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1.
Kaohsiung J Med Sci ; 39(6): 565-575, 2023 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-36974975

RESUMO

Eicosapentaenoic acid (EPA) has been reported to play an anti-inflammatory and antioxidative stress role in a series of human diseases, including major depressive disorder. However, its exact mechanism is still largely unknown. Mouse BV-2 cells were treated with lipopolysaccharide (LPS) to induce an in vitro inflammatory cell model of depression. Cytotoxic effects were assessed with MTT and lactate dehydrigebase release assays. Cytokine mediators were elevated by western blot and enzyme-linked immunosorbent assays. Autophagy-relators were determined by immunofluorescence and western blot analyses. Interaction relationships among molecules were evaluated utilizing chromatin immunoprecipitation and dual luciferase assays. Methylated miR-29a-3p was detected via methylation-specific polymerase chain reaction. EPA treatment at 60 µM had no cytotoxic effects on BV2 cells and significantly inhibited the LPS-induced inflammatory response and NLRP3 inflammasome but activated autophagy, while all these effects were reversed by the autophagy inhibitor 3-MA. Importantly, miR-29a-3p exhibited a role similar to that of EPA in LPS-treated BV2 cells. Mechanistically, EPA treatment elevated miR-29a-3p by repressing its promoter methylation. MAPK8 was a direct target of miR-29a-3p. Inhibition of miR-29a-3p greatly diminished the regulatory roles mediated by EPA in LPS-treated BV2 cells, while these roles were further impeded after MAPK8 silencing. To conclude, our data demonstrated that EPA treatment alleviated LPS-induced NLRP3 inflammasomes by activating autophagy via regulation of miR-29a-3p/MAPK8 signaling, which further elucidates the potential antidepressant mechanism of EPA.


Assuntos
Transtorno Depressivo Maior , MicroRNAs , Humanos , Camundongos , Animais , Inflamassomos/genética , MicroRNAs/genética , Proteína 3 que Contém Domínio de Pirina da Família NLR/genética , Ácido Eicosapentaenoico/farmacologia , Microglia , Lipopolissacarídeos/farmacologia , Autofagia/genética
2.
Cancers (Basel) ; 14(23)2022 Nov 23.
Artigo em Inglês | MEDLINE | ID: mdl-36497244

RESUMO

Pyroptosis, an inflammatory programmed cell death, is characterized by the caspase-mediated pore formation of plasma membranes and the release of large quantities of inflammatory mediators. In recent years, the morphological characteristics, induction mechanism and action process of pyroptosis have been gradually unraveled. As a malignant tumor with high morbidity and mortality, cervical cancer is seriously harmful to women's health. It has been found that pyroptosis is closely related to the initiation and development of cervical cancer. In this review the mechanisms of pyroptosis and its role in the initiation, progression and treatment application of cervical cancer are summarized and discussed.

3.
Nat Commun ; 12(1): 3481, 2021 06 09.
Artigo em Inglês | MEDLINE | ID: mdl-34108482

RESUMO

TcpC is a multifunctional virulence factor of uropathogenic E. coli (UPEC). Neutrophil extracellular trap formation (NETosis) is a crucial anti-infection mechanism of neutrophils. Here we show the influence of TcpC on NETosis and related mechanisms. We show NETosis in the context of a pyelonephritis mouse model induced by TcpC-secreting wild-type E. coli CFT073 (CFT073wt) and LPS-induced in vitro NETosis with CFT073wt or recombinant TcpC (rTcpC)-treated neutrophils are inhibited. rTcpC enters neutrophils through caveolin-mediated endocytosis and inhibits LPS-induced production of ROS, proinflammatory cytokines and protein but not mRNA levels of peptidylarginine deiminase 4 (PAD4). rTcpC treatment enhances PAD4 ubiquitination and accumulation in proteasomes. Moreover, in vitro ubiquitination kit analyses show that TcpC is a PAD4-targetd E3 ubiquitin-ligase. These data suggest that TcpC inhibits NETosis primarily by serving as an E3 ligase that promotes degradation of PAD4. Our findings provide a novel mechanism underlying TcpC-mediated innate immune evasion.


Assuntos
Proteínas de Escherichia coli/metabolismo , Armadilhas Extracelulares/metabolismo , Neutrófilos/metabolismo , Proteína-Arginina Desiminase do Tipo 4/metabolismo , Ubiquitinação , Fatores de Virulência/metabolismo , Animais , Cromatina/metabolismo , Citrulinação , Infecções por Escherichia coli/imunologia , Infecções por Escherichia coli/patologia , Proteínas de Escherichia coli/genética , Histonas/metabolismo , Evasão da Resposta Imune , Camundongos , Mutação , Complexo de Endopeptidases do Proteassoma/metabolismo , Proteína-Arginina Desiminase do Tipo 4/genética , Pielonefrite/imunologia , Pielonefrite/patologia , Transcrição Gênica , Ubiquitina-Proteína Ligases/genética , Ubiquitina-Proteína Ligases/metabolismo , Escherichia coli Uropatogênica/metabolismo , Escherichia coli Uropatogênica/patogenicidade , Fatores de Virulência/genética
4.
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
5.
J Immunol Res ; 2019: 4657928, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31930149

RESUMO

Immunosenescence comprises a set of dynamic changes occurring in innate and adaptive immune systems, and macrophage aging plays an important role in innate and adaptive immunosenescence. However, function and polarization changes in aging macrophages have not been fully evaluated, and no effective method for delaying macrophage senescence is currently available. The results of this study reveal that D-galactose (D-gal) can promote J774A.1 macrophage senescence and induce macrophage M1 polarization differentiation. Bifidobacterium lactis BB-12 can significantly inhibit J774A.1 macrophage senescence induced by D-gal. IL-6 and IL-12 levels in the BB-12 groups remarkably decreased compared with that in the D-gal group, and the M2 marker, IL-10, and Arg-1 mRNA levels increased in the BB-12 group. BB-12 inhibited the expression of p-signal transducer and activator of transcription 1 (STAT1) and promoted p-STAT6 expression. In summary, the present study indicates that BB-12 can attenuate the J774A.1 macrophage senescence and induce M2 macrophage polarization, thereby indicating the potential of BB-12 to slow down immunosenescence and inflamm-aging.


Assuntos
Bifidobacterium animalis/imunologia , Senescência Celular/efeitos dos fármacos , Galactose/farmacologia , Ativação de Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Animais , Bifidobacterium animalis/química , Bifidobacterium animalis/metabolismo , Diferenciação Celular/efeitos dos fármacos , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Senescência Celular/imunologia , Galactose/toxicidade , Inflamação/imunologia , Inflamação/metabolismo , Interleucina-10/metabolismo , Interleucina-12/metabolismo , Interleucina-6/metabolismo , Camundongos , Espécies Reativas de Oxigênio/metabolismo , Fator de Transcrição STAT1/metabolismo , Fator de Transcrição STAT6/metabolismo
6.
Med Oncol ; 33(2): 16, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26757927

RESUMO

Erlotinib is effective in NSCLC patients with known drug-sensitizing EGFR mutations, but its clinical efficacy in patients with wild-type EGFR or acquired resistance to erlotinib remains modest. Evodiamine is a chemical extracted from the Evodia rutaecarpa (Juss.) Benth, we showed that evodiamine could induce anti-proliferation and apoptosis in four wild-type EGFR NSCLC cell lines, and combining evodiamine with erlotinib might successfully inhibit cell proliferation and survival in wild-type EGFR NSCLC cells, characterized as erlotinib-resistant. In addition, evodiamine plus erlotinib significantly increased the apoptotic rate of NSCLC cells, as compared to single agent treatment alone. Further investigation of the mechanism underlying these effects revealed that evodiamine plus erlotinib might downregulate Mcl-1 expression through the mTOR/S6K1 control of its translation. Thus, our study has revealed evodiamine as a pertinent sensitizer to erlotinib and the strategy of combining erlotinib with evodiamine appears to be an attractive option for reversing resistance to erlotinib.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Carcinoma Pulmonar de Células não Pequenas/tratamento farmacológico , Neoplasias Pulmonares/tratamento farmacológico , Proteína de Sequência 1 de Leucemia de Células Mieloides/antagonistas & inibidores , Quinazolinas/farmacologia , Apoptose/efeitos dos fármacos , Carcinoma Pulmonar de Células não Pequenas/metabolismo , Carcinoma Pulmonar de Células não Pequenas/patologia , Linhagem Celular Tumoral , Receptores ErbB/metabolismo , Cloridrato de Erlotinib/administração & dosagem , Cloridrato de Erlotinib/farmacologia , Humanos , Neoplasias Pulmonares/metabolismo , Neoplasias Pulmonares/patologia , Mitocôndrias/efeitos dos fármacos , Mitocôndrias/metabolismo , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Quinazolinas/administração & dosagem , Proteínas Quinases S6 Ribossômicas 70-kDa/metabolismo , Serina-Treonina Quinases TOR/metabolismo
7.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 44(5): 584-8, 2015 09.
Artigo em Chinês | 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
8.
PLoS One ; 10(11): e0142881, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26587591

RESUMO

Treg cells play a crucial role in immune tolerance, but mechanisms that induce Treg cells are poorly understood. We here have described eosinophils in lamina propria (LP) that displayed high aldehyde dehydrogenase (ALDH) activity, a rate-limiting step during all-trans retinoic acid (ATRA) synthesis, and expressed TGF-ß1 mRNA and high levels of ATRA. Co-incubation assay confirmed that LP eosinophils induced the differentiation of naïve T cells into Treg cells. Differentiation promoted by LP eosinophils were inhibited by blocked either TGF-ß1 or ATRA. Peripheral blood (PB) eosinophils did not produce ATRA and could not induce Treg differentiation. These data identifies LP eosinophils as effective inducers of Treg cell differentiation through a mechanism dependent on TGF-ß1 and ATRA.


Assuntos
Aldeído Desidrogenase/biossíntese , Linfócitos T CD4-Positivos/metabolismo , Linfócitos T Reguladores/citologia , Fator de Crescimento Transformador beta1/biossíntese , Tretinoína/metabolismo , Aldeído Desidrogenase/imunologia , Animais , Linfócitos T CD4-Positivos/imunologia , Diferenciação Celular/imunologia , Eosinófilos/imunologia , Eosinófilos/metabolismo , Tolerância Imunológica , Ativação Linfocitária/imunologia , Camundongos , Mucosa/imunologia , Mucosa/metabolismo , RNA Mensageiro/biossíntese , RNA Mensageiro/imunologia , Linfócitos T Reguladores/imunologia , Fator de Crescimento Transformador beta1/imunologia
9.
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
10.
J Basic Microbiol ; 54(2): 111-9, 2014 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23457112

RESUMO

A majority of known eubacterial genomes are characteristic of GC skew, i.e., the leading strand has exceeding number of G over C. The cause of this compositional bias is still not very clear. In this study, we chose five pairs of genomes from distantly related bacterial genera, i.e., Buchnera, Haemophilus, Mycoplasma, Mycobacterium, and Synechococcus, each containing one with strong GC skew and the other with weak GC skew. Through comparison of the orthologous genes in these genera, we found that neither chromosomal rearrangement nor CDS skew has direct relationship with GC skew.


Assuntos
Bactérias/genética , DNA Bacteriano/genética , Genoma Bacteriano , Composição de Bases , Cromossomos Bacterianos/genética , Sintenia
11.
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
12.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 481-5, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24167126

RESUMO

TcpC is a homolog of the Toll/interleukin-1 receptor (TIR) domain and is secreted by uropathogenic E. coli strain CFT073. TcpC can bind to MyD88, hereby exerting inhibitory effects on macrophages. TcpC represents an important virulence factor that promotes bacterial survival and pathogenicity. TcpC plays a critical role in urinary tract infection, particularly in the pathogenesis of pyelonephritis. In this review,the progress and prospects in TcpC research are discussed.


Assuntos
Proteínas de Escherichia coli/fisiologia , Fatores de Virulência/fisiologia , Animais , Escherichia coli/patogenicidade , Humanos , Camundongos , Pielonefrite/microbiologia , Infecções Urinárias/microbiologia
13.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 486-91, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24167127

RESUMO

OBJECTIVE: To investigate the effects of Toll/interleukin 1 receptor domain-containing protein(TcpC)on macrophages and its mechanisms. METHODS: Murine macrophage J774A cells were co-cultured with TcpC producing wild type E. coli strain CFT073 (TcpC(wt)) or tcpc gene-deleted CFT073 mutant (TcpC(mut)) in Transwell system, respectively. Apoptosis of J774A cells co-cultured with TcpC(wt) or TcpC(mut) was analyzed by Annexin/PI double staining. The levels of reactive oxygen species (ROS) in J774A cells were determined by DCFH-DA staining after treatment with TcpC(wt) or TcpC(mut) at 6 h, 12 h,24 h or 36 h. After the ROS was scavenged by N-acetylcysteine (NAC), the changes of J774A cell apoptosis were also examined. The expression of caspase-3 in J774A cells co-cultured with TcpC(wt) or TcpC(mut) in the presence or absence of 0.1 mmol NAC was detected by Western blot. RESULTS: J774A cells co-cultured with TcpC(wt) for 24 h or 36 h showed significantly increased apoptosis (27.39% ± 4.05% and 28.45% ± 4.55%,respectively) when compared to control group (7.96% ± 1.63% and 10.55% ± 1.44%,P<0.01) or TcpC(mut) group (11.45% ± 2.77% and 19.26%± 2.89%,P<0.01). Levels of ROS in J774A cells treated with TcpC(wt) for 24 h (108.8 ± 9.73) or 36 h (100.3 ± 10.11) were significantly higher than those in control group (56.8 ± 4.11 and 52.8 ± 4.42,P<0.01) or TcpC(mut) (69.7 ± 5.66 and 62.6 ± 4.56, P < 0.01). The pro-apoptotic effects of TcpC(wt) on J774A cells were reversed by 0.1 or 1 mMol NAC treatment. Expression of caspase-3 in J774A cells co-cultured with TcpC(wt) (0.43 ± 0.04) decreased significantly when compared to control group (0.75 ± 0.08,P<0.05) or TcpC(mut) group (0.80 ± 0.12,P<0.05). However,total caspase-3 expression was restored in J774A cells co-cultured with TcpC(wt) in the presence of 0.1 mmol NAC (0.80 ± 0.09). CONCLUSION: TcpC can promote ROS production in macrophages,hereby inducing macrophage apoptosis.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Escherichia coli/farmacologia , Macrófagos/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Fatores de Virulência/farmacologia , Acetilcisteína/farmacologia , Animais , Caspase 3/metabolismo , Escherichia coli/metabolismo , Macrófagos/metabolismo , Camundongos
14.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 492-7, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24167128

RESUMO

OBJECTIVE: To investigate the effects of TcpC on human umbilical vascular endothelial cells (HUVECs) and its mechanisms. METHODS: HUVECs were co-cultured with TcpC secreting wild-type E. coli strain CFT073 (TcpC(wt)) or tcpc gene-deleted CFT073 mutant strain (TcpC(mut)) in transwell system,respectively. Apoptosis of HUVECs was analyzed by Annexin-V/PI double staining. Mitochondrial membrane depolarization was detected by JC-1 staining. Expression of apoptosis-related proteins in HUVECs was determined by Western blot. RESULTS: HUVECs showed morphological changes after co-cultured with TcpC(wt) for 24 h: the cells became detached and cell debris increased,and cell number was also decreased when compared to HUVECs co-cultured with TcpC(mut). The apoptosis of HUVEC cells co-cultured with TcpC(wt) for 24 h significantly increased,compared to that of control group and TcpC(mut) group (60.1% 9.7% compared with 9.0% 1.3% and 16.9% 0.4%,respectively, P<0.05); meanwhile the mitochondrial depolarization of HUVECs co-cultured with TcpC(wt) was significantly increased,compared to that in control and TcpC(mut) groups (64.5% 0.9% compared with 14.5% 2.1% and 15.6% 3.3%, respectively,P<0.05). Cleavage of PARP and inhibition of Mcl-1 and XIAP expression were seen in HUVECs co-cultured with TcpC(wt),but not in groups of control and TcpC(mut). CONCLUSION: TcpC secreted from CFT073 can induce apoptosis of HUVECs through mitochondrial pathway, in which PARP is cleaved and Mcl-1 and XIAP expressions are inhibited.


Assuntos
Apoptose/efeitos dos fármacos , Proteínas de Escherichia coli/farmacologia , Células Endoteliais da Veia Umbilical Humana/efeitos dos fármacos , Células Endoteliais da Veia Umbilical Humana/patologia , Fatores de Virulência/farmacologia , Células Cultivadas , Escherichia coli/metabolismo , Humanos , Potencial da Membrana Mitocondrial , Proteína de Sequência 1 de Leucemia de Células Mieloides/metabolismo , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Inibidoras de Apoptose Ligadas ao Cromossomo X/metabolismo
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 42(5): 578-82, 2013 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-24167142

RESUMO

OBJECTIVE: To evaluate the application of bone turnover markers bone alkaline phosphatase (BALP) and N-MID osteocalcin (N-MID) in monitoring of osteoporosis treatment with recombined parathyroid hormone 1-34 (rhPTH1-34). METHODS: The bone mineral density (BMD) of the lumbar spine L2-L4 and the proximal femur were examined by dual energy X-ray absorptiometry (DXA) before and 6 and 12 months after rhPTH 1-34 treatment. Meanwhile, serum levels of BALP and N-MID were detected by electro-chemiluminescence assay. RESULTS: Six months after rhPTH 1-34 treatment, the BMD of proximal femur remained unchanged, and the BMD of the lumbar L2-L4 spine increased from 0.753 g/cm(2) to 0.781 g/cm(2) (P<0.05); while serum levels of N-MID increased from 15.46 ng/ml to 27.07 ng/ml(P<0.01), BALP from 14.05 µg/ml to 24.31 µg/ml(P<0.01). Twelve months after drug administration, no significant changes were observed in BMD of proximal femur, and the BMD of the lumbar spine L2-L4 increased from 0.753 g/cm(2) to 0.807 g/cm(2)(P<0.01) while serum levels of N-MID and BALP increased from 15.46 ng/ml and 14.05µg/ml to 49.38 ng/ml and 33.99 µg/ml, respectively (both P<0.01). CONCLUSION: Serum levels of BALP and N-MID are more sensitive than BMD. Combination of two methods may provide better indicators for monitoring of osteoporosis treatment.


Assuntos
Fosfatase Alcalina/sangue , Densidade Óssea , Osteocalcina/sangue , Osteoporose/sangue , Osteoporose/tratamento farmacológico , Hormônio Paratireóideo/uso terapêutico , Idoso , Feminino , Fêmur/diagnóstico por imagem , Humanos , Vértebras Lombares/diagnóstico por imagem , Pessoa de Meia-Idade , Osteoporose/diagnóstico por imagem , Radiografia , Proteínas Recombinantes/uso terapêutico
16.
Zhonghua Yu Fang Yi Xue Za Zhi ; 47(2): 129-34, 2013 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-23719103

RESUMO

OBJECTIVE: To develop the national neglect norms for urban primary school students in China. METHODS: According to multi-stage stratified cluster sampling principle, 24 cities of 13 provinces (municipalities) in China were selected during December 1 to 31, 2008. A total of 1491 students in grade 1 - 3 and 2236 students in grade 4 - 6 were selected. Questionnaire was designed by authors and the final norms were determined through several statistical analysis methods, such as item analysis method, factor analysis method, reliability analysis method. The reliability analysis and validity analysis were used to test the stability and reliability of the norms. The evaluation criteria of the scale was determined by the percentile method, then the initial development of the norm was completed. RESULTS: The two questionnaires of grade 1 - 3 and grade 4 - 6 students consisted of 55 and 57 items, respectively, whose item loadings were ranged from 0.301 to 0.687 and 0.321 to 0.730, which met the statistical requirements. For grade 1 - 3 students, the scale's total Cronbach α coefficients was 0.914, the total split-half reliability coefficients was 0.896, the Cronbach α coefficients of four level was above 0.737 except medical and social neglect, split-half reliability was ranged from 0.461 to 0.757; for grade 4-6 students, the scale's total Cronbach α coefficients was 0.916, split-half reliability was 0.883, except social neglect, the Cronbach α coefficients of other level was ranged 0.457 to 0.856, split-half reliability was ranged from 0.500 to 0.798. The total neglect cut-off score of the two scales grade 1-3 and 4-6 were 125 and 155, respectively. CONCLUSION: The structure of two norms was reasonable. The scales have good stability and reliability.


Assuntos
Maus-Tratos Infantis/prevenção & controle , Estudantes , Inquéritos e Questionários , Criança , Maus-Tratos Infantis/estatística & dados numéricos , China/epidemiologia , Feminino , Humanos , Masculino , Reprodutibilidade dos Testes , Instituições Acadêmicas
17.
Oncol Rep ; 29(6): 2275-82, 2013 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-23588374

RESUMO

The present study showed that the combination of dasatinib and combretastatin A-4 (CA-4) exhibited synergistic cytotoxicity in multiple types of cancer, including ovarian, hepatocellular, lung and prostate carcinoma. The enhanced apoptosis induced by dasatinib plus CA-4 was accompanied by a greater extent of mitochondrial depolarization, caspase-3 activation and PARP cleavage in HO-8910 cells. Furthermore, elevated expression of Mcl-1 led to a reduced apoptosis induced by dasatinib plus CA-4, highlighting that downregulated Mcl-1 was necessary for the potentiating effect of dasatinib to CA-4-triggered apoptosis. A clear increase in γ-H2AX expression was observed in the dasatinib+CA-4 group compared with the mono-treatment groups, indicating that dasatinib plus CA-4 may induce double-strand breaks (DSBs) in HO-8910 cells. Moreover, the increased anticancer efficacy of dasatinib combined with CA-4 was further validated in a human HO-8910 ovarian cancer xenograft model in nude mice. Our study is the first to show that the combination of dasatinib with CA-4 could be a novel and promising therapeutic approach for the treatment of cancer.


Assuntos
Protocolos de Quimioterapia Combinada Antineoplásica/farmacologia , Animais , Protocolos de Quimioterapia Combinada Antineoplásica/uso terapêutico , Apoptose/efeitos dos fármacos , Caspase 3/metabolismo , Linhagem Celular Tumoral , Dano ao DNA , Dasatinibe , Sinergismo Farmacológico , Humanos , Camundongos , Camundongos Nus , Mitocôndrias/efeitos dos fármacos , Proteína de Sequência 1 de Leucemia de Células Mieloides , Poli(ADP-Ribose) Polimerase-1 , Poli(ADP-Ribose) Polimerases/metabolismo , Proteínas Proto-Oncogênicas c-bcl-2/metabolismo , Pirimidinas/administração & dosagem , Estilbenos/administração & dosagem , Tiazóis/administração & dosagem , Carga Tumoral/efeitos dos fármacos , Ensaios Antitumorais Modelo de Xenoenxerto
18.
Mol Cell Biochem ; 374(1-2): 13-20, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23124852

RESUMO

Recent studies have demonstrated that the Wnt/ß-catenin signaling plays an important role in stem cell aging. However, the mechanisms of cell senescence induced by Wnt/ß-catenin signaling are still poorly understood. Our preliminary study has indicated that activated Wnt/ß-catenin signaling can induce MSC aging. In this study, we reported that the Wnt/ß-catenin signaling was a potent activator of reactive oxygen species (ROS) generation in MSCs. After scavenging ROS with N-acetylcysteine, Wnt/ß-catenin signaling-induced MSC aging was significantly attenuated and the DNA damage and the expression of p16(INK4A), p53, and p21 were reduced in MSCs. These results indicated that the Wnt/ß-catenin signaling could induce MSC aging through promoting the intracellular production of ROS, and ROS may be the main mediators of MSC aging induced by excessive activation of Wnt/ß-catenin signaling.


Assuntos
Senescência Celular , Células-Tronco Mesenquimais/fisiologia , Espécies Reativas de Oxigênio/metabolismo , Proteínas Wnt/metabolismo , beta Catenina/metabolismo , Acetilcisteína/farmacologia , Animais , Diferenciação Celular , Proliferação de Células , Inibidor p16 de Quinase Dependente de Ciclina/biossíntese , Inibidor de Quinase Dependente de Ciclina p21/biossíntese , Dano ao DNA/efeitos dos fármacos , Interferência de RNA , RNA Interferente Pequeno , Ratos , Ratos Sprague-Dawley , Transdução de Sinais , Proteína Supressora de Tumor p53/biossíntese , beta Catenina/genética
19.
Acta Pharmacol Sin ; 34(2): 262-70, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23222270

RESUMO

AIM: To examine the anti-cancer effects of chamaejasmenin B and neochamaejasmin C, two biflavonones isolated from the root of Stellera chamaejasme L (known as the traditional Chinese herb Rui Xiang Lang Du) in vitro. METHODS: Human liver carcinoma cell lines (HepG2 and SMMC-7721), a human non-small cell lung cancer cell line (A549), human osteosarcoma cell lines (MG63, U2OS, and KHOS), a human colon cancer cell line (HCT-116) and a human cervical cancer cell line (HeLa) were used. The anti-proliferative effects of the compounds were measured using SRB cytotoxicity assay. DNA damage was detected by immunofluorescence and Western blotting. Apoptosis and cell cycle distribution were assessed using flow cytometry analysis. The expression of the related proteins was examined with Western blotting analysis. RESULTS: Both chamaejasmenin B and neochamaejasmin C exerted potent anti-proliferative effects in the 8 human solid tumor cell lines. Chamaejasmenin B (the IC(50) values ranged from 1.08 to 10.8 µmol/L) was slightly more potent than neochamaejasmin C (the IC(50) values ranged from 3.07 to 15.97 µmol/L). In the most sensitive A549 and KHOS cells, the mechanisms underlying the anti-proliferative effects were characterized. The two compounds induced prominent expression of the DNA damage marker γ-H2AX as well as apoptosis. Furthermore, treatment of the cells with the two compounds caused prominent G(0)/G(1) phase arrest. CONCLUSION: Chamaejasmenin B and neochamaejasmin C are potential anti-proliferative agents in 8 human solid tumor cell lines in vitro via inducing cell cycle arrest, apoptosis and DNA damage.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Neoplasias/tratamento farmacológico , Thymelaeaceae/química , Antineoplásicos Fitogênicos/isolamento & purificação , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Dano ao DNA/efeitos dos fármacos , Humanos , Neoplasias/genética , Neoplasias/patologia , Raízes de Plantas/química
20.
Zhonghua Liu Xing Bing Xue Za Zhi ; 33(1): 54-6, 2012 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-22575111

RESUMO

OBJECTIVE: To develop the National Norms of Negligence (NNN) for rural children aged 0 to 35 months. METHODS: According to multi-stage stratified cluster sampling principle, 10 provinces or municipalities (Jilin, Shanxi, Shanxi, Beijing, Anhui, Jiangsu, Hunan, Hubei, Yunnan, Chongqing) in China were selected. A national research group was formed collaboratively. A questionnaire was designed by ourselves. According to several statistical analysis methods, such as item, factor and reliability analysis etc. we determined the norm. The evaluation criteria of the scale were determined by percentile method. Finally, the reliability and validity of the norm were evaluated. RESULTS: In total, 2310 children were surveyed, in which the effective sample were 2227, with an effective rate as 96.4%. The scale consisted of 6 neglected dimensions and 65 items in total. The total Cronbach's a coefficient of the scale was 0.903, with the split-half reliability coefficient as 0.829, the parallel reliability as 0.720 and the re-test reliability as 0.678, respectively. The total neglect cut-off score of this scale was 139. CONCLUSION: The scale seemed to have perfect stability and reliability and all the statistical indicators met the psychometric demands.


Assuntos
Maus-Tratos Infantis/diagnóstico , Pré-Escolar , China , Feminino , Humanos , Lactente , Recém-Nascido , Masculino , Padrões de Referência , Reprodutibilidade dos Testes , População Rural , Inquéritos e Questionários
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