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1.
J Am Chem Soc ; 143(3): 1296-1300, 2021 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-33433203

RESUMO

Oligonucleotide-based materials such as spherical nucleic acid (SNA) have been reported to exhibit improved penetration through the epidermis and the dermis of the skin upon topical application. Herein, we report a self-assembled, skin-depigmenting SNA structure, which is based upon a bifunctional oligonucleotide amphiphile containing an antisense oligonucleotide and a tyrosinase inhibitor prodrug. The two components work synergistically to increase oligonucleotide cellular uptake, enhance drug solubility, and promote skin penetration. The particles were shown to reduce melanin content in B16F10 melanoma cells and exhibited a potent antimelanogenic effect in an ultraviolet B-induced hyperpigmentation mouse model.

2.
J Proteome Res ; 20(2): 1328-1340, 2021 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-33443437

RESUMO

Proteomics approaches designed to catalogue all open reading frames (ORFs) under a defined set of growth conditions of an organism have flourished in recent years. However, no proteome has been sequenced completely so far. Here, we generate the largest yeast proteome data set, including 5610 identified proteins, using a strategy based on optimized sample preparation and high-resolution mass spectrometry. Among the 5610 identified proteins, 94.1% are core proteins, which achieves near-complete coverage of the yeast ORFs. Comprehensive analysis of missing proteins showed that proteins are missed mainly due to physical properties. A review of protein abundance shows that our proteome encompasses a uniquely broad dynamic range. Additionally, these values highly correlate with mRNA abundance, implying a high level of accuracy, sensitivity, and precision. We present examples of how the data could be used, including reannotating gene localization, providing expression evidence of pseudogenes. Our near-complete yeast proteome data set will be a useful and important resource for further systematic studies.

3.
Small ; 17(4): e2006287, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33377275

RESUMO

Blood coagulation and inflammation are the earliest biological responses to implant surfaces. Implant nano-surfaces can significantly impact the osseointegration through the influence on the early phase of bone regeneration. However, the interplay between blood clot property and inflammatory reaction on nanosurfaces is rarely understood. Herein, titania nanotube arrays (TNAs) with different diameters are fabricated on titanium. In vitro evaluation with the whole blood indicates that TNA with a diameter of 15 nm (TNA 15) enables noteworthy platelet activation resulting in distinct clot features compared with that of pure Ti and TNA with a diameter of 120 nm (TNA 120). Further co-culture with macrophages on the clot or in the clot-conditioned medium shows that the clot on TNA 15 downregulates the inflammation and manipulates a favorable osteoimmunomodulatory environment for osteogenesis. In vivo studies further demonstrate that TNA 15 could downregulate the inflammation-related genes while upregulating growth metabolism-related genes in an early healing hematoma. Additionally, TNA 15 promotes de novo bone formation with improved extending of osteocyte dendrites, demonstrating the desired osseointegration. These findings indicate that surface nano-dimensions can significantly influence clot formation and appropriate clot features can manipulate a favorable osteoimmunomodulatory environment for bone regeneration and osseointegration.

4.
Biomed Pharmacother ; 133: 110954, 2021 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-33378992

RESUMO

Anemarrhena asphodeloides is an herb widely used to treat symptoms associated with diabetes in traditional Chinese medicine. However, its key components and metabolites have low bioavailability and poor host absorption. To clarify the anti-diabetic mechanism of A. asphodeloides extract (AAE), we examined the anti-diabetic effects of AAE in rats with diabetes induced by a high-fat diet and streptozotocin. Faeces levels of the main components and metabolites of AAE were significantly higher than levels in plasma, which indicated that gut microbiota might play important roles in its anti-diabetic effect. Microbiological studies showed that unabsorbed components increased the diversity of the gut microbiota, enriched potentially beneficial bacteria, and suppressed potentially harmful bacteria. In vitro studies showed that AAE promoted the proliferation of Blautia coccoides, a bacterium with positive implication for diabetes, in a dose-dependent manner. AAE also promoted pancreatic cell regeneration and restored the function of pancreatic islet cells via peroxiredoxin 4 overexpression. Overall, these results suggest that AAE alleviates diabetes via modulating gut microbiota and protein expression.


Assuntos
Anemarrhena , Bactérias/efeitos dos fármacos , Glicemia/efeitos dos fármacos , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Tipo 2/tratamento farmacológico , Microbioma Gastrointestinal/efeitos dos fármacos , Hipoglicemiantes/farmacologia , Intestinos/microbiologia , Ilhotas Pancreáticas/efeitos dos fármacos , Extratos Vegetais/farmacologia , Anemarrhena/química , Animais , Bactérias/crescimento & desenvolvimento , Biomarcadores/sangue , Glicemia/metabolismo , Proliferação de Células/efeitos dos fármacos , Diabetes Mellitus Experimental/sangue , Diabetes Mellitus Experimental/microbiologia , Diabetes Mellitus Experimental/patologia , Diabetes Mellitus Tipo 2/sangue , Diabetes Mellitus Tipo 2/microbiologia , Diabetes Mellitus Tipo 2/patologia , Dieta Hiperlipídica , Disbiose , Hipoglicemiantes/isolamento & purificação , Mediadores da Inflamação/sangue , Ilhotas Pancreáticas/metabolismo , Ilhotas Pancreáticas/patologia , Lipídeos/sangue , Masculino , Peroxirredoxinas/metabolismo , Extratos Vegetais/isolamento & purificação , Ratos Wistar , Estreptozocina
5.
ACS Appl Mater Interfaces ; 12(41): 45830-45837, 2020 Oct 14.
Artigo em Inglês | MEDLINE | ID: mdl-32936615

RESUMO

Herein, we report a novel strategy to enhance the antisense activity and the pharmacokinetics of therapeutic oligonucleotides. Through the DNA hybridization chain reaction, DNA hairpins modified with poly(ethylene glycol) (PEG) form a bottlebrush architecture consisting of a double-stranded DNA backbone, PEG side chains, and antisense overhangs. The assembled structure exhibits high PEG density on the surface, which suppresses unwanted interactions between the DNA and proteins (e.g., enzymatic degradation) while allowing the antisense overhangs to hybridize with the mRNA target and thereby deplete target protein expression. We show that these PEGylated bottlebrushes targeting oncogenic KRAS can achieve much higher antisense efficacy compared with unassembled hairpins with or without PEGylation and can inhibit the proliferation of lung cancer cells bearing the G12C mutant KRAS gene. Meanwhile, these structures exhibit elevated blood retention times in vivo due to the biological stealth properties of PEG and the high molecular weight of the overall assembly. Collectively, this self-assembly approach bears the characteristics of a simple, safe, yet highly translatable strategy to improve the biopharmaceutical properties of therapeutic oligonucleotides.

6.
Vet Microbiol ; 247: 108755, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32686648

RESUMO

Excessive cytokine production is an important component of the acute respiratory distress syndrome and multiple organ failure. Pneumonia can lead to an overexpression of cytokines, although comparatively little is known about the relevance and differences in cytokines between blood and lung. In this study, piglets were experimentally infected intranasally with Actinobacillus pleuropneumoniae (APP), and transcriptomes of lung tissue and peripheral blood mononuclear cells determined. In addition, the levels of 30 cytokines in broncheoalveolar lavage fluid (BALF) and sera were determined by ELISA. Post infection, there was an early increase in lung monocytes, and a later rise in inflammatory cytokines in BALF. Blood lymphocytes increased early in infection and there was a rise in inflammatory cytokines in the peripheral blood of infected piglets. Genes involved in cytokine production, leukocyte migration and differentiation, lymphocyte activation, and cytokine-mediated signaling pathways in the transcriptomes of lung tissue were significantly down-regulated early in infection. At this early phase of APP infection (0-6 h), the cytokines IL-1ß, MCP-1, and IL-5 in sera increased rapidly and significantly, while many cytokines in BALF decreased. At 48 h post-infection, cytokines in sera were no longer significantly increased, although some were up-regulated in BALF, and there was aggravated pathological damage in the lungs at this time. The data indicate there are substantial differences between immune cells and cytokines in the lung and peripheral blood of APP infected piglets at equivalent time points. The results increase our understanding of pig-APP host interactive biology, and will be important in formulating future therapeutic and preventative strategies to prevent disease caused by APP.

7.
Biomacromolecules ; 21(7): 2714-2725, 2020 07 13.
Artigo em Inglês | MEDLINE | ID: mdl-32459090

RESUMO

Immobilizing zwitterionic molecules on material surfaces has been a promising strategy for creating antifouling surfaces. Herein, we show the ability to surface derivatize an allyl-ether-functionalized thermoplastic polyurethane (TPU) with a zwitterionic thiol in a radically induced thiol-ene reaction. The thermoplastic polyurethane was synthesized to have an allyl-ether side functionality using a modified chain extender molecule. The zwitterion surface functionalization was achieved via thiol-ene reaction in aqueous conditions. The presence of chemically tethered zwitterion moieties on the TPU surface was confirmed using X-ray photoelectron spectroscopy (XPS). Protein adsorption experiments via quartz crystal microbalance (QCM) show reduced fibrinogen attachment for the zwitterion-derivatized TPU when compared to its nonfunctionalized controls. The Zwitterion-TPU also showed a log scale reduction in bacterial adherence. For Pseudomonas aeruginosa and Staphylococcus epidermidis, the Zwitterion-TPU resulted in around a 40 and 50% lower bacterial biomass accumulation, respectively, over the time scale of the experiment. The fibroblast cell viability of TPU remained unaffected by functionalization with zwitterion thiol. The results from our model experiments suggest that a zwitterion-modified TPU is a promising candidate for antifouling catheters.

8.
J Proteome Res ; 19(4): 1556-1564, 2020 04 03.
Artigo em Inglês | MEDLINE | ID: mdl-32155069

RESUMO

As a hepadnavirus, hepatitis B virus (HBV) can cause damage to extrahepatic organs. The kidney is one of the organs that is more susceptible to damage. Research studies on HBV-associated glomerulonephritis (HBV-GN) have been going on for decades. However, the underlying molecular mechanism remains obscure. Here, we applied a tandem mass tag (TMT) isobaric labeling-based method to quantitatively profile the kidney proteome of HBV transgenic mice to illustrate the pathological mechanisms of HBV-GN. Weighted correlation network analysis, a clustering method for gene expression, is used to cluster proteins. Totally, we identified 127 proteins that were highly associated with HBV expression out of a total of 5169 quantified proteins. Among them, the downregulated solute carrier (SLC) family proteins are involved in the process of HBV-GN. We also found that IL1B was upregulated in the kidney tissue of HBV transgenic mice. These findings suggest that HBV disrupts the small molecule transport network of the kidney, which contributes to the occurrence of HBV-GN. The transporter, particularly SLC family 7 member 7 (SLC7A7), is involved in this process, which might serve as an intervention target for HBV-GN. All MS data have been deposited to the ProteomeXchange Consortium via the iProX partner repository with the data set identifier PXD016450.

9.
Biomaterials ; 221: 119399, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31421314

RESUMO

Hernia repair outcomes have improved with more robust material options for surgeons and optimized surgical techniques. However, ventral hernia repairs remain challenging with an inherent risk of post-surgical adhesions in the peritoneal space which can occur regardless of interventional material or its surgical placement. Herein, amino acid-based poly(ester urea)s (PEUs) with varied amount of an allyl ether side chains were modified post polymerization modification with the zwitterionic sulfnate group (3-((3-((3-mercaptopropanoyl)oxy)propyl) dimethylammonio)propane-1-sulfonate) to promote anti-adhesive properties. These alloc-PEUs were processed using roll-to-roll fabrication methods to afford films that were amenable to surface functionalization via a zwitterion-thiol. Functional group availability on the surface was confirmed via fluorescence microscopy, x-ray photoelectron spectroscopy (XPS), and quartz crystal microbalance (QCM) measurements. Zwitterionic treated PEUs exhibited reduced fibrinogen adsorption in vitro when compared to unfunctionalized control polymer. A rat intrabdominal cecal abrasion adhesion model was used to assess the extent and tenacity of adhesion formation in the presence of the PEUs. The 10% alloc-PEU zwitterion functionalized material was found to reduce the extent and tenacity of adhesions when compared to adhesion controls and the unfunctionalized PEU controls.


Assuntos
Aminoácidos Neutros/metabolismo , Materiais Biocompatíveis/química , Materiais Biocompatíveis/uso terapêutico , Poliésteres/química , Poliésteres/uso terapêutico , Aderências Teciduais/prevenção & controle , Ureia/análogos & derivados , Animais , Feminino , Fibrinogênio/metabolismo , Herniorrafia/métodos , Técnicas de Microbalança de Cristal de Quartzo , Ratos , Ratos Sprague-Dawley , Ureia/uso terapêutico
10.
Mol Immunol ; 107: 115-122, 2019 03.
Artigo em Inglês | MEDLINE | ID: mdl-30716562

RESUMO

Rhodanese homology domains (RHODs) are the structural modules of ubiquitous tertiary that occur in three major evolutionary phyla. Despite the versatile and important physiological functions of RHODs containing proteins, little is known about their invertebrate counterparts. A novel HSP67B2-like single-domain rhodanese homologue, MdRDH1 from Musca domestica, whose expression can be induced by bacterial infection or oxidative stress. Silencing MdRDH1 through RNAi causes important accumulations of reactive oxygen species (ROS) and malondialdehyde (MDA), and increases mortality in the larvae treated with bacterial invasion. The E. coli with MdRDH1 and the mutant MdRDH1C135A are transformed, with significant rhodanese activity of the recombinant protein of MdRDH1 in vitro found, without no detection of enzyme activity of the mutant MdRDH1C135A, revealing that catalytic Cys135 in the active-site loop is essential in the sulfurtransferase activity of MdRDH1. When oxidative stress is insulted by phenazine methosulfate (PMS), the MdRDH1 transformed E. coli shows enhanced survival rates compared with those bacteria transformed with MdRDH1C135A. Our research indicates that MdRDH1 confers oxidative stress tolerance, thus rendering evidence for the idea that rhodanese family genes play a critical role in antioxidant defenses. This paper yields novel insights into the potential antioxidative and immune functions of HSP67B2-like rhodanese homologues in invertebrate.


Assuntos
Moscas Domésticas/enzimologia , Proteínas de Insetos/metabolismo , Tiossulfato Sulfurtransferase/metabolismo , Sequência de Aminoácidos , Animais , Doxorrubicina/farmacologia , Moscas Domésticas/microbiologia , Especificidade de Órgãos , Oxirredução , Estresse Oxidativo/efeitos dos fármacos , Filogenia , RNA Mensageiro/genética , RNA Mensageiro/metabolismo , Análise de Sequência de Proteína , Superóxido Dismutase/metabolismo , Tiossulfato Sulfurtransferase/química , Tiossulfato Sulfurtransferase/genética
11.
BMC Neurosci ; 19(1): 72, 2018 Nov 09.
Artigo em Inglês | MEDLINE | ID: mdl-30413143

RESUMO

BACKGROUND: Glycine receptors (GlyRs) are involved in the development of spinal pain sensitization. The GlyRα3 subunit has recently emerged as a key factor in inflammatory pain pathways in the spinal cord dorsal horn (DH). Our study is to identify the extent of location and cell types expressing different GlyR subunits in spinal cord and dorsal root ganglion (DRGs). To tease out the possible actions of GlyRs on pain transmission, we investigate the effects produced by GlyRs on acute inflammatory pain by behavioral testing using prostaglandin E2 (PGE2) intrathecal injection models. Furthermore, we investigate the changes of GlyR expression in DRGs and spinal cord in rats after the induction of acute inflammatory pain. RESULTS: Compared to the vehicle administration, the PGE2 intrathecal injection model produced significantly higher hyperalgesia, which started 3 h after PGE2 injection and lasted more than 5 h. PGE2 intrathecal injection significantly decreased GlyRα1 and GlyRα3 protein expressions in the L5 DH at 1 h and lasted to 5 h, and similar results were observed in the L5 DRG at 5 h. Confocal microscopic images showed the co-existence of punctate gephyrin and GlyRα3 immunoreactivity (IR) throughout the gray matter of the spinal cord, mainly in DH laminae I-III neurons and in ventral horn neurons. It also showed the co-existence of punctate gephyrin and GlyRα3 IR in DRG neurons. CONCLUSIONS: In this study, PGE2 intrathecal injection significantly decreased protein expression of gephyrin, GlyRα1 and GlyRα3 in spinal cord DH and DRG. The gephyrin and GlyRα3 were localized on neuron cells both in the DH and DRG.


Assuntos
Dor Aguda/metabolismo , Gânglios Espinais/metabolismo , Inflamação/metabolismo , Receptores da Glicina/metabolismo , Medula Espinal/metabolismo , Animais , Dinoprostona , Hiperalgesia/metabolismo , Injeções Espinhais , Masculino , Ratos Sprague-Dawley
12.
Ecotoxicol Environ Saf ; 163: 331-339, 2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30059877

RESUMO

Cadmium (Cd) is one of the most toxic metals released into the environment. Here, we investigated the protective role of Zn2+ and/or N-acetyl-L-cysteine (NAC) against Cd cytotoxicity in the erythrocytes of Arbor Acres (AA) broiler chickens. Four hundred one-day-old AA chickens were divided into 12 groups for in vitro and in vivo studies. Zn2+ and/or NAC was given to the Cd exposed AA chickens to assess their protective roles. This was accomplished by investigating nuclear morphological abnormalities, oxidative stress (SOD, CAT, GPx, GSH and T-AOC), cell apoptosis, ROS accumulation and mitochondrial membrane potential (MMP). Results showed that Cd led to dose- and time-dependent cytotoxicity in the erythrocytes of AA chickens characterized by morphological abnormalities, nucleus damage, increased apoptosis rate and antioxidants depletion. Zn2+ or NAC significantly decreased the erythrocyte apoptosis, ROS production and mitochondrial membrane depolarization caused by Cd. SOD, CAT, GPx, GSH and T-AOC activities significantly decreased both in serum and erythrocytes of Cd exposed AA chickens. The supplementation with Zn2+ or NAC alleviated Cd induced oxidative stress through promoting SOD or GPx/GSH activities respectively. NAC presented a better role in reducing apoptosis, improving antioxidant activities more than Zn2+ in vitro. The combined use of Zn2+ and NAC enhanced cytoprotection in Cd exposed erythrocytes of AA chickens compared to Zn2+ or NAC alone. In conclusion, Zn2+ and NAC exerted remarkable protective roles in Cd exposed erythrocytes of AA chickens by inhibiting cell apoptosis and oxidative stress, and this provides a promising approach to antagonize Cd poisoning in poultry.


Assuntos
Acetilcisteína/farmacologia , Antioxidantes/farmacologia , Cádmio/toxicidade , Eritrócitos/efeitos dos fármacos , Zinco/farmacologia , Animais , Apoptose/efeitos dos fármacos , Galinhas , Estresse Oxidativo/efeitos dos fármacos
13.
Biomaterials ; 178: 339-350, 2018 09.
Artigo em Inglês | MEDLINE | ID: mdl-29784475

RESUMO

The use of catheters is ubiquitous in medicine and the incidence of infection remains unacceptably high despite numerous advances in functional surfaces and drug elution. Herein we report the use of a thermoplastic polyurethane containing an allyl ether side-chain functionality (allyl-TPU) that allows for rapid and convenient surface modification with antimicrobial reagents, post-processing. This post-processing functionalization affords the ability to target appropriate TPU properties and maintain the functional groups on the surface of the device where they do not affect bulk properties. A series of quaternary ammonium thiol compounds (Qx-SH) possessing various hydrocarbon tail lengths (8-14 carbons) were synthesized and attached to the surface using thiol-ene "click" chemistry. A quantitative assessment of the amount of Qx-SH available on the surface was determined using fluorescence spectroscopy and X-ray photoelectron spectroscopy (XPS). Contact-killing assays note the Q8-SH composition has the highest antimicrobial activity, and a live/dead fluorescence assay reveals rapid contact-killing of Staphylococcus aureus (>75% in 5 min) and Escherichia coli (90% in 10 min) inocula. Scale-up and extrusion of allyl-TPU provides catheter prototypes for biofilm formation testing with Pseudomonas aeruginosa, and surface-functionalized catheters modified with Q8-SH demonstrate their ability to reduce biofilm formation.


Assuntos
Cateteres/microbiologia , Plásticos/farmacologia , Poliuretanos/farmacologia , Compostos de Amônio Quaternário/farmacologia , Temperatura , Animais , Antibacterianos/farmacologia , Bactérias/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , Fluorescência , Camundongos , Testes de Sensibilidade Microbiana , Viabilidade Microbiana/efeitos dos fármacos , Células NIH 3T3 , Espectroscopia Fotoeletrônica , Compostos de Amônio Quaternário/síntese química , Compostos de Amônio Quaternário/química , Compostos de Sulfidrila/química , Propriedades de Superfície
14.
Langmuir ; 33(51): 14657-14662, 2017 12 26.
Artigo em Inglês | MEDLINE | ID: mdl-29191017

RESUMO

Antifouling surfaces that are resistant to protein adsorption and cell adhesion are desirable for many biomedical devices, such as diagnostic devices, biosensors, and implants. In this study, we developed an antifouling hyperbranched polyglycerol (hPG) surface on hydroxyl poly-p-xylylene (PPX-OH). PPX-OH was deposited via chemical vapor deposition (CVD), and an hPG film was then developed via the ring-opening reaction of glycidol. The hPG film greatly reduced the adhesion of L929 cells and platelets as well as protein adsorption. The addition of alkenyl groups in the hPG layer allows the conjugation of biomolecules, such as peptides and biotin, and elicits specific biological interactions. Since the CVD deposition of PPX-OH could be applied to most types of materials, our approach makes it possible to decorate an antifouling hPG film on most types of materials. Our method could be applied to biosensors, diagnostics, and biomedical devices in the future.

15.
BMC Neurol ; 16(1): 215, 2016 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-27821089

RESUMO

BACKGROUND: Posterior reversible encephalopathy syndrome (PRES) has been associated with Guillain-Barre syndrome in rare cases. Here we report a patient in whom PRES was the presenting manifestation of Bickerstaff's brainstem encephalitis. CASE PRESENTATION: A 75-year-old woman presented with acute onset of hypertension, headache, blurred vision, and left eyelid drooping. Magnetic resonance imaging of the brain showed characteristic PRES lesions involving the parietal and occipital lobes bilaterally. On the 6th day after symptom onset, the patient developed complete ptosis and external ophthalmoplegia of both eyes, progressive ataxia, and bilateral lower limb weakness. Cerebrospinal fluid analyses revealed albuminocytological dissociation (protein: 66.6 mg/dL, WBC: 0/µl), and nerve conduction studies showed demyelinating sensorimotor polyneuropathy. The patient developed somnolence and a left extensor plantar response on the 8th day. A diagnosis of Bickerstaff's brainstem encephalitis was made. Treatment with plasmapheresis led to a rapid improvement of clinical symptoms. To date, only five similar cases have been reported, but this is the only case in which PRES developed prior to treatment. CONCLUSIONS: PRES can be a comorbid condition with Bickerstaff's brainstem encephalitis, either preceding or following treatment; caution should be used in patients with either syndrome who exhibit atypical presentations.


Assuntos
Tronco Encefálico , Encefalite/diagnóstico , Síndrome da Leucoencefalopatia Posterior/etiologia , Idoso , Tronco Encefálico/patologia , Diagnóstico Diferencial , Encefalite/complicações , Encefalite/diagnóstico por imagem , Encefalite/fisiopatologia , Feminino , Humanos , Imagem por Ressonância Magnética , Exame Neurológico
16.
J Chin Med Assoc ; 79(6): 304-8, 2016 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-26874681

RESUMO

BACKGROUND: Theta burst stimulation is a type of pattern-specific repetitive transcranial magnetic stimulation that requires less stimulation time and lower intensity to induce long-lasting effects comparable to those of other repetitive transcranial magnetic stimulation protocols. This pilot study investigated whether continuous theta burst stimulation (cTBS) on the primary motor cortex reduced headache frequency in patients with migraine. METHODS: Nine patients with migraine were recruited into our study. All patients received 20 cTBS sessions (bursts of 3 50-Hz TMS pulses at 200-ms intervals for 40 seconds), administered every weekday for 4 consecutive weeks. All patients kept headache diaries for 4 weeks before stimulation (baseline; T1), during stimulation (T2), and 4 weeks after stimulation (T3). The primary outcome measures were the changes of total headache and migraine days from baseline (Wilcoxon signed-rank test; T2 and T3 vs. T1). RESULTS: The number of total headache days was reduced at T2 and T3 compared with T1 [9.4 ± 6.2 days (p = 0.024) and 8.7 ± 10.1 days (p = 0.012) vs. 13.4 ± 10.1 days]. The number of migraine days was also reduced at T2 and T3 compared with T1 [2.9 ± 2.7 days (p = 0.021) and 1.0 ± 1.6 days (p = 0.008) vs. 8.6 ± 8.7 days]. CONCLUSION: Our results indicate that cTBS on the primary motor cortex might reduce the number of total headache and migraine days in patients with migraine. However, large-scale randomized controlled trials are necessary to further validate the findings.


Assuntos
Transtornos de Enxaqueca/terapia , Córtex Motor/fisiologia , Estimulação Magnética Transcraniana/métodos , Adulto , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados em Cuidados de Saúde , Projetos Piloto
17.
J Microbiol Immunol Infect ; 48(3): 291-5, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-24239064

RESUMO

OBJECTIVES: Stenotrophomonas maltophilia is a bacterial pathogen associated with health-care associated infections, particularly in immunocompromised patients. Members of the fluoroquinolone drug class are frequently used to treat S. maltophilia infection; however, S. maltophilia resistance to fluoroquinolones, especially levofloxacin, has been increasing. METHODS: We sought to identify risk factors associated with levofloxacin resistance using a case-control study. We examined sputum from 76 S. maltophilia-positive patients admitted to our hospital between January 1, 2010 and June 30, 2011. Case groups were defined as patients who had S. maltophilia infections resistant to levofloxacin, and control groups were defined as patients who had S. maltophilia infections susceptible to levofloxacin treatment. Patient information including demographics, previous antibiotic use, and other traits were recorded. In addition, S. maltophilia isolates from patient sputum were assessed for antibiotic resistance as well as for the presence of genes associated with drug resistance. RESULTS: Previous antibiotic treatment with first- or second-generation cephalosporin was found more often in the levofloxacin-susceptible group; by contrast, previous piperacillin/tazobactam treatment occurred more often in the levofloxacin-resistant group. Three genes associated with drug resistance, including SmeA, SmeD, and SpgM were not significantly different between these groups. CONCLUSION: Piperacillin/tazobactam treatment is associated with subsequent isolation of levofloxacin-resistant S. maltophilia from the respiratory tract.


Assuntos
Antibacterianos/farmacologia , Infecção Hospitalar/microbiologia , Farmacorresistência Bacteriana , Infecções por Bactérias Gram-Negativas/microbiologia , Levofloxacino/farmacologia , Infecções Respiratórias/microbiologia , Stenotrophomonas maltophilia/efeitos dos fármacos , Idoso , Idoso de 80 Anos ou mais , Antibacterianos/uso terapêutico , Estudos de Casos e Controles , Infecção Hospitalar/epidemiologia , Uso de Medicamentos , Feminino , Infecções por Bactérias Gram-Negativas/epidemiologia , Hospitais , Humanos , Levofloxacino/uso terapêutico , Masculino , Ácido Penicilânico/análogos & derivados , Ácido Penicilânico/uso terapêutico , Piperacilina/uso terapêutico , Combinação Piperacilina e Tazobactam , Infecções Respiratórias/epidemiologia , Fatores de Risco , Escarro/microbiologia , Stenotrophomonas maltophilia/isolamento & purificação
18.
Biomed Res Int ; 2014: 695797, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25250328

RESUMO

The purpose of this study was to investigate if PPARγ plays a role in the melanogenesis. B16/F10 cells were divided into five groups: control, melanin stimulating hormone (α-MSH), α-MSH+retinol, α-MSH+GW9662 (PPARγ antagonist), and GW9662. Cells in the control group were cultured in the Dulbecco's modified Eagle's medium (DMEM) for 48 hrs. To initiate the melanogenesis, cells in all α-MSH groups were cultured in medium containing α-MSH (10 nM) for 48 hrs. Cells were treated simultaneously with retinol (5 µM) in the α-MSH+retinol group. Instead of retinol, GW9662 (10 µM) was cocultured in the α-MSH+GW9662 group. Cells in the final group were cultured in the DMEM with GW9662. All the analyses were carried out 48 hours after treatments. The α-MSH was able to increase cell number, melanin production, and the activity of tyrosinase, the limiting enzyme in melanogenesis. These α-MSH-induced changes were prevented either by retinol or by GW9662. Further analyses of the activities of antioxidant enzymes including glutathione, catalase, and the superoxide dismutase (SOD) showed that α-MSH treatment raised the activity of SOD which was dependent on PPARγ level. According to our results, the α-MSH-induced melanogenesis was PPARγ dependent, which also modulated the expression of SOD.


Assuntos
Anilidas/administração & dosagem , Carcinogênese/efeitos dos fármacos , Melaninas/metabolismo , Melanoma/metabolismo , Melanoma/patologia , PPAR gama/antagonistas & inibidores , PPAR gama/metabolismo , Animais , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Camundongos , alfa-MSH/administração & dosagem
19.
BMC Musculoskelet Disord ; 15: 238, 2014 Jul 15.
Artigo em Inglês | MEDLINE | ID: mdl-25022571

RESUMO

BACKGROUND: Estradiol plays an important role in the regulation of collagen metabolism. Deficiency of estradiol has been reported to be associated with the degeneration of many connective tissues. However, the association of estradiol and hypertrophy of the ligamentum flavum was seldom explored. Therefore, we studied the effects of estradiol on cultured cells from the ligamentum flavum. METHODS: Primary cultures of human ligamentum flavum cells obtained from surgical specimens of 14 patients undergoing spinal surgery were used to investigate the effect of estradiol on cell proliferation and the expression of collagen, elastin, and matrix metalloproteinases. Downstream pathways of estrogen receptor underlying the regulation of metalloproteinases were also investigated. RESULTS: In our study, we revealed the existence of estrogen receptors on both female and male ligamentum flavum cells with a gender difference. 17ß-estradiol increased early (24 hours) proliferation of ligamentum flavum cells in a dose dependent manner and the effect could not be seen when the cell density increased. Estradiol with a concentration of 10(-9) M decreased collagen levels and increased the expression of MMP-13. Adding an antagonist of PI3K downstream pathway could reverse the expression of MMP-13 caused by estradiol. CONCLUSIONS: The results implied estradiol regulated the expression of MMP-13 via PI3K pathway and contributed to the homeostasis of extracellular matrix in the ligamentum flavum.


Assuntos
Proliferação de Células/efeitos dos fármacos , Colágeno/metabolismo , Estradiol/farmacologia , Ligamento Amarelo/efeitos dos fármacos , Idoso , Células Cultivadas , Colágeno/genética , Relação Dose-Resposta a Droga , Feminino , Humanos , Ligamento Amarelo/metabolismo , Ligamento Amarelo/patologia , Masculino , Metaloproteinase 13 da Matriz/genética , Metaloproteinase 13 da Matriz/metabolismo , Pessoa de Meia-Idade , Fosfatidilinositol 3-Quinase/metabolismo , Inibidores de Fosfoinositídeo-3 Quinase , Inibidores de Proteínas Quinases/farmacologia , Proteólise , Receptores Estrogênicos/efeitos dos fármacos , Receptores Estrogênicos/metabolismo , Transdução de Sinais/efeitos dos fármacos , Fatores de Tempo
20.
J Biol Chem ; 283(46): 31408-16, 2008 Nov 14.
Artigo em Inglês | MEDLINE | ID: mdl-18786925

RESUMO

Previously, we have demonstrated the induction of Src in lipopolysaccharide (LPS)-stimulated macrophages. In this study, we observed that pharmacological blockade or knockout of inducible nitric-oxide synthase (iNOS) reduced LPS-mediated Src induction and macrophage migration. Either SNAP (a NO donor) or 8-Br-cGMP (a cGMP analogue) could rescue these defects in iNOS-null macrophages, which indicated the participation of NO/cGMP in LPS-elicited Src expression and mobilization. In addition, Src family kinase (SFK)-specific inhibitor, PP2, inhibited SNAP- and 8-Br-cGMP-evoked motility implicating the involvement of SFKs downstream of NO/cGMP. Analysis of the expression of SFKs indicated LPS dramatically induced Src, which could be attributable to the increased level of the src transcript. Attenuation of Src by src-specific siRNA reduced LPS- and SNAP-evoked mobilization in Raw264.7 macrophages, and reintroduction of avian Src could rescue their motility. Furthermore, LPS-mediated Src induction led to increased FAK Pi-Tyr-397 and Pi-Tyr-861, which was also iNOS-dependent. With these findings, we concluded that iNOS was important for LPS-mediated macrophage locomotion and Src was a critical player in this process.


Assuntos
Movimento Celular/efeitos dos fármacos , Lipopolissacarídeos/farmacologia , Macrófagos/citologia , Macrófagos/enzimologia , Óxido Nítrico Sintase Tipo II/metabolismo , Quinases da Família src/metabolismo , Animais , Células Cultivadas , GMP Cíclico/análogos & derivados , GMP Cíclico/farmacologia , Proteína-Tirosina Quinases de Adesão Focal/metabolismo , Regulação Enzimológica da Expressão Gênica/efeitos dos fármacos , Guanilato Ciclase/antagonistas & inibidores , Guanilato Ciclase/metabolismo , Macrófagos/efeitos dos fármacos , Camundongos , Camundongos Knockout , Óxido Nítrico Sintase Tipo II/deficiência , Óxido Nítrico Sintase Tipo II/genética , Inibidores de Proteases/farmacologia , RNA Interferente Pequeno/genética , Ratos , Receptores Citoplasmáticos e Nucleares/antagonistas & inibidores , Receptores Citoplasmáticos e Nucleares/metabolismo , S-Nitroso-N-Acetilpenicilamina/farmacologia , Guanilil Ciclase Solúvel , Regulação para Cima/efeitos dos fármacos , Quinases da Família src/genética
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