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1.
BMC Public Health ; 24(1): 1283, 2024 May 10.
Artigo em Inglês | MEDLINE | ID: mdl-38730396

RESUMO

BACKGROUND: Although prior studies have demonstrated that children with high levels of fundamental movement skill (FMS) are more active throughout the day, little is known about children's FMS and their physical activity (PA) during different segments of the school day (e.g., recess, lunch break, and physical education). The present study focused on FMS and moderate-to-vigorous PA (MVPA) during school day and identifies the association between children's FMS and MVPA during different segments of the school day in China. METHODS: A total of 322 children (boys n = 163, girls n = 159; Mage = 8.12, SD = 1.22 years) from four elementary schools involved in this study. Children's FMS and MVPA were measured using the Test of Gross Motor Development-2nd edition (TGMD-2) and hip-mounted accelerometers. Data such as height, weight, and socio-economic status (SES) were also obtained. Multilevel mixed regression models were used to examine the cross-sectional associations between FMS and MVPA. Models were adjusted for gender, age, standardized body mass index, and SES. RESULTS: Children engaged in 32.19 min of MVPA during the whole school day. Boys were more active than girls and had higher object-control skills competency. Locomotor skills were positively associated with children's long recess (B = 1.063) and short recess time (B = 1.502) MVPA. Object-control skills were positively correlated with children's MVPA time during long recess (B = 1.244) and physical education (PE) lessons (B = 1.171). CONCLUSION: The findings highlight the importance of developing both locomotor and object-control skills in elementary schools to lead more MVPA engagement during different segments of the school day.


Assuntos
Destreza Motora , Instituições Acadêmicas , Humanos , Feminino , Masculino , Criança , China , Destreza Motora/fisiologia , Estudos Transversais , Exercício Físico , Acelerometria , Atividade Motora/fisiologia , Educação Física e Treinamento
2.
BMC Public Health ; 24(1): 1388, 2024 May 23.
Artigo em Inglês | MEDLINE | ID: mdl-38783202

RESUMO

BACKGROUND: Previous research has suggested that engaging in regular physical activity (PA) can help to reduce symptoms of depression and anxiety in university students. However, there is a lack of evidence regarding the impact of reducing sedentary behavior (SB) and increasing light-intensity PA (LPA) on these symptoms. This study aims to address this gap by using isotemporal substitution (IS) models to explore how substituting SB with LPA or moderate-to-vigorous PA (MVPA) affects depression and anxiety symptoms among university students. METHODS: The study recruited 318 university students with a mean age of 21.13 years. Accelerometers were used to objectively measure the time spent on SB, LPA, and MVPA, while depression and anxiety symptoms were assessed using the Center for Epidemiologic Studies Depression Scale (CES-D) and the Self-rating Anxiety Scale (SAS). IS models using multivariable linear regression were employed to estimate the associations between different behaviors and depression and anxiety symptoms when 30 min of one behavior was substituted with another. RESULTS: In the single-activity model, less SB (ß = 0.321, 95% CI: 0.089, 1.297) and more MVPA (ß = -0.142, 95% CI: -1.496, - 0.071) were found to be significantly and negatively associated with depression scores, while less SB (ß = 0.343, 95% CI: 0.057, 1.014), LPA (ß = 0.132, 95% CI: 0.049, 1.023), and more MVPA (ß = -0.077, 95% CI: -1.446, - 0.052) were significantly and negatively correlated with anxiety scores. The IS analysis revealed that substituting 30 min of SB with LPA (ß = -0.202, 95% CI: -1.371, - 0.146) or MVPA (ß = -0.308, 95% CI: -0.970, - 0.073) was associated with improvements in depressive symptoms. Substituting 30 min of SB with MVPA (ß = -0.147, 95% CI: -1.863, - 0.034) was associated with reduced anxiety symptoms. CONCLUSION: Replacing 30 min of SB with MVPA may alleviate depression and anxiety symptoms in university students. Further research is needed to explore the long-term effects of PA interventions on the mental health disorders of this population.


Assuntos
Acelerometria , Ansiedade , Depressão , Exercício Físico , Comportamento Sedentário , Estudantes , Humanos , Estudantes/psicologia , Estudantes/estatística & dados numéricos , Masculino , Feminino , Exercício Físico/psicologia , Universidades , Depressão/epidemiologia , Depressão/psicologia , Adulto Jovem , Ansiedade/epidemiologia , China/epidemiologia , Adolescente
3.
Cancer Res ; 2024 May 08.
Artigo em Inglês | MEDLINE | ID: mdl-38718297

RESUMO

Hepatocellular carcinoma (HCC) is an aggressive disease that occurs predominantly in men. Estrogen elicits protective effects against HCC development. Elucidation of the estrogen-regulated biological processes that suppress HCC could lead to improved prevention and treatment strategies. Here, we performed transcriptomic analyses on mouse and human liver cancer and identified LCAT as the most highly estrogen-upregulated gene and a biomarker of favorable prognosis. LCAT upregulation inhibited HCC in vitro and in vivo and mediated estrogen-induced suppression of HCC in an ESR1-dependent manner. LCAT facilitated high-density lipoprotein cholesterol (HDL-C) production and uptake via the LDLR and SCARB1 pathways. Consistently, high HDL-C levels corresponded to a favorable prognosis in HCC patients. The enhanced HDL-C absorption induced by LCAT impaired SREBP2 maturation, which ultimately suppressed cholesterol biosynthesis and dampened HCC cell proliferation. HDL-C alone inhibited HCC growth comparably to the cholesterol-lowering drug lovastatin, and SREBF2 overexpression abolished the inhibitory activity of LCAT. Clinical observations and cross-analyses of multiple databases confirmed the correlation of elevated LCAT and HDL-C levels to reduced cholesterol synthesis and improved HCC patient prognosis. Furthermore, LCAT deficiency mimicked whereas LCAT overexpression abrogated the tumor growth promoting effects of ovariectomy in HCC-bearing female mice. Most importantly, HDL-C and LCAT delayed the development of subcutaneous tumors in nude mice, and HDL-C synergized with lenvatinib to eradicate orthotopic liver tumors. Collectively, this study reveals that estrogen upregulates LCAT to maintain cholesterol homeostasis and dampen hepatocarcinogenesis. LCAT and HDL-C represent potential prognostic and therapeutic biomarkers for targeting cholesterol homeostasis as a strategy for treating HCC.

4.
Front Psychol ; 15: 1225011, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38655219

RESUMO

Studies have shown that product scarcity appeals affect consumers' perceived scarcity, willingness to pay, and other responses, and that scarcity appeal has the potential to cause consumers to pay higher attention to the product. However, there is a lack of research on the psychological responses of consumers to scarcity appeal from the perspective of perceived green washing. In this paper, three experiments are conducted to demonstrate the impact of product scarcity appeals on consumers' purchase intentions. The research shows that when green products use product scarcity appeals as a strategy, consumers' purchase intentions are affected, but consumers' information processing about the product is the most important determinant. Perceived green washing mediates the negative effect of product scarcity appeals on green product purchase intentions. And impression management motives moderate the negative effect of product scarcity appeals on green product purchase intentions. The findings of the study not only help companies to effectively adopt the right advertising strategies to improve their marketing effectiveness, but also help them to explore the market for green products.

5.
Foods ; 13(6)2024 Mar 14.
Artigo em Inglês | MEDLINE | ID: mdl-38540864

RESUMO

Previous studies have demonstrated that L. delbrueckii plays beneficial roles in modulating the gut microbiota, enhancing the intestinal barrier, and promoting animal growth. Postbiotics have a similar or even superior effect in protecting intestinal health compared to probiotics due to their excellent stability, extended shelf life, and safety. However, the protective effects and underlying mechanism of postbiotics from L. delbrueckii in intestinal inflammation remain unclear. In this study, we demonstrated the beneficial impact of postbiotics from L. delbrueckii on intestinal health by establishing a S. Typhimurium-induced intestinal inflammation model in mice, which included inactivated bacteria and supernatant. The results revealed that the probiotics and postbiotics from L. delbrueckii increased the survival rate and body weight of S. Typhimurium-induced mice, increased the level of IL-10, and decreased the levels of TNF-α and IL-6, thereby alleviating intestinal inflammation. Meanwhile, treatment with postbiotics decreased the levels of D-LA, DAO, and LPS and promoted the expression of Occludin, ZO-1, and Claudin-1 in the serum and jejunum, suggesting an improvement in intestinal barrier function by postbiotics. Additionally, the postbiotics modulated gut microbial diversity, increased the ratio of Firmicutes and Bacteroidetes, and restored the abundance of Muribaculaceae, Lachnospiraceae_NK4a136_groups, and Alloprevotella in S. Typhimurium-infected mice. Moreover, postbiotics from L. delbrueckii promoted the expansion of intestinal stem cells (ISCs) and increased the numbers of Paneth and Goblet cells. Taken together, these data revealed the beneficial role of postbiotics from L. delbrueckii in protecting against intestinal inflammation by promoting the expansion of ISCs.

7.
World J Gastroenterol ; 30(1): 91-107, 2024 Jan 07.
Artigo em Inglês | MEDLINE | ID: mdl-38293320

RESUMO

BACKGROUND: The pathogenicity of Helicobacter pylori is dependent on factors including the environment and the host. Although selenium is closely related to pathogenicity as an environmental factor, the specific correlation between them remains unclear. AIM: To investigate how selenium acts on virulence factors and reduces their toxicity. METHODS: H. pylori strains were induced by sodium selenite. The expression of cytotoxin-associated protein A (CagA) and vacuolating cytotoxin gene A (VacA) was determined by quantitative PCR and Western blotting. Transcriptomics was used to analyze CagA, CagM, CagE, Cag1, Cag3, and CagT. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction, and H. pylori colonization, inflammatory reactions, and the cell adhesion ability of H. pylori were assessed. RESULTS: CagA and VacA expression was upregulated at first and then downregulated in the H. pylori strains after sodium selenite treatment. Their expression was significantly and steadily downregulated after the 5th cycle (10 d). Transcriptome analysis revealed that sodium selenite altered the levels affect H. pylori virulence factors such as CagA, CagM, CagE, Cag1, Cag3, and CagT. Of these factors, CagM and CagE expression was continuously downregulated and further downregulated after 2 h of induction with sodium selenite. Moreover, CagT expression was upregulated before the 3rd cycle (6 d) and significantly downregulated after the 5th cycle. Cag1 and Cag3 expression was upregulated and downregulated, respectively, but no significant change was observed by the 5th cycle. C57BL/6A mice were infected with the attenuated strains subjected to sodium selenite induction. The extent of H. pylori colonization in the stomach increased; however, sodium selenite also induced a mild inflammatory reaction in the gastric mucosa of H. pylori-infected mice, and the cell adhesion ability of H. pylori was significantly weakened. CONCLUSION: These results demonstrate that H. pylori displayed virulence attenuation after the 10th d of sodium selenite treatment. Sodium selenite is a low toxicity compound with strong stability that can reduce the cell adhesion ability of H. pylori, thus mitigating the inflammatory damage to the gastric mucosa.


Assuntos
Infecções por Helicobacter , Helicobacter pylori , Selênio , Animais , Camundongos , Antígenos de Bactérias/genética , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Fatores de Virulência/genética , Fatores de Virulência/metabolismo , Selenito de Sódio/farmacologia , Camundongos Endogâmicos C57BL , Citotoxinas , Infecções por Helicobacter/metabolismo
8.
Respiration ; 103(2): 95-99, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38272003

RESUMO

INTRODUCTION: Fibrosing mediastinitis is a benign but fatal disorder characterized by the proliferation of fibrous tissue in the mediastinum, causing encasement of mediastinal organs and extrinsic compression of adjacent bronchovascular structures. FM-associated pulmonary hypertension (FM-PH) is a serious complication of FM, resulting from the external compression of lung vessels. Pathologic assessment is important for etiologic diagnosis and effective treatment of this disease. CASE PRESENTATION: A 59-year-old male patient presented at our hospital and was diagnosed with FM-PH. He declined surgical biopsy that is the reference standard for pathologic assessment, in consideration of the potential risks. Therefore, an endobronchial ultrasound examination was performed, which identified the subcarinal lesion. Under ultrasound guidance, four needle aspirations were carried out, followed by one cryobiopsy. Histopathological examination of transbronchial needle aspiration specimens was inconclusive, while samples from cryobiopsy suggested a diagnosis of idiopathic FM. Further immunophenotyping demonstrated the infiltration of lymphocytes, macrophages, and FOXP3-positive cells in FM-PH. CONCLUSION: Mediastinal cryobiopsy might be a novel and safe option for FM-PH patients who are unwilling or unsuitable for surgical procedure.


Assuntos
Hipertensão Pulmonar , Mediastinite , Hipertensão Arterial Pulmonar , Esclerose , Masculino , Humanos , Pessoa de Meia-Idade , Mediastino , Hipertensão Pulmonar/etiologia , Hipertensão Pulmonar/complicações , Mediastinite/complicações , Mediastinite/diagnóstico , Hipertensão Arterial Pulmonar/patologia
9.
Food Funct ; 15(3): 1237-1249, 2024 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-38227487

RESUMO

Gut hormones are produced by enteroendocrine cells (EECs) found along the intestinal epithelium, and these cells play a crucial role in regulating intestinal function, nutrient absorption and food intake. A hydrolyzed casein diet has been reported to promote the secretion of gut hormones through the regulation of EEC development, but the underlying mechanism remains unclear. Therefore, this study was conducted to investigate whether the hydrolyzed casein diet can regulate EEC differentiation by employing mouse and organoid models. Mice were fed diets containing either casein (casein group) or hydrolyzed casein (hydrolyzed casein group) as the sole protein source. The hydrolyzed casein diet upregulated the expression of transcription factors, induced EEC differentiation, increased fasting serum ghrelin concentrations and promoted gastrointestinal (GI) motility in the duodenum compared to the casein diet. Interestingly, these differences could be abolished when there is addition of antibiotics to the drinking water, suggesting a significant role of gut microbiota in the hydrolyzed casein-mediated EEC function. Further investigation showed that the hydrolyzed casein diet led to reduced microbial diversity, especially the abundance of Akkermansia muciniphila (A. muciniphila) on the duodenal mucosa. In contrast, gavage with A. muciniphila impaired EEC differentiation through attenuated neurog3 transcription factor (Ngn3) expression, mediated through the promotion of Notch signaling. Moreover, pasteurized A. muciniphila showed similar effects to enter organoids in vitro. Overall, we found that a hydrolyzed casein diet reduced the abundance of A. muciniphila and promoted Ngn3 controlling EEC differentiation and this pathway is associated with increased GI motility in mice. The findings provide new insights into the role of hydrolyzed casein in gut transit and guidelines for using hydrolyzed casein in safe formula milk.


Assuntos
Caseínas , Hormônios Gastrointestinais , Camundongos , Animais , Caseínas/metabolismo , Diferenciação Celular , Células Enteroendócrinas , Dieta , Fatores de Transcrição/metabolismo , Hormônios Gastrointestinais/metabolismo , Motilidade Gastrointestinal
10.
PLoS Biol ; 21(12): e3002413, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38048357

RESUMO

Brown adipose tissue (BAT) dissipates energy as heat, contributing to temperature control, energy expenditure, and systemic homeostasis. In adult humans, BAT mainly exists in supraclavicular areas and its prevalence is associated with cardiometabolic health. However, the developmental origin of supraclavicular BAT remains unknown. Here, using genetic cell marking in mice, we demonstrate that supraclavicular brown adipocytes do not develop from the Pax3+/Myf5+ epaxial dermomyotome that gives rise to interscapular BAT (iBAT). Instead, the Tbx1+ lineage that specifies the pharyngeal mesoderm marks the majority of supraclavicular brown adipocytes. Tbx1Cre-mediated ablation of peroxisome proliferator-activated receptor gamma (PPARγ) or PR/SET Domain 16 (PRDM16), components of the transcriptional complex for brown fat determination, leads to supraclavicular BAT paucity or dysfunction, thus rendering mice more sensitive to cold exposure. Moreover, human deep neck BAT expresses higher levels of the TBX1 gene than subcutaneous neck white adipocytes. Taken together, our observations reveal location-specific developmental origins of BAT depots and call attention to Tbx1+ lineage cells when investigating human relevant supraclavicular BAT.


Assuntos
Adipócitos Marrons , Tecido Adiposo Branco , Adulto , Humanos , Camundongos , Animais , Fatores de Transcrição , Tecido Adiposo Marrom/fisiologia , Adipócitos Brancos , Proteínas com Domínio T/genética
11.
J Adv Res ; 2023 Dec 19.
Artigo em Inglês | MEDLINE | ID: mdl-38128723

RESUMO

INTRODUCTION: Rumen epithelial parakeratosis, a common disease in ruminants caused by abnormalities in the ruminal stratified squamous epithelial keratinization process, negatively impacts ruminant health and performance. However, we still lack a comprehensive perception of the underlying mechanisms and the predisposing factors for this disorder. OBJECTIVES: Here, we investigated rumen epithelial cell heterogeneity, differentiation trajectories, and cornification to clarify the rumen epithelial keratinization process and discern the key ruminal metabolites contributing to rumen epithelial parakeratosis. METHODS: Twenty-four 14-day-old lambs were divided into three groups, including only milk feeding, milk plus alfalfa hay feeding, and milk plus corn-soybean concentrate starter feeding. At 42 days of age, the lambs were slaughtered, and rumen tissues were collected for single-cell RNA-sequencing (scRNA-seq), immunofluorescence, and quantitative real-time PCR (qRT-PCR) analyses. Ruminal fluid samples were collected for metabolomic analyses. Rumen epithelial organoid was used to verify the key ruminal metabolites contributing to parakeratosis. RESULTS: As expected, we observed that concentrate starter introduction resulted in rumen epithelial parakeratosis. Moreover, scRNA-seq analysis revealed a developmental impediment in the transition from differentiated keratinocytes to terminally differentiated keratinocytes (TDK) in lambs with concentrate starter introduction. Immunofluorescence and qRT-PCR analyses further verified the location and expression of marker genes of TDK. Metabolomic analysis showed a robust positive correlation between ruminal butyrate levels and rumen epithelial keratinization. More importantly, we successfully established a rumen organoid model capable of facilitating the study of the keratinization process in the rumen epithelia and further confirmed that high dose butyrate indeed contributed to rumen epithelial parakeratosis. CONCLUSION: Collectively, concentrate starter introduction induces ruminal epithelial parakeratosis by blocking keratinocyte differentiation with excessive ruminal butyrate accumulation in a neonatal lamb model. These findings enhance our understanding of rumen epithelial keratinization and provide valuable insights for addressing rumen epithelial parakeratosis using early nutritional intervention strategies.

12.
Commun Biol ; 6(1): 1202, 2023 11 25.
Artigo em Inglês | MEDLINE | ID: mdl-38007598

RESUMO

Adding adipose cells to cell-cultured meat can provide a distinctive aroma and juicy texture similar to real meat. However, a significant challenge still exists in obtaining seed cells that can be propagated for long periods, maintain their adipogenic potential, and reduce production costs. In this study, we present a cell strain derived from immortalized porcine preadipocytes that can be subculture for over 40 passages without losing differentiation capacity. This cell strain can be differentiated within 3D bioscaffolds to generate cell-cultured fat using fewer chemicals and less serum. Additionally, it can be expanded and differentiated on microcarriers with upscaled culture to reduce costs and labor. Moreover, it can co-differentiate with muscle precursor cells, producing a pattern similar to real meat. Therefore, our cell strain provides an exceptional model for studying and producing cell-cultured fat.


Assuntos
Adipócitos , Adipogenia , Suínos , Animais , Células Cultivadas , Diferenciação Celular
13.
J Biol Chem ; 299(12): 105428, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37926288

RESUMO

Sufficient activation of interferon signaling is critical for the host to fight against invading viruses, in which post-translational modifications have been demonstrated to play a pivotal role. Here, we demonstrate that the human KRAB-zinc finger protein ZNF268a is essential for virus-induced interferon signaling. We find that cytoplasmic ZNF268a is constantly degraded by lysosome and thus remains low expressed in resting cell cytoplasm. Upon viral infection, TBK1 interacts with cytosolic ZNF268a to catalyze the phosphorylation of Serine 178 of ZNF268a, which prevents the degradation of ZNF268a, resulting in the stabilization and accumulation of ZNF268a in the cytoplasm. Furthermore, we provide evidence that stabilized ZNF268a recruits the lysine methyltransferase SETD4 to TBK1 to induce the mono-methylation of TBK1 on lysine 607, which is critical for the assembly of the TBK1 signaling complex. Notably, ZNF268 S178 is conserved among higher primates but absent in rodents. Meanwhile, rodent TBK1 607th aa happens to be replaced by arginine, possibly indicating a species-specific role of ZNF268a in regulating TBK1 during evolution. These findings reveal novel functions of ZNF268a and SETD4 in regulating antiviral interferon signaling.


Assuntos
Interferon Tipo I , Proteínas Serina-Treonina Quinases , Animais , Humanos , Imunidade Inata , Fator Regulador 3 de Interferon/metabolismo , Interferon Tipo I/metabolismo , Interferons/metabolismo , Lisina/metabolismo , Fosforilação , Proteínas Serina-Treonina Quinases/genética , Proteínas Serina-Treonina Quinases/metabolismo , Transdução de Sinais , Linhagem Celular , Proteínas Repressoras/metabolismo , Metiltransferases/metabolismo
14.
J Affect Disord ; 2023 Oct 11.
Artigo em Inglês | MEDLINE | ID: mdl-37832731

RESUMO

OBJECTIVES: To evaluate the effect of different exercise interventions on depressive symptoms in children and adolescents. METHODS: Randomized controlled trials (RCT) published until May 2023 were screened in four databases. The Cochrane collaboration tool was used to assess the risk of bias for quality evaluation. Stata 16.0 software was used for both a pairwise meta-analysis and a series of frequentist network meta-analyses (NMA). RESULTS: A total of 35 RCTs and 5393 participants were included. Aerobic exercise had the most significant effect on depressive symptoms (66.2 %), followed by group training (62.5 %), resistance exercise (59.0 %), and aerobic combined with resistance exercise (57.9 %). Furthermore, children and adolescents younger than 15 years showed significant improvement in depressive symptoms (SMD = -0.41, 95 % CI (-0.63, -0.19), P < 0.01). The study also found a significant improvement in depression among healthy, obesity, and depressed populations (SMD = -0.25, 95 % CI (-0.41, -0.08), P < 0.01); SMD = -0.15, 95 % CI (-0.31, -0.00), P < 0.01; SMD = -0.75, 95 % CI (-1.32, -0.19), P < 0.01). Additionally, 30 min of exercise had a significant effect (SMD = -0.14, 95 % CI (-0,81, -0.01), P < 0.01), and 40-50 min of exercise had the best effect (SMD = -0.17, 95 % CI (-0,33, -0.02), P < 0.01). Lastly, exercise frequency of three times per week was significant in children and adolescents (SMD = -0.42, 95 % CI (-0,66, -0.18), P < 0.01). CONCLUSION: Exercise significantly improves depressive symptoms in children and adolescents, with aerobic exercise having the most significant effect. A 12-week, three-times-a-week, 40-50-min exercise intervention was found to be more effective in younger children and adolescents.

15.
Clin Transl Med ; 13(10): e1443, 2023 10.
Artigo em Inglês | MEDLINE | ID: mdl-37837399

RESUMO

BACKGROUND: Enhanced de novo lipogenesis is essential for hepatocellular carcinoma (HCC). Abnormally high cullin-associated and neddylation-dissociated 1 (CAND1) expression is associated with poor clinical prognosis in HCC. The SKP1-Cullin-1-F-box (SCF) complex consists of the SKP1, Cullin-1 and F-box proteins (FBPs) and performs multiple functions including adipogenesis. SCF complex was modulated by CAND1, but Whether and how the CAND1 promotes HCC by regulating SCF complex and lipogenesis are unknown. METHODS: HCC samples were used to analyze the correlations between CAND1 expression and clinicopathological characteristics such as survival and prognosis. The in vitro functions of CAND1, FBXO11 and heterogeneous nuclear ribonucleoprotein A2/B1 (hnRNPA2B1) were measured by cell proliferation, colony formation and migration assays. The in vivo functions were tested in multiple mouse liver cancer models including patient-derived xenograft (PDX), cell line-derived xenograft and AKT/NRASV12-induced primary liver cancer models. Injections of adeno-associated virus targeting CAND1 (AAV-shCAND1) were performed to evaluate the therapeutic efficacy of targeting CAND1. RNA-Seq and lipidomic assays followed by serial biochemical experiments including mass spectrometry, immunoprecipitation and GST pull-down were performed to dissect the underlying mechanisms. RESULTS: CAND1 promoted the expression of lipid synthesis genes by disrupting SCF complex assembly and lipid accumulation. Furthermore, we identified hnRNPA2B1 as a novel F-box protein 11 (FBXO11)-binding partner. FBXO11 directly bound to hnRNPA2B1 and promoted hnRNPA2B1 ubiquitination and subsequent degradation. Our evaluations of the therapeutic efficacy of AAV-shCAND1 injections confirmed that targeting the CAND1-SCFFBXO11 -hnRNPA2B1A signalling axis was therapeutically effective. CAND1 downregulation significantly reduced the tumour burden in a primary mouse liver cancer model and a PDX model. CONCLUSIONS: Our results highlight that CAND1 is associated with poor prognosis in HCC and regulates lipid metabolic reprogramming by dissociating the SCF complex. Targeting the CAND1-SCFFBXO11 -hnRNPA2B1 axis may be a novel strategy for HCC treatment.


Assuntos
Carcinoma Hepatocelular , Proteínas F-Box , Neoplasias Hepáticas , Animais , Camundongos , Humanos , Proteínas Culina/química , Proteínas Culina/genética , Proteínas Culina/metabolismo , Carcinoma Hepatocelular/genética , Proteínas Ligases SKP Culina F-Box/genética , Proteínas Ligases SKP Culina F-Box/metabolismo , Metabolismo dos Lipídeos/genética , Neoplasias Hepáticas/genética , Ubiquitinação/genética , Ribonucleoproteínas Nucleares Heterogêneas/genética , Ribonucleoproteínas Nucleares Heterogêneas/metabolismo , Lipídeos , Proteínas Quinases Associadas a Fase S/genética , Proteínas Quinases Associadas a Fase S/metabolismo , Proteína-Arginina N-Metiltransferases/metabolismo , Proteínas F-Box/metabolismo
16.
BMC Public Health ; 23(1): 1918, 2023 10 04.
Artigo em Inglês | MEDLINE | ID: mdl-37794338

RESUMO

OBJECTIVES: To evaluate the effect of different exercise interventions on depressive symptoms in children and adolescents. METHODS: Randomized controlled trials (RCT) published until May 2023 were screened in four databases. The Cochrane collaboration tool was used to assess the risk of bias for quality evaluation. Stata 16.0 software was used for both a pairwise meta-analysis and a series of frequentist network meta-analyses (NMA). RESULTS: A total of 35 RCTs and 5393 participants were included. Aerobic exercise had the most significant effect on depressive symptoms (66.2%), followed by group training (62.5%), resistance exercise (59.0%), and aerobic combined with resistance exercise (57.9%). Furthermore, children and adolescents younger than 15 years showed significant improvement in depressive symptoms (SMD=-0.41, 95% CI (-0.63, -0.19), P < 0.01). The study also found a significant improvement in depression among healthy, obesity, and depressed populations (SMD=-0.25, 95% CI (-0.41, -0.08), P < 0.01); SMD=-0.15, 95% CI (-0.31, -0.00), P < 0.01; SMD=-0.75, 95% CI (-1.32, -0.19), P < 0.01). Additionally, 30 min of exercise had a significant effect (SMD=-0.14, 95% CI (-0,81, -0.01), P < 0.01), and 40-50 min of exercise had the best effect (SMD=-0.17, 95% CI (-0,33, -0.02), P < 0.01). Lastly, exercise frequency of three times per week was significant in children and adolescents (SMD=-0.42, 95% CI (-0,66, -0.18), P < 0.01). CONCLUSION: Exercise significantly improves depressive symptoms in children and adolescents, with aerobic exercise having the most significant effect. A 12-week, three-times-a-week, 40-50-minute exercise intervention was found to be more effective in younger children and adolescents.


Assuntos
Depressão , Exercício Físico , Humanos , Criança , Adolescente , Metanálise em Rede , Depressão/prevenção & controle , Serviços de Saúde , Terapia por Exercício
17.
World J Gastroenterol ; 29(31): 4797-4808, 2023 Aug 21.
Artigo em Inglês | MEDLINE | ID: mdl-37664154

RESUMO

BACKGROUND: The relationship between copeptin and the severity of circulatory dysfunction and systemic stress response in patients with chronic liver disease (CLD) has been established. Nevertheless, the potential of serum copeptin levels to predict the prognosis of CLD patients remains unclear. AIM: To conduct a systematic review and meta-analysis to investigate the correlation between serum copeptin and transplant-free survival (TFS) in this population. METHODS: To achieve the objective of the meta-analysis, PubMed, Embase, the Cochrane Library, and the Web of Science were searched to identify observational studies with longitudinal follow-up. The Cochrane Q test was utilized to assess between-study heterogeneity, and the I2 statistic was estimated. Random-effects models were employed to combine the outcomes, taking into account the potential influence of heterogeneity. RESULTS: Ten datasets including 3133 patients were involved. The follow-up durations were 1 to 48 mo (mean: 12.5 mo). Overall, it was shown that a high level of serum copeptin was associated with a poor TFS [risk ratio (RR): 1.82, 95% confidence interval: 1.52-2.19, P < 0.001; I2 = 0%]. In addition, sensitivity analysis by omitting one dataset at a time showed consistent results (RR: 1.73-2.00, P < 0.05). Finally, subgroup analyses according to study country, study design, patient diagnosis, cutoff of copeptin, follow-up duration, and study quality score also showed similar results (P for subgroup difference all > 0.05). CONCLUSION: Patients with CLD who have high serum copeptin concentrations may be associated with a poor clinical prognosis.


Assuntos
Glicopeptídeos , Hepatopatias , Humanos , Prognóstico , Sobrevivência de Enxerto , Hepatopatias/diagnóstico
18.
BMC Pediatr ; 23(1): 411, 2023 08 22.
Artigo em Inglês | MEDLINE | ID: mdl-37608261

RESUMO

BACKGROUND: Anxiety, depression, and stress are the most common mental health problems in childhood. Exercise interventions in childhood help to promote mental health. OBJECTIVE: To investigate the relationship between exercise interventions and improvement of negative emotions such as anxiety, depression, and stress in children (5-12 years). METHODS: Articles were searched in five electronic databases from their inception to January 2023. The meta-analysis was performed using Stata 16.0. RESULTS: Twenty-three intervention studies included 6830 children. 1) The exercise intervention group was significantly better than the control group in improving negative emotions (Standard Mean Difference SMD=-0.25, 95% Confidence Intervals CI: -0.34 to -0.15, P < 0.01). Exercise intervention improved different kinds of negative emotions: anxiety (SMD=-0.19, 95% CI: -0.33 to -0.06, P < 0.01), depression (SMD=-0.22, 95% CI: -0.43 to -0.01, P < 0.01), and stress (SMD=-0.33, 95% CI: -0.53 to -0.14, P < 0.01); it was most effective at relieving problematic stress. Exercise interventions lasting 20-45 min were most effective in improving children's negative emotions (SMD=-0.38, 95% CI: -0.56 to -0.20, P < 0.01). An exercise intervention period of 10 weeks was more effective in improving children's negative mood (SMD=-0.26, 95% CI: -0.34 to -0.17, P = 0.274). CONCLUSION: Exercise interventions may improve negative emotions such as anxiety, depression, and stress in children. These findings may have clinical implications for children with negative affect. However, these studies showed a large heterogeneity, and the results should be interpreted with caution. Future studies should report the variability of exercise interventions by gender, age group, and type, intensity, and place of exercise.


Assuntos
Ansiedade , Exercício Físico , Criança , Humanos , Ansiedade/prevenção & controle , Bases de Dados Factuais , Terapia por Exercício , Saúde Mental , Pré-Escolar
19.
Front Physiol ; 14: 1193223, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37497435

RESUMO

Introduction: Childhood and adolescent overweight and obesity are global public health issues. Previous studies on exercise and overweight and obese children have produced inconsistent findings and lacked comparisons between different exercise modalities and intensities. Therefore, a network meta-analysis is necessary to provide evidence-based intervention programs. This study aims to identify the effects of different exercise modalities and intensities on changes in body composition in overweight and obese children and adolescents. Methods: A search for randomized controlled trials was conducted on Web of Science, PubMed, Scopus, and Embase involving exercise interventions aimed at improving body composition (body fat percentage, BMI, fat mass, fat-free mass, body weight) in overweight and obese children and adolescents. A random effects network meta-analysis was performed using STATA 14.0 software within a frequentist framework. The literature quality was assessed using the Cochrane Risk of Bias Tool 2.0. Results: Thirty-two papers involving 1,452 participants were included. There were six types of intervention involved in the study, including moderate intensity aerobic exercise, high-intensity aerobic exercise, moderate intensity resistance exercise, high-intensity resistance exercise, moderate intensity combined exercise, and high-intensity combined exercise. The network meta-analysis results revealed that high-intensity combined exercise was the best exercise mode for improving BMI [mean difference in kg/m2 = -1.65, 95% CI (-3.27, -0.02)] and reducing fat mass [mean difference in kg = -2.87, 95% CI (-4.84, -0.91)]. Moderate intensity combined exercise was the best mode for weight loss [mean difference in kg = -4.58, 95% CI (-5.94, -3.22)] and improvement in body fat percentage [mean difference in% = -2.52, 95% CI (-3.83, -1.20)]. High-intensity resistance exercise had the optimal effect in increasing fat-free mass [mean difference in kg = 1.10, 95% CI (0.22, 1.99)]. Conclusion: In conclusion, the study found that combined exercise, whether moderate or high intensity, was more effective than any other exercise modality in improving body fat percentage and BMI, reducing fat mass and weight. Resistance exercise was the most effective in increasing fat-free mass.

20.
Adv Mater ; 35(32): e2301206, 2023 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-37282350

RESUMO

In nanostructure assemblies, the superposition of current paths forms microscopic electric circuits, and different circuit networks produce varying results, particularly when utilized as transistor channels for computing applications. However, the intricate nature of assembly networks and the winding paths of commensurate currents hinder standard circuit modeling. Inspired by the quantum collapse of superposition states for information decoding in quantum circuits, the implementation of analogous current path collapse to facilitate the detection of microscopic circuits by modifying their network topology is explored. Here, the superposition and collapse of current paths in gate-all-around polysilicon nanosheet arrays are demonstrated to enrich the computational resources within transistors by engineering the channel length and quantity. Switching the ferroelectric polarization of Hf0.5 Zr0.5 O2 gate dielectric, which drives these transistors out-of-equilibrium, decodes the output polymorphism through circuit topological modifications. Furthermore, a protocol for the single-electron readout of ferroelectric polarization is presented with tailoring the channel coherence. The introduction of lateral path superposition results into intriguing metal-to-insulator transitions due to transient behavior of ferroelectric switching. This ability to adjust the current networks within transistors and their interaction with ferroelectric polarization in polycrystalline nanostructures lays the groundwork for generating diverse current characteristics as potential physical databases for optimization-based computing.

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