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1.
Rev. bras. med. esporte ; 29: e2022_0256, 2023. tab
Artigo em Inglês | LILACS-Express | LILACS | ID: biblio-1387945

RESUMO

ABSTRACT Introduction Increasing the bone mineral density of athletes can provide better basic physical conditions for basketball players, prevent fractures caused by osteopenia and reduce the occurrence of serious sports injuries. Objective Explore the effect of high-intensity training on bone mineral density in basketball players. Methods In this experiment, 30 subjects were divided into male and female groups, and high-intensity exercise training was performed for 60 minutes, three times a week, for eight weeks. The relevant indices were measured before and after training, and their data were classified and analyzed. Results High-intensity training can significantly improve the bone mineral density of basketball players, and the increase of bone mineral density of female basketball players is slightly lower than that of male players. In addition, the increase in bone mineral density can comprehensively improve athletes' muscular strength and physical fitness. Conclusion High-intensity training can improve basketball players' bone mineral density and sports skills, requiring promoting studies for its popularization in colleges and universities. Level of evidence II; Therapeutic studies - investigation of treatment outcomes.


RESUMO Introdução Aumentar o nível de densidade mineral óssea dos atletas pode proporcionar melhores condições físicas básicas para jogadores de basquetebol, prevenir fraturas causadas pela osteopenia e reduzir a ocorrência de lesões esportivas graves. Objetivo Explorar o efeito do treinamento de alta intensidade na densidade mineral óssea de jogadores de basquetebol. Métodos Neste experimento, 30 indivíduos foram divididos em grupo masculino e feminino, o treinamento de exercícios de alta intensidade foi realizado por 60 minutos, três vezes por semana durante um total de 8 semanas. Os índices relevantes foram medidos antes e após o treinamento, seus dados foram classificados e analisados. Resultados O treinamento de alta intensidade pode melhorar significativamente a densidade mineral óssea dos jogadores de basquetebol, e o aumento da densidade mineral óssea das jogadoras de basquetebol feminino é ligeiramente menor do que o dos jogadores masculinos. Além disso, o aumento da densidade mineral óssea pode melhorar de forma abrangente a força muscular e a aptidão física dos atletas. Conclusão O treinamento de alta intensidade pode promover a melhoria da densidade mineral óssea e habilidades esportivas dos jogadores de basquetebol, necessitando de estudos promotores para sua popularização em Faculdades e Universidades. Nível de evidência II; Estudos terapêuticos - investigação dos resultados do tratamento.


RESUMEN Introducción Aumentar el nivel de densidad mineral ósea de los deportistas puede proporcionar mejores condiciones físicas básicas a los jugadores de baloncesto, prevenir las fracturas causadas por la osteopenia y reducir la aparición de lesiones deportivas graves. Objetivo Explorar el efecto del entrenamiento de alta intensidad sobre la densidad mineral ósea en jugadores de baloncesto. Métodos En este experimento, 30 sujetos se dividieron en el grupo de hombres y mujeres, se realizó un entrenamiento de ejercicios de alta intensidad durante 60 minutos, tres veces por semana durante un total de 8 semanas. Se midieron los índices relevantes antes y después del entrenamiento, se clasificaron sus datos y se analizaron. Resultados El entrenamiento de alta intensidad puede mejorar significativamente la densidad mineral ósea de los jugadores de baloncesto, y el aumento de la densidad mineral ósea de las jugadoras de baloncesto es ligeramente inferior al de los jugadores. Además, el aumento de la densidad mineral ósea puede mejorar ampliamente la fuerza muscular y la forma física de los deportistas. Conclusión El entrenamiento de alta intensidad puede promover la mejora de la densidad mineral ósea y de las habilidades deportivas en los jugadores de baloncesto, siendo necesario promover estudios para su popularización en Colegios y Universidades. Nivel de evidencia II; Estudios terapéuticos - investigación de los resultados del tratamiento.

2.
Bioact Mater ; 21: 223-238, 2023 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-36157244

RESUMO

Stem cell-based tissue engineering has provided a promising platform for repairing of bone defects. However, the use of exogenous bone marrow mesenchymal stem cells (BMSCs) still faces many challenges such as limited sources and potential risks. It is important to develop new approach to effectively recruit endogenous BMSCs and capture them for in situ bone regeneration. Here, we designed an acoustically responsive scaffold (ARS) and embedded it into SDF-1/BMP-2 loaded hydrogel to obtain biomimetic hydrogel scaffold complexes (BSC). The SDF-1/BMP-2 cytokines can be released on demand from the BSC implanted into the defected bone via pulsed ultrasound (p-US) irradiation at optimized acoustic parameters, recruiting the endogenous BMSCs to the bone defected or BSC site. Accompanied by the daily p-US irradiation for 14 days, the alginate hydrogel was degraded, resulting in the exposure of ARS to these recruited host stem cells. Then another set of sinusoidal continuous wave ultrasound (s-US) irradiation was applied to excite the ARS intrinsic resonance, forming highly localized acoustic field around its surface and generating enhanced acoustic trapping force, by which these recruited endogenous stem cells would be captured on the scaffold, greatly promoting them to adhesively grow for in situ bone tissue regeneration. Our study provides a novel and effective strategy for in situ bone defect repairing through acoustically manipulating endogenous BMSCs.

3.
Environ Sci Ecotechnol ; 12: 100210, 2022 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-36338337

RESUMO

Sudden mega natural gas leaks of two Nord Stream pipelines in the Baltic Sea (Denmark) occurred from late September to early October 2022, releasing large amounts of methane into the atmosphere. We inferred the methane emissions of this event based on surface in situ observations using two inversion methods and two meteorological reanalysis datasets, supplemented with satellite-based observations. We conclude that approximately 220 ± 30 Gg of methane was released from September 26 to October 1, 2022.

4.
Chem Eng J ; 433(Pt 1)2022 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-36338580

RESUMO

Myocardial infarction (MI) is a major cause of disability and mortality worldwide. A cell permeable peptide V1-Cal has shown remarkable therapeutic effects on ML However, using V1-Cal to improve long-term cardiac function after MI is presently limited by its short half-life. Herein, we co-assembled V1-Cal with a well-known hydrogelator Nap-Phe-Phe-Tyr (NapFFY) to obtain a new supramolecular hydrogel V1-Cal/NapFFY. We found that the hydrogel could significantly enhance the therapeutic effects of V1-Cal on ventricular remodeling reduction and cardiac function improvement in a myocardial infarction rat model. In vitro experiments indicated that co-assembly of V1-Cal with NapFFY significantly increased mechanic strength of the hydrogel, enabling a sustained release of V1-Cal for more than two weeks. In vivo experiments supported that sustained release of V1-Cal from V1-Cal/NapFFY hydrogel could effectively decrease the expression and activation of TRPV1, reduce apoptosis and the release of inflammatory factors in a MI rat model. In particular, V1-Cal/NapFFY hydrogel significantly decreased infarct size and fibrosis, while improved cardiac function 28 days post MI. We anticipate that V1-Cal/NapFFY hydrogel could be used clinically to treat MI in the near future.

5.
Emerg Med Int ; 2022: 6823866, 2022.
Artigo em Inglês | MEDLINE | ID: mdl-36338951

RESUMO

Backgrounds: The novel coronavirus disease 2019 (COVID-19) has caused a global pandemic. Pancreatic injuries have been reported in COVID-19 patients. The present meta-analysis was conducted to compare the morbidity and outcomes of AP between COVID-19 positive and negative patients. Methods: Databases including Cochrane Library, PubMed, and EMBASE were systematically searched (until July 3rd 2022). Studies with English abstracts comparing the severity and outcomes of AP between COVID-19 positive and negative patients were included. Mean differences or odds ratios with a 95% confidence interval were employed for assess variables. Risk of publication bias was assessed with funnel plots. Results: Data from 7 studies with a total of 2816 AP patients were included. COVID-19 positive was associated with higher incidences of pancreatic necrosis (OR = 1.65; 95% CI: 1.13 to 2.42, P = 0.01; P = 0.82 for heterogeneity) and persistent organ failure (OR = 6.87; 95% CI: 2.37 to 19.98, P = 0.0004; P = 0.12 for heterogeneity), especially cardiovascular failure (OR = 2.92; 95% CI: 1.66 to 5.14, P = 0.0002; P = 0.58 for heterogeneity) and acute respiratory distress syndrome (ARDS) or acute lung injury (ALI) (OR = 3.03; 95% CI: 2.09 to 4.39, P < 0.00001; P = 0.20 for heterogeneity). COVID-19 infection induced a higher level of CRP (MD = 0.40; 95% CI: 0.16 to 0.64, P = 0.001; P < 0.00001 for heterogeneity) as well as coagulation disorders involving platelets, prothrombin time, activated partial thromboplastin time, and D-dimer (all P < 0.05). During hospitalization, COVID-19 positive was associated with higher ICU admission rate (OR = 2.76; 95% CI: 1.98 to 3.85 P < 0.00001; P = 0.47 for heterogeneity). COVID-19 positive AP was associated with a higher mortality rate (OR = 3.70; 95% CI: 2.60 to 5.25, P < 0.00001; P = 0.12 for heterogeneity). Discussion. The number of included studies is limited and none is RCT, thus the risks of publication and selective bias could not be ignored. COVID-19 deteriorated the severity and clinical outcomes of AP, with a high incidence of morbidity and mortality.

6.
Food Funct ; 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36385640

RESUMO

Hyperuricemia (HUA) affects human health and is involved in the pathogenesis of common chronic diseases. Previous studies showed that Ganoderma lucidum extract lowered HUA in animals. However, the active ingredient and pharmacological mechanism of Ganoderma lucidum extract in the improvement of HUA are unknown. The purpose of this study was to determine the anti-HUA efficacy and related mechanism of Ganoderma lucidum polysaccharide peptide (GLPP) using a potassium oxonate (PO)-induced mouse model and an adenosine-induced cell model. The experimental results showed that blood uric acid (UA) was decreased up to 40.6% by GLPP in HUA mice in a dose-dependent manner. Additionally, GLPP significantly reduced UA production by inhibiting the hepatic and blood adenosine deaminase (ADA) activity and increased UA excretion by decreasing the expression of glucose transporter 9 (GLUT9) and increasing the expression of organic anion transporter 1 (OAT1) in kidney. The adenosine-induced cell model showed that the inhibitory effect of GLPP on ADA activity may be the main reason for the alleviation of HUA by GLPP. Furthermore, PO-induced renal histopathological damage was also alleviated by GLPP in a dose-dependent manner. The experimental results in this study indicated that GLPP exerted anti-HUA effects via regulating the UA production and excretion, suggesting that GLPP could be developed into a therapeutic agent for HUA.

7.
J Biophotonics ; : e202200168, 2022 Nov 17.
Artigo em Inglês | MEDLINE | ID: mdl-36397661

RESUMO

Rapid screening for ischemic strokes in prehospital settings may improve patient outcomes by allowing early deployment of vascular recanalization therapies. However, there are no low-cost and convenient methods that can assess ischemic strokes in such a setting. Diffuse correlation spectroscopy (DCS) is a promising method for continuous, noninvasive transcranial monitoring of cerebral blood flow. In this study, we used a DCS system to detect cerebral hemodynamics before and after acute ischemic stroke in pigs. Seven adult porcines were chosen to establish ischemic stroke models via bilateral common carotid artery ligation (n=5) or air emboli (n=2). The results showed a significant difference in blood flow index (BFI) between the normal and ischemic groups. Relative blood flow index (rBFI) exhibited excellent results. Therefore, the diffuse optical method can assess the hemodynamic changes in acute cerebral ischemic stroke onset in pigs, and rBFI may be a promising biomarker for identifying cerebral ischemic stroke. This article is protected by copyright. All rights reserved.

8.
J Phys Chem B ; 126(44): 9016-9025, 2022 Nov 10.
Artigo em Inglês | MEDLINE | ID: mdl-36318969

RESUMO

Ion adsorption and hydrogen bond (HB) network reconstruction in electric double layer (EDL) have a profound impact on the interface properties. The microstructure in the bulk phase of 1.00-21.30 wt.% Na2SO3 aqueous solutions are investigated by X-ray scattering, confocal Raman spectroscopy, and classical molecular dynamics. The electronic properties of SO32- adsorption and the geometric structure of the HB network in the EDL at the titanium TiO2(101) surface are studied by density functional theory (DFT) and classical molecular dynamics. The SO32- strongly weakens the fully hydrogen-bonded water (FHW) and transforms it into partial hydrogen-bonded water (PHW). The HB transformation index (HBTI = PHW/FHW) shows a linear relationship with the mass fraction of Na2SO3. The TiOb-parallel adsorption configuration of SO32- enhances the ionicity of the Ob-Ti6 bond, resulting in the formation of oxygen vacancies at the titanium passive film surface. Besides, SO32- and Na+ are enriched and thermodynamic supersaturated in the inner Helmholtz layer (IHL), and the ions are diluted in the outer Helmholtz layer (OHL). The diffusion coefficient of SO32- and water molecules in EDL decreases seriously, which is easy to causes salt scaling on the surface of titanium passive film. This work provides evidence for the destruction of titanium passive film by SO32-.

11.
Schizophr Bull ; 2022 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-36402458

RESUMO

BACKGROUND AND HYPOTHESIS: Disrupted control of brain state transitions may contribute to the diverse dysfunctions of cognition, emotion, and behavior that are fundamental to schizophrenia. Control theory provides the rationale for evaluating brain state transitions from a controllability perspective, which may help reveal the brain mechanism for clinical features such as cognitive control deficits associated with schizophrenia. We hypothesized that brain controllability would be altered in patients with schizophrenia, and that controllability of brain networks would be related to clinical symptomatology. STUDY DESIGN: Controllability measurements of functional brain networks, including average controllability and modal controllability, were calculated and compared between 125 first-episode never-treated patients with schizophrenia and 133 healthy controls (HCs). Associations between controllability metrics and clinical symptoms were evaluated using sparse canonical correlation analysis. STUDY RESULTS: Compared to HCs, patients showed significantly increased average controllability (PFDR = .023) and decreased modal controllability (PFDR = .023) in dorsal anterior cingulate cortex (dACC). General psychopathology symptoms and positive symptoms were positively correlated with average controllability in regions of default mode network and negatively associated with average controllability in regions of sensorimotor, dorsal attention, and frontoparietal networks. CONCLUSIONS: Our findings suggest that altered controllability of functional activity in dACC may play a critical role in the pathophysiology of schizophrenia, consistent with the importance of this region in cognitive and brain state control operations. The demonstration of associations of functional controllability with psychosis symptoms suggests that the identified alterations in average controllability of brain function may contribute to the severity of acute psychotic illness in schizophrenia.

12.
Cancer Cell ; 40(11): 1306-1323.e8, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36332622

RESUMO

Prostate cancer adeno-to-neuroendocrine lineage transition has emerged as a mechanism of targeted therapeutic resistance. Identifying the direct molecular drivers and developing pharmacological strategies using clinical-grade inhibitors to overcome lineage transition-induced therapeutic resistance are imperative. Here, using single-cell multiomics analyses, we investigate the dynamics of cellular heterogeneity, transcriptome regulation, and microenvironmental factors in 107,201 cells from genetically engineered mouse prostate cancer samples with complete time series of tumor evolution seen in patients. We identify that FOXA2 orchestrates prostate cancer adeno-to-neuroendocrine lineage transition and that Foxa2 expression is significantly induced by androgen deprivation. Moreover, Foxa2 knockdown induces the reversal of adeno-to-neuroendocrine transition. The KIT pathway is directly regulated by FOXA2 and specifically activated in neuroendocrine prostate cancer (NEPC). Pharmacologic inhibition of KIT pathway significantly suppresses mouse and human NEPC tumor growth. These findings reveal that FOXA2 drives adeno-to-neuroendocrine lineage plasticity in prostate cancer and provides a potential pharmacological strategy for castration-resistant NEPC.


Assuntos
Carcinoma Neuroendócrino , Neoplasias da Próstata , Masculino , Humanos , Camundongos , Animais , Neoplasias da Próstata/patologia , Antagonistas de Androgênios/uso terapêutico , Linhagem Celular Tumoral , Regulação Neoplásica da Expressão Gênica , Carcinoma Neuroendócrino/metabolismo , Fator 3-beta Nuclear de Hepatócito/genética , Fator 3-beta Nuclear de Hepatócito/metabolismo
14.
Arch Microbiol ; 204(12): 700, 2022 Nov 11.
Artigo em Inglês | MEDLINE | ID: mdl-36367587

RESUMO

A Gram-stain-negative and short rod-shaped strain CBK1P-4T, isolated from surface-sterilized bark of Avicennia marina was investigated by a polyphasic taxonomic approach to resolve its taxonomic position. Strain CBK1P-4T grew at 10-30 °C (optimum, 25 °C), pH 5.0-9.0 (optimum, pH 5.5) and in the presence of 0-9% (w/v) NaCl (optimum, 1-2%). Phylogenetic analysis based on 16S rRNA gene sequences revealed that strain CBK1P-4T belonged to the genus Jiella and was most closely related to species of the genus Jiella (97.4-98.3%). The genome comparisons between strain CBK1P-4T and the closely related species indicated that average nucleotide identity and digital DNA-DNA hybridization values were below the recommended thresholds for assigning strains to the same species (95-96% and 70%, respectively). The cell wall peptidoglycan contained meso-diaminopimelic acid as diagnostic diamino acid. The principal fatty acids were C18:1ω7c and C19:0cycloω8c. The polar lipids were mainly comprised of phosphatidylcholine, diphosphatidylglycerol, phosphatidylglycerol, phosphatidylmonomethylethanolamine, phosphatidylethanolamine, two unidentified aminolipids, one unidentified phospholipid and one unidentified glycolipid. The dominant respiratory quinone was ubiquinone-10. The DNA G + C content of strain CBK1P-4T was 66.7%. Based on the phenotypic features, phylogenetic analysis as well as genome analysis, we conclude that strain CBK1P-4T represents a novel Jiella species, for which the name Jiella avicenniae sp. nov. is proposed. The type strain is CBK1P-4T (= CGMCC 1.18742T = JCM 34330T).


Assuntos
Alphaproteobacteria , Avicennia , Avicennia/genética , Avicennia/microbiologia , RNA Ribossômico 16S/genética , Filogenia , Casca de Planta/microbiologia , Técnicas de Tipagem Bacteriana , DNA Bacteriano/genética , Análise de Sequência de DNA , Alphaproteobacteria/genética , Fosfolipídeos/análise , Ácidos Graxos/análise , Ubiquinona/química
15.
Microb Pathog ; : 105876, 2022 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-36379370

RESUMO

Enterobacter hormaechei is an opportunistic pathogen and is found in a large variety of food including animal-derived food. In recent years, bacteria present a severe clinical challenge due to their increasing resistance to antibiotics. Bacteriophages have gained attention as a new antibacterial strategy. In this study, we isolated a novel E. hormaechei bacteriophage IME278 from hospital sewage in Beijing, China. Bacteriophage IME278 had a double-stranded linear DNA genome with 40,164 bp and 51.99% GC content. Whole-genome alignments showed IME278 shared 87% homology with other phages in the National Center for Biotechnology Information (NCBI) database. And phylogenetic analysis demonstrated that IME278 was highly similar to bacteriophages belonging to the genus Kayfunavirus, family Autographiviridae, indicating IME278 can be classified as a new member of the Autographiviridae family. Transmission electron microscopy revealed that IME278 had an icosahedral head 51.72 nm in diameter and a tail 151.28 nm in length. Bacteriophage IME278 was able to survive under high temperature (50 °C-70 °C) and its activity decreased significantly above 70 °C and almost completely inactivated at 80 °C. Bacteriophage IME278 could survive in a wide pH range (4.0-11.0) and it was stable in chloroform (up to 5%). The phage was sensitive to UV irradiation. Bacteriophage IME278 had a latent period of 40 min and reached a plateau stage at 150 min and its cleavage was approximately 8.21 × 108/3.66 × 108 = 2.24. The biocontrol potential of bacteriophage IME278 was evaluated in a model that artificially contaminated pork with E. hormaechei 529 and the result revealed that IME278 could effectively control bacterial contamination on pork. The in-depth analysis of the biological characteristics, whole genome sequencing, and bioinformatics of IME278 has laid the foundation for the biocontrol application and the treatment of bacteria using bacteriophages.

16.
J Ethnopharmacol ; : 115893, 2022 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-36368565

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Panax japonicus C. A. Meye (PJ) has unique effects on diseases by "qi" stagnation and blood stasis in ancient. Modern studies have shown that PJ can treat diabetic kidney disease (DKD) caused by deficiency and blood stasis. AIM OF THE STUDY: This study evaluated the potential effects of PJ on DKD, a microvascular complication, and investigated its possible mechanisms. MATERIALS AND METHODS: In this study, the chemical constituents of PJ were analyzed by HPLC. In vivo studies, we constructed a diabetic mice model by HDF combined with STZ, then administered PJ to diabetic mice for 6 weeks. Blood lipid, BUN, 24h urine protein, and renal tissue HE staining were detected to comprehensively evaluate the protective effect of PJ on DKD. Metabolomics investigated the metabolic pathways influenced by PJ in the treatment of DKD. Moreover, the potential targets and signal pathways were investigated using network pharmacology. Finally, molecular docking predicts affinity of active compounds and core targets, and western blotting was used to detect core target expression levels. RESULTS: In vivo study, PJ can reduce hyperlipidemia, serum BUN, and 24-hour urinary protein in diabetic mice, and protect the pathological changes in renal tissue. Metabolomics results showed that PJ had significant regulatory effect on unsaturated fatty acids, glycerophospholipid metabolism, and purine metabolism. Network pharmacology showed that MAPK1, MAPK8, Bcl-2, and Caspase 3 were the core targets in PJ against DKD. Molecular docking revealed that Bcl-2 and Caspase 3 have a strong affinity for Chikusetsusaponin Iva, Ginsenoside Rb1, and Ginsenoside Rg1. Moreover, when compared to the model group, the PJ group had higher levels of anti-apoptosis protein Bcl-2 and lower levels of pro-apoptosis protein Caspase 3. CONCLUSION: PJ can reduce blood lipids, regulate the biosynthesis of unsaturated fatty acids and purine metabolism, thereby alleviating the renal injury of diabetic mice. Moreover, it can regulate the Bcl-2/caspase 3 apoptosis signaling pathway to prevent the apoptosis of renal cells and protect the renal function of diabetic mice.

17.
Food Funct ; 13(22): 11896-11914, 2022 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-36321482

RESUMO

Luteolin is a natural flavonoid exhibiting multiple pharmacological activities. Renal anaemia is an important complication of chronic kidney disease (CKD). Whether luteolin can ameliorate renal interstitial fibrosis-induced renal anaemia remains unclear. We examined the therapeutic effects of luteolin in in vitro and in vivo models of renal interstitial fibrosis-induced renal anaemia. After high-throughput sequencing analysis of animal samples, we screened differentially expressed genes (DEGs) associated with luteolin-mediated improvements, performed GO and KEGG functional and pathway enrichment analyses, and validated the mechanism in vitro and in vivo. In vivo, haemoglobin and haematocrit were increased significantly, blood urea nitrogen and creatinine were decreased significantly, and the degree of renal interstitial injury and fibrosis was significantly alleviated in luteolin-treated mice compared with model mice. Erythropoietin (EPO) and hypoxia inducible factor 2A (HIF2A) levels were significantly increased and alpha smooth muscle actin (α-SMA), collagen I (COLI) and fibronectin (FN) levels were significantly decreased. Transcriptomic analysis revealed significant increases in sirtuin 1 (SIRT1) and forkhead box O3 (FOXO3) after luteolin intervention; these effects were validated in vitro and in vivo. Combined treatment with luteolin and the SIRT1 activator resveratrol or the SIRT1 inhibitor sirtinol and SIRT1-siRNA transfection revealed that blocking SIRT1 reduced FOXO3 expression and significantly decreased the benefits of luteolin, while resveratrol had the opposite effects. Molecular docking analysis indicated a stable conformation between luteolin and SIRT1. In vitro and in vivo systematic and transcriptomic studies showed that luteolin attenuates renal anaemia caused by renal fibrosis through the SIRT1/FOXO3 pathway.


Assuntos
Anemia , Nefropatias , Camundongos , Animais , Sirtuína 1/genética , Sirtuína 1/metabolismo , Luteolina/farmacologia , Resveratrol , Simulação de Acoplamento Molecular , Fibrose , Nefropatias/etiologia , Nefropatias/genética , Anemia/etiologia , Anemia/genética
18.
BMC Med ; 20(1): 424, 2022 11 03.
Artigo em Inglês | MEDLINE | ID: mdl-36329481

RESUMO

BACKGROUND: Gestational age (GA) is associated with later cognition and behavior. However, it is unclear how specific cognitive domains and brain structural development varies with the stepwise change of gestational duration. METHODS: This large-scale longitudinal cohort study analyzed 11,878 early adolescents' brain volume maps at 9-10 years (baseline) and 5685 at 11-12 years (a 2-year follow-up) from the Adolescent Brain Cognitive Development (ABCD) study. According to gestational age, adolescents were divided into five categorical groups: ≤ 33 weeks, 34-35 weeks, 36 weeks, 37-39 weeks, and ≥ 40 weeks. The NIH Toolbox was used to estimate neurocognitive performance, including crystallized and fluid intelligence, which was measured for 11,878 adolescents at baseline with crystallized intelligence and relevant subscales obtained at 2-year follow-up (with participant numbers ranging from 6185 to 6310 depending on the cognitive domain). An additional large population-based cohort of 618,070 middle adolescents at ninth-grade (15-16 years) from the Danish national register was utilized to validate the association between gestational age and academic achievements. A linear mixed model was used to examine the group differences between gestational age and neurocognitive performance, school achievements, and grey matter volume. A mediation analysis was performed to examine whether brain structural volumes mediated the association between GA and neurocognition, followed with a longitudinal analysis to track the changes. RESULTS: Significant group differences were found in all neurocognitive scores, school achievements, and twenty-five cortical regional volumes (P < 0.05, Bonferroni corrected). Specifically, lower gestational ages were associated with graded lower cognition and school achievements and with smaller brain volumes of the fronto-parieto-temporal, fusiform, cingulate, insula, postcentral, hippocampal, thalamic, and pallidal regions. These lower brain volumes mediated the association between gestational age and cognitive function (P = 1 × 10-8, ß = 0.017, 95% CI: 0.007-0.028). Longitudinal analysis showed that compared to full term adolescents, preterm adolescents still had smaller brain volumes and crystallized intelligence scores at 11-12 years. CONCLUSIONS: These results emphasize the relationships between gestational age at birth and adolescents' lower brain volume, and lower cognitive and educational performance, measured many years later when 9-10 and 11-12 years old. The study indicates the importance of early screening and close follow-up for neurocognitive and behavioral development for children and adolescents born with gestational ages that are even a little lower than full term.


Assuntos
Encéfalo , Recém-Nascido Prematuro , Recém-Nascido , Criança , Adolescente , Humanos , Lactente , Idade Gestacional , Estudos Longitudinais , Encéfalo/diagnóstico por imagem , Cognição , Imageamento por Ressonância Magnética/métodos
19.
Int J Mol Sci ; 23(21)2022 Oct 31.
Artigo em Inglês | MEDLINE | ID: mdl-36362064

RESUMO

Cardiac shock wave therapy (CSWT) is a novel therapeutic procedure for patients with angina that is refractory to conventional therapy. We investigated the potential mechanism and therapeutic efficacy of non-R-wave-triggered CSWT to attenuate myocardial dysfunction in a large animal model of hypertensive cardiomyopathy. Sustained elevated blood pressure (BP) was induced in adult pigs using a combination of angiotensin-II and deoxycorticosterone acetate (DOCA). Two sessions of non-R-wave-triggered CSWT were performed at 11 and 16 weeks. At 10 weeks, systolic and diastolic blood pressure, LV posterior wall thickness and intraventricular septum thickness significantly increased in both the hypertension and CSWT groups. At 20 weeks, +dP/dt and end-systolic pressure-volume relationship (ESPVR) decreased significantly in the hypertension group but not the CSWT group, as compared with week 10. A significant improvement in end-diastolic pressure-volume relationship (EDPVR) was observed in the CSWT group. The CSWT group exhibited significantly increased microvascular density and vascular endothelial growth factor (VEGF) expression in the myocardium. Cytokine array demonstrated that the CSWT group had significantly reduced inflammation compared with the hypertension group. Our results demonstrate that non-R-wave-triggered CSWT is safe and can attenuate LV systolic and diastolic dysfunction via enhancement of myocardial neovascularization and anti-inflammatory effect in a large animal model of hypertensive cardiomyopathy.


Assuntos
Cardiomiopatias , Tratamento por Ondas de Choque Extracorpóreas , Hipertensão , Animais , Suínos , Tratamento por Ondas de Choque Extracorpóreas/métodos , Fator A de Crescimento do Endotélio Vascular , Angina Pectoris , Cardiomiopatias/etiologia , Cardiomiopatias/terapia , Hipertensão/complicações , Hipertensão/terapia
20.
Molecules ; 27(21)2022 Nov 04.
Artigo em Inglês | MEDLINE | ID: mdl-36364400

RESUMO

More than one hundred cannabinoids have been found in cannabis. Δ9-Tetrahydrocannabinol (THC) is the recognized addictive constituent in cannabis; however, the mechanisms underlying THC-induced toxicity remain elusive. To better understand cannabis-induced toxicity, the present study compared the metabolic pathways of THC and its isomer cannabidiol (CBD) in human and mouse liver microsomes using the metabolomic approach. Thirty-two metabolites of THC were identified, including nine undescribed metabolites. Of note, two glutathione (GSH) and two cysteine (Cys) adducts were found in THC's metabolism. Molecular docking revealed that THC conjugates have a higher affinity with GSH and Cys than with the parent compound, THC. Human recombinant cytochrome P450 enzymes, and their corresponding chemical inhibitors, demonstrated that CYP3A4 and CYP1B1 were the primary enzymes responsible for the formation of THC-GSH and THC-Cys, thus enabling conjugation to occur. Collectively, this study systematically compared the metabolism of THC with the metabolism of CBD using the metabolomic approach, which thus highlights the critical role of metabolomics in identifying novel drug metabolites. Moreover, this study also facilitates mechanistic speculation in order to expand the knowledge of drug metabolism and safety.


Assuntos
Canabidiol , Cannabis , Alucinógenos , Humanos , Camundongos , Animais , Canabidiol/farmacologia , Dronabinol/farmacologia , Simulação de Acoplamento Molecular , Cannabis/química , Psicotrópicos , Microssomos Hepáticos , Metabolômica
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