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1.
Ying Yong Sheng Tai Xue Bao ; 32(12): 4447-4456, 2021 Dec.
Artigo em Chinês | MEDLINE | ID: mdl-34951286

RESUMO

With the acceleration of industrialization, the toxic effect of heavy metal cadmium (Cd) pollution has become prominent. In order to explore the molecular mechanism of the physiological regulation of Caulerpa lentillifera under Cd stress, we analyzed the transcriptome of Cd-stressed (Hcd2+) algae tissues using RNA-Seq. A total of 702 differentially expressed genes (DEGs) were screened between the control and Hcd2+ groups, out of which 257 genes were up-regulated and 445 genes were down-regulated in the Hcd2+ group. We conducted functional annotation and enrichment analysis of the obtained DEGs. The results showed that various biological functions of C. lentillifera were affected under Cd2+stress, which eventually showed growth inhibition. Results of GO enrichment analysis showed that the production and removal of reactive oxygen species (ROS) in C. lentillifera were out of balance and caused oxidative damage such as DNA damage. Results of KEGG enrichment analysis showed that many photosynthesis-related pathways were inhibited, indicating that Cd2+ stress led to disorder of photosynthetic reaction of C. lentillifera.


Assuntos
Caulerpa , Metais Pesados , Cádmio/toxicidade , Caulerpa/genética , Perfilação da Expressão Gênica , Metais Pesados/toxicidade , Transcriptoma
2.
Sci Rep ; 11(1): 2668, 2021 01 29.
Artigo em Inglês | MEDLINE | ID: mdl-33514798

RESUMO

Our aim was to detect type 2 innate lymphoid cells (ILC2s)-related cytokines of infants with bronchiolitis by using Elisa, Liquidchip technology and RT-PCR and investigated its correlation with bronchiolitis. We recruited 26 infants with bronchiolitis and 20 healthy infants as control from Xiangya Hospital. Compared to the control group, the serum levels of interleukin-5 (IL-5) [41.99 (21.11) vs 25.70 (19.64)], IL-9 [27.04 (37.51) vs 8.30 (0.54)], IL-13 [184.05 (132.81) vs 121.75 (176.13)], IL-33 [83.70 (46.69) vs 11.23 (55.31)] and thymic stromal lymphopoietin (TSLP) [31.42 (5.41) vs 28.76 (2.56)] were significantly increased in infants with bronchiolitis (P < 0.05), while the level of IgE had no significant difference between the two groups [19.05 (14.15) vs 14.85 (20.2), P > 0.05]. The mRNA expression of IL-17RB (9.83 ± 0.35 vs 9.19 ± 0.58), TSLP (16.98 ± 2.12 vs 15.07 ± 2.25), retinoid acid receptor related orphan receptor α (7.18 ± 0.71 vs 5.46 ± 1.09) and trans-acting T-cell-specific transcription factor 3 (4.86 ± 0.66 vs 4.19 ± 0.90) were significantly increased in infants with bronchiolitis versus the control group (P < 0.05), while there was no statistical significance for suppression of tumorigenicity 2 (5.59 ± 0.68 vs 5.41 ± 0.87, P > 0.05). Our findings suggested that ILC2s possibly play a specific role in immunopathology of bronchiolitis.


Assuntos
Bronquiolite/imunologia , Linfócitos/imunologia , Bronquiolite/genética , Bronquiolite/patologia , Pré-Escolar , Citocinas/genética , Citocinas/imunologia , Feminino , Regulação da Expressão Gênica/imunologia , Humanos , Imunoglobulina E/imunologia , Lactente , Masculino
3.
Zhongguo Dang Dai Er Ke Za Zhi ; 22(4): 387-390, 2020 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-32312380

RESUMO

A girl, aged 4 years and 3 months, presented with cyanosis of the lips shortly after birth. She then experienced shortness of breath after activity 1 year ago and acrocyanosis 3 months ago, with obvious acropachy and toe deformity. Laboratory examinations revealed an increase in hemoglobin (178 g/L) and a reduction in arterial partial pressure of oxygen (37.7 mm Hg). Plain and contrast-enhanced CT scans of the lungs showed a large area of dense shadow and multiple nodules with clear boundaries in the right lower lung, as well as thickening of the arteries and dilatation of the veins in the right lower lung. Magnetic resonance angiography of the pulmonary artery showed large arteriovenous malformation in the lung. The child was diagnosed with congenital pulmonary arteriovenous fistula and was given interventional embolization of the pulmonary arterial fistula. The child was followed up at 3 months after surgery. The symptoms of shortness of breath and cyanosis disappeared, and activity tolerance, heart rate, hemoglobin, red blood cell count, and transcutaneous oxygen saturation all returned to normal.


Assuntos
Cianose , Fístula Arteriovenosa , Malformações Arteriovenosas , Pré-Escolar , Embolização Terapêutica , Feminino , Humanos , Artéria Pulmonar
4.
Zhongguo Dang Dai Er Ke Za Zhi ; 21(3): 282-286, 2019 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-30907355

RESUMO

A girl, aged 8 years, developed jaundice and liver dysfunction in the neonatal period, with congenital glaucoma diagnosed on day 5 after birth, hypertension and unusual facies (broad forehead, hypertelorism and deep-set eyes). Cholestasis was the main type of liver dysfunction. Cardiac macrovascular CTA showed stenosis at the abdominal aorta and the beginning of the bilateral renal arteries. Whole exon sequencing revealed a heterozygous frameshift mutation, c.1485delC (absence of cytosine), in exon 12 of the JAG1gene. The girl was diagnosed with Alagille syndrome and was given transaminase-lowering, cholagogic and antihypertensive treatment with multiple drugs. There were significant reductions in serum levels of alanine aminotransferase, aspartate aminotransferase and total bile acid, but blood pressure fluctuated between 102-140 mm Hg/53-89 mm Hg. After renal artery angiography and balloon dilatation angioplasty, the girl was given oral administration of antihypertensive drugs, and blood pressure was controlled at a level of 110-120 mm Hg/60-80 mm Hg. The rare disease Alagille syndrome should be considered when a child has refractory hypertension with the involvement of multiple systems, especially liver dysfunction with cholestasis as the main manifestation. Genetic causes should be analyzed for a early diagnosis.


Assuntos
Hipertensão , Hepatopatias , Síndrome de Alagille , Pressão Sanguínea , Criança , Feminino , Humanos , Hipertensão/etiologia , Hepatopatias/etiologia , Artéria Renal
5.
Oncol Rep ; 41(1): 341-350, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30542705

RESUMO

The ß2­adrenergic receptor (ß2­AR, encoded by the ADRB2 gene) is a member of the G­protein­coupled receptor superfamily that can be stimulated by catecholamines. Studies in vivo and in vitro have confirmed that ß­blockers (ß­AR antagonists) exert antitumor effects on various tumors. Furthermore, ADRB2 single­nucleotide polymorphisms (SNPs) have been identified to alter the expression and conformation of ß2­AR, which may alter the ß­blocker drug response. The aim of the present study was to investigate the effect of ß­blockers on triple­negative breast cancer cells and determine whether ADRB2 SNPs affect the response to ß­blocker drugs. Propranolol and ICI 118,551 significantly inhibited the viability of MDA­MB­231 cells, arrested cell cycle progression at G0/G1 and S phase and induced cell apoptosis. Western blot analysis indicated that the phosphorylation levels of extracellular­signal­regulated kinase (ERK)1/2 and the expression levels of cyclo­oxygenase 2 (COX­2) were significantly decreased following ß­blocker treatment. Four haplotypes, which comprised ADRB2 SNPs rs1042713 and rs1042714, were transfected into 293 cells. After 24 and 48 h of transfection, ADRB2 mRNA expression was significantly decreased in mutant groups compared with the wild­type group. The ADRB2 SNPs exerted no effect on cell viability, but did affect the drug response of ICI 118,551. Furthermore, ADRB2 SNPs also affected the regulatory function of ICI 118,551 on the ERK/COX­2 signaling pathway. Collectively, propranolol and ICI 118,551 inhibited the viability of MDA­MB­231 cells by downregulating the ERK/COX­2 signaling pathway and inducing apoptosis. The results of the present study indicated that SNPs rs1042713 and rs1042714 of ADRB2 affected the response to ICI 118,551, and the underlying molecular mechanism was elucidated.


Assuntos
Antagonistas Adrenérgicos beta/farmacologia , Receptores Adrenérgicos beta 2/genética , Transdução de Sinais/efeitos dos fármacos , Neoplasias de Mama Triplo Negativas/tratamento farmacológico , Antagonistas Adrenérgicos beta/uso terapêutico , Apoptose/efeitos dos fármacos , Linhagem Celular Tumoral , Sobrevivência Celular/efeitos dos fármacos , Ciclo-Oxigenase 2/metabolismo , Regulação para Baixo/efeitos dos fármacos , Ensaios de Seleção de Medicamentos Antitumorais , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Pontos de Checagem da Fase G2 do Ciclo Celular/efeitos dos fármacos , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Células HEK293 , Humanos , Fosforilação/efeitos dos fármacos , Polimorfismo de Nucleotídeo Único , Propanolaminas/farmacologia , Propanolaminas/uso terapêutico , Propranolol/farmacologia , Propranolol/uso terapêutico , Receptores Adrenérgicos beta 2/metabolismo , Neoplasias de Mama Triplo Negativas/genética
6.
Pharm Biol ; 56(1): 511-518, 2018 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31070532

RESUMO

CONTEXT: Statins have been widely used in acute pulmonary embolism (APE), while simvastatin has been well-established for the prevention of pulmonary hypertension, which was supposed to be an attractive recommendation for APE treatment. OBJECTIVE: The current article studies the effect of simvastatin on the SIRT2/NF-κB pathway in rats with APE. MATERIALS AND METHODS: Sprague-Dawley rats were divided into four groups (n = 24 per group): control group, rats were treated with saline once daily for 14 days before administration of saline (sham group) or a suspension of autologous emboli (APE group), or rats were treated with simvastatin (10 mg/kg) for 14 days before administration of autologous emboli (APE + simvastatin) group. The RVSP, mPAP and the arterial blood gas was analyzed. Besides, plasma inflammatory cytokines and MMPs levels, as well as the expression of SIRT2/NF-κB pathway were determined. RESULTS: Compared with the control and sham groups, the levels of mPAP (31.06 ± 3.47 mmHg), RVSP (35.12 ± 6.02 mmHg), A-aDO2 (33.14 ± 6.16 mmHg) and MMP-9 (6.89 ± 0.84 ng/mL) activity were significantly elevated, but PaO2 (66.87 ± 7.85 mmHg) was highly decreased in rats from APE group at 24 h after APE. Meanwhile, the inflammatory changes were aggravated by the enhanced levels of TNF-α (138.85 ± 22.69 pg/mL), IL-1ß (128.47 ± 22.14 pg/mL), IL-6 (103.16 ± 13.58 pg/mL) and IL-8 (179.28 ± 25.79 pg/mL), as well as increased NF-κB (5.29 ± 0.47 fold), but reduced SIRT2 (59 ± 6% reduction), and eNOS (61 ± 5% reduction) mRNA in APE rats. APE rats treated with simvastatin led to a significant opposite trend of the above indexes. CONCLUSIONS: Simvastatin protects against APE-induced pulmonary artery pressure, hypoxemia and inflammatory changes probably due to the regulation of SIRT2/NF-κB signalling pathway, which suggest that simvastatin may have promising protective effects in patients with APE.


Assuntos
Inibidores de Hidroximetilglutaril-CoA Redutases/uso terapêutico , NF-kappa B/antagonistas & inibidores , Embolia Pulmonar/tratamento farmacológico , Sinvastatina/uso terapêutico , Sirtuína 2/antagonistas & inibidores , Animais , Inibidores de Hidroximetilglutaril-CoA Redutases/farmacologia , Masculino , NF-kappa B/metabolismo , Embolia Pulmonar/metabolismo , Embolia Pulmonar/patologia , Ratos , Ratos Sprague-Dawley , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/fisiologia , Sinvastatina/farmacologia , Sirtuína 2/metabolismo , Resultado do Tratamento
7.
Biomed Res Int ; 2017: 4189678, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28331852

RESUMO

Sulindac is a nonsteroidal anti-inflammatory drug, which is clinically used for the ailments of various inflammations. This study investigated the allele frequencies of FMO3 E158K and E308G and evaluated the influences of these two genetic polymorphisms on the pharmacokinetics of sulindac and its metabolites in Chinese healthy male volunteers. Eight FMO3 wild-type (FMO3 HHDD) subjects and seven FMO3 homozygotes E158K and E308G mutant (FMO3 hhdd) subjects were recruited from 247 healthy male volunteers genotyped by PCR-RFLP method. The plasma concentrations of sulindac, sulindac sulfide, and sulindac sulfone were determined by UPLC, while the pharmacokinetic parameters of the two different FMO3 genotypes were compared with each other. The frequencies of FMO3 E158K and E308G were 20.3% and 20.1%, respectively, which were in line with Hardy-Weinberg equilibrium (D' = 0.977, r2 = 0.944). The mean values of Cmax, AUC0-24, and AUC0-∞ of sulindac were significantly higher in FMO3 hhdd group than those of FMO3 HHDD group (P < 0.05), while the pharmacokinetic parameters except Tmax of sulindac sulfide and sulindac sulfone showed no statistical difference between the two groups. The two FMO3 mutants were in close linkage disequilibrium and might play an important role in the pharmacokinetics of sulindac in Chinese healthy male volunteers.


Assuntos
Anti-Inflamatórios não Esteroides/administração & dosagem , Inflamação/tratamento farmacológico , Oxigenases/genética , Sulindaco/administração & dosagem , Adulto , Anti-Inflamatórios não Esteroides/farmacocinética , Frequência do Gene , Genótipo , Voluntários Saudáveis , Humanos , Inflamação/genética , Desequilíbrio de Ligação , Masculino , Polimorfismo de Fragmento de Restrição , Sulindaco/análogos & derivados , Sulindaco/farmacocinética
8.
Pharmacogenomics ; 18(3): 293-316, 2017 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-28112586

RESUMO

Glucocorticoids (GCs) are widely used for treating asthma, rheumatoid arthritis, nephrotic syndrome, acute lymphoblastic leukemia and other autoimmune diseases. However, in a subgroup of patients, failure to respond to GCs is known as GC resistance or GC insensitivity. This represents an important barrier to effective treatment and a clinical problem requiring an urgent solution. Genetic variation in the GC pathway is a significant factor in interindividual differences in GC treatment. This article reviews the pharmacogenetics of GCs in diverse diseases based on the GC pathway.


Assuntos
Doenças Autoimunes/tratamento farmacológico , Doenças Autoimunes/genética , Variação Genética/genética , Glucocorticoides/uso terapêutico , Medicina de Precisão/métodos , Doenças Autoimunes/diagnóstico , Glucocorticoides/farmacologia , Humanos , Polimorfismo de Nucleotídeo Único/genética , Medicina de Precisão/tendências , Transdução de Sinais/efeitos dos fármacos , Transdução de Sinais/genética , Resultado do Tratamento
9.
Pharmacogenomics ; 17(18): 2007-2014, 2016 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-27918244

RESUMO

AIM: The clinical efficacy of valproic acid (VPA) varies greatly among epileptic patients. To find the potential genetic factors related to VPA responses, the pharmacogenetics study was conducted. METHODS: Two hundred and one Chinese Han epileptic patients who were treated by VPA for at least 1 year were recruited. Up to 24 SNPs in 11 candidate genes that correlate with the metabolism, transport or target of VPA were genotyped. RESULTS: Three SNPs, rs1731017 (ABAT), rs2304016 (SCN2A) and rs1054899 (ALDH5A1) were found associated with VPA responses with the p-values of 0.003, 0.007 and 0.048, respectively. Further interaction analysis showed that the interaction between rs17183814 (ABAT) and rs1641022 (SCN2A) was also correlated with the response of VPA (p = 0.006). CONCLUSION: This study found three SNPs and one interaction among ABAT, SCN2A and ALDH5A1 were significantly associated with VPA response, which indicated that these genes may play important roles in the pharmacological mechanism of VPA.


Assuntos
4-Aminobutirato Transaminase/genética , Anticonvulsivantes/uso terapêutico , Epilepsia/tratamento farmacológico , Canal de Sódio Disparado por Voltagem NAV1.2/genética , Polimorfismo de Nucleotídeo Único , Succinato-Semialdeído Desidrogenase/genética , Ácido Valproico/uso terapêutico , Adolescente , Criança , Pré-Escolar , Epilepsia/genética , Feminino , Humanos , Masculino , Adulto Jovem
10.
Anal Methods ; 8(17): 3550-3563, 2016 May 07.
Artigo em Inglês | MEDLINE | ID: mdl-27695531

RESUMO

The compound medicine of betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BDP) is widely used for diverse glucocorticoid-sensitive acute and chronic diseases such as asthma, rheumatoid arthritis and systemic lupus erythematosus. It will be useful and beneficial to validate sensitive method for the determination of BSP, BDP and their metabolites for their pharmacokinetic study. Hereby, an ultra-high pressure liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) has been validated for the determination of BSP, BDP and their metabolites betamethasone (BOH), betamethasone 17-monodipropionate (B17P) and betamethasone 21-monodipropionate (B21P) in human plasma. Liquid-liquid extraction with ether and n-hexane (v/v, 4:1) was used for sample preparation of BDP, BOH, B17P and B21P with beclomethasone dipropionate as internal standard (IS), while solid phase extraction was adopted for sample preparation of BSP using prednisolone as IS. The chromatographic separation was performed on a Hypurity C18 column (150 mm×2.1 mm, 5 µm) for BOH, BDP, B21P and B17P, and a Luna C18 (2) column (150 mm×2.0 mm, 5 µm) for BSP. Electrospray ionization interfaced with positive multiple reaction monitoring (MRM) scan mode was used for mass spectrometric detection. The standard calibration curves were linear within the range of 2.525 × 10-9-403.9 × 10-9 mol·dm-3 for BSP, 0.125 × 10-9-55.81 × 10-9 mol·dm-3 for BDP, 0.278 × 10-9-74.95 × 10-9 mol·dm-3 for BOH, 0.098 × 10-9-4.688 × 10-9 mol·dm-3 for B17P and 0.226 × 10-9-5.411 × 10-9 mol·dm-3 for B21P, respectively. The validated method was successfully applied to a bioequivalence study in 23 healthy subjects after they were injected with this compound medicine BSP and BDP.

11.
Int J Mol Med ; 38(2): 643-9, 2016 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-27277186

RESUMO

Endothelial progenitor cells (EPCs) play an important role in aging-associated senescence, thereby potentially contributing to vascular pathologies. Visfatin, identified as a new adipocytokine, is closely associated with the senescence of human cells. However, the effects of visfatin on the oxidized low-density lipoprotein (ox-LDL)-induced senescence of EPCs has not yet been explored, to the best of our knowledge. For this purpose, in the present study, we examined the effects of visfatin in ox-LDL-stimulated EPCs as well as the underlying mechanism responsible for these effects. We found that visfatin attenuated the ox-LDL-induced senescence of EPCs by repressing ß-galactosidase expression and recovering telomerase activity. Western blot analysis confirmed that visfatin induced a dose-dependent increase in sirtuin 1 (SIRT1) expression in EPCs and ox-LDL exposure decreased SIRT1 expression. Silencing SIRT1 abolished the inhibition of EPC senescence and the suppression of p53 expression induced by visfatin. Moreover, visfatin attenuated the inhibition of phosphorylation of Akt, phosphoinositide-3-kinase (PI3K) and extracellular signal-regulated kinase (ERK) induced by ox-LDL. Taken together, these findings suggest that the treatment of EPCs with visfatin markedly attenuates the ox-LDL-induced senescence of EPCs by upregulating SIRT1 expression through the PI3K/Akt/ERK pathway.


Assuntos
Senescência Celular/efeitos dos fármacos , Células Progenitoras Endoteliais/citologia , Células Progenitoras Endoteliais/metabolismo , Lipoproteínas LDL/farmacologia , Nicotinamida Fosforribosiltransferase/metabolismo , Transdução de Sinais/efeitos dos fármacos , Sirtuína 1/genética , Regulação para Cima/efeitos dos fármacos , Células Progenitoras Endoteliais/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/metabolismo , Humanos , Fosfatidilinositol 3-Quinases/metabolismo , Proteínas Proto-Oncogênicas c-akt/metabolismo , Sirtuína 1/metabolismo , Proteína Supressora de Tumor p53/metabolismo
12.
Int J Clin Pharmacol Ther ; 54(2): 144-56, 2016 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-26754304

RESUMO

OBJECTIVE: Since the 1960s, fentanyl has been used to replace morphine nd other opioids due to its higher potency in the treatment of acute pain; since the 1990s, it has also been administrated to control chronic pain by using transdermal fentanyl device system. It is crucial and of utmost importance and crucial to validate a sensitive method for the quantification of transdermal fentanyl in human plasma. MATERIALS AND METHODS: A rapid, simple and sensitive high performance liquid chromatography tandem mass spectrometry (HPLC-MS/MS) method has been established and validated for the determination of transdermal fentanyl in human plasma using fentanyl-D5 as an internal standard (IS). Following liquid-liquid extraction (LLE) with n-hexane, the extracts were separated on a Thermo Hypersil ODS(C18) column (2.1 × 150 mm i.d., 5 µm) interfaced with a triple-quadrupole tandem mass spectrometer using positive electrospray ionization. RESULTS AND CONCLUSIONS: Quantification of fentanyl was carried out by multiple reaction monitoring (MRM) of the transitions at m/z 337.1→188.0 for fentanyl and 341.9→187.9 for IS. The lower limit of quantification was 9.75 pg×mL-1, and the test showed a linear range of 9.75 - 10,000 pg×mL-1. The validated method was subsequently applied to a bioequivalence (BE) study in 24 healthy Chinese volunteers by using transdermal fentanyl patches.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Fentanila/farmacocinética , Espectrometria de Massas por Ionização por Electrospray/métodos , Espectrometria de Massas em Tandem/métodos , Administração Cutânea , Adulto , Área Sob a Curva , Estabilidade de Medicamentos , Fentanila/administração & dosagem , Fentanila/química , Humanos , Extração Líquido-Líquido , Masculino , Fatores de Tempo
13.
Pharmacogenomics ; 17(1): 74-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-26652861

RESUMO

ß-ARs are extensively spread in different tissues of our body, which could be activated by neurotransmitters norepinephrine and epinephrine to mediate physiological function and abnormal states including cancer. Recently, ß-AR blockers could have significant implications in cancer therapy. But the precise molecular mechanisms are far from being fully understood. Through identifying the ß-AR system signal pathways relevant to cancer, we can understand the mechanisms of ß-blockers used for cancer treatment. What's more, retrospective clinical data made ß-blockers jump out of the traditional field of cardiovascular disease and strengthened our confidence in cancer therapy. At last, genetic studies of ß-adrenergic system offered crucial genes to analyze the effects of polymorphisms on cancer susceptibility, therapy response and prognosis of cancer patients.


Assuntos
Antagonistas Adrenérgicos beta/uso terapêutico , Antineoplásicos/uso terapêutico , Neoplasias/genética , Polimorfismo Genético , Receptores Adrenérgicos beta/genética , Quimioterapia Adjuvante , Humanos , Neoplasias/tratamento farmacológico , Neoplasias/metabolismo , Receptores Adrenérgicos beta/fisiologia , Transdução de Sinais
14.
Biosci Rep ; 35(3)2015 Apr 28.
Artigo em Inglês | MEDLINE | ID: mdl-26182382

RESUMO

Airway mucin secretion is important pathophysiologically and as a model of polarized epithelial regulated exocytosis. We find the trafficking protein, SNAP23 (23-kDa paralogue of synaptosome-associated protein of 25 kDa), selectively expressed in secretory cells compared with ciliated and basal cells of airway epithelium by immunohistochemistry and FACS, suggesting that SNAP23 functions in regulated but not constitutive epithelial secretion. Heterozygous SNAP23 deletant mutant mice show spontaneous accumulation of intracellular mucin, indicating a defect in baseline secretion. However mucins are released from perfused tracheas of mutant and wild-type (WT) mice at the same rate, suggesting that increased intracellular stores balance reduced release efficiency to yield a fully compensated baseline steady state. In contrast, acute stimulated release of intracellular mucin from mutant mice is impaired whether measured by a static imaging assay 5 min after exposure to the secretagogue ATP or by kinetic analysis of mucins released from perfused tracheas during the first 10 min of ATP exposure. Together, these data indicate that increased intracellular stores cannot fully compensate for the defect in release efficiency during intense stimulation. The lungs of mutant mice develop normally and clear bacteria and instilled polystyrene beads comparable to WT mice, consistent with these functions depending on baseline secretion that is fully compensated.


Assuntos
Pulmão/citologia , Pulmão/metabolismo , Mucinas/metabolismo , Proteínas Qb-SNARE/metabolismo , Proteínas Qc-SNARE/metabolismo , Animais , Células Epiteliais/metabolismo , Camundongos Endogâmicos C57BL , Camundongos Mutantes , Proteínas Qb-SNARE/genética , Proteínas Qc-SNARE/genética
15.
Artigo em Inglês | MEDLINE | ID: mdl-26170892

RESUMO

Cortex Eucommiae (Du-zhong) is the dried bark of the Eucommia ulmoides Oliv. The natural products identified from Du-zhong include lignans, iridoids, flavonoids, polysaccharides, terpenes, and proteins, Liu et al. (2012). Lignans, the main bioactive components, were protective against hypertensive renal injury in spontaneous hypertensive rats in our previous study, Li et al. (2012). Moreover, Eucommia lignans also diminished aldose reductase (AR) overexpression in the kidney, Li et al. (2012). However, the pathological mechanism underlying the protective effects of Eucommia lignans remains unknown. Cellular proliferation was reported to contribute to important pathological changes in hypertensive renal injuries, and increased angiotensin II (Ang II) expression was reported to be essential for target-organ damage during hypertension. Ang II is the main effective peptide in the renin-angiotensin system and is considered to be a key mediator in the development of hypertensive nephropathy, Rüster and Wolf (2011). Our preliminary results showed that Eucommia lignans had inhibitory effects on Ang II-induced proliferation of rat mesangial cells. In the present study, we investigated the effects of Eucommia ulmoides on Ang II-induced proliferation and apoptosis of rat mesangial cells. Cell cycle-related genes P21 and P27, and cell apoptosis-related genes Bax and Bcl-2, were determined.

16.
Zhongguo Dang Dai Er Ke Za Zhi ; 14(9): 697-702, 2012 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-22989442

RESUMO

OBJECTIVE: To study the role of neuroglobin (Ngb) in the pathologic process of contusion and laceration of brain in children. METHODS: The proteins in the brain tissue were extracted by two-dimensional gel electrophoresis in 3 children undergoing brain ventricular neoplasms resection (normal brain tissue) and in 8 children with contusion and laceration of brain. The image analysis was done using the PDQuest 7.0 software. The differential protein spots were detected and analyzed with Applied Biosystems Voyager System 4307 MALDI-TOF Mass Spectrometer and bioinformatical skills. Ngb expression in the brain tissue was measured using immunohistochemisty. Ngb expression in plasma was measured using ELISA in 15 children with contusion and laceration of brain and 10 healthy children. RESULTS: Expression maps of the brain tissue were established by two-dimensional gel electrophoresis in children with contusion and laceration of brain and healthy children. Six differential protein spots were found and 5 of them were identified by mass spectrum. Immunohistochemisty assay showed that Ngb expression in the brain tissue in children with contusion and laceration of brain was significantly higher than in normal controls (P<0.05). ELISA results showed that Ngb expression in the plasma increased significantly 6, 12, 18, 24 and 48 hours after trauma in children with contusion and laceration of brain compared with healthy children (P<0.01). CONCLUSIONS: Ngb may play an important role in the pathologic process of contusion and laceration of brain in children.


Assuntos
Lesões Encefálicas/metabolismo , Globinas/análise , Proteínas do Tecido Nervoso/análise , Adolescente , Criança , Eletroforese em Gel Bidimensional , Ensaio de Imunoadsorção Enzimática , Feminino , Humanos , Imuno-Histoquímica , Masculino , Neuroglobina , Espectrometria de Massas por Ionização e Dessorção a Laser Assistida por Matriz
17.
Huan Jing Ke Xue ; 33(3): 932-7, 2012 Mar.
Artigo em Chinês | MEDLINE | ID: mdl-22624390

RESUMO

Inoculating common sterilized soil with different non-sterilized soils was used to investigate the potentials of altered microbial communities to change rate and temperature sensitivity of soil microbial respiration. Results showed that accumulative CO2 emission of sterilized Hailun black soils inoculated with non-sterilized Harbin black soil, Fengqiu fluvo-aquic soil and Qiyang red soil were 684.25, 753.97 and 644.91 microg, respectively, at 15 degrees C; were 963.06, 1 015.44 and 852.31 microg, respectively, at 25 degrees C; and were 1 252.55, 380.36 and 1 177.88 microg, respectively, at 35 degrees C. The soil accumulative CO2 emissions increased with pH of inoculant soils, but did not relate to organic content of and geographical distance from inoculant soils. Difference of microbial respiration rates among the three inoculant soils kept for 104, 277 and 1 177 h at 15 degrees C, 25 degrees C and 35 degrees C, respectively. Temperature sensitivity quotients (Q10) of microbial respiration of sterilized Hailun black soils inoculated with non-sterilized Harbin black soil, Fengqiu fluvo-aquic soil and Qiyang red soil were 1.63, 1.49 and 1.80, respectively, during 0-104 h; were 1.43, 1.39 and 1.46, respectively, during 0-277 h and were 1.35, 1.35 and 1.35, respectively, during 0-1 609 h. The Q10 decreased with pH of inoculant soils and incubation time. The results suggest that altered microbial community would change rate and temperature sensitivity of soil microbial respiration.


Assuntos
Bactérias/metabolismo , Dióxido de Carbono/análise , Consumo de Oxigênio/fisiologia , Microbiologia do Solo , Solo/química , Carbono/análise , Concentração de Íons de Hidrogênio , Temperatura
18.
Inflammation ; 33(3): 180-8, 2010 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-20033479

RESUMO

This study aimed to examine effects of adjunctive baicalin therapy to ampicillin for experimental bacterial meningitis in rabbits. After Escherichia Coli inoculation, mean leukocyte counts, concentrations of protein, tumor necrosis factor-alpha (TNF-alpha), interleukin-1 (IL-1) and lactate in cerebrospinal fluid (CSF), brain water content and mean arterial and intracranial pressures substantially increased in the meningitis group. Ampicillin alone for 5 h markedly exacerbated the enhanced leukocyte counts and protein concentration, and showed no significant effect on the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicalin (7-D-glucuronic acid-5,6-dihydroxyflavone, C(21)H(18)O(11)) completely counteracted ampicillin-induced exacerbation, and further alleviated the enhanced mean leukocyte counts and protein concentration when combined with ampicillin. Adjunctive baicalin also significantly ameliorated the elevated CSF TNF-alpha, IL-1 and lactate concentration, mean arterial and intracranial pressures, and brain water content. Baicillin, as an adjunctive treatment exerted multiple therapeutic effects in experimental bacterial meningitis.


Assuntos
Ampicilina/farmacologia , Anti-Infecciosos/farmacologia , Infecções por Escherichia coli/tratamento farmacológico , Flavonoides/farmacologia , Meningites Bacterianas/tratamento farmacológico , Animais , Antibacterianos/farmacologia , Pressão Sanguínea/efeitos dos fármacos , Edema Encefálico/líquido cefalorraquidiano , Edema Encefálico/tratamento farmacológico , Proteínas do Líquido Cefalorraquidiano/líquido cefalorraquidiano , Modelos Animais de Doenças , Diuréticos Osmóticos/farmacologia , Quimioterapia Combinada , Infecções por Escherichia coli/líquido cefalorraquidiano , Interleucina-1/líquido cefalorraquidiano , Pressão Intracraniana/efeitos dos fármacos , Ácido Láctico/líquido cefalorraquidiano , Contagem de Leucócitos , Manitol/farmacologia , Meningites Bacterianas/líquido cefalorraquidiano , Coelhos , Fator de Necrose Tumoral alfa/líquido cefalorraquidiano , Água/metabolismo
20.
Yi Chuan ; 26(3): 409-13, 2004 May.
Artigo em Chinês | MEDLINE | ID: mdl-15640030

RESUMO

tmRNA is a dual small RNA similar to a tRNA and a mRNA which plays an important role in an unusual mode of translation--trans translation. Recently, it was found that tmRNA had something to do with regulating gene expression and cell cycle. So the researchers have paid much attention on such area. Furthermore, it is an important part in RNomics era. This article reviews the progress about the structure and function of tmRNA in recent years.


Assuntos
Biossíntese de Proteínas/fisiologia , RNA Bacteriano/química , Sequência de Bases , Ciclo Celular , Escherichia coli/genética , Regulação da Expressão Gênica , Dados de Sequência Molecular , Neisseria/genética , RNA Bacteriano/genética , RNA Bacteriano/fisiologia , RNA Mensageiro/química , RNA Mensageiro/genética , RNA Mensageiro/fisiologia , RNA de Transferência/química , RNA de Transferência/genética , RNA de Transferência/fisiologia , Transdução de Sinais/fisiologia , Synechocystis/genética
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