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1.
Nutr Metab Cardiovasc Dis ; 34(2): 270-280, 2024 02.
Artigo em Inglês | MEDLINE | ID: mdl-38151436

RESUMO

AIM: This meta-analysis aimed to investigate the prognostic value of galectin-3 among patients with stroke. DATA SYNTHESIS: Electronic databases, such as PubMed, Web of Science, Embase, Cochrane, and Clinical Trials, were utilized for conducting searches from database inception to November 2022. Two reviewers independently screened the papers, extracted the data, and used the Newcastle-Ottawa Scale to determine the risk of bias. Stata 17 was employed to conduct the meta-analysis, while the funnel plot was utilized to identify potential publication bias. Subgroup and meta-regression analyses were employed to examine the sources of heterogeneity. Nine studies that satisfied the inclusion criteria were included. Galectin-3 levels were higher post-stroke in patients with poor outcomes and mortality compared to those in patients with good outcomes (standardized mean difference [SMD], 2.83; 95 % confidence interval [CI], 1.25-4.40; P<0.001) and stroke survivors (SMD, 1.18; 95 % CI, 0.96-1,39; P< 0.001), and elevated galectin-3 levels were associated with poor stroke outcomes (odds ratio [OR], 1.19; 95 % CI, 1.06-1.33; P<0.001). Further, higher post-stroke galectin-3 levels were associated with a higher risk of mortality (OR, 1.16; 95 % CI, 1.08-1.25; P<0.001), and this relationship was maintained after trim-and-fill analyses (OR, 1.14; 95 % CI, 1.06-1.22). CONCLUSIONS: Galectin-3 levels post-stroke are increased in patients with a poor prognosis, and this elevation is associated with poor stroke outcomes and mortality. It is recommended that further high-caliber investigations with expanded sample sizes corroborate the outcomes of this study.


Assuntos
Galectina 3 , Acidente Vascular Cerebral , Humanos , Bases de Dados Factuais , Prognóstico , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/terapia , Sobreviventes
2.
Drug Dev Res ; 85(2): e22169, 2024 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-38477422

RESUMO

Neutrophils are a crucial component of the innate immune system and play a pivotal role in various physiological processes. From a physical perspective, hitchhiking is considered a phenomenon of efficient transportation. The combination of neutrophils and hitchhikers has given rise to effective delivery systems both in vivo and in vitro, thus neutrophils hitchhiking become a novel approach to disease treatment. This article provides an overview of the innovative and feasible application of neutrophils as drug carriers. It explores the mechanisms underlying neutrophil function, elucidates the mechanism of drug delivery mediated by neutrophil-hitchhiking, and discusses the potential applications of this strategy in the treatment of cancer, immune diseases, inflammatory diseases, and other medical conditions.


Assuntos
Nanopartículas , Neoplasias , Humanos , Neutrófilos , Sistemas de Liberação de Medicamentos , Portadores de Fármacos , Nanopartículas/uso terapêutico
3.
Parasitol Res ; 122(12): 2859-2870, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-37801131

RESUMO

Prosthogonimiasis poses a threat to the reproductive system of poultry and wild birds, which are the definitive hosts of the parasite causing this disease. However, the parasite infection of the second intermediate host (dragonfly), the primary vector of this pathogen, is rarely reported. In this study, the prevalence of Prosthogonimus infection in dragonflies was investigated from June 2019 to October 2022 in Heilongjiang Province, northeast China. The species of metacercariae isolated from dragonfly were identified by morphological characteristics, molecular biology techniques, and animal infection experiments. The results showed that 11 species of dragonflies and one damselfly were identified and among six of the dragonflies infected by Prosthogonimus metacercariae, Sympetrum depressiusculum (28.53%) had the highest infection rate among all positive dragonflies, followed by Sympetrum vulgatum (27.86%) and Sympetrum frequens (20.99%), which are preferred hosts, and the total prevalence was 20.39% (2061/10,110) in Heilongjiang Province. Three species of Prosthogoniumus metacercariae were isolated, including Prosthogonimus cuneatus, Prosthogonimus pullucidus, and Prosthogonimus sp., among which P. cuneatus was the dominant species in dragonflies in Heilongjiang Province. This is the first report on the prevalence of Prosthogonimus in dragonflies in China, which provides baseline data for the control of prosthogonimiasis in Heilongjiang Province and a reference for the prevention of prosthogonimiasis in other areas of China.


Assuntos
Odonatos , Trematódeos , Animais , Metacercárias , China/epidemiologia , Prevalência
4.
J Nanosci Nanotechnol ; 19(9): 5900-5905, 2019 Sep 01.
Artigo em Inglês | MEDLINE | ID: mdl-30961756

RESUMO

A simple and efficient method is proposed for the synthesis of bimetallic AuPd nanowire networks (NWs) with tunable compositions by using KBr as a structure-directing agent and NaBH4 as a reducing agent. TEM, XRD and XPS results show that the AuPd NWs have a unique one-dimensional network structure. Electrochemical tests indicate that the AuPd NWs catalysts have excellent electrocatalytic activity and durability for methanol oxidation due to the special one-dimensional nanostructure and many structural defects at the junction. The Au1Pd1 NWs show better catalytic activity, which is 2.03 times higher than that of the commercial Pd/C catalyst.

5.
Biochem Biophys Res Commun ; 456(1): 167-72, 2015 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-25446121

RESUMO

Gastrointestinal disorder is a common symptom induced by diverse pathophysiological conditions that include food tolerance, chemotherapy, and irradiation for therapy. Prostaglandin E2 (PGE2) level increase was often reported during gastrointestinal disorder and prostaglandin synthetase inhibitors has been used for ameliorate the symptoms. Exogenous administration of PGE2 induces gastrointestinal disorder, however, the mechanism of action is not known. Therefore, we tested PGE2 effect on visceral afferent sensory neurons of the rat. Interestingly, PGE2 itself did not evoked any response but enhanced serotonin (5-HT)-evoked currents up to 167% of the control level. The augmented 5-HT responses were completely inhibited by a 5-HT type 3 receptor antagonist, ondansetron. The PGE2-induced potentiation were blocked by a selective E-prostanoid type 4 (EP4) receptors antagonist, L-161,982, but type 1 and 2 receptor antagonist AH6809 has no effect. A membrane permeable protein kinase A (PKA) inhibitor, KT5720 also inhibited PGE2 effects. PGE2 induced 5-HT current augmentation was observed on 15% and 21% of the stomach and ileum projecting neurons, respectively. Current results suggest a synergistic signaling in visceral afferent neurons underlying gastrointestinal disorder involving PGE2 potentiation of 5-HT currents. Our findings may open a possibility for screen a new type drugs with lower side effects than currently using steroidal prostaglandin synthetase inhibitors by selectively targeting EP4 receptor/PKA pathway without interrupt prostaglandin synthesis.


Assuntos
Dinoprostona/farmacologia , Íleo/efeitos dos fármacos , Gânglio Nodoso/efeitos dos fármacos , Células Receptoras Sensoriais/metabolismo , Serotonina/metabolismo , Estômago/efeitos dos fármacos , Fibras Aferentes Viscerais/metabolismo , Animais , Anti-Inflamatórios/farmacologia , Carbazóis/farmacologia , Relação Dose-Resposta a Droga , Gastroenteropatias/tratamento farmacológico , Íleo/inervação , Masculino , Neurônios Aferentes/metabolismo , Ondansetron/farmacologia , Técnicas de Patch-Clamp , Prostaglandinas/metabolismo , Pirróis/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores 5-HT3 de Serotonina/metabolismo , Transdução de Sinais , Estômago/inervação , Tiofenos/farmacologia , Triazóis/farmacologia , Xantonas/farmacologia
6.
Korean J Physiol Pharmacol ; 18(2): 149-53, 2014 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-24757377

RESUMO

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.

7.
Int J Oncol ; 64(3)2024 03.
Artigo em Inglês | MEDLINE | ID: mdl-38240092

RESUMO

Gastric cancer is one of the most common malignancies and has relatively high morbidity and mortality rates. Exosomes are nanoscale extracellular vesicles that originate from a diverse array of cells and may be found throughout various bodily fluids. These vesicles are endogenous nanocarriers in their natural state with the unique ability to transport lipids, proteins, DNA and RNA. Exosomes contain DNA, RNA, proteins, lipids and other bioactive components that have crucial roles in the transmission of information and regulation of cell activities in gastric cancer. This paper begins with an exploration of the composition, formation and release mechanisms of exosomes. Subsequently, the role of exosomes in the tumor microenvironment is reviewed in terms of the immune cell population, nonimmune cell population and other factors. Finally, the current status and challenges of exosome­based research on the progression, diagnosis and therapeutic methods of gastric cancer are summarized. This holistic review offers insight that may guide future research directions for exosomes and potentially pave the way for novel therapeutic interventions in the management of gastric cancer.


Assuntos
Exossomos , Neoplasias , Neoplasias Gástricas , Humanos , Neoplasias Gástricas/patologia , Exossomos/metabolismo , Microambiente Tumoral , Neoplasias/patologia , RNA/metabolismo , Proteínas/metabolismo , DNA , Lipídeos
8.
Planta Med ; 79(15): 1408-12, 2013 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-23975867

RESUMO

Flavonoid-rich ethanol extracts of licorice root have sedative and anxiolytic effects. Glabridin is a major flavonoid component from licorice which we evaluated by examining GABA responses in acutely isolated dorsal raphe neurons of the rat. Neurons were recorded with patch-clamp methods at a holding potential of - 50 mV. Glabridin potentiated GABA-induced responses by positively modulating GABAA receptor responses with different concentration range. GABA (2 × 10(-6) M)-evoked currents were potentiated in a stepwise pattern increasing glabridin concentration. Between 10(-12) and 10(-8) M glabridin increased GABA responses by about 140 % of the control. At concentrations above 10(-7) M, a much larger, dose-dependent potentiation occurred before reaching a plateau at 3 × 10-6 M glabridin. A hypnotic drug, zolpidem, also induced biphasic concentration-potentiation relationship. The glabridin potentiation ratio was 2.2 times larger than the maximum potentiation to the benzodiazepine receptor full agonist diazepam. Benzodiazepine receptor antagonist, flumazenil (3 × 10(-7) M), failed to inhibit glabridin (3 × 10(-7) M)-induced potentiation. This result implies that glabridin may exhibit sedative and hypnotic effects by potentiating GABAergic inhibition in dorsal raphe neurons by GABAA receptor actions.


Assuntos
Encéfalo/efeitos dos fármacos , GABAérgicos/farmacologia , Glycyrrhiza/química , Hipnóticos e Sedativos/farmacologia , Isoflavonas/farmacologia , Fenóis/farmacologia , Extratos Vegetais/farmacologia , Receptores de GABA-A/metabolismo , Animais , Ansiolíticos/farmacologia , Encéfalo/metabolismo , Diazepam/farmacologia , Relação Dose-Resposta a Droga , Flumazenil/farmacologia , Neurônios/efeitos dos fármacos , Neurônios/metabolismo , Pentobarbital/farmacologia , Raízes de Plantas , Piridinas/farmacologia , Ratos , Ratos Sprague-Dawley , Zolpidem , Ácido gama-Aminobutírico/farmacologia
9.
IBRO Neurosci Rep ; 15: 327-334, 2023 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-38025662

RESUMO

In the first synapse of the blood-pressure-regulating pathway, a neurokinin (NK) family peptide substance P (SP) is release with an excitatory neurotransmitter, glutamate, to enhance the sensitivity of the baroreflex responses. However, the underlying mechanisms of action are not yet well understood. The effects of NK receptor antagonists and agonists on solitary tract stimulation-evoked excitatory postsynaptic responses were recorded using whole-cell patch-clamp recordings of neurons in the medial portion of the nucleus tractus solitarius (mNTS) in the brainstem. SP reduced the amplitude of the evoked excitatory postsynaptic currents (eEPSCs) and shifted the holding current inward, in a dose-dependent manner. The concentrations of SP needed to induce such responses were different between capsaicin-sensitive unmyelinated (C-type) and capsaicin-resistant myelinated (A-type) neurons. The perfusion of a NK1 receptor antagonist, sendide, reduced the amplitude of eEPSCs in all tested neurons but did not affect the levels of the holding current. A Neurokinin type 1 receptor (NK1 receptor) agonist, [Sar9, Met(O2)11]-SP, reduced the amplitude of the eEPSCs and shifted the holding current inward in capsaicin-resistant neurons; however, it failed to induce any significant changes in the capsaicin-sensitive neurons. Furthermore, a selective Neurokinin type 3 receptor (NK3 receptor) antagonist, SB223412, failed to induce any changes in any tested neuron. In current-clamp experiments, sendide reduced solitary tract (ST)-stimulation evoked firing of action potentials in both A- and C-type neurons. [Sar9, Met(O2)11]-SP suppressed the firing of the action potentials in C-type but not A-type neurons. In spontaneous synaptic recordings, SP reduced frequency of the sEPSCs in CAP sensitive neuron but NK1 agonist reduced at capsaicin resistant neurons. Taken together, the findings show that ST activation leads to the co-transmission of SP and glutamate and enhances baroreflex sensitivity by potentiating the amplitude of eEPSC in an NK1 receptor activity-dependent manner.

10.
Acta Trop ; 232: 106469, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35430263

RESUMO

Prosthogonimus cuneatus and Prosthogonimus pellucidus (Trematoda: Prosthogonimidae) are common flukes of poultry and other birds which can cause severe impacts on animal health and losses to the poultry industry. However, there are limited studies on the molecular epidemiology, population genetics, and systematics of Prosthogonimus species. In the present study, the complete mitochondrial (mt) genomes of P. cuneatus and P. pellucidus were determined to be 14,829 bp and 15,013 bp in length, respectively. Both mt genomes contain 12 protein-coding genes (PCGs) (cox1-3, nad1-6, nad4L, cytb, and atp6), 22 transfer RNA genes, two ribosomal RNA genes, and one non-coding region. Our comparative analysis shows that the atp6 genes of P. cuneatus and P. pellucidus are longer than any previously published atp6 genes of other trematodes. The lengths of the atp6 genes of P. cuneatus and P. pellucidus in this study seem unusual, and should therefore be studied further. The mt genes of P. cuneatus and P. pellucidus are transcribed in the same direction, and the gene arrangements are identical to those of Plagiorchis maculosus, Tamerlania zarudnyi, and Tanaisia sp., but different from those of Eurytrema pancreaticum, Dicrocoelium chinensis, and Brachycladium goliath. The mt genome A + T contents of P. cuneatus and P. pellucidus are 64.47% and 65.34%, respectively. In the 12 PCGs, ATG is the most common initiation codon, whereas TAG is the most common termination codon. The sequence identity of the same 12 PCGs among the eight trematodes (P. cuneatus, P. pellucidus, Pl. maculosus, D. chinensis, E. pancreaticum, B. goliath, T. zarudnyi, Tanaisia sp.) of Xiphidiata are 55.5%-81.7% at the nucleotide level and 43.9%-82.5% at the amino acid level. The nucleotide similarities among the complete mt genomes of the eight trematodes range from 54.1%-81.5%. Phylogenetic analysis based on the aligned concatenated amino acid sequences of the 12 PCGs shows that P. cuneatus and P. pellucidus cluster together and are sister to T. zarudnyi and Tanaisia sp., and this clade is more closely related to E. pancreaticum, Dicrocoelium spp. and Lyperosomum longicauda in the family Dicrocoeliidae, than it is to species in the families Plagiorchiidae and Brachycladiidae. These are the first reported complete mt genomes of Prosthogonimidae, and these data will provide additional molecular resources for further studies of Prosthogonimidae taxonomy, population genetics, and systematics.


Assuntos
Genoma Mitocondrial , Trematódeos , Animais , Genes Mitocondriais , Nucleotídeos , Filogenia , Análise de Sequência de DNA , Trematódeos/genética
11.
Int J Parasitol Parasites Wildl ; 17: 35-42, 2022 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-34976723

RESUMO

Tetrameres grusi is a significant parasitic nematode of cranes that is classified into suborder Spirurina. However, for more than a century, this classification has been controversial. Mitochondrial genomes are valuable resources for parasite taxonomy, population genetics and systematics studies. Here, the mitochondrial genome of T. grusi was determined and subsequently compared with those from Spirurina species using concatenated datasets of amino acid sequences predicted from mitochondrial protein-coding genes. The complete mitochondrial genome of T. grusi is circular with 13,709 bp, and it contains 12 protein-coding genes, 22 transfer RNA genes, two ribosomal RNA genes and one non-coding region. All of the protein-coding genes are transcribed in the same direction. There were 18 intergenic spacers of 1-44 bp, and six locations with gene overlaps, ranging from 1 bp to 28 bp, in the mitochondrial genome of T. grusi. The AT content of this mitochondrial genome was 71.56%. This was similar to mitochondrial genomes of other Spirurina species, which also exhibited strong AT content bias, not only in the nucleotide composition but also in codon usage. The sequenced mitogenomes of the 25 Spirurina nematodes showed three classes of gene arrangements based on the 12 protein-coding genes, and the gene arrangement of the T. grusi mitochondrial genome belonged to the Class I. Phylogenetic analyses using mitochondrial genomes of 25 Spirurina nematodes revealed that T. grusi (Habronematoidea) was closer to Gongylonema pulchrum (Spiruroidea) than Spirocerca lupi (Thelazioidea). The availability of the complete mitochondrial genome sequence of T. grusi provides new and useful genetic markers for further studies on Spirurina nematodes.

12.
Biochem Biophys Res Commun ; 413(4): 637-42, 2011 Oct 07.
Artigo em Inglês | MEDLINE | ID: mdl-21945440

RESUMO

Isoliquiritigenin (ILTG) is a chalcone compound and has valuable pharmacological properties such as antioxidant, anti-inflammatory, anticancer, and antiallergic activities. Recently, the anxiolytic effect of ILTG has been reported; however, its action mechanism and hypnotic activity have not yet been demonstrated. Therefore, we investigated the hypnotic effect and action mechanism of ILTG. ILTG significantly potentiated the pentobarbital-induced sleep in mice at doses of 25 and 50mg/kg. The hypnotic activity of ILTG was fully inhibited by flumazenil (FLU), a specific gamma-aminobutyric acid type A (GABA(A))-benzodiazepine (BZD) receptor antagonist. The binding affinity of ILTG was 0.453 µM and was found to be higher than that of the reference compound, diazepam (DZP, 0.012 µM). ILTG (10(-5)M) potentiated GABA-evoked currents to 151% of the control level on isolated dorsal raphe neurons. ILTG has 65 times higher affinity for GABA(A)-BZD receptors than DZP, and the dissociation constant for ILTG was 4.0 × 10(-10)M. The effect of ILTG on GABA currents was blocked by 10(-7)M FLU and ZK-93426. These results suggest that ILTG produces hypnotic effects by positive allosteric modulation of GABA(A)-BZD receptors.


Assuntos
Chalconas/farmacologia , Moduladores GABAérgicos/farmacologia , Hipnóticos e Sedativos/farmacologia , Receptores de GABA-A/metabolismo , Regulação Alostérica , Animais , Benzodiazepinas/farmacologia , Células Cultivadas , Chalconas/química , Hipnóticos e Sedativos/química , Camundongos , Neurônios/efeitos dos fármacos , Fenobarbital/farmacologia , Ratos , Ratos Sprague-Dawley , Receptores de GABA-A/química
13.
Oncogene ; 24(12): 1973-81, 2005 Mar 17.
Artigo em Inglês | MEDLINE | ID: mdl-15674326

RESUMO

Hematopoietic cytokines play crucial roles in regulation of cell cycle progression and apoptosis of hematopoietic cells. However, the effects of cytokines on cellular responses to chemotherapeutic agents and the mechanisms involved have remained elusive. Here we report that erythropoietin or IL-3 promotes G2/M arrest and prevents apoptosis induced by the topoisomerase II inhibitor etoposide in murine hematopoietic 32D cells and human leukemic UT7 cells. Erythropoietin or IL-3 significantly enhanced etoposide-induced activation-specific phosphorylation of Chk1, a checkpoint kinase that inhibits Cdc2 activation by Cdc25 phosphatases, and led to the inhibition of Cdc2 kinase activity with the persistent inhibitory phosphorylation on Tyr15. The inhibitory Cdc2 phosphorylation and G2/M block by etoposide were enhanced or inhibited by overexpression of Chk1 or by the specific Chk1 inhibitor SB218078, respectively. The G2/M arrest induced by etoposide was also enhanced or inhibited by expression of a constitutively activated or dominant-negative Akt mutant, respectively. Furthermore, SB216763 or LiCl, a specific inhibitor for the GSK3 kinase inhibited by Akt, enhanced the Chk1 phosphorylation and G2/M arrest by etoposide. These results indicate that hematopoietic cytokines protect etoposide-treated cells from DNA damage-induced apoptosis by promoting, through the PI3K/Akt/GSK3 signaling pathway, G2/M checkpoint that is dependent on Chk1-mediated inhibition of Cdc2.


Assuntos
Apoptose/efeitos dos fármacos , Divisão Celular/fisiologia , Citocinas/farmacologia , Etoposídeo/farmacologia , Fase G2/fisiologia , Quinase 3 da Glicogênio Sintase/metabolismo , Proteínas Quinases/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas Proto-Oncogênicas/metabolismo , Animais , Ciclo Celular/efeitos dos fármacos , Divisão Celular/efeitos dos fármacos , Linhagem Celular , Linhagem Celular Tumoral , Quinase 1 do Ponto de Checagem , Eritropoetina/farmacologia , Citometria de Fluxo , Fase G2/efeitos dos fármacos , Quinase 3 da Glicogênio Sintase/efeitos dos fármacos , Humanos , Interleucina-3/farmacologia , Leucemia , Camundongos , Fosforilação , Fosfotirosina/metabolismo , Proteínas Serina-Treonina Quinases/efeitos dos fármacos , Proteínas Proto-Oncogênicas/efeitos dos fármacos , Proteínas Proto-Oncogênicas c-akt
14.
PLoS One ; 10(10): e0139889, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26473729

RESUMO

Gene-set-based analysis (GSA), which uses the relative importance of functional gene-sets, or molecular signatures, as units for analysis of genome-wide gene expression data, has exhibited major advantages with respect to greater accuracy, robustness, and biological relevance, over individual gene analysis (IGA), which uses log-ratios of individual genes for analysis. Yet IGA remains the dominant mode of analysis of gene expression data. The Connectivity Map (CMap), an extensive database on genomic profiles of effects of drugs and small molecules and widely used for studies related to repurposed drug discovery, has been mostly employed in IGA mode. Here, we constructed a GSA-based version of CMap, Gene-Set Connectivity Map (GSCMap), in which all the genomic profiles in CMap are converted, using gene-sets from the Molecular Signatures Database, to functional profiles. We showed that GSCMap essentially eliminated cell-type dependence, a weakness of CMap in IGA mode, and yielded significantly better performance on sample clustering and drug-target association. As a first application of GSCMap we constructed the platform Gene-Set Local Hierarchical Clustering (GSLHC) for discovering insights on coordinated actions of biological functions and facilitating classification of heterogeneous subtypes on drug-driven responses. GSLHC was shown to tightly clustered drugs of known similar properties. We used GSLHC to identify the therapeutic properties and putative targets of 18 compounds of previously unknown characteristics listed in CMap, eight of which suggest anti-cancer activities. The GSLHC website http://cloudr.ncu.edu.tw/gslhc/ contains 1,857 local hierarchical clusters accessible by querying 555 of the 1,309 drugs and small molecules listed in CMap. We expect GSCMap and GSLHC to be widely useful in providing new insights in the biological effect of bioactive compounds, in drug repurposing, and in function-based classification of complex diseases.


Assuntos
Antineoplásicos/química , Antineoplásicos/farmacologia , Bases de Dados Genéticas , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Redes Reguladoras de Genes , Genes Neoplásicos , Feminino , Células HL-60 , Humanos , Células MCF-7 , Masculino
15.
Brain Res ; 1432: 1-6, 2012 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-22119393

RESUMO

Propofol, an intravenous anesthetic, is broadly used for general anesthesia and diagnostic sedations due to its fast onset and recovery. Propofol depresses respiratory and cardiovascular reflex responses, however, their underlying mechanisms are not well known. Cardiorespiratory information from visceral afferent vagus nerves is integrated in the nucleus tractus solitarii (NTS). Cardiac and respiratory signals transducing vagal afferent neurons release the excitatory neurotransmitter glutamate onto NTS neurons in an activity dependent manner and trigger negative feedback reflex responses. In this experiment, the effects of propofol on glutamatergic synaptic responses at NTS neurons was tested using patch clamp methods. Glutamatergic excitatory postsynaptic currents (EPSC) were recorded at chloride reversal potential (-49mV) without γ-aminobutyric acid type A (GABA(A)) receptor antagonists. Propofol (≥3µM) facilitated frequency of the spontaneous EPSCs in a concentration dependent manner without altering amplitude and decay time. The GABA(A) receptor selective antagonist, gabazine (6µM), attenuated propofol effects on glutamate release. Propofol (10µM) evoked glutamate release was also blocked in the presence of the voltage dependent Na(+) and Ca(2+) channel blockers TTX (0.3µM) and Cd(2+) (0.2mM), respectively. In addition, the Na(+)-K(+)-Cl(-) cotransporter type 1 antagonist bumetanide (10µM) also inhibited propofol evoked increase in sEPSC frequency. These results suggest that propofol evoked glutamate release onto NTS neurons by GABA(A) receptor-mediated depolarization of the presynaptic excitatory terminals.


Assuntos
Anestésicos Intravenosos/farmacologia , Potenciais Pós-Sinápticos Excitadores/efeitos dos fármacos , Neurônios Aferentes/efeitos dos fármacos , Propofol/farmacologia , Núcleo Solitário/efeitos dos fármacos , Animais , Potenciais Pós-Sinápticos Excitadores/fisiologia , Masculino , Neurônios Aferentes/fisiologia , Técnicas de Cultura de Órgãos , Ratos , Ratos Sprague-Dawley , Núcleo Solitário/citologia , Núcleo Solitário/fisiologia
16.
J Burn Care Res ; 33(4): e180-5, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-22210067

RESUMO

Free anterolateral thigh flap is considered by most surgeons to be the proper choice for restoring scalp defect in the adult population. However, in the pediatric burn population with scalp large defects, the use of this flap has not been well described. From December 2005 to June 2009, 11 free anterolateral thigh flaps were performed to cover scalp defects in eight male children and three female children aged between 3.1 and 5.9 years (mean age: 5.0 years). Causes for the lesions include boiling liquid (5 cases), frictional heat (4 cases), and electricity (2 cases). Defect sites include parietal region (6 cases), occipital region (3 cases), temporal region (1 cases), and forehead (1 case). The size of the flaps ranged from 10 to 25 cm in length and from 8 to 18 cm in width. All the patients were followed up from 5.0 months to 2.1 years after the operation. Satisfactory contour results were shown. The overall flap success rate was 100%. There were no complications such as infections or hematomas after surgery. All the donor sites were covered with no morbidity observed. The free anterolateral thigh flap provides immediate vascularized coverage in scalp large defect that were unable to be treated by other methods, such as local flap or tissue expansion. Despite the smaller diameter of the vessels in pediatric population than that in adults, it is conceivable that this flap should be the reasonable and reliable method of large scalp defect coverage in pediatric population.


Assuntos
Queimaduras/cirurgia , Retalhos de Tecido Biológico/irrigação sanguínea , Procedimentos de Cirurgia Plástica/métodos , Couro Cabeludo/lesões , Couro Cabeludo/cirurgia , Queimaduras/diagnóstico , Criança , Pré-Escolar , Estudos de Coortes , Estética , Feminino , Rejeição de Enxerto , Sobrevivência de Enxerto , Humanos , Escala de Gravidade do Ferimento , Masculino , Estudos Retrospectivos , Medição de Risco , Coxa da Perna/cirurgia , Cicatrização/fisiologia
17.
J Hazard Mater ; 192(2): 559-67, 2011 Aug 30.
Artigo em Inglês | MEDLINE | ID: mdl-21664050

RESUMO

Polysulfone (PSF) membranes are broadly applied in many fields owing to good physicochemical stability, resistance to oxidation and chlorine. But when treated with wastewater containing oil, PSF membranes are easily contaminated due to their hydrophilicity, causing declining flux and lifespan of the membranes thereby limiting their large scale applications. In order to enhance the hydrophilic and anti-fouling capability of PSF membranes for treating wastewater containing oil, sulfated Y-doped zirconia particles (SO(4)(2-)/ZrO(2)-Y(2)O(3) or SZY particles) were firstly synthesized and then doped into polysulfone to fabricate a novel hybrid membrane (SZY/PSF). The optimum preparation conditions of SZY particles were studied and determined. SZY particles were characterized by X-ray diffraction (XRD), Fourier transform infrared (FTIR), specific surface area and transmission electron microscopy (TEM). Wastewater containing oil (80mg/L) was used to investigate the separation properties of SZY/PSF membranes. The results show that the oil concentration in the permeation is 0.67mg/L, which meets the recycle standard of the Chinese oil-field (SY/T 5329-94, oil concentration <10mg/L). It is concluded that doping SZY particles into polysulfone can reasonably resist membrane fouling and SZY/PSF membranes can be considered feasible in treating wastewater containing oil.


Assuntos
Membranas Artificiais , Polímeros/química , Sulfatos/química , Sulfonas/química , Zircônio/química , Microscopia Eletrônica de Transmissão , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
18.
J Hazard Mater ; 186(1): 390-5, 2011 Feb 15.
Artigo em Inglês | MEDLINE | ID: mdl-21122987

RESUMO

Polysulfone (PSF) membranes are broadly applied in many fields owing to good physicochemical stability, resistance to oxidation and chlorine. But when treated with wastewater containing oil, PSF membranes are easy to be contaminated for its hydrophobicity, which can result in the declining of flux and lifespan of the membrane and limit their application in large scale. To enhance the capability of PSF membrane in the above circumstances, phosphorylated Zr-doped hybrid silica particles (SZP particles) were firstly prepared. SZP particles have various point defects inside their structure and lots of hydroxide radicals on their surface. SZP particles were added to the porous matrix of PSF to prepare a novel composite membrane (SZP/PSF) through a phase inversion process. Finally, the optimum preparation conditions of SZP/PSF composite membranes were determined. The optimum conditions are: the mass ratio of PSF, PEG400 and SZP is 12:10:10; ultrasound 10 min inside each 30 min; the pre-evaporating time is 10s. Optimized SZP/PSF composite membrane was characterized by scanning electron microscope (SEM) and ultrafiltration experiment. The results indicate that SZP particles can be uniformly dispersed in SZP/PSF composite membranes with excellent hydrophilic property, antifouling capability and tensile strength. Therefore, it can be concluded that the optimized SZP/PSF composite membrane is desirable in the treatment of wastewater containing oil and wastewater.


Assuntos
Membranas Artificiais , Zircônio/química , Microscopia Eletrônica de Varredura , Fosforilação , Dióxido de Silício/química
19.
Brain Res ; 1383: 36-42, 2011 Apr 06.
Artigo em Inglês | MEDLINE | ID: mdl-21316356

RESUMO

Culinary use of the pungent spices has potential health benefits including a reduction in food intake. Pungent spices often contain ingredients that activate members of the transient receptor potential (TRP) family A1 and evoke pain from capsaicin-sensitive somatosensory neurons. TRPA1 channel have also been identified on cranial visceral afferent neurons but their distribution and functional contributions are poorly understood. Visceral vagal neurons transduce mechanical and chemical signals from peripheral organs to the nucleus tractus solitarii. Many capsaicin-sensitive vagal afferents participate in peripheral satiety signaling that includes cholecystokinin (CCK) sensitive neurons. To assess signaling, the TRPA1 selective agonist allyl isothiocyanate (AITC) was tested together with CCK and capsaicin (200nM), a TRPV1 specific agonist. In isolated nodose neurons, AITC (0.05-0.2mM) evoked concentration-dependent inward currents in 38% of the tested neurons. The TRPA1 specific antagonist HC-030031 (10µM) blocked AITC responses. TRPA1 responses were mixed across neurons that were capsaicin-sensitive and -insensitive. However CCK evoked inward currents only on capsaicin-sensitive neurons and 28% of the CCK-sensitive neurons expressed TRPA1. Our results indicate that TRPA1 is co-expressed with TRPV1 in CCK-sensitive nodose neurons. The findings indicate a potential mechanism by which spices can act within cranial visceral afferent pathways mediating satiety and contribute to the reduction of the food intake associated with spiced diets.


Assuntos
Anquirinas/metabolismo , Canais de Cálcio/metabolismo , Colecistocinina/metabolismo , Neurônios Aferentes/metabolismo , Gânglio Nodoso/metabolismo , Canais de Cátion TRPV/metabolismo , Animais , Técnicas de Patch-Clamp , Ratos , Ratos Sprague-Dawley , Resposta de Saciedade/fisiologia , Especiarias , Canal de Cátion TRPA1 , Canais de Cátion TRPC
20.
Biochem Biophys Res Commun ; 326(3): 645-51, 2005 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-15596148

RESUMO

The BCR/ABL fusion tyrosine kinase activates various intracellular signaling pathways, thus causing chronic myeloid leukemia (CML). Here we demonstrate that the inducible expression of BCR/ABL in a murine hematopoietic cell line, TonB210, leads to the activation of the Ras family small GTPase Rap1, which is inhibited by the ABL kinase inhibitor imatinib. The Rap1 activity in a CML cell line, K562, was also inhibited by imatinib. Inhibition of Rap1 activation by a dominant negative mutant of Rap1, Rap1-N17, or SPA-1 inhibited the BCR/ABL-induced activation of Elk-1. BCR/ABL also activated in a kinase activity-dependent manner the B-Raf kinase, which is an effector molecule of Rap1 and a potent activator of the MEK/Erk/Elk-1 signaling pathway. Together, these data suggest that, in addition to the well-established Ras/Raf-1 pathway, BCR/ABL activates the alternative signaling pathway involving Rap1 and B-Raf to activate Erk, which may play important roles in leukemogenesis.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Proteínas de Fusão bcr-abl/metabolismo , MAP Quinase Quinase Quinases/metabolismo , Proteínas Proto-Oncogênicas B-raf/metabolismo , Proteínas rap1 de Ligação ao GTP/metabolismo , Animais , Células-Tronco Hematopoéticas/metabolismo , Camundongos , Proteínas rac de Ligação ao GTP/metabolismo , Proteínas ras/metabolismo
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