritin level, and the process is mediated by alterations in Akt-FOXO3a signaling pathway.


Assuntos
Homocisteína , Proteínas Proto-Oncogênicas c-akt , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Ferro , Estresse Oxidativo , Proteínas Proto-Oncogênicas c-akt/genética , Proteínas Proto-Oncogênicas c-akt/metabolismo
7.
Int J Mol Sci ; 22(6)2021 Mar 23.
Artigo em Inglês | MEDLINE | ID: mdl-33806756

RESUMO

The popularity of fasting and restricted food intake is increasing. While the body's adaptability to dietary insufficiency is crucial for health, molecular mechanisms of adaptive changes are not well understood. Here, we compared the effects of fasting and exercise on the expression of leukocyte genes and proteins involved in the storage, export, and acquisition of iron, an essential element with physiological roles. Healthy men participated in the study (age, 30-70 years; body weight, 60-100 kg; body mass index, 20-29.9 kg/m2). The participants performed an exercise test with a gradually increasing intensity until the individual maximum exercise capacity was reached, before and after 8-d fast. Blood samples were collected before, immediately after, and 3 h after exercise. Gene expression was analyzed by reverse-transcription quantitative polymerase chain reaction and protein levels were analyzed by immunobloting. Eight days of total starvation diet affected the body composition and decreased exercise capacity. Further, fasting decreased the expression of genes associated with iron storage and export, and increased the expression of genes involved in iron acquisition. Conversely, only PCBP2 protein increased after fasting; however, an upward trend was apparent for all proteins. In conclusion, the body adapts to starvation by adjusting iron economy.


Assuntos
Proteínas de Transporte de Cátions/genética , Jejum , Regulação da Expressão Gênica , Ferro/metabolismo , Leucócitos/metabolismo , Adulto , Proteínas de Transporte de Cátions/metabolismo , Jejum/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Estresse Oxidativo , Fatores Sexuais , Fatores de Tempo
8.
J Strength Cond Res ; 35(8): 2255-2262, 2021 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-30893279

RESUMO

ABSTRACT: Kozlowska, M, Zurek, P, Rodziewicz, E, Góral, K, Zmijewski, P, Lipinska, P, Laskowski, R, Walentukiewicz, AK, Antosiewicz, J, and Ziemann, E. Immunological response and match performance of professional tennis players of different age groups during a competitive season. J Strength Cond Res 35(8): 2255-2262, 2021-We aimed to investigate the effect of physical workloads on immunological response, match performance, and iron metabolism in professional tennis players of different age groups throughout the tournament season and to determine the interdependence of vitamin D status and inflammation. Thirty-eight young, male tennis players with a top national ranking (1-25) participated in this study and were assigned to the following age groups: cadets (CG), juniors (JG), and seniors (SG). Blood samples were collected at the beginning, midpoint, and end of the tournament season to assess the proinflammatory cytokine (tumor necrosis factor-alpha [TNF-α]), anti-inflammatory myokines (interleukin [IL]-6 and IL-10), heat shock proteins (HSP70, HSP27), iron metabolism markers, and vitamin D concentrations. The total number of matches (won and lost) at the national and international events was recorded. The IL-6 and IL-10 concentrations significantly increased across all groups in the middle and end of the tournament season (effect large and very likely). The TNF-α concentration was elevated at the end of the season in CG and SG. The increase in TNF-α concentration corresponded with an increase in hepcidin concentration in these groups. The significant increase in HSP27 concentration was only noticed in SG with normal vitamin D concentrations. In JG and SG, a mild seasonal increase in vitamin D concentration was noted, but still it was insufficient. The immunological response was not affected by the number of tennis matches; however, the anti-inflammatory effect was regulated by higher concentrations of vitamin D. Unexpectedly, most tennis players had vitamin D deficiency. Iron status remained unchanged.


Assuntos
Desempenho Atlético , Sistema Imunitário , Tênis , Atletas , Citocinas , Proteínas de Choque Térmico HSP27 , Humanos , Interleucina-10 , Interleucina-6 , Masculino , Estações do Ano , Fator de Necrose Tumoral alfa , Vitamina D/sangue
9.
Int J Mol Sci ; 21(18)2020 Sep 05.
Artigo em Inglês | MEDLINE | ID: mdl-32899447

RESUMO

Physical training and antioxidant supplementation may influence iron metabolism through reduced oxidative stress and subsequent lowering of mRNA levels of genes that are easily induced by this stress, including those responsible for iron homeostasis. Fifteen elderly women participated in our 12-week experiment, involving six weeks of training without supplementation and six weeks of training supported by oral supplementation of 1000 mg of vitamin C daily. The participants were divided into two groups (n = 7 in group 1 and n = 8 in group 2). In group 1, we applied vitamin C supplementation in the first six weeks of training, while in group 2 during the remaining six weeks of training. In both phases, the health-related training occurred three times per week. Training accompanied by vitamin C supplementation did not affect prooxidative/antioxidative balance but significantly decreased ferritin heavy chain (FTH) and ferritin light chain (FTL) mRNA in leukocytes (for FTH mRNA from 2^64.24 to 2^11.06, p = 0.03 in group 1 and from 2^60.54 to 2^16.03, p = 0.01 in group 2, for FTL mRNA from 2^20.22 to 2^4.53, p = 0.01 in group 2). We concluded that vitamin C supplementation might have caused a decrease in gene expression of two important antioxidative genes (FTH, FTL) and had no effect on plasma prooxidative/antioxidative balance.


Assuntos
Ácido Ascórbico/farmacologia , Exercício Físico/fisiologia , Ferritinas/metabolismo , Idoso , Antioxidantes/farmacologia , Apoferritinas/genética , Ácido Ascórbico/metabolismo , Suplementos Nutricionais , Feminino , Ferritinas/efeitos dos fármacos , Ferritinas/genética , Humanos , Ferro/metabolismo , Leucócitos/efeitos dos fármacos , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , RNA Mensageiro/metabolismo
10.
Int J Mol Sci ; 20(2)2019 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-30634386

RESUMO

Metabolic reprogramming in skeletal muscles in the human and animal models of amyotrophic lateral sclerosis (ALS) may be an important factor in the diseases progression. We hypothesized that swim training, a modulator of cellular metabolism via changes in muscle bioenergetics and oxidative stress, ameliorates the reduction in muscle strength in ALS mice. In this study, we used transgenic male mice with the G93A human SOD1 mutation B6SJL-Tg (SOD1G93A) 1Gur/J and wild type B6SJL (WT) mice. Mice were subjected to a grip strength test and isolated skeletal muscle mitochondria were used to perform high-resolution respirometry. Moreover, the activities of enzymes involved in the oxidative energy metabolism and total sulfhydryl groups (as an oxidative stress marker) were evaluated in skeletal muscle. ALS reduces muscle strength (-70% between 11 and 15 weeks, p < 0.05), modulates muscle metabolism through lowering citrate synthase (CS) (-30% vs. WT, p = 0.0007) and increasing cytochrome c oxidase and malate dehydrogenase activities, and elevates oxidative stress markers in skeletal muscle. Swim training slows the reduction in muscle strength (-5% between 11 and 15 weeks) and increases CS activity (+26% vs. ALS I, p = 0.0048). Our findings indicate that swim training is a modulator of skeletal muscle energy metabolism with concomitant improvement of skeletal muscle function in ALS mice.


Assuntos
Esclerose Lateral Amiotrófica/metabolismo , Esclerose Lateral Amiotrófica/fisiopatologia , Metabolismo Energético , Força Muscular , Músculo Esquelético/metabolismo , Natação , Esclerose Lateral Amiotrófica/etiologia , Animais , Biomarcadores , Modelos Animais de Doenças , Complexo IV da Cadeia de Transporte de Elétrons/metabolismo , Humanos , Camundongos , Camundongos Transgênicos , Mitocôndrias/genética , Mitocôndrias/metabolismo , Músculo Esquelético/fisiopatologia , Estresse Oxidativo , Superóxido Dismutase-1/genética , Superóxido Dismutase-1/metabolismo
11.
Biogerontology ; 18(4): 517-524, 2017 08.
Artigo em Inglês | MEDLINE | ID: mdl-28229255

RESUMO

Excess body iron accumulation and oxidative stress has been associated with ageing. Regular exercise has been shown to reduce oxidative stress and induce some changes in iron metabolism. However, the effects of exercise on both of these parameters have been poorly investigated. In our study, 35 elderly women participated in 12 weeks of Nordic walking (NW) training (three times a week). We demonstrated that the training caused a significant reduction in malondialdehyde advanced oxidation protein products-markers of oxidative stress but had no effects on paraoxonase 1 activity. These changes were associated with the decrease of blood ferritin (99.4 ± 62.7 vs. 81.4 ± 61.7 ng/ml p < 0.05). Measurement of physical fitness revealed that the training caused a significant improvement in performance and a negative correlation between the blood ferritin and endurance test was recorded (r = -0.34, p = 0.03). In addition, a significant correlation between blood ferritin and fasting glucose level was noted. The training induced a rise of HDL cholesterol from 70.8 ± 19.3-75.3 ± 21.1, p < 0.05, whereas other lipid parameters remained unchanged. In conclusion, NW training reduced body iron stores and it was associated with lower oxidative stress and better endurance.


Assuntos
Envelhecimento/sangue , Terapia por Exercício/métodos , Envelhecimento Saudável/sangue , Ferro/sangue , Estresse Oxidativo , Caminhada , Produtos da Oxidação Avançada de Proteínas/sangue , Fatores Etários , Idoso , Biomarcadores/sangue , Glicemia/metabolismo , Tolerância ao Exercício , Feminino , Ferritinas/sangue , Avaliação Geriátrica , Humanos , Lipídeos/sangue , Malondialdeído/sangue , Pessoa de Meia-Idade , Fatores Sexuais , Fatores de Tempo , Resultado do Tratamento
12.
Bioorg Med Chem ; 25(1): 126-131, 2017 01 01.
Artigo em Inglês | MEDLINE | ID: mdl-28029457

RESUMO

A series of N-alkyl benzisoselenazol-3(2H)-ones has been obtained and transformed to corresponding diselenides by the reduction with sodium borohydride. Additionally, efficient methodology for the oxidative Se-N bond formation by potassium iodate has been presented, new conversion of diselenide to benzisoselenazolone was observed. The GPx-like activity of all synthetized derivatives has been evaluated by NMR. N-Allyl diselenide was up to five times better antioxidant than ebselen. Anticancer capacity towards MCF7 and DU145 cancer cells has been also tested. The highest antiproliferative activity was obtained for N-cyclohexyl benzisoselenazolone.


Assuntos
Antioxidantes/química , Antioxidantes/farmacologia , Azóis/química , Azóis/farmacologia , Glutationa Peroxidase/química , Glutationa Peroxidase/farmacologia , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Antineoplásicos/química , Antineoplásicos/farmacologia , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Isoindóis
13.
J Pediatr Hematol Oncol ; 39(5): e240-e243, 2017 07.
Artigo em Inglês | MEDLINE | ID: mdl-28406842

RESUMO

Iron participates in oxygen transport, energetic, metabolic, and immunologic processes. There are 2 main causes of iron overload: hereditary hemochromatosis which is a primary cause, is a metabolic disorder caused by mutations of genes that control iron metabolism and secondary hemochromatosis caused by multitransfusions, chronic hemolysis, and intake of iron rich food. The most common type of hereditary hemochromatosis is caused by HFE gene mutation. In this study, we analyzed iron metabolism in 100 healthy Polish children in relation to their HFE gene status. The wild-type HFE gene was predominant being observed in 60 children (60%). Twenty-five children (25%), presented with heterozygotic H63D mutation, and 15 children (15%), presented with other mutations (heterozygotic C282Y and S65C mutation, compound heterozygotes C282Y/S65C, C282Y/H63D, H63D homozygote). The mean concentration of iron, the level of ferritin, and transferrin saturation were statistically higher in the group of HFE variants compared with the wild-type group. H63D carriers presented with higher mean concentration of iron, ferritin levels, and transferrin saturation compared with the wild-type group. Male HFE carriers presented with higher iron concentration, transferrin saturation, and ferritin levels than females. This preliminary investigation demonstrates allelic impact on potential disease progression from childhood.


Assuntos
Proteína da Hemocromatose/genética , Hemocromatose/epidemiologia , Ferro/metabolismo , Mutação , Adolescente , Criança , Pré-Escolar , Feminino , Ferritinas/sangue , Genótipo , Hemocromatose/sangue , Hemocromatose/genética , Humanos , Ferro/sangue , Masculino , Polônia/epidemiologia , Fatores Sexuais , Transferrina/análise
14.
Molecules ; 22(3)2017 Mar 20.
Artigo em Inglês | MEDLINE | ID: mdl-28335518

RESUMO

New chiral camphane-derived benzisoselenazol-3(2H)-ones and corresponding diselenides have been synthetized using a convenient one-pot procedure. Se-N bond was efficiently converted to an Se-Se bond, which could also be easily re-oxidized to the initial benzisoselenazolone moiety. The antioxidant activity of camphor derivatives was evaluated and compared to the reactivity of a series of N-amino acid benzisoselenazol-3(2H)-ones obtained by a modified procedure involving the improved synthesis and isolation of the diseleno bis(dibenzoic) acid. The most efficient peroxide scavengers, N-bornyl and N-leucine methyl ester benzisoselenazol-3(2H)-ones, were further evaluated as cytotoxic agents on four cancer cell lines (MCF-7, HEP G2, HL 6, and DU 145) and normal cell line PNT1A. The highest antiproliferative potential was evaluated for two compounds bearing a 3-methylbutyl carbon chain, N-leucine methyl ester and N-3-methylbutyl benzisoselenazol-3(2H)-ones.


Assuntos
Antineoplásicos/síntese química , Antioxidantes/síntese química , Compostos Organosselênicos/síntese química , Tiazóis/síntese química , Antineoplásicos/química , Antineoplásicos/farmacologia , Antioxidantes/química , Antioxidantes/farmacologia , Azóis/química , Catálise , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Humanos , Isoindóis , Células MCF-7 , Estrutura Molecular , Compostos Orgânicos , Compostos Organosselênicos/química , Compostos Organosselênicos/farmacologia , Tiazóis/química , Tiazóis/farmacologia
15.
Acta Psychol (Amst) ; 243: 104145, 2024 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-38245936

RESUMO

BACKGROUND: The prevalence of depressive symptoms (DS) among physically active individuals tends to be lower compared to sedentary controls. This association seems to be moderated by gender and level of physical activity (PA). The objective of this meta-analysis was to assess the relationship between PA and DS in males based on different levels of PA. METHODS: A systematic review and meta-analyses were conducted following the PRISMA Statement for Systematic Reviews. The literature search was conducted from January 1, 2003 to February 20, 2023. Cross-sectional and cohort studies including male participants aged 18 years or older were included in the analysis. Evidence from selected studies was synthesised as differences between odds ratios to assess whether DS were exhibited among those who were engaged in low, moderate, and high PA via random-effects meta-analyses. This study is registered on PROSPERO, number CRD42023417219. RESULTS: Out of 1737 records identified, 5 eligible studies were included with a total of 35,811 participants. Results indicated significant effects of moderate PA on DS (OR = 0.68; 95 % C.I. 0.50-0.93). No effect of low and high PA on DS was found (OR = 0.79; 95 % C.I. 0.52-1.20 and OR = 0.78; 95 % C.I. 0.47-1.30). CONCLUSION: Males who engage in moderate PA present lower prevalence of DS compared to no-PA reference. Such associations were not found for low or high PA. Hence, mental health benefits of PA could possibly be achieved at appropriate levels of PA. High heterogeneity between the studies should be considered when interpreting the results.


Assuntos
Depressão , Exercício Físico , Humanos , Masculino , Depressão/epidemiologia , Estudos Transversais , Estudos de Coortes
16.
Biochim Biophys Acta Mol Basis Dis ; 1870(3): 167014, 2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38171451

RESUMO

Swim training has increased the life span of the transgenic animal model of amyotrophic lateral sclerosis (ALS). Conversely, the progress of the disease is associated with the impairment of iron metabolism and insulin signaling. We used transgenic hmSOD1 G93A (ALS model) and non-transgenic mice in the present study. The study was performed on the muscles taken from trained (ONSET and TERMINAL) and untrained animals at three stages of the disease: BEFORE, ONSET, and TERMINAL. In order to study the molecular mechanism of changes in iron metabolism, we used SH-SY5Y and C2C12 cell lines expression vector pcDNA3.1 and transiently transfected with specific siRNAs. The progress of ALS resulted in decreased P-Akt/Akt ratio, which is associated with increased proteins responsible for iron storage ferritin L, ferritin H, PCBP1, and skeletal muscle iron at ONSET. Conversely, proteins responsible for iron export- TAU significantly decrease. The training partially reverses changes in proteins responsible for iron metabolism. AKT silencing in the SH-SY5Y cell line decreased PCBP2 and ferroportin and increased ferritin L, H, PCBP1, TAU, transferrin receptor 1, and APP. Moreover, silencing APP led to an increase in ferritin L and H. Our data suggest that swim training in the mice ALS model is associated with significant changes in iron metabolism related to AKT activity. Down-regulation of AKT mainly upregulates proteins involved in iron import and storage but decreases proteins involved in iron export.


Assuntos
Esclerose Lateral Amiotrófica , Neuroblastoma , Camundongos , Animais , Humanos , Proteínas Proto-Oncogênicas c-akt/metabolismo , Esclerose Lateral Amiotrófica/genética , Esclerose Lateral Amiotrófica/metabolismo , Superóxido Dismutase-1/metabolismo , Transdução de Sinais , Ferro/metabolismo , Modelos Animais de Doenças , Ferritinas/metabolismo , Proteínas de Ligação a RNA/metabolismo
17.
Front Endocrinol (Lausanne) ; 15: 1403491, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38933822

RESUMO

Introduction: Tryptophan's (Trp) metabolites are undervalued markers of human health. Their serum concentrations are modified by physical exercise and other factors, among which fasting has a well-documented role. Although this mechanism is hardly explored, thus, the study aimed to determine the effect of the 8-day fasting period and the impact of such a procedure on a single bout of an endurance exercise on the concentration of kynurenine pathway (KP) metabolites. Methods: 10 participants fasted for 8 days, and 10 as a control group participated in the study. The exercise was performed at baseline after an overnight fast and repeated post 8 days. Results: The 8 days of fasting increased the resting 3-hydroxy-L-kynurenine (3HK), picolinic acid (PA), kynurenic acid (KYNA), and xanthurenic acid (XA) serum concentration. Also elevated phenylalanine (Phe) and tyrosine (Tyr) levels were recorded, suggesting expanded proteolysis of muscle proteins. In turn, physical activity caused a decrease in the concentration of 3-hydroxyanthranilic acid (3HAA) and PA after fasting. The obtained results were not recorded in controls. Conclusion: The results of this study show that the health-promoting effects of fasting are associated with changes in the KYN pathway. The increase in the concentration of PA and XA metabolites following fasting is capable of penetrating the blood-brain barrier, and KYNA, which initiates several beneficial changes, supports this assumption.


Assuntos
Exercício Físico , Jejum , Cinurenina , Humanos , Masculino , Jejum/sangue , Cinurenina/sangue , Cinurenina/metabolismo , Exercício Físico/fisiologia , Adulto , Adulto Jovem , Descanso/fisiologia , Voluntários Saudáveis , Ácido Cinurênico/sangue , Triptofano/sangue , Triptofano/metabolismo , Biomarcadores/sangue , Ácidos Picolínicos
18.
Sci Rep ; 14(1): 4102, 2024 02 19.
Artigo em Inglês | MEDLINE | ID: mdl-38374149

RESUMO

The effects of long-term omega-3 polyunsaturated fatty acid (n-3 PUFA) supplementation during endurance training on tryptophan (Trp) metabolism and mental state of healthy individuals have not been evaluated so far. Concentrations of plasma Trp, its metabolites and IL-6 were assessed in 26 male runners before and after a 12-week training program combined with supplementation of n-3 PUFAs (O-3 + TRAIN group) or medium chain triglycerides (MCTs; TRAIN group). After the 12-week program participants' mood before and after stress induction was also assessed. The effects of the same supplementation protocol were evaluated also in 14 inactive subjects (O-3 + SEDEN group). Concentrations of 3-hydroxykynurenine (3-HK) and picolinic acid (PA) significantly increased only in the O-3 + TRAIN group (p = 0.01; [Formula: see text] = 0.22 and p = 0.01; [Formula: see text]= 0.26). Favorable, but not statistically significant changes in the concentrations of kynurenic acid (KYNA) (p = 0.06; [Formula: see text]= 0.14), xanthurenic acid (XA) (p = 0.07; [Formula: see text]= 0.13) and 3-hydroxyanthranilic acid (3-HAA) (p = 0.06; [Formula: see text]= 0.15) and in the ratio of neurotoxic to neuroprotective metabolites were seen also only in the O-3 + TRAIN group. No changes in mood and IL-6 concentrations were observed in either group. Supplementation with n-3 PUFAs during endurance training has beneficial effects on Trp's neuroprotective metabolites.Trial registry: This study was registered at ClinicalTrials.gov with identifier NCT05520437 (14/07/2021 first trial registration and 2018/31/N/NZ7/02962 second trial registration).


Assuntos
Treino Aeróbico , Ácidos Graxos Ômega-3 , Humanos , Masculino , Ácidos Graxos Ômega-3/metabolismo , Triptofano/metabolismo , Interleucina-6 , Triglicerídeos , Suplementos Nutricionais
19.
Cell Immunol ; 283(1-2): 12-7, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23850671

RESUMO

This investigation assessed effects of high-intensity interval exercise (HIE; triple Wingate anaerobic test) on inflammatory markers, iron metabolism and hepcidin concentrations. Group of highly trained judo athletes (TR) and non-trained control males (CG) completed a triple Wingate test separated by 4.5min rest. Venous blood samples were collected before, immediately after, 1h, 24h, and 5days following exercise and analysed for serum of IL-6, IL-10, iron, and ferritin. Physiological response to exercise was also determined. Concentration of IL-6 and hepcidin increased 1h after exercise in both groups (p<0.05). Hepcidin returned post testing 24h in TR, whereas in CG it remained elevated during 5days following exercise. Changes in hepcidin did not correlate with shifts in serum IL-6, iron and ferritin concentrations. Gathered data suggest that following HIE, hepcidin increased independently of IL-6 and neither blood nor storage iron affected this phenomena.


Assuntos
Peptídeos Catiônicos Antimicrobianos/sangue , Atletas , Exercício Físico/fisiologia , Ensaio de Imunoadsorção Enzimática , Hepcidinas , Humanos , Interleucina-6/sangue , Masculino , Resistência Física/fisiologia , Adulto Jovem
20.
Exp Physiol ; 98(10): 1457-68, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23733522

RESUMO

The significance of the reduction of the cholesterol pool in heart mitochondria after exercise is still unknown. Recently, published data have suggested that cholesterol may influence the components of mitochondrial contact site and affect mitochondrial swelling. Therefore, the aim of this study was to determine whether the decreased cholesterol content in heart mitochondria caused by prolonged swimming may provoke changes in their bioenergetics and result in an increased resistance to calcium chloride-induced mitochondrial swelling. Male Wistar rats were divided into a sedentary control group and an exercise group. The rats exercised for 3 h, burdened with an additional 3% of their body weight. Their hearts were removed immediately after completing the exercise. The left ventricle was divided and used for experiments. Mitochondrial cholesterol content, membrane fluidity and mitochondrial bioenergetics were measured in the control and exercised rat heart mitochondria. To assess whether mitochondrial modifications are linked to disruption of lipid microdomains, methyl-ß-cyclodextrin, a well-known lipid microdomain-disrupting agent and cholesterol chelator, was applied to the mitochondria of the control group. Cholesterol depletion, increased membrane fluidity and increased resistance to calcium chloride-induced swelling were observed in postexercise heart crude mitochondrial fraction. Similar results were achieved in control mitochondria treated with 2% methyl-ß-cyclodextrin. All of the mitochondrial bioenergetics parameters were similar between the groups. Therefore, the disruption of raft-like microdomains appears to be an adaptive change in the rat heart following exercise.


Assuntos
Colesterol/metabolismo , Mitocôndrias Cardíacas/metabolismo , Dilatação Mitocondrial/fisiologia , Animais , Cloreto de Cálcio/farmacologia , Ácido Láctico/sangue , Masculino , Fluidez de Membrana , Dilatação Mitocondrial/efeitos dos fármacos , Estresse Oxidativo , Condicionamento Físico Animal , Ratos , Ratos Wistar , Natação
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