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Mitochondria, an important organelle implicated in programmed cell death, assumes a crucial role in necroptosis. However, the regulatory mechanisms through which mitochondria participates in necroptosis are largely unknown. To address this knowledge gap, our study aimed to identify mitochondrial proteins that engage in interactions with receptor-interacting protein kinase 3 (RIPK3), a significant upstream kinase involved in necroptosis. Among the candidates, BNIP3 and BNIP3L exhibited significant higher binding scores to RIPK3 compared to others. Computational modeling revealed specific interactions, as RIPK3 specifically binds to a conserved α-helix region within BNIP3 and BNIP3L. Validation experiments confirmed the significance of these helical peptides for RIPK3 binding. Conserved peptides were also identified in BNIP3 and BNIP3L proteins from various animal species, including humans. The binding between human RIPK3 and BNIP3/BNIP3L peptides demonstrated perfect shape and charge complementation, with highly conserved interface residues. Moreover, peptide binding stabilized an active conformation of RIPK3, potentially enhancing its kinase activity. These findings uncover the interactions between RIPK3 and BNIP3/BNIP3L, providing insights into RIPK3 regulation and its role in necroptosis.
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Proteínas Mitocondriais , Necroptose , Animais , Humanos , Proteínas Mitocondriais/genética , Proteínas Mitocondriais/metabolismo , Apoptose , Proteínas Reguladoras de Apoptose/metabolismo , Fosforilação , Proteína Serina-Treonina Quinases de Interação com Receptores/genética , Proteína Serina-Treonina Quinases de Interação com Receptores/metabolismo , Proteínas de Membrana/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Proteínas Supressoras de Tumor/metabolismoRESUMO
Metabolism is one of the most complex cellular biochemical reactions, providing energy and substances for basic activities such as cell growth and proliferation. Early studies have shown that glucose is an important nutrient in osteoblasts. In addition, amino acid metabolism and fat metabolism also play important roles in bone reconstruction. Mammalian circadian clocks regulate the circadian cycles of various physiological functions. In vertebrates, circadian rhythms are mediated by a set of central clock genes: muscle and brain ARNT like-1 (Bmal1), muscle and brain ARNT like-2 (Bmal2), circadian rhythmic motion output cycle stagnates (Clock), cryptochrome 1 (Cry1), cryptochrome2 (Cry2), period 1 (Per1), period 2 (Per2), period 3 (Per3) and neuronal PAS domain protein 2 (Npas2). Negative feedback loops, controlled at both the transcriptional and posttranslational levels, adjust these clock genes in a diurnal manner. According to the results of studies on circadian transcriptomic studies in several tissues, most rhythmic genes are expressed in a tissue-specific manner and are affected by tissue-specific circadian rhythms. The circadian rhythm regulates several activities, including energy metabolism, feeding time, sleeping, and endocrine and immune functions. It has been reported that the circadian rhythms of mammals are closely related to bone metabolism. In this review, we discuss the regulation of the circadian rhythm/circadian clock gene in osteoblasts/osteoclasts and the energy metabolism of bone, and the relationship between circadian rhythm, bone remodeling, and energy metabolism. We also discuss the therapeutic potential of regulating circadian rhythms or changing energy metabolism on bone development/bone regeneration.
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Relógios Circadianos , Ritmo Circadiano , Animais , Osso e Ossos , Relógios Circadianos/genética , Ritmo Circadiano/genética , Metabolismo Energético , Fatores de TranscriçãoRESUMO
Organoid, formed from organ-specific cells, is a group of self-renewal and self-organizing cells growing in a 3-dimensional structure. With the recent progress on microenvironment regulation, stem cell differentiation and organ development, organoids have been constructed and used as promising tools for a wide range of multidisciplinary biomedical applications. Exercise disrupts the internal environment homeostasis, which brings a series of physiological alterations to the digestive system. The current animal or human models are necessary, but not sufficient to monitor the fluctuating microenvironment of gastrointestinal epithelial cells or hepatocytes during exercise. This review described the construction and application of digestive system organoids, as well as the effect of exercise on the microenvironment of intestinal epithelial cells and hepatocytes. The perspective applications of digestive system organoids in exercise physiology were also stated. Using organoid technologies, the possible mechanisms of the exercise-induced dynamic physiological changes would be explored in a new dimension.
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Intestinos , Organoides , Animais , Diferenciação Celular , Células Epiteliais , Hepatócitos , HumanosRESUMO
An amendment to this paper has been published and can be accessed via a link at the top of the paper.
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Exercise plays an important role in the prevention and treatment of chronic liver disease and associated metabolic disorders. A single bout of exercise induces tissue blood flow redistribution, which decreases splanchnic circulation and leads to physiologic hypoxia in the gastrointestinal system and liver. The transcription factor, hypoxia inducible factor-1α (HIF-1α), and its regulator, prolylhydroxylase 2 (PHD2), play pivotal roles in the response to oxygen flux by regulating downstream gene expression levels in the liver. We hypothesized that exercise increases the HIF-1α levels in the liver, and that the hepatic PHD2/HIF-1α axis is involved in postexercise restoration of systemic energy homeostasis. Through constant O2 consumption, CO2 production, food and water intake, and physical activity detection with metabolic chambers, we observed that one 30-min session of swimming exercise enhances systemic energy metabolism in mice. By using the noninvasive bioluminescence imaging ROSA26 oxygen-dependent domain Luc mouse model, we reveal that exercise increases in vivo HIFα levels in the liver. Intraperitoneal injections of the PHD inhibitor, dimethyloxalylglycine, mimicked exercise-induced HIFα increase, whereas the HIF-1α inhibitor, PX-478, blocked this effect. We next constructed liver-specific knockout (LKO) mouse models with albumin- Cre-mediated, hepatocyte-specific Hif1a and Phd2 deletion. Compared with their controls, Hif1a-LKO and Phd2-LKO mice exhibited distinct patterns of hepatic metabolism-related gene expression profiles. Moreover, Hif1a-LKO mice failed to restore systemic energy homeostasis after exercise. In conclusion, the current study demonstrates that a single bout of exercise disrupts systemic energy homeostasis, increasing the HIF-1α levels in the liver. These findings also provide evidence that the hepatic PHD2/HIF-1α axis is involved in postexercise systemic metabolic homeostasis.-Luo, B., Xiang, D., Wu, D., Liu, C., Fang, Y., Chen, P., Hu, Y.-P. Hepatic PHD2/HIF-1α axis is involved in postexercise systemic energy homeostasis.
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Homeostase/genética , Prolina Dioxigenases do Fator Induzível por Hipóxia/genética , Fígado/metabolismo , Pró-Colágeno-Prolina Dioxigenase/metabolismo , Animais , Linhagem Celular Tumoral , Expressão Gênica/genética , Regulação da Expressão Gênica/genética , Camundongos Transgênicos , Oxigênio/metabolismo , Prolil Hidroxilases/genética , RNA Mensageiro/genéticaRESUMO
BACKGROUND Many heart failure (HF) cases are caused by idiopathic dilated cardiomyopathy (iDCM). This study explored the mechanisms of the development and progression of HF caused by iDCM. MATERIAL AND METHODS The gene expression profiles of 102 samples were downloaded from the GEO database (GSE5406). Differentially expressed genes (DEGs) were identified through GO analysis and a KEGG pathway analysis, respectively. A protein-protein interaction (PPI) network was constructed and analyzed to screen potential regulatory proteins. In addition, MCODE and a cytoHubba plugin were used to identify the module and hub genes of DEGs. Finally, transcription factors (TFs) were predicted using PASTAA. We did not perform whole-exome sequencing (WES) for detecting mitochondrial DNA (mtDNA). RESULTS A total of 197 DEGs were screened, and 3 modules, and 4 upregulated and 11 downregulated hub genes were screened. The GO analysis focused on the terms and 12 KEGG pathways were enriched. The FOS, TIMP1, and SERPINE1 hub genes, as well as some key TFs, demonstrated important roles in the progression of HF caused by iDCM. CEBPD, CEBOB, CDC37L1, and SRGN may be new targets for HF in iDCM patients. CONCLUSIONS The identified DEGs and their enriched pathways provide references for exploring the mechanisms of the development and progression of HF patients with iDCM. Moreover, modules, hub genes, and TFs may be useful in the treatment and diagnosis of HF patients with iDCM. However, mtDNA was not investigated.
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Cardiomiopatia Dilatada/genética , Perfilação da Expressão Gênica/métodos , Insuficiência Cardíaca/genética , Biologia Computacional/métodos , Bases de Dados Genéticas , Ontologia Genética , Redes Reguladoras de Genes , Humanos , Mapas de Interação de Proteínas , Transdução de Sinais/genética , Fatores de Transcrição/genética , TranscriptomaRESUMO
Resveratrol (RSV), a phytoalexin, has shown to prevent endothelial dysfunction and reduce diabetic vascular complications and the risk of cardiovascular diseases. The aim of this study was to investigate the signaling mechanisms underlying the protecting effects of RSV against endothelial dysfunction during hyperglycemia in vitro and in vivo. Human umbilical vein endothelial cells (HUVECs) were treated with RSV, and then exposed to high glucose (HG, 30 mmol/L). Akt-Ser473 phosphorylation, eNOS-Ser1177 phosphorylation, and PTEN protein levels in the cells were detected using Western blot. For in vivo studies, WT and Akt-/- mice were fed a normal diet containing RSV (400 mg·kg-1·d-1) for 2 weeks, then followed by injection of STZ to induce hyperglycemia (300 mg/dL). Endothelial function was evaluated using aortic rings by assessing ACh-induced vasorelaxation. RSV (5-20 µmol/L) dose-dependently increased Akt-Ser473 phosphorylation, accompanied by increased eNOS-Ser1177 phosphorylation in HUVECs; these effects were more prominent under HG stimulation. Transfection with Akt siRNA abolished RSV-enhanced eNOS phosphorylation and NO release. Furthermore, RSV (5-20 µmol/L) dose-dependently decreased the levels of PTEN, which was significantly increased under HG stimulation, and PTEN overexpression abolished RSV-stimulated Akt phosphorylation in HG-treated HUVECs. Moreover, RSV dramatically increased 26S proteasome activity, which induced degradation of PTEN. In in vivo studies, pretreatment with RSV significantly increased Akt and eNOS phosphorylation in aortic tissues and ACh-induced vasorelaxation, and improved diabetes-induced endothelial dysfunction in wild-type mice but not in Akt-/- mice. RSV attenuates endothelial function during hyperglycemia via activating proteasome-dependent degradation of PTEN, which increases Akt phosphorylation, and consequentially upregulation of eNOS-derived NO production.
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Endotélio Vascular/efeitos dos fármacos , Hiperglicemia/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Estilbenos/farmacologia , Acetilcolina/farmacologia , Animais , Células Cultivadas , Relação Dose-Resposta a Droga , Ativação Enzimática/efeitos dos fármacos , Glucose/farmacologia , Células Endoteliais da Veia Umbilical Humana , Humanos , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase Tipo III/metabolismo , PTEN Fosfo-Hidrolase/metabolismo , Fosforilação , Proteínas Proto-Oncogênicas c-akt/genética , RNA Interferente Pequeno/farmacologia , Resveratrol , Vasodilatação/efeitos dos fármacosRESUMO
An operationally simple method for the copper-mediated trifluoromethylthiolation of iodopyridinones employing (bpy)CuSCF3 (1; bpy = 2,2'-bipyridine) as a trifluoromethylthiolating reagent is presented. Various types of iodopyridinones are applicable and the trifluoromethylthiolated pyridinones are obtained in moderate to excellent yields. This method tolerates a variety of protecting groups on the nitrogen atom of pyridinones. In addition, scalability of the reaction is demonstrated.
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The aim of this study was to evaluate the effect of overload training on the function of peritoneal macrophages in rats, and to test the hypothesis that glutamine in vivo supplementation would partly reverse the eventual functional alterations induced by overload training in these cells. Forty male Wistar rats were randomly divided into 5 groups: control group (C), overload training group (E1), overload training and restore one week group (E2), glutamine-supplementation group (EG1), and glutamine-supplementation and restore 1-week group (EG2). All rats, except those placed on sedentary control were subjected to 11 weeks of overload training protocol. Blood hemoglobin, serum testosterone, and corticosterone of rats were measured. Moreover, the functions (chemotaxis, phagocytosis, cytokines synthesis, reactive oxygen species generation) of peritoneal macrophages were determined. Data showed that blood hemoglobin, serum testosterone, corticosterone and body weight in the overload training group decreased significantly as compared with the control group. Meanwhile, the chemotaxis capacity (decreased by 31%, p = .003), the phagocytosis capacity (decreased by 27%, p = .005), the reactive oxygen species (ROS) generation (decreased by 35%, p = .003) and the cytokines response capability of macrophages were inhibited by overload training. However, the hindering of phagocytosis and the cytokines response capability of macrophages induced by overload training could be ameliorated and reversed respectively, by dietary glutamine supplementation. These results suggest that overload training impairs the function of peritoneal macrophages, which is essential for the microbicidal actions of macrophages. This may represent a novel mechanism of immunodepression induced by overload training. Nonetheless, dietary glutamine supplementation could partly reverse the impaired macrophage function resulting from overload training.
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Suplementos Nutricionais , Glutamina/farmacologia , Sistema Imunitário/efeitos dos fármacos , Macrófagos/fisiologia , Condicionamento Físico Animal , Esforço Físico/fisiologia , Animais , Quimiotaxia , Citocinas/metabolismo , Sistema Imunitário/citologia , Masculino , Neutrófilos/metabolismo , Fagocitose , Distribuição Aleatória , Ratos Wistar , Espécies Reativas de Oxigênio/metabolismoRESUMO
Bioactive oxidized linoleic acid metabolites (OXLAMs) include 13- and 9-hydroxy-octadecadienoic acid (13-HODE + 9-HODE) and have been linked to oxidative stress, inflammation, and numerous pathological and physiological states. The purpose of this study was to measure changes in plasma 13-HODE + 9-HODE following a 75-km cycling bout and identify potential linkages to linoleate metabolism and established biomarkers of oxidative stress (F2-isoprostanes) and inflammation (cytokines) using a metabolomics approach. Trained male cyclists (N = 19, age 38.0 ± 1.6 yr, wattsmax 304 ± 10.5) engaged in a 75-km cycling time trial on their own bicycles using electromagnetically braked cycling ergometers (2.71 ± 0.07 h). Blood samples were collected preexercise, immediately post-, 1.5 h post-, and 21 h postexercise, and analyzed for plasma cytokines (IL-6, IL-8, IL-10, tumor necrosis factor-α, monocyte chemoattractant protein-1, granulocyte colony-stimulating factor), F2-isoprostanes, and shifts in metabolites using global metabolomics procedures with gas chromatography mass spectrometry (GC-MS) and liquid chromatography mass spectrometry (LC-MS). 13-HODE + 9-HODE increased 3.1-fold and 1.7-fold immediately post- and 1.5 h postexercise (both P < 0.001) and returned to preexercise levels by 21-h postexercise. Post-75-km cycling plasma levels of 13-HODE + 9-HODE were not significantly correlated with increases in plasma cytokines but were positively correlated with postexercise F2-isoprostanes (r = 0.75, P < 0.001), linoleate (r = 0.54, P = 0.016), arachidate (r = 0.77, P < 0.001), 12,13-dihydroxy-9Z-octadecenoate (12,13-DiHOME) (r = 0.60, P = 0.006), dihomo-linolenate (r = 0.57, P = 0.011), and adrenate (r = 0.56, P = 0.013). These findings indicate that prolonged and intensive exercise caused a transient, 3.1-fold increase in the stable linoleic acid oxidation product 13-HODE + 9-HODE and was related to increases in F2-isoprostanes, linoleate, and fatty acids in the linoleate conversion pathway. These data support the use of 13-HODE + 9-HODE as an oxidative stress biomarker in acute exercise investigations.
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Ciclismo , Metabolismo Energético , Ácidos Linoleicos Conjugados/sangue , Ácidos Linoleicos/sangue , Metabolômica , Esforço Físico , Adulto , Biomarcadores/sangue , Cromatografia Líquida de Alta Pressão , Citocinas/sangue , F2-Isoprostanos/sangue , Cromatografia Gasosa-Espectrometria de Massas , Humanos , Mediadores da Inflamação/sangue , Masculino , Metabolômica/métodos , Pessoa de Meia-Idade , Oxirredução , Estresse Oxidativo , Espectrometria de Massas em Tandem , Fatores de TempoRESUMO
The purpose of this study was to examine the effect of moderate exercise on repeated restraint stress (RRS)-induced intestinal barrier dysfunction and explore possible mechanisms in a mouse model. Male Balb/c mice (6weeks) were randomized into 7 groups: CON functioned as controls with no intervention; RRS was subjected to 6h per day RRS for 7 consecutive days; RRS+SWIM received 30min per day of swimming prior to RRS; CON+SWIM only received 30min per day of swimming; and the other groups received one session of 30min swimming prior to sacrifice at 1-, 3- and 6h recovery. Intestinal permeability was quantified with FITC-dextran. Bacterial translocation was determined by quantification of bacterial colony forming units (CFUs) in cultured mesenteric lymph nodes (MLN), and with fluorescence in situ hybridization (FISH). Antimicrobial related gene expression at baseline and 1h after one session of 30min swimming was tested by quantitative real-time polymerase chain reaction (Q-PCR) in small intestinal segments. Protein expression of 5 genes with statistically significant increase was measured at baseline, and 1-, 3- and 6h post-swimming using enzyme-linked immunosorbent assay (ELISA). Thirty minutes per day of swimming before RRS attenuated bacterial translocations and maintained intestinal permeability. Gene expression and protein levels for four antimicrobial peptides (α-defensin 5, ß-defensin 1, RegIIIß and RegIIIγ) were significantly increased after one 30min swimming session. In conclusion, moderate exercise attenuated chronic stress-induced intestinal barrier dysfunction in mice, possibly due to augmentation of antimicrobial responses in the small intestine.
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Peptídeos Catiônicos Antimicrobianos/genética , Mucosa Intestinal/metabolismo , Condicionamento Físico Animal/fisiologia , Estresse Psicológico/metabolismo , Animais , Fenômenos Fisiológicos Bacterianos , Expressão Gênica , Intestinos/patologia , Masculino , Camundongos , Camundongos Endogâmicos BALB C , Permeabilidade , Restrição Física , Natação/fisiologiaRESUMO
Adaptogens modulate intracellular signaling and increase expression of heat shock protein 72 (HSP72). Rhodiola rosea (RR) is a medicinal plant with demonstrated adaptogenic properties. The purpose of this study was to measure the influence of RR supplementation on exercise-induced muscle damage, delayed onset of muscle soreness (DOMS), plasma cytokines, and extracellular HSP72 (eHSP72) in experienced runners completing a marathon. Experienced marathon runners were randomized to RR (n=24, 6 female, 18 male) or placebo (n=24, 7 female, 17 male) groups and under double-blinded conditions ingested 600mg/day RR extract or placebo for 30days prior to, the day of, and seven days post-marathon. Blood samples were collected, and vertical jump and DOMS assessed the day before, 15min post- and 1.5h post-marathon. DOMS was also assessed for seven days post-marathon. Marathon race performance did not differ between RR and placebo groups (3.87±0.12h and 3.93±0.12h, respectively, p=0.722). Vertical jump decreased post-marathon (time effect, p<0.001) with no difference between groups (interaction effect, p=0.673). Post-marathon DOMS increased significantly (p<0.001) but the pattern of change did not differ between groups (p=0.700). Myoglobin (Mb), creatine phosphokinase (CPK), aspartate aminotransferase (AST), alanine aminotransferase (ALT), interleukin (IL)-6, IL-8, IL-10, monocyte chemotactic protein-1 (MCP-1), granulocyte-colony-stimulating factor (G-CSF), C-reactive protein (CRP), and eHSP72 all increased post-marathon (all p<0.001), with no group differences over time (all p>0.300). In conclusion, RR supplementation (600mg/day) for 30days before running a marathon did not attenuate the post-marathon decrease in muscle function, or increases in muscle damage, DOMS, eHSP72, or plasma cytokines in experienced runners.
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Exercício Físico/fisiologia , Músculo Esquelético/lesões , Mialgia/tratamento farmacológico , Fitoterapia , Rhodiola , Adulto , Creatina Quinase/sangue , Método Duplo-Cego , Feminino , Proteínas de Choque Térmico HSP72/metabolismo , Humanos , Inflamação/sangue , Leucócitos/metabolismo , Masculino , Mialgia/sangue , Mioglobina/sangue , Extratos Vegetais/uso terapêutico , Corrida/fisiologiaRESUMO
Functional overreaching has been linked to alterations in immunity and host pathogen defense, but little is known as to whether or not running and cycling evoke different responses. This study compared inflammation, muscle damage and soreness, and innate immune function responses to a 3-day period of intensified exercise in trained long distance runners (N=13, age 34.4±2.4year) and cyclists (N=22, age 36.6±1.7year, P=0.452). Upper respiratory tract infection (URTI) symptomatology was monitored for 12weeks using the Wisconsin Upper Respiratory Symptom Survey (WURSS), and subjects from both athletic groups came to the lab during week five and exercised 2.5h/day for 3days in a row at 70% VO2max. Blood samples were collected before and after the 3-day period of exercise, with recovery samples collected 1-, 14-, and 38h-post-exercise. Samples were analyzed for muscle damage [creatine kinase (CK), myoglobin (MYO)], inflammation (CRP, IL-6, IL-8, IL-10, MCP), and innate immunity [granulocyte and monocyte phagocytosis (GR-PHAG and MO-PHAG) and oxidative burst activity (GR-OBA and MO-OBA)]. Runners compared to cyclists experienced significantly more muscle damage (CK 133% and MYO 404% higher post-3days exercise), inflammation (CRP 87%, IL-6 256%, IL 8 61%, IL-10 32%, MCP 29%), and delayed onset of muscle soreness (DOMS, 87%). The 3-day period of exercise caused significant downturns in GR-PHAG, MO-PHAG, GR-OBA, MO-OBA by 14- and 38h-recovery, but the pattern of change did not differ between groups. No group differences were measured for 12-week URTI severity (18.3±5.6 and 16.6±4.0, P=0.803) and symptom scores (33.4±12.6 and 24.7±5.8, P=0.477). These data indicate that a 3-day period of functional overreaching results in substantially more muscle damage and soreness, and systemic inflammation in runners compared to cyclists, but without group differences for 12-week URTI symptomatology and post-exercise decrements in innate immune function.
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Exercício Físico/fisiologia , Imunidade Inata/fisiologia , Corrida/fisiologia , Adulto , Feminino , Granulócitos/fisiologia , Humanos , Inflamação/sangue , Masculino , Pessoa de Meia-Idade , Monócitos/fisiologia , Mialgia/imunologia , Explosão Respiratória , Infecções Respiratórias/imunologia , Adulto JovemRESUMO
PURPOSE: Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3) inflammasome is important in inflammation of several diabetic complications. However, the potential role of NLRP3 inflammasome in the inflammatory process of diabetic cardiomyopathy (DCM) remains unclear. Although rosuvastatin (RSV) has an anti-inflammatory effect on some cardiovascular diseases, its influence on DCM is incompletely understood. We aimed to explore the effect on and underlying mechanism of RSV in DCM, and whether NLRP3 is a target for RSV. METHODS: Type 2 diabetes was induced in rat. The characteristics of type 2 DCM were evaluated by metabolic tests, echocardiography and histopathology. The expression of factors was determined by real-time RT-PCR and western blot. Eight-week RSV treatment and NLRP3 gene silencing were used to investigate the effect and underlying target of RSV in DCM. RESULTS: Compared with controls, diabetic rats showed severe metabolic disorder, cardiac dysfunction, fibrosis, disorganized ultrastructure, and excessive activation of thioredoxin interacting/inhibiting protein (TXNIP, p < 0.05), NLRP3 inflammasome (NLRP3, p < 0.01; apoptosis-associated speck-like protein containing a caspase recruitment domain [ASC], p < 0.05; caspase-1, p < 0.01), interleukin-1ß (p < 0.01) and mitogen-activated protein kinases (MAPKs, all p < 0.01). Compared with diabetes alone, RSV ameliorated the overexpression of NLRP3 inflammasome (NLRP3, p < 0.05; ASC, p < 0.05; pro-caspase-1 p < 0.05, caspase-1 p20, p < 0.01) and MAPKs (all p < 0.05), which paralleled the cardiac protection of RSV. Silencing NLRP3 ameliorated cardiac remodeling and dysfunction. The beneficial effects of RSV in vehicle-treated rats were all abrogated in NLRP3-silenced rats. CONCLUSIONS: The beneficial effect of RSV on DCM depended on inhibited NLRP3 inflammasome, and correlated with suppression of the MAPKs.
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Diabetes Mellitus Tipo 2/complicações , Cardiomiopatias Diabéticas/tratamento farmacológico , Fluorbenzenos/farmacologia , Pirimidinas/farmacologia , Receptores Citoplasmáticos e Nucleares/genética , Sulfonamidas/farmacologia , Animais , Western Blotting , Proteínas de Transporte , Caspase 1/metabolismo , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Inativação Gênica , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Inflamassomos/efeitos dos fármacos , Inflamassomos/metabolismo , Interleucina-1beta/metabolismo , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/metabolismo , Proteína 3 que Contém Domínio de Pirina da Família NLR , Ratos , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Rosuvastatina CálcicaRESUMO
The aim of this review is to highlight the research and review papers that reflect the current developments in Exercise Immunology, including the interventions on immunosuppression after extreme performance, the effect of exercise on immunosenescence, and the immunomodulating role of exercise in stress and disease. We discuss the papers in accordance with these themes, summarizing their important contributions, and providing directions for future research.
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Exercício Físico , Humanos , Tolerância ImunológicaRESUMO
Introduction: Not all type 2 diabetes mellitus (T2DM) patients exhibit insulin resistance (IR). Our objective is to identify the most effective sex-specific index for predicting IR in T2DM. This will be achieved through a comparative analysis of the sex-specific attributes of waist to hip circumference ratio (WHR), visceral fat area to hip circumference ratio (VHR), and visceral fat area to subcutaneous fat area ratio (VSR). Methods: Receiver operating characteristic curve analysis was conducted to estimate the area under the curve for WHR, VHR, and VSR. Subsequently, logistic regression was employed to analyze the relationship between VHR and IR. Results: There were significant differences between males and females in anthropometric measurements, biochemical data, and obesity prevalence. ROC analysis revealed that the area under the curve (AUC) for predicting male IR was 0.67, 0.71, and 0.62 for WHR, VHR, and VSR, respectively. For females, the AUC values were 0.63, 0.69, and 0.60, respectively. In multivariate logistic regression analysis, adjusting for confounding factors, compared to the lowest tertile of VHR, the odds ratio (OR) of the highest tertile was 2.2 (95% CI: 1.47-3.3, P<0.001) for males and 2.1 (95% CI: 1.24-3.57, P=0.005) for females. Conclusion: VHR emerges as the most reliable predictor of IR risk in individuals with T2DM.
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All organisms have various circadian, behavioral, and physiological 24-h periodic rhythms, which are controlled by the circadian clock. The circadian clock controls various behavioral and physiological rhythms. In mammals, the primary circadian clock is present in the suprachiasmatic nucleus of the hypothalamus. The rhythm of the circadian clock is controlled by the interaction between negative and positive feedback loops, consisting of crucial clock regulators (including Bmal1 and Clock), three cycles (mPer1, mPer2, and mPer3), and two cryptochromes (Cry1 and Cry2). The development of early mammalian embryos is an ordered and complex biological process that includes stages from fertilized eggs to blastocysts and undergoes important morphological changes, such as blastocyst formation, cell multiplication, and compaction. The circadian clock affects the onset and timing of embryonic development. The circadian clock affects many biological processes, including eating time, immune function, sleep, energy metabolism, and endocrinology, therefore, it is also crucial for overall health, growth and development after birth. This review summarized the effects of the circadian clock in the body's physiological activities. A new strategy is proposed for the prevention of malformations or diseases by regulating the circadian clock or changing circadian rhythms.
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Introduction: Serum magnesium is a crucial mineral within the human body. It is imperative for diabetic patients to maintain optimal serum magnesium levels. We focus on the relationship between glycemic control and serum magnesium in type 2 diabetes mellitus (T2DM). Methods: The retrospective, observational, cross-sectional study comprised 1694 patients recruited from the People's Hospital of Yuxi. Fasting blood samples were collected for analysis, accompanied by the recording of participants' demographic characteristics. Patients were categorized into two groups based on whether their glycosylated hemoglobin (HbA1c) levels < 7%. A t-test was employed to identify significant differences between the two groups. Correlation coefficients were calculated using Pearson's method. A Logistic regression analysis was conducted to assess the association between variables and glycemic control. A linear regression analysis was performed to assess the relationship between serum magnesium levels and HbA1c. Results: Patients with poor glycemic control exhibited elevated age, low-density lipoprotein (LDL-C), fasting plasma glucose (FPG), and homeostasis model assessment (HOMA-IR) compared to those with good glycemic control (P < 0.001). Additionally, total cholesterol (TC) levels were significantly higher in patients with poor glycemic control. Conversely, high-density lipoprotein (HDL-C) and serum magnesium levels were lower in patients with poor glycemic control. Serum magnesium levels exhibited negative correlations with HOMA-IR (r = -0.05, P < 0.05), HbA1c (r = -0.29, P < 0.05), and FPG (r = -0.20, P < 0.05). Moreover, serum magnesium was significantly associated with reduced odds of glycemic control (OR = 0.0005, 95% CI 0.0001-0.0027, P < 0.001). Conclusion: The serum magnesium level in patients with T2DM is closely associated with glycemic control.
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Aim: This investigation aims to assess the predictive value of the glycemic dispersion index (GDI), calculated by incorporating glycated hemoglobin, fasting plasma glucose, and 2-hour postprandial plasma glucose, in predicting major adverse cardiovascular events (MACE) within a 12-month timeframe for diabetic patients with concomitant acute coronary syndrome (ACS). Methods: A retrospective study was conducted on 3261 diabetic patients with ACS who were hospitalized in the Department of Cardiology, the Sixth Affiliated Hospital of Kunming Medical University, from January 2016 to July 2022. Based on the inclusion and exclusion criteria, 512 patients were ultimately enrolled in the study. Their general information and laboratory test indicators were collected, and the occurrence of MACE within 12 months after admission was followed up and recorded for the enrolled patients, With the last follow-up having been concluded on July 31, 2023. The enrolled patients were stratified into four groups (Q1, Q2, Q3, Q4) based on their GDI values, from the lowest to the highest. Cox proportional hazards regression analysis and Kaplan-Meier survival analysis were employed to investigate the risk factors associated with MACE occurrence across these groups and to assess the cumulative risk of MACE over time within each group. Results: The percentages of enrolled patients experiencing MACE in groups Q1 to Q4 were 10.16%, 12.50%, 15.63%, and 16.41%, respectively. GDI independently predicted the hazards for MACE in enrolled patients. The cumulative risk of MACE over time was considerably more significant in those with a GDI>4.21 than those with a GDI≤4.21. Conclusion: The elevated GDI is correlated with an augmented risk of MACE in diabetic patients with concomitant ACS, thereby serving as an early indicator for assessing the unfavorable clinical prognosis of patients. This study offers novel insights into glycemic variability monitoring, enhancing prevention and treatment strategies for cardiovascular disease in people with diabetes.
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Introduction: Dyslipidemia commonly complicates type 2 diabetes mellitus, yet the relationship between glycosylated hemoglobin and blood lipid levels remains uncertain. Methods: This retrospective cross-sectional study included 27,158 participants from the People's Hospital of Yuxi. Statistical comparisons for continuous variables utilized analysis of variance (ANOVA), while chi-square analysis was employed for categorical variables. Boxplots assessed the concentration, dispersion, and deviation of total cholesterol (TC), triglycerides (TG), low-density lipoprotein (LDL-C), and high-density lipoprotein (HDL-C) distribution. A linear regression analysis examined the association between HbA1c and lipid profile, complemented by a fitting curve to visualize trends. Results: Participants who developed diabetes exhibited higher age and elevated Body mass index (BMI), systolic blood pressure (SBP), diastolic blood pressure (DBP), TC, TG, LDL-C, and FPG levels compared to those without diabetes (p < 0.001). Linear regression analysis demonstrated significant associations between HbA1c values and TC, TG, LDL-C, and HDL-C (p < 0.001). The plotted curve indicated that as TC, TG, and LDL levels increased, HbA1c levels rose, while HDL levels decreased. Conclusion: HbA1c was positively correlated with TC, TG, LDL-C, and negatively correlated with HDL-C in the population in the central Yunnan Plateau.