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1.
Front Cell Infect Microbiol ; 14: 1375312, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38779562

RESUMO

Competence development is essential for bacterial transformation since it enables bacteria to take up free DNA from the surrounding environment. The regulation of teichoic acid biosynthesis is tightly controlled during pneumococcal competence; however, the mechanism governing this regulation and its impact on transformation remains poorly understood. We demonstrated that a defect in lipoteichoic acid ligase (TacL)-mediated lipoteichoic acids (LTAs) biosynthesis was associated with impaired pneumococcal transformation. Using a fragment of tacL regulatory probe as bait in a DNA pulldown assay, we successfully identified several regulatory proteins, including ComE. Electrophoretic mobility shift assays revealed that phosphomimetic ComE, but not wild-type ComE, exhibited specific binding to the probe. DNase I footprinting assays revealed the specific binding sequences encompassing around 30 base pairs located 31 base pairs upstream from the start codon of tacL. Expression of tacL was found to be upregulated in the ΔcomE strain, and the addition of exogenous competence-stimulating peptide repressed the tacL transcription in the wild-type strain but not the ΔcomE mutant, indicating that ComE exerted a negative regulatory effect on the transcription of tacL. Mutation in the JH2 region of tacL upstream regulatory sequence led to increased LTAs abundance and displayed higher transformation efficiency. Collectively, our work identified the regulatory mechanisms that control LTAs biosynthesis during competence and thereby unveiled a repression mechanism underlying pneumococcal transformation.


Assuntos
Proteínas de Bactérias , Regulação Bacteriana da Expressão Gênica , Lipopolissacarídeos , Streptococcus pneumoniae , Ácidos Teicoicos , Transformação Bacteriana , Ácidos Teicoicos/biossíntese , Ácidos Teicoicos/metabolismo , Proteínas de Bactérias/genética , Proteínas de Bactérias/metabolismo , Lipopolissacarídeos/biossíntese , Streptococcus pneumoniae/genética , Streptococcus pneumoniae/metabolismo , Transcrição Gênica , Regiões Promotoras Genéticas , Competência de Transformação por DNA , Mutação , Ligação Proteica , Ligases/genética , Ligases/metabolismo
2.
Int J Biol Macromol ; 251: 126306, 2023 Aug 12.
Artigo em Inglês | MEDLINE | ID: mdl-37573922

RESUMO

In this study, konjac glucomannan (KGM) and its derivatives were gavaged as dietary fiber supplements, followed by a single dose of antibiotic cocktail (Abx) containing amoxicillin, neomycin, metronidazole and vancomycin in mice. The effects of dietary fiber on the pharmacokinetics and tissue distribution of each antibiotic were investigated. The results showed that the specific effects of KGM and its derivatives on the absorption, distribution, and elimination of certain antibiotics varied and depended on the nature of the fibers and the characteristics of the antibiotics. Explicitly, the ingestion of KGM and its derivatives enhanced the absorption of metronidazole by 1.7 times and hindered that of amoxicillin by nearly 36 % without affecting the absorption of neomycin sulfate and vancomycin. KGM and its derivatives had no effect on the distribution of amoxicillin and metronidazole, but DKGM and KGM hindered the distributions of neomycin sulfate (from 1.25 h to 1.62 h) and vancomycin (from 0.95 h to 1.14 h), respectively. KGM and its derivatives promoted the elimination of amoxicillin by nearly 38 % while prolonging that of metronidazole by >50 %. KOGM boosted the elimination of neomycin sulfate and vancomycin, but KGM differed from DKGM in acting on the elimination of both.

3.
Chem Pharm Bull (Tokyo) ; 71(4): 262-268, 2023.
Artigo em Inglês | MEDLINE | ID: mdl-37005250

RESUMO

Apple is an important dietary agent for human and apple polyphenols (AP) are the main secondary metabolites of apples. In this study, the protective effects of AP on hydrogen peroxide (H2O2)-induced oxidative stress damage in human colon adenocarcinoma Caco-2 cells were investigated by cell viability, oxidative stress change as well as cell apoptosis. Pre-adding AP could significantly increase the survival rate of H2O2-treated Caco-2 cells. Besides, the activities of antioxidant enzymes superoxide dismutase (SOD), glutathione peroxidase (GSH-PX) and catalase (CAT) were elevated. While the malondialdehyde (MDA) content which is the major oxidant products of polyunsaturated fatty acids (PUFA) reduced after AP treatment. In addition, AP also suppressed the emergence of DNA fragment and decreased the expression of apoptosis-related protein Caspase-3. These results demonstrated that AP could ameliorate H2O2-induced oxidative stress damage in Caco-2 cells, which could serve as a reference for further studies of apple natural active products and deep study of the anti-oxidative stress mechanism.


Assuntos
Adenocarcinoma , Neoplasias do Colo , Humanos , Peróxido de Hidrogênio/farmacologia , Células CACO-2 , Polifenóis/farmacologia , Adenocarcinoma/tratamento farmacológico , Neoplasias do Colo/tratamento farmacológico , Estresse Oxidativo , Antioxidantes/farmacologia , Apoptose , Catalase/metabolismo , Catalase/farmacologia , Sobrevivência Celular
4.
Carbohydr Polym ; 292: 119639, 2022 Sep 15.
Artigo em Inglês | MEDLINE | ID: mdl-35725199

RESUMO

Deacetylated Konjac Glucomannan (DKGM) and Konjac Oligo-glucomannan (KOGM) as two most widely used derivatives in food industry are structurally and physiologically distinct from Konjac glucomannan (KGM). However, the roles of their distinct structures and physicochemical properties in directing microbiota community and the following outcomes are not fully understood. This paper aims to build links between structural complexity of KGM and its derivatives and microbial metabolism. Results showed that structural alterations changed molecular chain aggregation and water binding ability, thus affected the susceptibility to enzymatic degradation, leading to the distinct microbial composition and outcomes profile. Explicitly, KOGM was distinctive in higher abundances of Catenibacterium and Megasphaera, and lacking Prevotella, which was additionally enriched by KGM and DKGM. KOGM, owned the same butyrate-dominant profile with KGM, was utilized fast. However, KGM possessed the highest fermentability. Severe deacetylation reduced fermentability and led DKGM to a propionate-dominant pattern.


Assuntos
Microbioma Gastrointestinal , Mananas/química , Água
5.
J Cell Biochem ; 120(10): 18152-18161, 2019 10.
Artigo em Inglês | MEDLINE | ID: mdl-31190353

RESUMO

Sevoflurane (SEVO) is widely applied as an anesthetic. More recently, its antitumor capacity has been reported. However, potent mechanisms are still incompletely ascertained. In our current study, we attempted to elucidate a potent mechanism associated with microRNA (miR)-29a/DNA methyltransferase 3 alpha (Dnmt3a) in hepatocellular carcinoma (HCC) cells. After transfection and stimulation with SEVO, biological activities of Huh7 and HepG2 cells were evaluated using the cell counting kit-8, Annexin V-fluorescein isothiocyanate apoptosis detection kit, 24-well cell migration assay kit, and tumor invasion 24-well plates. miR-29a and protein expression were quantified with quantitative reverse transcription polymerase chain reaction and Western blot assay, respectively. A Dual-Luciferase Reporter Assay System was used to verify whether miR-29a targets Dnmt3a. We found that SEVO alleviated cell viability, aggrandized apoptosis, and impeded migration and invasion of the Huh7 and HepG2 cells. Besides, SEVO enhanced phosphatase and tensin homolog (PTEN) expression, and phosphorylated expression of phosphatidylinositol 3 kinase (PI3K), and protein kinase B (AKT) was eliminated by SEVO. Of note, SEVO restored miR-29a which was downregulated in HCC tissues and cells. miR-29a inhibitor abolished the positive effects of SEVO on the biological processes. Dual-Luciferase Reporter assay showed miR-29a repressed Dnmt3a expression via targeting its 3'-untranslated region. Further, exogenous expression of Dnmt3a partially repressed PTEN and enhanced phosphorylated expression of PI3K and AKT which were originally elevated or diminished by SEVO. In conclusion, SEVO restored the expression of miR-29a, which posttranscriptionally downregulated Dnmt3a, and then exhibited an antitumor property in HCC cells.


Assuntos
Carcinoma Hepatocelular/genética , DNA (Citosina-5-)-Metiltransferases/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Neoplasias Hepáticas/genética , MicroRNAs/genética , Sevoflurano/farmacologia , Regiões 3' não Traduzidas/genética , Antineoplásicos/farmacologia , Apoptose/efeitos dos fármacos , Apoptose/genética , Carcinoma Hepatocelular/metabolismo , Carcinoma Hepatocelular/patologia , Linhagem Celular , Linhagem Celular Tumoral , Movimento Celular/efeitos dos fármacos , Movimento Celular/genética , Sobrevivência Celular/efeitos dos fármacos , Sobrevivência Celular/genética , DNA (Citosina-5-)-Metiltransferases/metabolismo , DNA Metiltransferase 3A , Células Hep G2 , Humanos , Neoplasias Hepáticas/metabolismo , Neoplasias Hepáticas/patologia , PTEN Fosfo-Hidrolase/metabolismo , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Transdução de Sinais/efeitos dos fármacos
6.
Pak J Pharm Sci ; 31(3): 835-840, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-29716863

RESUMO

The Changshu tablet (CST), one kind of Chinese patent medicine with astringent to the intestine and relieving diarrhea, was made by the root of Rose odorata Sweet var. gigantean (Coll.et Hemsl.) Rehd.et Wils. Although CST has a long history of clinical application, but the research of its chemical composition is less. So the objective of this study was to investigate the main constituents and preliminarily research its effect of the contraction of isolated intestine in vitro. The contents of total polyphenols (126.23mg/g) and total triterpenoids (132.75mg/g) in CST were determined by ultraviolet spectrophotometry. Procyanidin B3, epigallo catechin, catechin, epicatechin, (-)-fisetinidol-(4α, 8)-(-)-catechin, (4α, 8)-(-)-fisetinidol-(-)-epicatechins and (+)-guibourtinidol-(4ß, 8)-epicatechin were identified and determined by high performance liquid chromatography and their contents were distributed from 0.04mg/g to 1.46 mg/g. CST showed significant inhibitory effect against acetylcholine-induced contraction on the rat-isolated intestinal smooth muscle with a dose-dependent manner from 0.06 to 0.6mg/mL. The maxim inhibition rates of CST on duodenum, jejunum, ileum and colon were 65.70±3.47%, 79.74±1.27%, 58.90±1.87% and 45.75±2.21% respectively. These results indicated that CST has a spasmolytic role in gastrointestinal motility which was probably mediated through inhibition of muscarinic receptors. All these findings promote the improvement of the quality control standard of CST and provide pharmacological foundation for clinical application of CST in gastrointestinal tract.


Assuntos
Acetilcolina/toxicidade , Medicamentos de Ervas Chinesas/farmacologia , Motilidade Gastrointestinal/efeitos dos fármacos , Contração Muscular/efeitos dos fármacos , Músculo Liso/efeitos dos fármacos , Rosa , Animais , Relação Dose-Resposta a Droga , Motilidade Gastrointestinal/fisiologia , Masculino , Contração Muscular/fisiologia , Músculo Liso/fisiologia , Técnicas de Cultura de Órgãos , Raízes de Plantas , Ratos , Ratos Sprague-Dawley , Comprimidos , Vasodilatadores/toxicidade
7.
Front Pharmacol ; 8: 619, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28928666

RESUMO

Ulcerative colitis (UC) is a recurrent, chronic intestinal disease. Available treatments for UC are poor effective and/or cause severe adverse events. X-box binding protein 1 (XBP1) and nuclear factor-κB (NF-κB) have been reported to play important roles in UC. Specifically, deletion or downregulation of XBP1 leads to spontaneous enteritis and results in imbalanced secretion of NF-κB and other proinflammatory cytokines. (±)-8-acetonyl-dihydrocoptisine, i.e., (±)-8-ADC, is a monomer semi-synthesized from coptisine. In vitro, (±)-8-ADC activated the transcriptional activity of XBP1, inhibited expression of NF-κB, and reduced production of proinflammatory cytokines, such as tumor necrosis factor alpha (TNF-α) and interleukin-1 beta (IL-1ß), in lipopolysaccharide-stimulated IEC6 cells. Therefore, silencing XBP1 would reduce the inhibition effect of (±)-8-ADC on NF-κB expression and the cytokines secretion in vitro. In a dextran sulfate sodium-induced colitis mouse model, oral administration of (±)-8-ADC ameliorated weight loss and colon contracture, and decreased the average disease activity index score and pathological damage. Simultaneously, (±)-8-ADC also increased XBP1 expression, and decreased NF-κB expression and secretion of myeloperoxidase, TNF-α, IL-6 and IL-1ß in the colon. Therefore, (±)-8-ADC may ameliorate UC via the XBP1-NF-κB pathway and should be considered as a therapeutic candidate for UC.

8.
Eur J Pharm Sci ; 109: 56-64, 2017 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-28757346

RESUMO

There is a severe lack of effective treatments for ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. The identification of valid targets and new drugs is an urgent need. In this study, we identified the XBP-1 agonist HLJ2 as a promising treatment candidate. In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myeloperoxidase (MPO) activity and reduced production of the inflammatory cytokines TNF-α, IL-1ß, and IL-6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demonstrated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microorganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2-treated mice compared with untreated mice. Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.


Assuntos
Anti-Inflamatórios/uso terapêutico , Colite Ulcerativa/tratamento farmacológico , Compostos Heterocíclicos de 4 ou mais Anéis/uso terapêutico , Proteína 1 de Ligação a X-Box/agonistas , Animais , Anti-Inflamatórios/farmacologia , Linhagem Celular , Colite Ulcerativa/sangue , Colite Ulcerativa/microbiologia , Colite Ulcerativa/patologia , Colo/efeitos dos fármacos , Colo/microbiologia , Colo/patologia , Citocinas/sangue , Sulfato de Dextrana , Fezes/microbiologia , Microbioma Gastrointestinal/efeitos dos fármacos , Microbioma Gastrointestinal/genética , Compostos Heterocíclicos de 4 ou mais Anéis/farmacologia , Mucosa Intestinal/efeitos dos fármacos , Mucosa Intestinal/microbiologia , Mucosa Intestinal/patologia , Masculino , Camundongos Endogâmicos C57BL , RNA Ribossômico 16S/genética , Ratos
9.
Artigo em Chinês | WPRIM (Pacífico Ocidental) | ID: wpr-666585

RESUMO

OBJECTIVE To identify the valid targets and new drugs of ulcerative colitis (UC), a recurrent and intractable inflammatory bowel disease. METHODS and RESULTS In an in vivo mouse model of DSS-induced colitis, HLJ2 decreased weight loss, colon contracture, disease activity index (DAI), colon mucosa damage index (CMDI) and histopathological index (HI). HLJ2 also decreased myelo?peroxidase(MPO) activity and reduced production of the inflammatory cytokines TNF- α, IL- 1β, andIL- 6. HLJ2 improved intestinal mucosa damage induced by dextran sodium sulfate (DSS) and increased the expression of ZO-1 and claudin-1. Fecal 16s rRNA high-throughput sequencing demon?strated a significant improvement in UC intestinal dysbacteriosis in mice treated with HLJ2, including increased abundance of probiotics such as Lachnospiraceae, Prevotellaceae, and Lactobacillaceae. At the same time there was a reduction in the abundance of pathogenic or conditional pathogenic microor?ganisms such as Bacteroidaceae, Porphyromonadaceae, Deferribacteraceae, and Pseudomonadaceae in HLJ2- treated mice compared with untreated mice. CONCLUSION Our results demonstrated that the XBP1 agonist HLJ2 inhibits inflammation, regulates the intestinal flora, and protects the intestinal mucosa. It is thus a potential therapeutic agent for ulcerative colitis.

10.
Sensors (Basel) ; 15(9): 23618-39, 2015 Sep 17.
Artigo em Inglês | MEDLINE | ID: mdl-26393589

RESUMO

This paper presents relative orientation and position detection methods for jumping sensor nodes (JSNs) recycling. The methods are based on motion captures of the JSNs by an RGB-D sensor mounted on a carrier robot and the dynamic cooperation between the carrier and the JSNs. A disc-like label with two different colored sides is mounted on the top of the JSNs. The RGB-D sensor can detect the motion of the label to calculate the orientations and positions of the JSNs and the carrier relative to each other. After the orientations and positions have been detected, the JSNs jump into a cabin mounted on the carrier in dynamic cooperation with the carrier for recycling. The performances of the proposed methods are tested with a prototype system. The results show that the carrier can detect a JSN from up to 2 m away and sense its relative orientation and position successfully. The errors of the JSN's orientation and position detections relative to the carrier could be reduced to the values smaller than 1° and 1 cm, respectively, by using the dynamic cooperation strategies. The proposed methods in this paper could also be used for other kinds of mobile sensor nodes and multi-robot systems.

11.
IEEE Trans Haptics ; 8(4): 410-20, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26054074

RESUMO

Recent works regarding real texture perception demonstrate that physical factors such as stiffness and spatial period play a fundamental role in texture perception. This research used a multidimensional scaling (MDS) analysis to further characterize and quantify the effects of the simulation parameters on haptic texture rendering and perception. In a pilot experiment, 12 haptic texture samples were generated by using a 3-degrees-of-freedom (3-DOF) force-feedback device with varying spatial period, height, and stiffness coefficient parameter values. The subjects' perceptions of the virtual textures indicate that roughness, denseness, flatness and hardness are distinguishing characteristics of texture. In the main experiment, 19 participants rated the dissimilarities of the textures and estimated the magnitudes of their characteristics. The MDS method was used to recover the underlying perceptual space and reveal the significance of the space from the recorded data. The physical parameters and their combinations have significant effects on the perceptual characteristics. A regression model was used to quantitatively analyze the parameters and their effects on the perceptual characteristics. This paper is to illustrate that haptic texture perception based on force feedback can be modeled in two- or three-dimensional space and provide suggestions on improving perception-based haptic texture rendering.


Assuntos
Estimulação Física/métodos , Percepção do Tato , Interface Usuário-Computador , Adulto , Algoritmos , Elasticidade , Retroalimentação , Humanos , Estimulação Física/instrumentação , Projetos Piloto , Psicofísica , Análise de Regressão , Adulto Jovem
12.
Shanghai Arch Psychiatry ; 26(2): 88-94, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25092954

RESUMO

BACKGROUND: Increased serum prolactin and weight gain are common side effects of atypical antipsychotics but few studies have assessed the long-term pattern of these adverse effects. AIM: Compare the effects of risperidone and quetiapine on serum prolactin and weight over 12 months of treatment among female patients with first-episode schizophrenia. METHODS: Eighty female inpatients with first-episode schizophrenia were randomly assigned to receive risperidone (n=40) or quetiapine (n=40) for 12 months. Prolactin concentration, weight and height were measured one day before starting treatment and 1, 3, 6, 9 and 12 months after initiating treatment. Severity of symptoms was assessed at the same time periods using the Positive and Negative Syndrome Scale (PANSS). RESULTS: Thirty-one patients in the risperidone group and 33 patients in the quetiapine group completed the 12 months of treatment. PANSS scores decreased at each follow-up assessment for both groups; the improvement was significantly greater in the risperidone group after 3 months and 6 months of treatment but by the 9th month of treatment the level of improvement in the two groups was similar. In the quetiapine group serum prolactin remained stable throughout the 12 months but in the risperidone group the serum prolactin level increased 3.5- to 5.2-fold over the one-year follow-up. Weight gain was seen in both groups, particularly during the first 3 months of treatment: 62% of the increase in BMI in both groups had occurred by the end of the 3rd month of treatment. No between-group differences in weight changes were observed. The correlation between changes in weight and changes in prolactin levels were weakly positive: rs=0.17(p=0.104) in the risperidone group and r=0.07 (p=0.862) in the quetiapine group. CONCLUSIONS: Risperidone and quetiapine had similar efficacy in the first year of treatment of first-episode schizophrenia though risperidone was more rapidly effective. Use of risperidone was associated with chronic hyperprolactinemia but this did not occur with quetiapine. Long-term use of both drugs was associated with sustained weight gain; the timing and magnitude of the weight gain is similar for the two drugs. Weight gain was not strongly related to changes in prolactin levels.

13.
Sci China Life Sci ; 56(2): 181-8, 2013 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-23329155

RESUMO

The skin is the largest organ of the body and is a potential route of exposure to sunscreens and cosmetics containing nanoparticles; however, the permeability of the skin to these nanoparticles is currently unknown. In this paper, we studied the transdermal delivery capacity through mouse skin of water-soluble CdSeS quantum dots (QDs) and the deposition of these QDs in the body. QD solution was coated onto the dorsal hairless skin of male ICR mice. Fluorescence microscopy and transmission electron microscopy (TEM) were used to observe the distribution of QDs in the skin and organs, and inductively coupled plasma-mass spectrometry (ICP-MS) was used to measure the (111)Cd content to indicate the concentration of QDs in plasma and organs. Experimental results indicate that QDs can penetrate into the dermal layer and are limited to the uppermost stratum corneum layers and the hair follicles. Through blood circulation, QDs deposit mostly in liver and kidney and are difficult to clear. (111)Cd concentration was greater than 14 ng g(-1) in kidney after 120 h after 0.32 nmol QDs was applied to a mouse. These results suggest that QDs have in vivo transdermal delivery capacity through mouse skin and are harmful to the liver and kidney.


Assuntos
Pontos Quânticos , Pele/metabolismo , Administração Cutânea , Animais , Cádmio/administração & dosagem , Cádmio/farmacocinética , Cádmio/toxicidade , Células HEK293 , Humanos , Isótopos/administração & dosagem , Isótopos/farmacocinética , Isótopos/toxicidade , Rim/efeitos dos fármacos , Rim/metabolismo , Fígado/efeitos dos fármacos , Fígado/metabolismo , Masculino , Espectrometria de Massas , Camundongos , Camundongos Endogâmicos ICR , Microscopia Eletrônica de Transmissão , Microscopia de Fluorescência , Nanopartículas/administração & dosagem , Nanopartículas/toxicidade , Permeabilidade , Pele/ultraestrutura
14.
Eur J Pharmacol ; 628(1-3): 261-7, 2010 Feb 25.
Artigo em Inglês | MEDLINE | ID: mdl-19919832

RESUMO

Exendin-4 is an incretin mimetic that has been developed for the treatment of patients with type 2 diabetes. EXf is an available carboxy-terminal truncated fragment of exendin-4 with two amino acid substitutions. The purpose of these studies was to evaluate the biological activity of EXf. After a single subcutaneous injection, EXf significantly decreased plasma glucose concentration and glucose excursion following the administration of an oral glucose challenge both in non-diabetic (ICR), monosodium l-glutamate induced insulin resistance (MSG-IR) and diabetic KK-ay mice. Meanwhile, EXf resulted in an increase of first-phase insulin secretion in normal mice and KK-ay mice following the glucose challenge. EXf was also shown to inhibit small intestinal transit in rodent models. EXf activated the cAMP response element (CRE) of the rat insulin I gene promoter (RIP1) GFP-construct in a dose-dependent manner in the cultured mouse insulinoma cell line, termed NIT-1, and this agonist activity was blocked by the glucagon-like peptide 1 (GLP-1) receptor antagonist exendin(9-39). In summary, EXf, an analogue of exendin-4, has agonist activity to GLP-1 receptor in vitro and glucoregulatory activities in vivo, thus it can be considered as a new candidate for the treatment of type 2 diabetes.


Assuntos
Peptídeos/química , Peptídeos/farmacologia , Peçonhas/química , Sequência de Aminoácidos , Animais , Sequência de Bases , Glicemia/metabolismo , Linhagem Celular , AMP Cíclico/genética , Exenatida , Jejum , Feminino , Insulina/genética , Insulina/metabolismo , Secreção de Insulina , Intestino Delgado/efeitos dos fármacos , Intestino Delgado/fisiologia , Masculino , Camundongos , Dados de Sequência Molecular , Período Pós-Prandial , Gravidez , Regiões Promotoras Genéticas/genética , Ratos , Elementos de Resposta/genética , Transcrição Gênica/efeitos dos fármacos
15.
Acta Pharmacol Sin ; 31(1): 35-42, 2010 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-20023693

RESUMO

AIM: To examine the mechanisms underlying the effects of atorvastatin on glucose and lipid metabolism. METHODS: Mice with insulin resistance and obesity induced by monosodium glutamate (MSG) were used. Atorvastatin (80 mg.kg(-1).d(-1)) or vehicle control treatment was given orally once a day for 30 days. Plasma levels of total cholesterol, triglycerides, low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C), and free fatty acids were monitored. Serum insulin and glucose concentrations were used to calculate the insulin resistance index and insulin sensitivity index using a homeostasis model. Body length, waistline circumference, intraperitoneal adipose tissue mass, and total body mass were measured. Semi-quantitative RT-PCR and Western analysis were used to determine the expression of inflammatory factors and proteins involved in inflammation signaling pathways. RESULTS: Atorvastatin improved insulin sensitivity, ameliorated glucose tolerance, and decreased plasma levels of total cholesterol, triglycerides, LDL-C, HDL-C and free fatty acids. Semi-quantitative RT-PCR and Western analysis revealed increased expression of interleukin 6 (IL-6) and tumor necrosis factor alpha (TNF-alpha) in serum and adipose tissue in MSG obese mice. Atorvastatin treatment decreased expression of IL-6, TNF-alpha, nuclear factor kappaB (NF-kappaB) and I-kappa-B (IkappaB) kinase-beta, but increased the expression of IkappaB, in adipose tissue. CONCLUSION: Atorvastatin is a potential candidate for the prevention and therapy of diseases associated with insulin resistance such as type 2 diabetes mellitus and cardiovascular disease. One possible mechanism underlying the effects of atorvastatin on glucose and lipid metabolism may be to ameliorate a state of chronic inflammation.


Assuntos
Ácidos Heptanoicos/farmacologia , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Resistência à Insulina , Obesidade/tratamento farmacológico , Pirróis/farmacologia , Tecido Adiposo/efeitos dos fármacos , Tecido Adiposo/metabolismo , Administração Oral , Animais , Atorvastatina , Glicemia/efeitos dos fármacos , Western Blotting , Modelos Animais de Doenças , Feminino , Insulina/sangue , Insulina/metabolismo , Metabolismo dos Lipídeos/efeitos dos fármacos , Camundongos , Camundongos Endogâmicos ICR , Obesidade/fisiopatologia , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos , Glutamato de Sódio
16.
J Genet Genomics ; 35(1): 25-32, 2008 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-18222406

RESUMO

A total of 321 individuals from six cattle populations of four species in a bovine subfamily in China were studied using 12 pairs of microsatellite markers. The genetic diversities within and between populations were calculated. The phylogenetic trees were constructed by (delta mu)(2) and DA distances, and the divergence times between populations were estimated by (delta mu)(2). Altogether, 144 microsatellite alleles were detected including 24 private alleles and nine shared alleles. Chinese Holstein had the largest number of private alleles (10), whereas, Bohai black and Buffalo had the smallest number of private alleles (2). Chinese Holstein showed the highest genetic variability. Its observed number of alleles (Na), mean effective number of alleles (MNA), and mean heterozygosity (He) were 7.7500, 4.9722, and 0.7719, respectively, whereas, the Buffalo and Yak showed low genetic variability. In the phylogenetic trees, Luxi and Holstein grouped first, followed by Bohai and Minnan. Yak branched next and buffalo emerged as the most divergent population from other cattle populations. Luxi and Bohai were estimated to have diverged 0.039-0.105 million years ago (MYA), however, buffalo and Holstein diverged 0.501-1.337 MYA. The divergence time of Yak versus Minnan, Holstein and buffalo was 0.136-0.363, 0.273-0.729, and 0.326-0.600 MYA, respectively.


Assuntos
Bovinos/genética , Variação Genética , Repetições de Microssatélites/genética , Animais , Bovinos/classificação , China , Conservação dos Recursos Naturais , Evolução Molecular , Marcadores Genéticos , Técnicas de Amplificação de Ácido Nucleico , Filogenia , Padrões de Referência
17.
Sensors (Basel) ; 8(11): 7259-7274, 2008 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-27873927

RESUMO

Observing microclimate changes is one of the most popular applications of wireless sensor networks. However, some target environments are often too dangerous or inaccessible to humans or large robots and there are many challenges for deploying and maintaining wireless sensor networks in those unfriendly environments. This paper presents a mobile sensor network system for solving this problem. The system architecture, the mobile node design, the basic behaviors and advanced network capabilities have been investigated respectively. A wheel-based robotic node architecture is proposed here that can add controlled mobility to wireless sensor networks. A testbed including some prototype nodes has also been created for validating the basic functions of the proposed mobile sensor network system. Motion performance tests have been done to get the positioning errors and power consumption model of the mobile nodes. Results of the autonomous deployment experiment show that the mobile nodes can be distributed evenly into the previously unknown environments. It provides powerful support for network deployment and maintenance and can ensure that the sensor network will work properly in unfriendly environments.

18.
Yi Chuan ; 29(9): 1103-9, 2007 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-17855261

RESUMO

One hundred and forty seven alleles were detected when thirteen microsatellite loci were analyzed applying fluorescence-multiplex PCR technology in eight buffalo populations were analyzed, including six indigenous Chinese native breeds (DechangXinglongFuzhongWenzhouDongliuFu'an), and two introduced breeds (MurrahNili-Ravi). Seven populations have their own unique alleles, total number is twenty-three. As to all the eight populations, effective number of alleles (Ne) was between 2.2908 and 4.2308, heterozygosity (H) between 0.4951 and 0.7194, and polymorphism information content (PIC) between 0.4495 and 0.6776. Eleven of the thirteen microsatellite loci were of high polymorphism and were then the appropriate, polymorphism marker could be used to analyze properly genetic diversity of the involved buffalo populations. Cluster analysis indicated that Fuzhong and Dongliu were clustered together, then with an independent cluster of Xinglong. Wenzhou and Fu'an were clustered together, Dechang was an independent cluster. Murrah and Nili-Ravi were clustered together.


Assuntos
Búfalos/genética , Repetições de Microssatélites/genética , Animais , Búfalos/classificação , Análise por Conglomerados , Frequência do Gene , Variação Genética , Genética Populacional , Genótipo , Filogenia , Reação em Cadeia da Polimerase
19.
Biochem Genet ; 45(3-4): 195-209, 2007 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-17265139

RESUMO

Levels of genetic differentiation, gene flow, and genetic structure of three indigenous cattle populations (Luxi, Bohai, and Minnan) and two reference cattle populations (Chinese Holstein and Qinhai yak) in China were estimated using the information from 12 microsatellites, and 141 microsatellite alleles were identified. The mean number of alleles per locus ranged from 2.9005 in yak to 4.9722 in Holstein. The observed heterozygosity ranged from 0.5325 (yak) to 0.7719 (Holstein); 29 private alleles were detected. The global heterozygote deficit across all populations amounted to 58.5% (p < 0.001). The overall significant (p < 0.001) deficit of heterozygotes because of inbreeding within breeds amounted to 43.2%. The five cattle populations were highly differentiated (F (st) = 26.9%, p < 0.001) at all loci. The heterozygote deficit within the population was highest in Luxi cattle and lowest in yak. The average number of effective migrants exchanged per generation was highest (1.149) between Luxi and Holstein, and lowest (0.509) between Luxi and yak. With the application of prior population information, cluster analysis achieved posterior probabilities from 91% to 98% of correctly assigning individuals to populations. Combining the information of cluster analysis, gene flow, and Structure analysis, the five cattle populations belong to three genetic clusters, a taurine (Luxi and Chinese Holstein), a zebu (Bohai and Minnan), and a yak cluster. This indicates that Bohai black is closer to Bos indicus than Luxi cattle. The evolution and development of three indigenous cattle populations are discussed.


Assuntos
Bovinos/genética , Heterogeneidade Genética , Animais , China , Fluxo Gênico/genética , Geografia , Endogamia , Repetições de Microssatélites/genética , Filogenia
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