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1.
Pharmaceuticals (Basel) ; 16(6)2023 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-37375842

RESUMO

The activity of polysaccharides is usually related to molecular weight. The molecular weight of polysaccharides is critical to their immunological effect in cancer therapy. Herein, the Codonopsis polysaccharides of different molecular weights were isolated using ultrafiltration membranes of 60- and 100-wDa molecular weight cut-off to determine the relationship between molecular weight and antitumor activities. First, three water-soluble polysaccharides CPPS-I (<60 wDa), CPPS-II (60-100 wDa), and CPPS-III (>100 wDa) from Codonopsis were isolated and purified using a combination of macroporous adsorption resin chromatography and ultrafiltration. Their structural characteristics were determined through chemical derivatization, GPC, HPLC, FT-IR, and NMR techniques. In vitro experiments indicated that all Codonopsis polysaccharides exhibited significant antitumor activities, with the tumor inhibition rate in the following order: CPPS-II > CPPS-I > CPPS-III. The treatment of CPPS-II exhibited the highest inhibition rate at a high concentration among all groups, which was almost as efficient as that of the DOX·HCL (10 µg/mL) group at 125 µg/mL concentration. Notably, CPPS-II demonstrated the ability to enhance NO secretion and the antitumor ability of macrophages relative to the other two groups of polysaccharides. Finally, in vivo experiments revealed that CPPS-II increased the M1/M2 ratio in immune system regulation and that the tumor inhibition effect of CPPS-II + DOX was superior to that of DOX monotherapy, implying that CPPS-II + DOX played a synergistic role in regulating the immune system function and the direct tumor-killing ability of DOX. Therefore, CPPS-II is expected to be applied as an effective cancer treatment or adjuvant therapy.

2.
Exp Biol Med (Maywood) ; 248(11): 966-978, 2023 06.
Artigo em Inglês | MEDLINE | ID: mdl-37377100

RESUMO

N-acetylcysteine (NAC) has been reported to improve social interaction behavior, irritability, self-injury, and anxiety-like behavior in autism. However, the molecular mechanism underlying the therapeutic roles of NAC in autism remains unknown. This study mainly aimed to investigate the therapeutic effect of NAC on valproic acid (VPA)-induced autism model and the underlying mechanisms. Our results showed that NAC ameliorated the deficits in sociability and the anxiety- and repetitive-like behaviors displayed by VPA-exposed rats. In addition, VPA exposure induced autophagic deficiency and enhanced Notch-1/Hes-1 pathway activity based on lowered Beclin-1 and LC3B levels, while increased expression of p62, Notch-1, and Hes-1 expression at the protein level. However, NAC recovered VPA-induced autophagic deficiency and reduced Notch-1/Hes-1 pathway activity in a VPA-exposed autism rat model and SH-SY5Y neural cells. The present results demonstrated that NAC improves autism-like behavioral abnormalities by inactivating Notch-1/Hes-1 signaling pathway and recovering autophagic deficiency. Taken together, this study helps to elucidate a novel molecular mechanism that underlies the therapeutic actions of NAC in autism and suggests its potential to ameliorate behavioral abnormalities in neurodevelopmental disorders.


Assuntos
Transtorno Autístico , Neuroblastoma , Efeitos Tardios da Exposição Pré-Natal , Ratos , Humanos , Animais , Feminino , Transtorno Autístico/tratamento farmacológico , Acetilcisteína/farmacologia , Comportamento Animal , Ácido Valproico/efeitos adversos , Modelos Animais de Doenças , Efeitos Tardios da Exposição Pré-Natal/induzido quimicamente
3.
Food Res Int ; 169: 112882, 2023 07.
Artigo em Inglês | MEDLINE | ID: mdl-37254330

RESUMO

The development of food-derived Xanthine Oxidase (XO) inhibitors is critical to the treatment of hyperuricemia and oxidative stress-related disease. Few studies report on milk protein hydrolysates' XO inhibitory activity, with the mechanism of their interaction remaining elusive. Here, different commercial enzymes were used to hydrolyze α-lactalbumin and bovine colostrum casein. The two proteins hydrolyzed by alkaline protease exhibited the most potent XO inhibitory activity (bovine casein: IC50 = 0.13 mg mL-1; α-lactalbumin: IC50 = 0.28 mg mL-1). Eight potential XO inhibitory peptides including VYPFPGPI, GPVRGPFPIIV, VYPFPGPIPN, VYPFPGPIHN, QLKRFSFRSFIWR, LVYPFPGPIHN, AVFPSIVGR, and GFININSLR (IC50 of 4.67-8.02 mM) were purified and identified from alkaline protease hydrolysates by using gel filtration, LC-MS/MS and PeptideRanker. The most important role of inhibiting activity of peptides is linked to hydrophobic interactions and hydrogen bonding based on the results of molecular docking and molecular dynamics simulation. The enzymatic hydrolysate of α-lactalbumin and bovine colostrum casein could be a competitive candidates for hyperuricemia-resisting functional food.


Assuntos
Hiperuricemia , Lactalbumina , Animais , Bovinos , Feminino , Gravidez , Lactalbumina/química , Xantina Oxidase , Caseínas/química , Cromatografia Líquida , Colostro , Simulação de Acoplamento Molecular , Espectrometria de Massas em Tandem , Peptídeos/química , Inibidores Enzimáticos/farmacologia
4.
Int J Biol Macromol ; 239: 124110, 2023 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-36958441

RESUMO

Hydrophobic drug delivery vectors suffer significant challenges in cancer therapy, including efficient encapsulation and tumor targeting ability. In the present study, Rhodiola rosea polysaccharides (RHPs), which have the ability to modulate Tumor-associated macrophages and typical structural characteristics, were employed as an immunoactive vector for drug delivery. Folic acid (FA) and stearic acid (SA) were chemically modified to the backbone of RHPs to obtain the self-assembly and tumor-targeting behavior. Further, the hydrophobic drug, doxorubicin (DOX), was encapsulated in the RHPs derivatives (FA-RHPs-SA) with high efficiency. Additionally, the optimally formed DOX@FA-RHPs-SA had a uniform size distribution of approximately 196 nm and a pH-sensitive release capacity in different acidic conditions. In vitro experiments demonstrated that tumor cells could efficiently uptake DOX@FA-RHPs-SA. Furthermore, the modulatory function of the FA-RHPs-SA on RAW264.7 macrophages was also demonstrated in the transition from M0 to M1 phenotypes, and the M2 differentiated into the M1. Finally, the in vivo antitumor study revealed that the inhibitory effect of DOX@FA-RHPs-SA was superior to the DOX monotherapy treatment, and the new preparation functioned synergistically by inducing tumor cell apoptosis and modulating immune cell function. In conclusion, this study described an RHPs-based hydrophobic delivery vector and achieved an additional helpful antitumor effect by modulating Tumor-associated macrophages.


Assuntos
Nanopartículas , Rhodiola , Neoplasias de Mama Triplo Negativas , Humanos , Macrófagos Associados a Tumor , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Doxorrubicina/química , Sistemas de Liberação de Medicamentos , Nanopartículas/química , Ácido Fólico/química , Imunoterapia , Polissacarídeos/farmacologia , Polissacarídeos/química , Portadores de Fármacos/química
5.
Food Chem ; 373(Pt A): 130999, 2022 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-34710694

RESUMO

Human health can be damaged by free radicals, and antioxidant peptides are excellent radical scavengers. Antioxidant tripeptides data set based on 2,2'-azino-bis (3-ethylbenzothiazoline-6-sulofnic acid) (ABTS) assay was created, 9 types of descriptors were integrated and 4 quantitative structure-activity relationship (QSAR) models were constructed in this study. Several structural factors influencing the activity of antioxidant tripeptides and the dominant amino acids at each position of tripeptides were revealed by the optimal model. Ten food-derived tripeptides with higher activity were selected for synthesis and activity determination. Molecular docking results demonstrated that these tripeptides were stably bound to the Keap1 receptor, further elucidating the antioxidant mechanism. It was known from the simulation of gastrointestinal digestion experiments that the model results possessed a guiding effect on the selection of proteins with high antioxidant activity. The performance of the model was proved to be robust after validation.


Assuntos
Antioxidantes , Fator 2 Relacionado a NF-E2 , Humanos , Proteína 1 Associada a ECH Semelhante a Kelch , Simulação de Acoplamento Molecular , Peptídeos
6.
J Agric Food Chem ; 68(43): 12132-12140, 2020 Oct 28.
Artigo em Inglês | MEDLINE | ID: mdl-32915574

RESUMO

Food-derived angiotensin I-converting enzyme (ACE) inhibitory peptides could potentially be used as safe supportive therapeutic products for high blood pressure. Theoretical approaches are promising methods with the advantage through exploring the relationships between peptide structures and their bioactivities. In this study, peptides with ACE inhibitory activity were collected and curated. Quantitative structure-activity relationship (QSAR) models were developed by using the combination of various machine learning approaches and chemical descriptors. The resultant models have revealed several structure features accounting for the ACE inhibitions. 14 new dipeptides predicted to lower blood pressure by inhibiting ACE were selected. Molecular docking indicated that these dipeptides formed hydrogen bonds with ACE. Five of these dipeptides were synthesized for experimental testing. The QSAR models developed were proofed to design and propose novel ACE inhibitory peptides. Machine learning algorithms and properly selected chemical descriptors can be promising modeling approaches for rational design of natural functional food components.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Aprendizado de Máquina , Peptídeos/química , Peptidil Dipeptidase A/química , Ligação de Hidrogênio , Modelos Moleculares , Simulação de Acoplamento Molecular
7.
Food Chem ; 254: 80-86, 2018 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-29548476

RESUMO

Organophosphorus pesticides (OPPs) are widely used in agricultural production but cause serious pollution. Alkaline phosphatase (ALP) has been implemented to enhance the degradation of OPPs. Deciphering the structural and energetic determinants of OPPs-ALP interaction harbors the potential to understand key biodegradation processes of pesticides at the molecular level. With this aim, the binding modes of OPPs and ALP were studied using computational methods as molecular docking.The CASTp server was used to predict the active site residues. The Discovery Studio Visualizer was used for docking analysis. The results show that OPPs have high binding affinities to ALP with the free energy in the range of-7.68 to-4.06 Kcal mol-1. OPPs and ALP mainly form hydrogen bonds, and amino acid residues, Gln375, Asp55, and Thr413 play important roles in the catalysis process. The experimental data of the OPPs instability in the ALP system is consistent with the binding energy.


Assuntos
Fosfatase Alcalina/metabolismo , Simulação de Acoplamento Molecular , Compostos Organofosforados/metabolismo , Praguicidas/metabolismo , Biodegradação Ambiental , Catálise , Compostos Organofosforados/química , Praguicidas/química , Termodinâmica
8.
Am J Ther ; 24(6): e659-e666, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-26488362

RESUMO

In this study, a randomized trial was conducted to compare the clinical effectiveness of proximal femoral locking compression plate (PFLCP), dynamic hip screw (DHS), and proximal femoral nail antirotation (PFNA) for unstable intertrochanteric femoral fracture treatment. Ninety patients diagnosed with unstable intertrochanteric femoral fracture were enrolled in this study at the department of orthopedics at Linyi Second People's Hospital between May 2010 and May 2012. Fractures were classified according to Tronzo-Evans classification, and the patients were randomly divided into 3 groups, PFLCP, DHS, and PFNA, with 30 patients in each group. The length of incision, operative time, intraoperative blood loss, postoperative drainage, postoperative weight-bearing ambulation time, and duration of fracture union were significantly lower in patients who underwent PFNA and PFLCP compared to patients treated with DHS. Furthermore, when the same clinical parameters were used for comparison, the PFNA group showed markedly lower values compared with the PFLCP group. The total incidence of postoperative complications was significantly different among the PFNA, PFLCP, and DHS groups, with the PFNA group exhibiting markedly lower complication rates compared with PFLCP and DHS groups. However, PFLCP and DHS groups did not show significant differences in the incidence of postoperative complications. Notably, the Harris hip score of PFNA group was markedly higher than the DHS group. In conclusion, our results provide convincing evidence that PFNA may be the most effective internal fixation treatment of unstable intertrochanteric femoral fracture.


Assuntos
Fixação Intramedular de Fraturas/instrumentação , Fixação Intramedular de Fraturas/métodos , Fraturas do Quadril/cirurgia , Complicações Pós-Operatórias/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Perda Sanguínea Cirúrgica/estatística & dados numéricos , Pinos Ortopédicos , Placas Ósseas , Parafusos Ósseos , Feminino , Fixação Intramedular de Fraturas/efeitos adversos , Humanos , Incidência , Masculino , Duração da Cirurgia , Complicações Pós-Operatórias/etiologia , Período Pós-Operatório , Fatores de Tempo , Resultado do Tratamento
9.
Mol Neurobiol ; 54(4): 3102-3116, 2017 05.
Artigo em Inglês | MEDLINE | ID: mdl-27039309

RESUMO

Realgar, a type of mineral drug-containing arsenic, exhibits neurotoxicity. Brain glutathione (GSH) is crucial to protect the nervous system and to resist arsenic toxicity. Therefore, the main aim of this study was to explore the neurotoxic mechanisms of realgar and the protective effects of glycyrrhetinic acid (GA) by observing the effects of GA on the hippocampal GSH biosynthetic pathway after exposure to realgar. Institute of Cancer Research (ICR) mice were randomly divided into five groups: a control group, a GA control group, a realgar alone group, a low-dose GA intervention group, and a high-dose GA intervention group. Cognitive ability was tested using an object recognition task (ORT). The ultrastructures of the hippocampal neurons and synapses were observed. mRNA and protein levels of EAAT1, EAAT2, EAAT3, xCT, Nrf2, HO-1, γ-GCS (GCLC, GCLM), and MRP-1 were measured, as was the cellular localization of EAAT3, xCT, MRP-1, and Nrf2. The levels of GSH in the hippocampus, the levels of glutamate (Glu) and cysteine (Cys) in the extracellular fluid of hippocampal CA1 region, and the levels of active sulfur in the brain were also investigated. The results indicate that realgar lowered hippocampal GSH levels, resulting in ultrastructural changes in hippocampal neurons and synapses and deficiencies in cognitive ability, ultimately inducing neurotoxicity. GA could trigger the expression of Nrf2, HO-1, EAAT1, EAAT2, EAAT3, xCT, MRP-1, GCLC, and GCLM. Additionally, the expression of γ-GT and the supply levels of Glu and Cys increased, ultimately causing a significant increase in hippocampal GSH to alleviate realgar-induced neurotoxicity. In conclusion, the findings from our study indicate that GA can antagonize decreased brain GSH levels induced by realgar and can lessen the neurotoxicity of realgar.


Assuntos
Sistema X-AG de Transporte de Aminoácidos/metabolismo , Sistema y+ de Transporte de Aminoácidos/metabolismo , Arsenicais/farmacologia , Glutationa/metabolismo , Ácido Glicirretínico/farmacologia , Hipocampo/metabolismo , Proteínas Associadas à Resistência a Múltiplos Medicamentos/metabolismo , Fator 2 Relacionado a NF-E2/metabolismo , Sulfetos/farmacologia , Animais , Região CA1 Hipocampal/efeitos dos fármacos , Região CA1 Hipocampal/metabolismo , Líquido Extracelular/efeitos dos fármacos , Líquido Extracelular/metabolismo , Hipocampo/efeitos dos fármacos , Hipocampo/ultraestrutura , Masculino , Camundongos , Camundongos Endogâmicos ICR , Proteínas do Tecido Nervoso/metabolismo , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Neurônios/ultraestrutura , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Enxofre/metabolismo , Sinapses/efeitos dos fármacos , Sinapses/metabolismo , Sinapses/ultraestrutura
10.
3 Biotech ; 6(1): 73, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-28330143

RESUMO

Biodegradation of the pesticides is considered as one of the safest and cheapest ways. The aim of the present study was to reveal if the inoculated Lactic acid bacteria widely used in silage could provide beneficial safety to guarantee dairy feedstuffs and fresh milk. Organophosphorus pesticides (OPPs) degradation in whole corn silage was investigated. Two OPPs, chlorpyrifos and phorate, were added to the whole corn, which was inoculated with L. plantarum 1.0315, L. plantarum 1.0624, L. plantarum 1.0622 and their combination at room temperature for 10 weeks. OPPs residues in the whole corn silage at different weeks were analyzed by gas chromatography after OPPs extraction and purification. The degradation rate constants were calculated according to the OPPs residues results at different fermentation stage. The data showed that the inoculated microorganisms and strain combination exhibited obvious acceleration on OPPs degradation as the wild microorganisms did, and resulted in decreased levels of OPPs from 24.9 to 33.4 %. Strains combination brought about greater OPPs degradation than single strain or the wild microorganisms. Compared to phorate, clorpyrifos had lower degradation rate constants (0.0274-0.0381 vs. 0.0295-0.0355 week-1) and was more stable. The present result indicates safety benefit of lactic acid bacteria on corn silage besides lactic acid fermentation.

11.
Food Chem ; 164: 173-8, 2014 Dec 01.
Artigo em Inglês | MEDLINE | ID: mdl-24996321

RESUMO

Skimmed milk spiked with five organophosphorus pesticides (OPPs), chlorpyrifos, diazinon, fenitrothion, malathion and methyl parathion, was fermented by ten lactic acid bacteria (LAB) and four strain combinations at 42°C for 24h. OPPs left in the samples at different times were extracted, purified, detected by gas chromatography and calculated for degradation rate constants, based on a first-order reaction model. OPPs degradation was enhanced by the inoculated LAB, resulting in 0.8-225.4% increase in the rate constants. Diazinon and methyl parathion were more stable whereas chlorpyrifos, fenitrothion and malathion were more labile. Lactobacillus brevis 1.0209 showed the strongest acceleration on OPPs degradation while strain combination could bring about a synergy between the strains of lower ability. Phosphatase production of the strains might be one of the key factors responsible for the enhanced OPPs degradation, as the detected phosphatase activities were positively correlated to the measured degradation rate constants of OPPs (r=0.636-0.970, P<0.05).


Assuntos
Proteínas de Bactérias/metabolismo , Levilactobacillus brevis/metabolismo , Leite/química , Compostos Organofosforados/metabolismo , Praguicidas/metabolismo , Monoéster Fosfórico Hidrolases/metabolismo , Animais , Bovinos , Clorpirifos/química , Clorpirifos/metabolismo , Cromatografia Gasosa , Fenitrotion/química , Fenitrotion/metabolismo , Cinética , Ácido Láctico/análise , Levilactobacillus brevis/química , Levilactobacillus brevis/enzimologia , Malation/metabolismo , Compostos Organofosforados/química , Praguicidas/química
12.
J Immunotoxicol ; 10(1): 49-58, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-22953760

RESUMO

As a new type of persistent organic pollutant, perfluorooctane sulfonate (PFOS) has raised great concern in recent years due to its ubiquitous distribution in the general environment and its long elimination half-life in humans. PFOS has toxic and carcinogenic effects in animals and humans, but the effects of PFOS on apoptosis are still not clear. The present study aimed to determine the mode of cell death and its mechanism in splenocytes and thymocytes from adult male C57BL/6 mice administered 0, 1, 5, or 10 mg PFOS/kg/day by gavage daily for 7 days. The results showed that more apoptotic cells were present in PFOS-treated mice than in control mice. PFOS induced production of reactive oxygen species (ROS), dissipation of mitochondria membrane potential, and apoptosis of splenocytes and thymocytes. Moreover, activities of superoxide dismutase, catalase, and glutathione reductase were increased, whereas activities of glutathione-S-transferase and glutathione peroxidase were decreased, in splenocytes. Glutathione contents were reduced as well. Differential expressions of proteins such as p53, Bax, caspase-3, and caspase-9 were significantly up-regulated in PFOS-exposed hosts, whereas Bcl-2 expression was significantly down-regulated. One possible mechanism for the findings here was that PFOS could overwhelm homeostasis of anti-oxidative systems, boost ROS generation, impact on mitochondria, and affect protein expression of apoptotic regulators, the latter of which resulted in initiation of the apoptosis program. Results from this study may provide a new insight into the potential adverse effects of PFOS exposure on humans, at the cellular level.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Apoptose , Poluentes Ambientais/toxicidade , Fluorocarbonos/toxicidade , Baço/efeitos dos fármacos , Timo/efeitos dos fármacos , Ácidos Alcanossulfônicos/administração & dosagem , Animais , Apoptose/efeitos dos fármacos , Proteínas Reguladoras de Apoptose/genética , Proteínas Reguladoras de Apoptose/metabolismo , Células Cultivadas , Poluentes Ambientais/administração & dosagem , Feminino , Fluorocarbonos/administração & dosagem , Regulação da Expressão Gênica/efeitos dos fármacos , Humanos , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Potencial da Membrana Mitocondrial/imunologia , Camundongos , Camundongos Endogâmicos C57BL , Oxirredução/efeitos dos fármacos , Estresse Oxidativo/efeitos dos fármacos , Espécies Reativas de Oxigênio/metabolismo , Baço/patologia , Timo/patologia , Proteína Supressora de Tumor p53/genética , Proteína Supressora de Tumor p53/metabolismo
13.
Toxicol Appl Pharmacol ; 264(2): 292-9, 2012 Oct 15.
Artigo em Inglês | MEDLINE | ID: mdl-22959464

RESUMO

Perfluorooctane sulfonate (PFOS) is a persistent environmental contaminant found in human and wildlife tissues. It has been reported that PFOS can cause atrophy of the immune organs and apoptosis of immunocytes in rodents. However, the mechanism behind such cause is still unclear. To understand the model of cell death and its mechanism on lymphoid cells in vivo, we conducted a dose/response experiment in which 4 groups of male adult C57BL/6 mice (12 mice per group) were dosed daily by oral gavage with PFOS at 0, 0.0167, 0.0833, or 0.8333mg/kg/day, yielding targeted Total Administered Dose (TAD) of 0, 1, 5, or 50mg PFOS/kg, respectively, over 60days. The results showed that spleen and thymus weight were significantly reduced in the highest PFOS-dose-group (TAD 50mg PFOS/kg) compared to the control group, whereas liver weight was significantly increased. We analyzed the cell death via apoptosis with an annexin-V/propidium iodide assay by flow cytometry, and observed that both the percentage of apoptosis and the expression of the pro-apoptotic proteins p53 in splenocytes and thymocytes increased in a dose-related manner after PFOS treatment. We also observed that PFOS induced p53-dependent apoptosis through the cooperation between the Bcl-xl down regulation without changing the Bcl-2 and Bax expression. The down regulation of Bcl-xl was strongly indicating mitochondrial involvement in apoptosis. It is confirmed by the release of cytochrome c and activation of caspase-3. All of these findings establish an important role of p53 and mitochondrial function in PFOS induced toxic environment in the host.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Apoptose/efeitos dos fármacos , Fluorocarbonos/toxicidade , Imunossupressores/toxicidade , Baço/citologia , Timócitos/efeitos dos fármacos , Proteína Supressora de Tumor p53/fisiologia , Ácidos Alcanossulfônicos/sangue , Animais , Fator de Indução de Apoptose/metabolismo , Caspase 3/biossíntese , Contagem de Células , Ciclo Celular/efeitos dos fármacos , Separação Celular , Sobrevivência Celular/efeitos dos fármacos , Citocromos c/biossíntese , Citometria de Fluxo , Fluorocarbonos/sangue , Imunossupressores/sangue , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos C57BL , Necrose , Tamanho do Órgão/efeitos dos fármacos , Baço/efeitos dos fármacos , Baço/metabolismo , Timócitos/metabolismo , Proteína X Associada a bcl-2/biossíntese , Proteína bcl-X/biossíntese , Proteína bcl-X/genética
14.
Environ Toxicol ; 27(5): 285-96, 2012 May.
Artigo em Inglês | MEDLINE | ID: mdl-20737580

RESUMO

Previous studies indicate that exposure to perfluorooctanesulfonate (PFOS), a ubiquitous and highly persistent environmental contaminant, induces immunotoxicity in mice. However, few studies have specifically assessed the effects of PFOS on inflammation. This study utilized a standard 60-day oral exposure period to assess the effects of PFOS on the response of inflammatory cytokines [tumor necrosis factor α (TNF-α), interleukin-1 ß (IL-1ß), and interleukin-6 (IL-6)]. Adult male C57BL/6 mice were dosed daily by oral gavage with PFOS at 0, 0.0083, 0.0167, 0.0833, 0.4167, 0.8333 or 2.0833 mg/kg/day to yield a targeted Total Administered Dose (TAD) over 60 days of 0, 0.5, 1, 5, 25, 50, or 125 mg PFOS/kg, respectively. The percentage of peritoneal macrophages (CD11b+ cells) was significantly increased at concentrations ≥ 1 mg PFOS/kg TAD in a dose-dependent manner. Ex vivo IL-1ß production by peritoneal macrophages was elevated substantially at concentrations of ≥ 5 mg PFOS/kg TAD. Moreover, PFOS exposure markedly enhanced the ex vivo production of TNF-α, IL-1ß and IL-6 by peritoneal and splenic macrophages when stimulated either in vitro or in vivo with lipopolysaccharide (LPS). The serum levels of these inflammatory cytokines observed in response to in vivo stimulation with LPS were elevated substantially by exposure to PFOS. PFOS exposure elevated the expression of pro-inflammatory cytokines TNF-α, IL-1ß, IL-6, and proto-oncogene, c-myc, in the spleen. These data suggest that exposure to PFOS modulates the inflammatory response, and further research is needed to determine the mechanism of action.


Assuntos
Ácidos Alcanossulfônicos/toxicidade , Fluorocarbonos/toxicidade , Animais , Citocinas/sangue , Citocinas/metabolismo , Relação Dose-Resposta a Droga , Inflamação/sangue , Inflamação/induzido quimicamente , Inflamação/metabolismo , Interleucina-1beta/sangue , Interleucina-1beta/metabolismo , Interleucina-6/sangue , Interleucina-6/metabolismo , Macrófagos Peritoneais/efeitos dos fármacos , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Baço/efeitos dos fármacos , Baço/metabolismo , Fator de Necrose Tumoral alfa/sangue , Fator de Necrose Tumoral alfa/metabolismo
15.
Zhejiang Da Xue Xue Bao Yi Xue Ban ; 40(3): 281-5, 2011 05.
Artigo em Chinês | MEDLINE | ID: mdl-21671488

RESUMO

OBJECTIVE: To assess the acceptability of pre-exposure prophylaxis (Pr-EP) among the female sex workers in Xinjiang. METHODS: A volunteer-based, anonymous and one-to-one questionnaire survey was conducted in 762 female sex workers (FSW) in Urumqi and Kelamayi of Xinjiang Uyghur Autonomous Region. RESULT: Among 762 FSW surveyed, 673 (88.32%) was not aware of pre-exposure prophylaxis with an awareness rate of 11.55%. The awareness rate of FSWs working in high-end entertainment venues was higher than that of FSWs working in medium-low end entertainment venues(P<0.001). Five hundred and twenty eight FSWs (69.29%) were willing to take Pr-EP, 145 (19.03%) were unwilling to take the medicine and 89 (11.68%) were possible to use the Pr-EP. There was no significant difference in willingness of using Pr-EP among FSWs working in high and medium-low end entertainment venuew (P=0.285). The subjects who were willing to take Pr-EP mainly concerned of the drug security, effectiveness and cost. The main reasons for not willing to take Pr-EP were: not having risk of infecting HIV, suspecting effectiveness of Pr-EP and worrying about side effects. CONCLUSION: The acceptability to use Pr-EP in female sex workers of Xinjiang is relatively high and the drug security, effectiveness and cost will influence the promotion and application of Pr-EP in the future.


Assuntos
Quimioprevenção , Infecções por HIV/prevenção & controle , Conhecimentos, Atitudes e Prática em Saúde , Aceitação pelo Paciente de Cuidados de Saúde , Trabalho Sexual , Adulto , China , Feminino , Humanos , Inquéritos e Questionários , Adulto Jovem
16.
J Neurosurg Spine ; 13(3): 319-23, 2010 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-20809723

RESUMO

OBJECT: The aim of this study was to investigate the clinical significance of both the signal intensity ratio obtained from MR imaging and clinical manifestations on the prognosis of patients with cervical ossification of the posterior longitudinal ligament. METHODS: The authors retrospectively reviewed the records of 58 patients with cervical ossification of the posterior longitudinal ligament who underwent cervical laminoplasty from February 1999 to July 2007. Magnetic resonance imaging (1.5-T) was performed in all patients before surgery. Sagittal T2-weighted images of the cervical spinal cord compressed by the ossified posterior longitudinal ligament showed increased intramedullary signal intensity, whereas the sagittal images obtained at the C7-T1 disc levels were of normal intensity. The signal intensity ratio between regions of intramedullary increased signal intensity and the normal C7-T1 disc level was calculated based on the signal intensity values generated from the MR imaging workstation. Patients were divided into 3 groups according to their signal intensity ratio (high, intermediate, and low signal intensity groups). RESULTS: There were significant differences between the 3 groups regarding recovery rate (p < 0.001), age (p = 0.022), duration of disease (p = 0.001), Babinski sign (p < 0.001), ankle clonus (p < 0.001), and both pre- and postoperative Japanese Orthopaedic Association score (p < 0.001). There was no significant difference in sex among the 3 groups (p = 0.391). CONCLUSIONS: Patients with low signal intensity ratios that changed on T2-weighted imaging experienced a good surgical outcome. Low increased signal intensity might reflect mild neuropathological alteration in the spinal cord and greater recuperative potential. An increased signal intensity ratio with positive pyramidal signs indicates less recuperative potential of the spinal cord and a poor surgical outcome.


Assuntos
Diagnóstico por Computador/métodos , Ligamentos Longitudinais/patologia , Imageamento por Ressonância Magnética/métodos , Ossificação do Ligamento Longitudinal Posterior/patologia , Ossificação do Ligamento Longitudinal Posterior/cirurgia , Idoso , Vértebras Cervicais , Feminino , Seguimentos , Humanos , Ligamentos Longitudinais/diagnóstico por imagem , Ligamentos Longitudinais/cirurgia , Masculino , Pessoa de Meia-Idade , Ossificação do Ligamento Longitudinal Posterior/diagnóstico por imagem , Prognóstico , Estudos Retrospectivos , Tomografia Computadorizada por Raios X , Resultado do Tratamento
17.
Zhonghua Fu Chan Ke Za Zhi ; 45(3): 174-8, 2010 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-20450752

RESUMO

OBJECTIVE: To compare the value of ultrasound and magnetic resonance imaging (MRI) in detecting fetal spine and spinal cord dysplasia. METHODS: Thirty women with complicated pregnancies, age from 22 to 41 years, gestation from 23-38 weeks, were studied with MRI within 72 hours after ultrasound studies and revealed 19 cases of fetal spine with irregular, 7 cases of vertebral canal widened partly and 4 cases of anomalies of spinal curvature. Autopsy or imaging was conducted when pregnancy was terminated. A close follow-up was given for cases continuing pregnancy within 12 months after delivery. RESULTS: (1) Nineteen cases of fetal spine with irregular in ultrasound, the coincidence of antenatal sonographic diagnosis was 42% (8/19), the coincidence of antenatal MRI diagnosis was 89% (17/19). Seven cases of vertebral canal widened partly in ultrasound, the coincidence of antenatal sonographic diagnosis was 0, the coincidence of antenatal MRI diagnosis was 7/7. Four cases of anomalies of spinal curvature in ultrasound, the coincidence of antenatal sonographic diagnosis was 2/4, the coincidence of antenatal MRI diagnosis was 3/4.(2) By MRI study, one cases were conformed their ultrasound diagnosis, eleven cases were completed their ultrasound diagnosis, nine cases were made the same diagnosis as ultrasound and six cases were corrected diagnosis. By MRI and ultrasound study one case of hemivertebra, one case of butterfly vertebra and one case of dorsal dermal sinus were missed diagnosis. Ultrasound had limits and low specificity especially in fetal spinal cord. CONCLUSIONS: MRI can show the spinal cord and its lesion intuitively and has advantages in displaying fetal anomaly of spine and spinal cord. MRI is a valuable complement to sonography in difficult cases and diagnostic accuracy can be significantly improved.


Assuntos
Imageamento por Ressonância Magnética , Defeitos do Tubo Neural/diagnóstico , Medula Espinal/diagnóstico por imagem , Coluna Vertebral/diagnóstico por imagem , Ultrassonografia Pré-Natal , Adulto , Feminino , Feto/anormalidades , Seguimentos , Idade Gestacional , Humanos , Lactente , Recém-Nascido , Gravidez , Diagnóstico Pré-Natal/métodos , Medula Espinal/anormalidades , Coluna Vertebral/anormalidades
18.
Hepatogastroenterology ; 57(104): 1510-4, 2010.
Artigo em Inglês | MEDLINE | ID: mdl-21443112

RESUMO

BACKGROUND/AIMS: Heparanase (HPA) influences tumourigenesis and tumour progression by various mechanisms, including angiogenesis. Cyclooxygenase-2 (COX-2) was strongly correlated with microvessel density, and that COX-2 expression is up-regulated by HPA in esophageal cancer. In this study, we examined the relationship between HPA expression and that of COX-2 in colon carcinoma. The aim of this study was to determine whether the expression of HPA is related to the angiogenesis in colorectal cancer and whether it could be involved in clinical behaviour of colon carcinoma. METHODOLOGY: HPA and COX-2 was analyzed with Immunohistochemistry and Western blot. Microvessels in colon carcinoma were examined by using anti-CD34 antibody. Statistical analysis was applied to test for the prognostic and diagnostic associations. RESULTS: Immunohistochemistry revealed that HPA was expressed at low level in normal colonic mucosa (4/78, 5.1%), but at higher level in tumor tissues (63/78, 80.7%) and closely correlated with tumor lymph node metastasis (p < 0.05). This result was further confirmed by Western blot analysis. Furthermore, carcinomas with high HPA expression demonstrated high COX-2 expression and high MVD (microvesseldensity) labelled with CD34. In addition, mortality was higher in patients with HPA+ phenotype and HPA was an independent predictor of overall survival (p < 0.05). CONCLUSIONS: Our findings indicated that HPA might be an important biomarker for malignant transformation and be involved in promoting colon carcinoma metastasis by increasing angiogenesis.


Assuntos
Neoplasias Colorretais/enzimologia , Ciclo-Oxigenase 2/metabolismo , Glucuronidase/metabolismo , Neovascularização Patológica/enzimologia , Adulto , Idoso , Western Blotting , Feminino , Humanos , Técnicas Imunoenzimáticas , Masculino , Microcirculação , Pessoa de Meia-Idade
19.
Guang Pu Xue Yu Guang Pu Fen Xi ; 29(2): 413-7, 2009 Feb.
Artigo em Chinês | MEDLINE | ID: mdl-19445217

RESUMO

The method of retrieving the concentration of trace gases using of the diagnostic absorption of trace gases based on the scattered sunlight is called passive DOAS. It has been developed so fast in recent years because it remains simple and is prone to being combined with different platform. While retrieving the column density of trace gases with the scattered sunlight as light source, it will be affected strongly by solar Fraunhofer lines, which is also called Ring effect. It makes it hard to retrieve trace gases concentration and affects measurement precision, especially for lower concentration. The influence of Ring effect and its relation with solar zenith angle in stable day will be introduced in the present paper, and the modification will be provided so that different Ring spectrum is selected according to different solar zenith angle. The slant column density (SCD) of NO2 for 3 stable days was retrieved with this modification. It was proved that the modification is possible.

20.
Ai Zheng ; 27(11): 1217-21, 2008 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-19000457

RESUMO

BACKGROUND & OBJECTIVE: Although human pituitary tumor transforming gene 1 (hPTTG1) is overexpressed in malignant tumors such as colorectal cancer, its correlation to clinicopathologic parameters and its value in diagnosis and prognosis prediction of colorectal cancer are still not clear. We investigated the expression of hPTTG1 in colorectal cancer tissues, and elucidated its correlation to some clinicopathologic parameters of colorectal cancer. METHODS: The expression of hPTTG1 in 60 specimens of colorectal cancer and corresponding noncancerous tissues were examined with real-time fluorescent quantitative polymerase chain reaction, and its correlation to seven clinicopathologic parameters were analyzed. RESULTS: The mRNA level of hPTTG1 was significantly higher in colorectal cancer tissues than in corresponding noncancerous tissues (0.42+/-0.07 vs. 0.03+/-0.01, P<0.001), significantly higher in colorectal cancer tissues with serum CEA level of > 5 ng/mL than in those with CEA of < 5 ng/mL (22.79+/-7.42 vs. 9.34+/-2.61, P<0.001), significantly higher in colorectal cancer tissues with diameter of > or = 3.5 cm than in those with diameter of < 3.5 cm (15.80+/-8.80 vs. 10.91+/-5.22, P<0.05), significantly lower in Dukes'A, B tumors than in Dukes' C, D tumors (9.03+/-0.35 and 9.58+/-2.93 vs. 15.88+/-8.09 and 25.69+/-7.67, P<0.001), and significantly higher in colorectal cancer tissues with lymph node metastasis (17.63+/-8.47), liver metastasis (31.07+/-4.10) and other organ metastasis (22.78+/-6.39) than in those without metastasis (11.15+/-6.65) (P<0.001). hPTTG1 expression had no relationship with patients' age, sex and histological type (P>0.05). CONCLUSIONS: hPTTG1 is overexpressed in colorectal cancer. It is closely related to the progression of colorectal cancer, and may be helpful for prognosis prediction of colorectal cancer.


Assuntos
Adenocarcinoma/metabolismo , Neoplasias do Colo/metabolismo , Proteínas de Neoplasias/metabolismo , Reação em Cadeia da Polimerase/métodos , Neoplasias Retais/metabolismo , Adenocarcinoma/sangue , Adenocarcinoma/patologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígeno Carcinoembrionário/sangue , Neoplasias do Colo/sangue , Neoplasias do Colo/patologia , Feminino , Humanos , Neoplasias Hepáticas/secundário , Metástase Linfática , Masculino , Pessoa de Meia-Idade , Proteínas de Neoplasias/genética , Estadiamento de Neoplasias , RNA Mensageiro/metabolismo , Neoplasias Retais/sangue , Neoplasias Retais/patologia , Securina , Carga Tumoral
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