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1.
Eur J Immunol ; : e2350655, 2024 Jul 07.
Artigo em Inglês | MEDLINE | ID: mdl-38973083

RESUMO

Sepsis arises from an uncontrolled inflammatory response triggered by infection or stress, accompanied by alteration in cellular energy metabolism, and a strong correlation exists between these factors. Alpha-ketoglutarate (α-KG), an intermediate product of the TCA cycle, has the potential to modulate the inflammatory response and is considered a crucial link between energy metabolism and inflammation. The scavenger receptor (SR-A5), a significant pattern recognition receptor, assumes a vital function in anti-inflammatory reactions. In the current investigation, we have successfully illustrated the ability of α-KG to mitigate inflammatory factors in the serum of septic mice and ameliorate tissue damage. Additionally, α-KG has been shown to modulate metabolic reprogramming and macrophage polarization. Moreover, our findings indicate that the regulatory influence of α-KG on sepsis is mediated through SR-A5. We also elucidated the mechanism by which α-KG regulates SR-A5 expression and found that α-KG reduced the N6-methyladenosine level of macrophages by up-regulating the m6A demethylase ALKBH5. α-KG plays a crucial role in inhibiting inflammation by regulating SR-A5 expression through m6A demethylation during sepsis. The outcomes of this research provide valuable insights into the relationship between energy metabolism and inflammation regulation, as well as the underlying molecular regulatory mechanism.

2.
PLoS Pathog ; 17(3): e1009481, 2021 03.
Artigo em Inglês | MEDLINE | ID: mdl-33788895

RESUMO

TcpC is a virulence factor of uropathogenic E. coli (UPEC). It was found that TIR domain of TcpC impedes TLR signaling by direct association with MyD88. It has been a long-standing question whether bacterial pathogens have evolved a mechanism to manipulate MyD88 degradation by ubiquitin-proteasome pathway. Here, we show that TcpC is a MyD88-targeted E3 ubiquitin ligase. Kidney macrophages from mice with pyelonephritis induced by TcpC-secreting UPEC showed significantly decreased MyD88 protein levels. Recombinant TcpC (rTcpC) dose-dependently inhibited protein but not mRNA levels of MyD88 in macrophages. Moreover, rTcpC significantly promoted MyD88 ubiquitination and accumulation in proteasomes in macrophages. Cys12 and Trp106 in TcpC are crucial amino acids in maintaining its E3 activity. Therefore, TcpC blocks TLR signaling pathway by degradation of MyD88 through ubiquitin-proteasome system. Our findings provide not only a novel biochemical mechanism underlying TcpC-medicated immune evasion, but also the first example that bacterial pathogens inhibit MyD88-mediated signaling pathway by virulence factors that function as E3 ubiquitin ligase.


Assuntos
Proteínas de Escherichia coli/metabolismo , Fator 88 de Diferenciação Mieloide/metabolismo , Transdução de Sinais/fisiologia , Escherichia coli Uropatogênica/patogenicidade , Fatores de Virulência/metabolismo , Animais , Linhagem Celular , Feminino , Humanos , Evasão da Resposta Imune/fisiologia , Macrófagos , Camundongos , Camundongos Endogâmicos C57BL , Pielonefrite/imunologia , Pielonefrite/microbiologia , Receptores Toll-Like/metabolismo , Ubiquitina-Proteína Ligases/metabolismo , Escherichia coli Uropatogênica/imunologia , Escherichia coli Uropatogênica/metabolismo , Virulência/fisiologia
3.
Mol Med ; 28(1): 159, 2022 12 20.
Artigo em Inglês | MEDLINE | ID: mdl-36539694

RESUMO

BACKGROUND: This study aims to explore the protective role of ethanol extract from Chimonanthus nitens Oliv. leaf (COE) in hyperlipidemia via the leptin/Janus kinase 2 (JAK2)/signal transducer and activator of transcription 3 (STAT3) pathway. METHODS: Male Sprague‒Dawley rats were randomly divided into 6 groups (n = 8): normal-fat diet (NMD), high-fat diet (HFD), HFD treated with simvastatin (SIM, 5 mg/kg/day), and HFD treated with COE (40, 80, 160 mg/kg/day). Lipid parameters, oxidative stress factors, serum leptin, body weight, hepatic wet weight and liver index were measured. Proteins in the leptin/JAK2/STAT3 pathway in liver tissues were determined using western blotting. Additionally, the expression levels of cytochrome P450 family 7 subfamily A member 1 (CYP7A1) and 3-hydroxy-3-methylglutaryl-CoA reductase (HMGCR) were quantified using western blotting and quantitative real-time polymerase chain reaction (qPCR). RESULTS: COE decreased HFD-induced increases in body weight, hepatic wet weight and the liver index. HFD-induced hyperlipidemia and oxidative stress were observed in rat serum and livers. Additionally, COE repressed these two symptoms in rats fed a HFD. Moreover, COE caused CYP7A1 upregulation and HMGCR downregulation in HFD-fed rats. Mechanistically, COE induced the expression of leptin receptor (OB-Rb) and JAK2 and STAT3 phosphorylation in HFD-treated rats. CONCLUSION: COE activates the leptin/JAK2/STAT3 pathway, leading to an improvement in liver function and lipid metabolism and ultimately alleviating hyperlipidemia in rats. Therefore, COE may be a potential hypolipidemic drug for the treatment of hyperlipidemia.


Assuntos
Hiperlipidemias , Leptina , Ratos , Masculino , Animais , Leptina/metabolismo , Leptina/farmacologia , Leptina/uso terapêutico , Hiperlipidemias/tratamento farmacológico , Hiperlipidemias/metabolismo , Etanol/metabolismo , Etanol/farmacologia , Etanol/uso terapêutico , Ratos Sprague-Dawley , Fator de Transcrição STAT3/metabolismo , Janus Quinase 2/metabolismo , Fígado/metabolismo , Dieta Hiperlipídica/efeitos adversos , Folhas de Planta/metabolismo , Peso Corporal
4.
Cytotherapy ; 22(12): 699-711, 2020 12.
Artigo em Inglês | MEDLINE | ID: mdl-32893120

RESUMO

BACKGROUND AIMS: To assess the impacts of stem cell therapy on clinical outcomes in patients with non-ischemic cardiomyopathy (NICM). The effect of stem cell therapy on prognosis is unclear and controversial. METHODS: The authors performed a systematic review and meta-analysis of the effects of autologous stem cell transplantation in patients with NICM on a composite outcome of all-cause mortality and heart transplantation, left ventricular ejection fraction (LVEF), left ventricular end-diastolic diameter (LVEDD), New York Heart Association (NYHA) classification, 6-minute walk test (6-MWT) distance and serum brain natriuretic peptide (BNP) level, considering studies published before March 19, 2020. RESULTS: Twelve trials with 623 subjects met inclusion criteria. Compared with the control group, stem cell therapy improved LVEF (weighted mean difference [WMD], 4.08%, 95% confidence interval [CI], 1.93-6.23, P = 0.0002) and 6-MWT distance (WMD, 101.49 m, 95% CI, 45.62-157.35, P = 0.0004) and reduced BNP level (-294.94 pg/mL, 95% CI, -383.97 to -205.90, P < 0.00001) and NYHA classification (-0.70, 95% CI, -0.98 to -0.43, P < 0.00001). However, LVEDD showed no significant difference between the two groups (WMD, -0.09 cm, 95% CI, -0.23 to 0.06, P = 0.25). In 10 studies (535 subjects) employing the intracoronary route for cell delivery, mortality and heart transplantation were decreased (risk ratio [RR], 0.73, 95% CI, 0.52-1.00, P = 0.05). Furthermore, in four studies (248 subjects) with peripheral CD34+ cells, either all-cause mortality (RR, 0.44, 95% CI, 0.23-0.86, P = 0.02) or mortality and heart transplantation (RR, 0.45, 95% CI, 0.27-0.77, P = 0.003) improved in the treatment group compared with the control. The trial sequential analysis suggested the information size of LVEF, 6-WMT and BNP has been adequate for evidencing the benefits of stem cells on NICM. However, to determine the potential survival benefit, more clinical data are required to make the statistical significance in meta-analysis more conclusive. CONCLUSIONS: This meta-analysis demonstrates that stem cell therapy may improve survival, exercise capacity and cardiac ejection fraction in NICM, which suggests that stem cells are a promising option for NICM treatment.


Assuntos
Cardiomiopatias/terapia , Isquemia Miocárdica/complicações , Transplante de Células-Tronco , Cardiomiopatias/etiologia , Cardiomiopatias/mortalidade , Cardiomiopatias/fisiopatologia , Humanos , Masculino , Pessoa de Meia-Idade , Isquemia Miocárdica/fisiopatologia , Viés de Publicação , Ensaios Clínicos Controlados Aleatórios como Assunto , Transplante de Células-Tronco/efeitos adversos , Volume Sistólico/efeitos dos fármacos , Transplante Autólogo , Teste de Caminhada
5.
BMC Cancer ; 20(1): 895, 2020 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-32948132

RESUMO

BACKGROUND: Increased fucosylation is associated with the chemoresistance phenotype. Meanwhile, fucosyltransferase IV (FUT4) amounts are frequently elevated in lung cancer and may be related to increased chemoresistance. METHODS: In the present work, FUT4's role in cisplatin-induced apoptosis was assessed in A549 and H1975 cells, respectively. To clarify whether the FUT4 gene attenuates chemosensitivity in tumor cells, we constructed FUT4siRNA and evaluated its effects on cisplatin-induced apoptosis and cell growth inhibition. Cell viability, apoptosis, migration and invasion assay were conducted to investigate cisplatin sensitivity. The activation of EGFR/AKT/FOXO1 signaling were measured by western blot. The translocation of FOXO1 was assessed by IFC using Laser Scanning Confocal Microscope. RESULTS: We found that FUT4 knockdown dose-dependently increased cisplatin-associated cytotoxicity. Furthermore, FUT4 silencing induced apoptosis and inhibited proliferation in A549 and H1975 cells by suppressing Akt and FOXO1 phosphorylation induced by cisplatin administration, which resulted in nuclear translocation of FOXO1. CONCLUSION: These results suggested FUT4 might control chemoresistance to cisplatin in lung cancer by suppressing FOXO1-induced apoptosis.


Assuntos
Antineoplásicos/uso terapêutico , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Carcinoma Pulmonar de Células não Pequenas/genética , Cisplatino/uso terapêutico , Proteína Forkhead Box O1/metabolismo , Fucosiltransferases/metabolismo , Neoplasias Pulmonares/tratamento farmacológico , Neoplasias Pulmonares/genética , Apoptose , Carcinoma Pulmonar de Células não Pequenas/patologia , Cisplatino/farmacologia , Humanos , Neoplasias Pulmonares/patologia , Transfecção
6.
Bioorg Med Chem Lett ; 30(2): 126795, 2020 01 15.
Artigo em Inglês | MEDLINE | ID: mdl-31759850

RESUMO

High throughput screening for ß-lactamase inhibitors afforded biphenyl hits such as 1. Hit confirmation and X-ray soaking experiments with Pseudomonas Aeruginosa AmpC enzyme led to the identification of an aryl boronic acid-serine complex 4, which was formed from phenyl boronic acid 8 (an impurity in compound 1) and ethylene glycol (the cryoprotectant in the soaking experiment).


Assuntos
Proteínas de Bactérias/antagonistas & inibidores , Ácidos Borônicos/química , Inibidores de beta-Lactamases/química , beta-Lactamases/química , Proteínas de Bactérias/metabolismo , Ácidos Borônicos/síntese química , Ácidos Borônicos/metabolismo , Desenho de Fármacos , Pseudomonas aeruginosa/enzimologia , Inibidores de beta-Lactamases/síntese química , Inibidores de beta-Lactamases/metabolismo , beta-Lactamases/metabolismo
7.
Clin Exp Pharmacol Physiol ; 47(3): 466-477, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31675454

RESUMO

Autophagy and cellular senescence are two critical responses of mammalian cells to stress and may have a direct relationship given that they respond to the same set of stimuli, including oxidative stress, DNA damage, and telomere shortening. Mesenchymal stem cells (MSCs) have emerged as reliable cell sources for stem cell transplantation and are currently being tested in numerous clinical trials. However, the effects of autophagy on MSC senescence and corresponding mechanisms have not been fully evaluated. Several studies demonstrated that autophagy level increases in aging MSCs and the downregulation of autophagy can delay MSC senescence, which is inconsistent with most studies that showed autophagy could play a protective role in stem cell senescence. To further study the relationship between autophagy and MSC senescence and explore the effects and mechanisms of premodulated autophagy on MSC senescence, we induced the up- or down-regulation of autophagy by using rapamycin (Rapa) or 3-methyladenine, respectively, before MSC senescence induced by D-galactose (D-gal). Results showed that pretreatment with Rapa for 24 hours remarkably alleviated MSC aging induced by D-gal and inhibited ROS generation. p-Jun N-terminal kinases (JNK) and p-38 expression were also clearly decreased in the Rapa group. Moreover, the protective effect of Rapa on MSC senescence can be abolished by enhancing the level of ROS, and p38 inhibitor can reverse the promoting effect of H2 O2 on MSC senescence. In summary, the present study indicates that autophagy plays a protective role in MSC senescence induced by D-gal, and ROS/JNK/p38 signalling plays an important mediating role in autophagy-delaying MSC senescence.


Assuntos
Autofagia/fisiologia , Senescência Celular/fisiologia , Galactose/toxicidade , Proteínas Quinases JNK Ativadas por Mitógeno/metabolismo , Sistema de Sinalização das MAP Quinases/fisiologia , Células-Tronco Mesenquimais/metabolismo , Espécies Reativas de Oxigênio/metabolismo , Animais , Autofagia/efeitos dos fármacos , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Inibidores Enzimáticos/farmacologia , Feminino , Imidazóis/farmacologia , Proteínas Quinases JNK Ativadas por Mitógeno/antagonistas & inibidores , Sistema de Sinalização das MAP Quinases/efeitos dos fármacos , Masculino , Células-Tronco Mesenquimais/efeitos dos fármacos , Piridinas/farmacologia , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley
8.
Anal Bioanal Chem ; 411(17): 3941-3949, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31119348

RESUMO

Glycoprotein detection holds great potential for early diagnosis of diverse diseases. For this purpose, the combination of quartz crystal microbalance (QCM) sensor and molecular imprinting has attracted increasing attention. Nonetheless, the recently common imprinted films fabricated on QCM electrode are thick and rigid, lacking flexibility in aqueous phase. Alternatively, small molecules immobilized on the electrode to construct molecular scale film could address this problem, while stabilization of the imprinted sites remains challenging. Herein, a co-assembly complex was obtained by the mixture of template and multifunctional oligomer, which was then immobilized on the amino-modified transducer surface through epoxy-amino reaction to form a protein-imprinted film. Afterward, the remaining epoxy groups in oligomer chains were cross-linked to conserve and stabilize the orientation of imprinted sites after template elution. Template rebinding tests show that cross-linked film has much higher imprinting factors than that of the non-cross-linked counterpart. Furthermore, control proteins that are distinct in properties and structures were employed to demonstrate the selectivity of this approach, and the imprinted assay reveals high affinity and specificity towards template protein. Graphical Abstract.


Assuntos
Glicoproteínas/análise , Impressão Molecular , Polímeros/química , Técnicas de Microbalança de Cristal de Quartzo , Eletrodos
9.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 48(6): 617-624, 2019 12 25.
Artigo em Zh | MEDLINE | ID: mdl-31955535

RESUMO

OBJECTIVE: To investigate the effects of resveratrol (Res) on aging of marrow mesenchymal stem cells (MSCs), and to explore its mechanism. METHODS: MSCs were isolated from young SD rats and cultured in vitro. The optimal D-gal concentration for induction of MSCs senescence was determined. Then MSCs were randomly divided into four groups, namely the control group, 10µmol/L, 50µmol/L and 100µmol/L Res groups. After the cells were treated with different concentration of Res for 48 h, the senescence-associated changes were examined with senescence-associated-ß-galactosidase (SA-ß-gal) staining; the expression of p53, p16 and γ-H2AX was evaluated by Western blot. The total active oxygen species (ROS) level was determined by flow cytometry with DCFH-DA staining. In order to assess the effect of Res on the mitochondrial function, MitoSox Red staining was used to detect mitochondrial ROS levels in each group, mitochondrial membrane potential was detected by JC-1 assay, mPTP method was used to detect mitochondrial membrane channel opening level, and Western blot was used to detect the expression level of cytoplasmic cytochrome C (Cyt-C). RESULTS: D-gal 10 and 50 g/L significantly increased the number of SA-ß-gal positive cells and the level of mitochondrial ROS (all P<0.01). Therefore, 10 g/L D-gal was used to induce the senescence of MSCs in subsequent experiment. Compared with the control group, the number of SA-ß-gal positive cells in Res groups significantly decreased (all P<0.01), the expression of p53, p16 and γ-H2AX decreased, and the total and mitochondrial ROS level also decreased (all P<0.01). Moreover, mitochondrial membrane potential, open level of mitochondrial membrane channels and the levels of cytoplasm Cyt-C in the Res treatment groups decreased compared with the control group (P<0.05 or P<0.01). CONCLUSIONS: Resveratrol can protect the mitochondrial function of MSCs, and effectively delay the MSC senescence.


Assuntos
Senescência Celular , Células-Tronco Mesenquimais , Resveratrol , Animais , Antioxidantes/farmacologia , Células Cultivadas , Senescência Celular/efeitos dos fármacos , Células-Tronco Mesenquimais/efeitos dos fármacos , Ratos , Ratos Sprague-Dawley , Espécies Reativas de Oxigênio , Resveratrol/farmacologia
10.
J Biol Chem ; 292(26): 11021-11033, 2017 06 30.
Artigo em Inglês | MEDLINE | ID: mdl-28465350

RESUMO

Muscle and bone are closely associated in both anatomy and function, but the mechanisms that coordinate their synergistic action remain poorly defined. Myostatin, a myokine secreted by muscles, has been shown to inhibit muscle growth, and the disruption of the myostatin gene has been reported to cause muscle hypertrophy and increase bone mass. Extracellular vesicle-exosomes that carry microRNA (miRNA), mRNA, and proteins are known to perform an important role in cell-cell communication. We hypothesized that myostatin may play a crucial role in muscle-bone interactions and may promote direct effects on osteocytes and on osteocyte-derived exosomal miRNAs, thereby indirectly influencing the function of other bone cells. We report herein that myostatin promotes expression of several bone regulators such as sclerostin (SOST), DKK1, and RANKL in cultured osteocytic (Ocy454) cells, concomitant with the suppression of miR-218 in both parent Ocy454 cells and derived exosomes. Exosomes produced by Ocy454 cells that had been pretreated with myostatin could be taken up by osteoblastic MC3T3 cells, resulting in a marked reduction of Runx2, a key regulator of osteoblastic differentiation, and in decreased osteoblastic differentiation via the down-regulation of the Wnt signaling pathway. Importantly, the inhibitory effect of myostatin-modified osteocytic exosomes on osteoblast differentiation is completely reversed by expression of exogenous miR-218, through a mechanism involving miR-218-mediated inhibition of SOST. Together, our findings indicate that myostatin directly influences osteocyte function and thereby inhibits osteoblastic differentiation, at least in part, through the suppression of osteocyte-derived exosomal miR-218, suggesting a novel mechanism in muscle-bone communication.


Assuntos
Diferenciação Celular , Exossomos/metabolismo , MicroRNAs/metabolismo , Músculo Esquelético/metabolismo , Miostatina/metabolismo , Osteócitos/metabolismo , Via de Sinalização Wnt/fisiologia , Proteínas Adaptadoras de Transdução de Sinal , Animais , Linhagem Celular , Exossomos/genética , Glicoproteínas/genética , Glicoproteínas/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Camundongos , MicroRNAs/genética , Miostatina/genética , Ligante RANK/genética , Ligante RANK/metabolismo
11.
Biomacromolecules ; 19(11): 4270-4276, 2018 11 12.
Artigo em Inglês | MEDLINE | ID: mdl-30231201

RESUMO

Cationic polymers have emerged as appealing nonviral gene vectors for decades, which, however, suffer from the paradox between low molecular weight and high transfection efficacy. Low molecular weight cationic polymers (LCPs) are well cell tolerated but are perplexed by orders-of-magnitude less efficacy compared to their macromolecular counterparts. The deficiency mainly lies in weak DNA binding of polymers and difficulty in endosomal escape of formulated polyplexes. Herein, we demonstrate that, through zinc (Zn) coordinated modification of LCPs, the high transfection efficiency and low molecular weight (thus low cytotoxicity) can be achieved simultaneously. The Zn coordinated ligand shows a high affinity to phosphate components and therefore will largely benefit the DNA packaging and endosomal membrane destabilization, addressing the defects of LCPs in gene delivery. Zn coordinative functionalization of LCPs breaks up the "efficacy-toxicity" paradox and provides great promise for the development of clinically efficient and safe nonviral gene vectors.


Assuntos
Cátions/química , Neoplasias do Colo/terapia , Eritrócitos/metabolismo , Células-Tronco Mesenquimais/metabolismo , Polímeros/administração & dosagem , Transfecção/métodos , Zinco/química , Animais , Neoplasias do Colo/genética , Neoplasias do Colo/patologia , Eritrócitos/citologia , Feminino , Técnicas de Transferência de Genes , Terapia Genética , Vetores Genéticos/administração & dosagem , Humanos , Células-Tronco Mesenquimais/citologia , Camundongos , Camundongos Endogâmicos BALB C , Peso Molecular , Polímeros/química , Ovinos , Células Tumorais Cultivadas , Ensaios Antitumorais Modelo de Xenoenxerto
12.
Bioorg Med Chem Lett ; 26(19): 4743-4747, 2016 10 01.
Artigo em Inglês | MEDLINE | ID: mdl-27575474

RESUMO

A series of benzimidazole analogs have been synthesized to improve the profile of the previous lead compounds tarocin B and 1. The syntheses, structure-activity relationships, and selected biochemical data of these analogs are described. The optimization efforts allowed the identification of 21, a fluoro-substituted benzimidazole, exhibiting potent TarO inhibitory activity and typical profile for a wall teichoic acid (WTA) biosynthesis inhibitor. Compound 21 displayed a potent synergistic and bactericidal effect in combination with imipenem against diverse methicillin-resistant Staphylococci.


Assuntos
Antibacterianos/farmacologia , Benzimidazóis/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Ácidos Teicoicos/antagonistas & inibidores , Animais , Antibacterianos/química , Benzimidazóis/química , Testes de Sensibilidade Microbiana , Ratos , Relação Estrutura-Atividade , Ácidos Teicoicos/biossíntese
13.
J Cell Mol Med ; 19(2): 408-17, 2015 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-25388762

RESUMO

Regular use of aspirin after diagnosis is associated with longer survival among patients with mutated-PIK3CA colorectal cancer, but not among patients with wild-type PIK3CA cancer. In this study, we showed that clinically achievable concentrations of aspirin and ABT-737 in combination could induce a synergistic growth arrest in several human PIK3CA wild-type cancer cells. In addition, our results also demonstrated that long-term combination treatment with aspirin and ABT-737 could synergistically induce apoptosis both in A549 and H1299 cells. In the meanwhile, short-term aspirin plus ABT-737 combination treatment induced a greater autophagic response than did either drug alone and the combination-induced autophagy switched from a cytoprotective signal to a death-promoting signal. Furthermore, we showed that p38 acted as a switch between two different types of cell death (autophagy and apoptosis) induced by aspirin plus ABT-737. Moreover, the increased anti-cancer efficacy of aspirin combined with ABT-737 was further validated in a human lung cancer A549 xenograft model. We hope that this synergy may contribute to failure of aspirin cancer therapy and ultimately lead to efficacious regimens for cancer therapy.


Assuntos
Apoptose/efeitos dos fármacos , Aspirina/farmacologia , Autofagia/efeitos dos fármacos , Compostos de Bifenilo/farmacologia , Neoplasias/tratamento farmacológico , Nitrofenóis/farmacologia , Sulfonamidas/farmacologia , Proteínas Quinases p38 Ativadas por Mitógeno/metabolismo , Linhagem Celular Tumoral , Humanos , Neoplasias/metabolismo , Piperazinas/farmacologia
14.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(10): 850-2, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26813713

RESUMO

The neglect situation of rural children in China is serious, which is more serious than the same age group of urban children, especially the behind children are more severe. Child neglect deeply affects children's physical and mental health of children and adolescents in rural areas (from physical neglect, emotional neglect, education neglect, safety neglect, medical neglect and social neglect six aspects). To effectively prevent and control rural child neglect and promote the development of the physical and mental health of rural children and adolescents in China, we must adopt comprehensive measures including social, family and children three aspects. We need to cause the attention of the government and the society, improve the prevention of child neglect of social support networks, promote the social multi departments cooperation and efforts, and from the different angles to take effective intervention measure. To strengthen family intervention for the neglected children, to provide support and help to parents and families, as much as possible to eliminate or reduce the influence factors of child neglect. Should be aimed at high-risk group of child neglect, to adopt the principle of "early detection, early intervention", through to help and support to prevent or reduce the occurrence of neglect.


Assuntos
Maus-Tratos Infantis , População Rural , Apoio Social , Adolescente , Criança , China , Humanos , Saúde Mental , Pais , Segurança
15.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(10): 873-8, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26813718

RESUMO

OBJECTIVE: To investigate the situation and the influential factors of child neglect between left-behind children and living-with-parents children aged 6-17 years in the rural areas in western China. METHODS: Students were randomly selected according to the principle of multi-stage stratified cluster sampling and they were from three cities in Shanxi and four districts in Chongqing. Among the 4,131 children, there were 1,874 students in the 6-11 years group and the left-behind children accounted for 50.21% (941/1,874) in this group. There were 2,257 students in the 12-17 years old group and the left-behind children accounted for 53.35% (1,204/2,257) in this group. The questionnaire named "Evaluation on Neglect for Elementary and Secondary School Students Aged 6-17 Years in Rural Areas in China" was used in the field investigation. The students' neglect frequency was described by neglect rate and the factors affecting students' neglect were analyzed by means of binary logistic regression. RESULTS: In the 6-11 years old group, the neglect rates of left-behind children and living-with-parents children were 63.03% (474/752) and 43.87% (347/791), respectively (χ2=58.86, P<0.001). In the 12-17 years old group, the neglect rates of left-behind children and living-with-parents children were 60.64% (627/1 034) and 53.57% (495/924), respectively (χ2=9.96, P<0.001). For factors influencing left-behind children, compared to the factors about boys, younger mother (≤40 years old), presence of parents' income reduction within the last year and nuclear family, the factors about girls, elder mother (41-49 years), absence of parents' income reduction within the last year and three-generation family or single-parent family were associated with lower neglect risk, and OR values were 0.67, 0.68, 0.70, 0.73, and 0.43 (P<0.05); compared to the factors about Han nationality, only child, with separate room at home, and resident children, the factors about other nationalities, non-only child, no separate room at home, and non-resident children were associated with high neglect risk, and OR values were 1.85, 1.34, 1.46, and 1.32 (P<0.05); compared to the lower father's education background (primary school or uneducated), the higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.66, 0.50, and 0.25 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.57-3.79 (P<0.05). For factors influencing non-left-behind children, compared to the factors about younger mother (≤40 years old), changes of patient's work in the last year, presence of parents' income reduction within the last year and nuclear family, the factors about elder mother (41-49 years), no changes of patients' work in the last year, absence of parents' income reduction within the last year and three-generation family or single-parent family were associated with lower neglect risk, and OR values were 0.69, 0.71, 0.75, 0.82, and 0.56 (P<0.05); compared to the factors about Han nationality, only child and younger father (≤40 years old), other nationalities, the factors about non-only child, and elder father (41-49 years) were associated with high neglect risk, and OR values were 1.45, 1.56, and 1.57 (P<0.05); compared to lower father's education background (primary school or uneducated), higher father's education background (junior middle school, senior middle school, technical secondary school, college and above) was associated with lower neglect risk, and OR values were 0.65 and 0.49 (P<0.05); compared to good relationship between children and parents as well as good relationship between parents, fair or poor relationship was associated with high neglect risk, and OR values were 1.56-7.69 (P<0.05). CONCLUSION: The situation of child neglect among left-behind children aged 6-17 years in rural areas of the two provinces in western China was serious, their neglect rates were higher than those of living-with-parents children, and there were many risk factors affecting the neglect rates of the two group children.


Assuntos
Maus-Tratos Infantis , Criança Abandonada , Fatores de Risco , População Rural , Adolescente , Criança , China , Demografia , Feminino , Humanos , Renda , Modelos Logísticos , Masculino , Mães , Pais , Pesquisa , Instituições Acadêmicas , Estudantes , Inquéritos e Questionários
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(10): 860-5, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26813716

RESUMO

OBJECTIVE: To analyze pupils' neglect status aged 6-11 years in China's rural. METHODS: According to the principle of multi-stage stratified cluster sampling, to extract 7,943 pupils aged 6-11 years for the survey from 56 primary schools in 28 counties in nine provinces, from December 2012 to March 2013. Proceed questionnaire survey by the scale from "Neglect Evaluation Norms for pupils aged 6-8 years in Rural Areas of China" and "Neglect Evaluation Norms for pupils aged 9-11 years in Rural Areas of China". And analyze neglect rates and neglect degrees of the different grades, gender, family types and different levels of neglect. RESULTS: The total neglect rate of China's rural pupils aged 6-8 and 9-11 years was 40.2% (1,258/3,130) and 42.5% (1,498/3,526) respectively, which differences had no statistical significant (χ2=3.59, P=0.058); the total neglect degree was 46.04±8.87 and 44.78±10.43 respectively, which differences had statistical significant (t=5.01, P<0.001); the differences of neglect rates and neglect degrees between male (41.4% (657/1,587) and 46.28±8.76) and female (39.0% (601/1,543) and 45.78±8.97) of aged 6-8 were all no statistical significant (χ2=1.87, P=0.171; t=1.49, P=0.136); the neglect rates and neglect degrees of male (46.3% (816/1,763) and 45.53±10.11) were higher than female (38.7% (682/1,763) and 44.06±10.69) in the group of aged 9-11, which differences were all statistical significant (χ2=20.84, t=3.97, P<0.001); the male neglect rate in the group of aged 6-8 in social neglect (11.7% (198/1,691)) and the neglect degree in educational neglect (48.09±9.70) were higher than female (9.4% (155/1,648) and 47.37±9.89), which differences were all statistical significance (χ2=14.55, P<0.001, t=2.22, P=0.026), the male neglect rate in the group of aged 9-11 in physical neglect (20.4% (398/1,954)) was higher than female (16.7% (326/1 957)), which differences had statistical significance (χ2=8.92, P=0.003). CONCLUSION: The neglect status of Chinese pupils aged 6-11 years in rural was serious, and we should find out risk factors and provide efficient prevention measures.


Assuntos
Maus-Tratos Infantis , População Rural , Criança , China , Feminino , Humanos , Masculino , Exame Físico , Pupila , Fatores de Risco , Instituições Acadêmicas , Inquéritos e Questionários
17.
Zhonghua Yu Fang Yi Xue Za Zhi ; 49(10): 866-72, 2015 Oct.
Artigo em Zh | MEDLINE | ID: mdl-26813717

RESUMO

OBJECTIVE: To investigate the major influence factors of child neglect among rural areas children aged 3-6 years in China. METHODS: According to multi-stage stratified cluster sampling, distribution characteristics and the level of economic development, we randomly sampled 10 provinces, 26 cities (8 capital cities, 16 prefecture-level cities and 2 municipalities) using lottery method. Depending on the different level of economic and cultural, we sampled one medium county from each city (municipalities sampled two counties), a total of 28 counties. All towns were divided into high, medium and low three levels in accordance with economic and cultural, each level sampled one town, each conty sampled three towns, a total of 84 towns were sampled. Each town sampled 40 children, including 20 boys and 20 girls (including each 10 children aged 3 to 6, half and half boys and girls). 4 096 rural children aged 3-6 years old were sampled and surveyed of China. Based on "the Neglect Norms for Children Aged 3 to 6 Years Old in Rural Areas of China" explored the risk factors of child neglect. SPSS 18. 0 for windows was employed for statistics analysis. Multifactorial analysis was conducted through multivariate Logistic Regression. RESULTS: The total neglected rate of the rural children aged 3 to 6 was 53.7% (2,047/3,810), and the total neglected degree was 44.42±7.57. The multivariate logistic regression analysis showed that, neglected risk of the boys was higher than the girls (OR=1.30, 95% CI: 1.13-1.49), neglected risk of children were higher, when their mothers were migrant workers (OR=2.18, 95% CI: 1.59-3.00); the lower educational level of mothers, the higher neglected risk of children, the children in families that mothers only received primary education or was uneducated were most likely to be neglected (OR=2.92, 95% CI: 1.91-4.47), the second was the families that mothers received primary education (OR=1.86, 95% CI: 1.29-2.69); the lower the household income, the easier to be neglected the children, the easiest one was the household income less than 5000 RMB (OR=2.85, 95% CI: 2.14-3.79), the second was 5000-9,999 RMB (OR=1.76, 95% CI: 1.40-2.20); the relationship between children and mothers was distanced, neglect risk of children was higher (OR=3.88, 95% CI: 1.31-11.52); left behind children were easier to be neglected (OR=1.30, 95% CI: 1.09-1.54). CONCLUSION: The influence factors among children aged 3-6 years in the rural areas of China were boys, mother's occupation, maternal education level, the relationship between children and mothers, household income and left-behind children.


Assuntos
Maus-Tratos Infantis , Demografia , População Rural , Pré-Escolar , China , Análise Fatorial , Feminino , Humanos , Masculino , Mães , Fatores de Risco , Inquéritos e Questionários , Migrantes
18.
Wei Sheng Yan Jiu ; 44(5): 756-60, 2015 Sep.
Artigo em Zh | MEDLINE | ID: mdl-26591770

RESUMO

OBJECTIVE: 10 learn about the neglected conditions and intuence factors of middle school students aged 12 to 17 years old in rural areas of Shaanxi Province and Chongqing City. METHODS: The scale and evaluation method formulated in "The Normal Value of Evaluation on the Neglect of Middle School Students from 12 to 17 Years Old in Rural China" was adopted. 2257 respondents among which there were 1157 male students and 1,100 female students in the rural areas of Shaanxi Province and Chongqing City were selected according to the principle of multi-stage stratified cluster sampling. The severe degree of neglect was reflected through the indicator of neglect degree. The method of binary Logistic regression analysis was adopted to analyze the influence factors of neglect. Results The total neglect degree of respondents was (51. 80 ± 9. 06). The neglect degree of middle school students in the rural areas of Chongqing was (53. 21 ± 9. 03). The neglect degree of middle school students in the rural areas of Shaanxi was 50. 50 8. 90. The statistical significance was found in the difference between the two groups (U =6. 17, P <0. 01). The neglect degree of male students was (51. 93 ± 8. 67) while the neglect degree of female students was (51. 66 ± 9. 46). The statistical significance was not found in the difference between the two groups of total neglect degree of different sexes (U = 0. 60, P > 0. 05). The statistical significance was noticed in the differences of neglect degrees of middle school students in different grades at all levels (P <0. 05). The neglect degrees of junior three and senior three students were relatively high. Their total neglect degrees were (53. 54 ± 9. 70) and (53. 36 ± 8. 69) respectively. Except social neglect and safety neglect, there was statistical significance in the differences of neglect degrees of students with different family backgrounds at all levels (P <0. 01). The neglect degree of middle school students in a remarried family was the highest. The total neglect degree was (56. 92 ± 8. 83). The factors influencing the neglect of middle school students were shown in the result of Logistic regression analysis, including the educational level of their fathers, whether they had a separate room, family types, whether the working places of their parents changed in one year, whether the incomes of their parents decreased in one year, their relationship with their parents and the relationship between their parents. CONCLUSION: The neglected conditions of middle school students in the rural areas of Shaanxi Province and Chongqing City are relatively severe and the factors influencing the neglect of children include the educational level of their fathers, whether they have a separate room, family types, whether the working places of their parents changed in one year, whether the incomes of their parents decrease in one year, their relationship with their parents and the relationship between their parents.


Assuntos
Maus-Tratos Infantis/estatística & dados numéricos , População Rural , Estudantes , Adolescente , Adulto , Criança , China/epidemiologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Pais , Segurança , Fatores Socioeconômicos , Inquéritos e Questionários
19.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 44(5): 584-8, 2015 09.
Artigo em Zh | MEDLINE | ID: mdl-26713536

RESUMO

Kidney dendritic cells(DC) play important roles in the pathogenesis of kidney diseases. Kidney DC presents anti-inflammatory effects in certain kidney diseases, sometimes presents pro-inflammation in other diseases, and sometimes their effects are changing in different stages of the disease, suggesting that the differentiation and function of kidney DC may be influenced by microenvironment. This article reviews the origin and distribution of kidney DC subsets and their roles in the pathogenesis of kidney diseases such as lupus nephritis and pyelonephritis, and the functional regulation of kidney DC by proximal tubule epithelial cells.


Assuntos
Células Dendríticas/citologia , Nefropatias/imunologia , Rim/citologia , Diferenciação Celular , Células Dendríticas/imunologia , Células Epiteliais/citologia , Humanos , Inflamação/imunologia , Nefrite Lúpica/imunologia , Pielonefrite/imunologia
20.
Graefes Arch Clin Exp Ophthalmol ; 252(1): 63-70, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24150707

RESUMO

BACKGROUND: Lutein and zeaxanthin are thought to have beneficial effects on protecting the lens against cataract formation, but findings from epidemiologic studies have been inconsistent. We aimed to conduct a meta-analysis of prospective cohort studies to examine the association between dietary lutein and zeaxanthin intake and risk of age-related cataract (ARC). METHODS: We systematically searched MEDLINE, EMBASE, Web of Science, and Cochrane Library databases up to March 2013. Reference lists from retrieved articles were also reviewed. The adjusted relative risks (RRs) from each study were extracted to calculate a pooled estimate with its 95 % confidence interval (CI). The dose-response relationships were assessed by using generalized least-squares trend estimation. RESULTS: Six prospective cohort studies were identified involving 4,416 cases and 41,999 participants. For the comparison between the highest and the lowest categories of dietary lutein and zeaxanthin intake, significant inverse association were found for nuclear cataract (RR: 0.75; 95 % CI: 0.65, 0.85), but not for cortical cataract (RR: 0.85; 95 % CI: 0.53, 1.17) and for posterior subcapsular cataract (RR: 0.77; 95 % CI: 0.40, 1.13). Dose-response analysis showed that every 300 µg/d increment in dietary lutein and zeaxanthin intake was associated with a 3 %, 1 %, or 3 % reduction in the risk of nuclear cataract (RR: 0.97; 95 % CI: 0.94, 0.99), cortical cataract (RR: 0.99; 95 % CI: 0.95, 1.02), or posterior subcapsular cataract (RR: 0.97; 95 % CI: 0.93, 1.01) respectively. CONCLUSIONS: Dietary lutein and zeaxanthin intake is associated with a reduced risk of ARC, especially nuclear cataract in a dose-response manner, indicating a beneficial effect of lutein and zeaxanthin in ARC prevention.


Assuntos
Envelhecimento , Catarata/epidemiologia , Dieta , Luteína/administração & dosagem , Xantofilas/administração & dosagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Bases de Dados Factuais , Relação Dose-Resposta a Droga , Comportamento Alimentar , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Fatores de Risco , Zeaxantinas
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