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1.
Phytother Res ; 36(8): 3248-3264, 2022 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-35599350

RESUMO

Intestinal mucus barrier dysfunction is closely involved in the pathogenesis of inflammatory bowel diseases (IBD). To investigate the protective effect and underlying mechanism of arctigenin, a phytoestrogen isolated from the fruits of Arctium lappa L., on the intestinal mucus barrier under colitis condition. The role of arctigenin on the intestinal mucus barrier and the apoptosis of goblet cells were examined by using both in vitro and in vivo assays. Arctigenin was demonstrated to promote the mucus secretion and maintain the integrity of mucus barrier, which might be achieved by an increase in the number of goblet cells via inhibiting apoptosis. Arctigenin selectively inhibited the mitochondrial pathway-mediated apoptosis. Moreover, arctigenin elevated the protein level of prohibitin 1 (PHB1) through blocking the ubiquitination via activation of estrogen receptor ß (ERß) to competitively interact with PHB1 and disrupt the binding of tripartite motif 21 (TRIM21) with PHB1. ERß knock down in the colons of mice with DSS-induced colitis resulted in significant reduction of the protection of arctigenin and DPN against the mucosal barrier. Arctigenin can maintain the integrity of the mucus barrier by inhibiting the apoptosis of goblet cells through the ERß/TRIM21/PHB1 pathway.


Assuntos
Colite , Doenças Inflamatórias Intestinais , Animais , Apoptose , Colite/induzido quimicamente , Receptor beta de Estrogênio/metabolismo , Furanos , Células Caliciformes/metabolismo , Células Caliciformes/patologia , Doenças Inflamatórias Intestinais/tratamento farmacológico , Doenças Inflamatórias Intestinais/patologia , Lignanas , Camundongos , Camundongos Endogâmicos C57BL , Muco/metabolismo , Fitoestrógenos , Proibitinas
2.
Pharm Biol ; 60(1): 394-403, 2022 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-35271397

RESUMO

CONTEXT: Pterostilbene (PTE), a common polyphenol compound, exerts an anti-inflammatory effect in many diseases, including acute lung injury (ALI). OBJECTIVE: This study explores the potential mechanism of PTE pre-treatment against lipopolysaccharide (LPS)-induced ALI. MATERIALS AND METHODS: Sixty Sprague-Dawley rats were divided into control, ALI, 10 mg/kg PTE + LPS, 20 mg/kg PTE + LPS, and 40 mg/kg PTE + LPS groups. At 24 h before LPS instillation, PTE was administered orally. At 2 h before LPS instillation, PTE was again administered orally. After 24 h of LPS treatment, the rats were euthanized. The levels of inflammatory cells and inflammatory factors in the bronchoalveolar lavage fluid (BALF), the expression of nuclear receptor subfamily 4 group A member 1 (NR4A1), and the nuclear factor (NF)-κB pathway-related protein levels were detected. NR4A1 agonist was used to further investigate the mechanism of PTE pre-treatment. RESULTS: After PTE pre-treatment, the LPS induced inflammation was controlled and the survival rate was increased to 100% from 70% after LPS treatment 24 h. For lung injury score, it decreased to 1.5 from 3.5 after treating 40 mg/kg PTE. Compared with the control group, the expression of NR4A1 in the ALI group was decreased by 20-40%. However, the 40 mg/kg PTE pre-treatment increased the NR4A1 expression by 20-40% in the lung tissue. The results obtained with pre-treatment NR4A1 agonist were similar to those obtained by pre-treatment 40 mg/kg PTE. CONCLUSIONS: PTE pre-treatment might represent an appropriate therapeutic target and strategy for preventing ALI induced by LPS.


Assuntos
Lesão Pulmonar Aguda/prevenção & controle , Anti-Inflamatórios/farmacologia , Membro 1 do Grupo A da Subfamília 4 de Receptores Nucleares/metabolismo , Estilbenos/farmacologia , Lesão Pulmonar Aguda/patologia , Animais , Anti-Inflamatórios/administração & dosagem , Modelos Animais de Doenças , Relação Dose-Resposta a Droga , Inflamação/tratamento farmacológico , Inflamação/patologia , Lipopolissacarídeos , Masculino , Ratos , Ratos Sprague-Dawley , Estilbenos/administração & dosagem
3.
BMC Pregnancy Childbirth ; 20(1): 6, 2019 Dec 31.
Artigo em Inglês | MEDLINE | ID: mdl-31892352

RESUMO

BACKGROUND: The 90% effective dose (ED90) of oxytocin infusion has been previously estimated to be 16.2 IU h- 1. However, bolus administration of oxytocin prior to the infusion may decrease the infusion dose required. The aim of this study was to estimate the ED95 for oxytocin infusion after a bolus at elective caesarean delivery (CD) in nonlaboring parturients. METHODS: We performed a randomized, triple blinded study in 150 healthy termparturients scheduled for elective CD under epidural anaesthesia. After delivery of the infant and i.v. administration of 1 IU oxytocin as a bolus, Participants were randomized to receive oxytocin infusion at a rate of 0, 1, 2, 3, 5, or 8 IU h- 1, to be given for a total of 1 h. Uterine tone assessed by the blinded obstetrician as either adequate or inadequate. Secondary outcomes included estimated blood loss (EBL), requirement for supplemental uterotonic agents, and development of side effects. RESULTS: The 95% effective dose (ED95) of oxytocin infusion was estimated to be 7.72 IU h- 1 (95% confidence interval 5.80-12.67 IU h- 1). With increasing oxytocin infusion rate, the proportion of parturients who needed rescue oxytocin bolus or secondary uterotonic agents decreased. No significant among-group differences in the EBL and oxytocin-related side effects were observed. CONCLUSIONS: In parturients who receive a 1 IU bolus of oxytocin during elective cesarean delivery, an infusion rate of oxytocin at 7.72 IU h- 1 will produce adequate uterine tone in 95% of parturients. These results suggest that the total dose of oxytocin administered in the postpartum period can be decreased when administered as an infusion after oxytocin bolus.


Assuntos
Cesárea/métodos , Ocitócicos/administração & dosagem , Ocitocina/administração & dosagem , Adulto , Relação Dose-Resposta a Droga , Esquema de Medicação , Procedimentos Cirúrgicos Eletivos/métodos , Feminino , Humanos , Infusões Intravenosas , Gravidez , Projetos de Pesquisa , Resultado do Tratamento , Útero/efeitos dos fármacos , Adulto Jovem
4.
BMC Pulm Med ; 19(1): 122, 2019 Jul 08.
Artigo em Inglês | MEDLINE | ID: mdl-31286925

RESUMO

BACKGROUND: Granulomatosis with polyangiitis (GPA) is characterised by the main violation of the upper and lower respiratory tract and kidney. GPA is considered a systemic vasculitis of medium-sized and small blood vessels where aortic involvement is extremely rare. CASE PRESENTATION: A 28-year-old male was admitted to the hospital due to 4 h of chest pain. Computed tomography scan of the aorta showed a thickened aortic wall, pulmonary lesions, bilateral pleural effusion and pericardial effusion. The aortic dissection should be considered. An emergency operation was performed on the patient. Surgical biopsies obtained from the aortic wall showed destructive changes, visible necrosis, granulation tissue hyperplasia and a large number of acute and chronic inflammatory cells. Nearly a year later, the patient was re-examined for significant pulmonary lesions. His laboratory studies were significantly positive for anti-neutrophilic antibody directed against proteinase 3. Finally, the diagnosis of GPA was obviously established. CONCLUSIONS: Although GPA rarely involves the aorta, we did not ignore the fact that GPA may involve large blood vessels. In addition, GPA should be included in the systemic vasculitis that can give rise to aortitis and even aortic dissection.


Assuntos
Dissecção Aórtica/diagnóstico por imagem , Aortite/diagnóstico por imagem , Granulomatose com Poliangiite/diagnóstico , Pulmão/patologia , Adulto , Anticorpos Anticitoplasma de Neutrófilos/sangue , Dor no Peito/etiologia , Ecocardiografia , Granulomatose com Poliangiite/complicações , Granulomatose com Poliangiite/fisiopatologia , Humanos , Masculino , Mieloblastina/imunologia , Tomografia Computadorizada por Raios X
5.
Molecules ; 24(7)2019 Mar 27.
Artigo em Inglês | MEDLINE | ID: mdl-30934681

RESUMO

Enhancing the thermostability of (R)-selective amine transaminases (AT-ATA) will expand its application in the asymmetric synthesis of chiral amines. In this study, mutual information and coevolution networks of ATAs were analyzed by the Mutual Information Server to Infer Coevolution (MISTIC). Subsequently, the amino acids most likely to influence the stability and function of the protein were investigated by alanine scanning and saturation mutagenesis. Four stabilized mutants (L118T, L118A, L118I, and L118V) were successfully obtained. The best mutant, L118T, exhibited an improved thermal stability with a 3.7-fold enhancement in its half-life (t1/2) at 40 °C and a 5.3 °C increase in T5010 compared to the values for the wild-type protein. By the differential scanning fluorimetry (DSF) analysis, the best mutant, L118T, showed a melting temperature (Tm) of 46.4 °C, which corresponded to a 5.0 °C increase relative to the wild-type AT-ATA (41.4 °C). Furthermore, the most stable mutant L118T displayed the highest catalytic efficiency among the four stabilized mutants.


Assuntos
Aspergillus/fisiologia , Mutação , Transaminases/metabolismo , Aminas/química , Aminas/metabolismo , Estabilidade Enzimática , Cinética , Conformação Molecular , Mutagênese Sítio-Dirigida , Relação Estrutura-Atividade , Termodinâmica , Transaminases/química
6.
Biochem Biophys Res Commun ; 503(3): 1703-1709, 2018 09 10.
Artigo em Inglês | MEDLINE | ID: mdl-30049439

RESUMO

Glutamate decarboxylase (GAD), which is a unique pyridoxal 5-phosphate (PLP)-dependent enzyme, can catalyze α-decarboxylation of l-glutamate (L-Glu) to γ-aminobutyrate (GABA). The crystal structure of GAD in complex with PLP from Lactobacillus brevis CGMCC 1306 was successfully solved by molecular-replacement, and refined at 2.2 Šresolution to an Rwork factor of 18.76% (Rfree = 23.08%). The coenzyme pyridoxal 5-phosphate (PLP) forms a Schiff base with the active-site residue Lys279 by continuous electron density map, which is critical for catalysis by PLP-dependent decarboxylase. Gel filtration showed that the active (pH 4.8) and inactive (pH 7.0) forms of GAD are all dimer. The residues (Ser126, Ser127, Cys168, Ile211, Ser276, His278 and Ser321) play important roles in anchoring PLP cofactor inside the active site and supporting its catalytic reactivity. The mutant T215A around the putative substrate pocket displayed an 1.6-fold improvement in catalytic efficiency (kcat/Km) compared to the wild-type enzyme (1.227 mM-1 S-1 versus 0.777 mM-1 S-1), which was the highest activity among all variants tested. The flexible loop (Tyr308-Glu312), which is positioned near the substrate-binding site, is involved in the catalytic reaction, and the conserved residue Tyr308 plays a vital role in decarboxylation of L-Glu.


Assuntos
Glutamato Descarboxilase/química , Glutamato Descarboxilase/metabolismo , Levilactobacillus brevis/enzimologia , Simulação de Acoplamento Molecular , Sequência de Aminoácidos , Cristalografia por Raios X , Glutamato Descarboxilase/genética , Mutagênese Sítio-Dirigida , Alinhamento de Sequência
7.
Pharmacology ; 102(5-6): 300-306, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30253391

RESUMO

Remifentanil-induced hyperalgesia (RIH) is known to be associated with oxidative stress and inflammation. Betulinic acid (BA) was reported to reduce visceral pain owing to its anti-oxidative and anti-inflammatory potential. Here, we -explored whether BA can attenuate RIH through inhibiting oxidative stress and inflammation in spinal dorsal horn. Sprague-Dawley rats were randomly divided into 4 groups: Control, Incision, RIH, and RIH pre-treated with BA. After pretreated with BA (25 mg/kg, i.g.) for 7 days, rats were subcutaneously infused with remifentanil (40 µg/kg) for 30 min during right plantar incision surgery to induce RIH. The paw withdrawal mechanical threshold (PWMT), paw withdrawal thermal latency (PWTL), spinal oxidative stress and inflammatory mediators were determined. Intraoperative remifentanil infusion induced postoperative hyperalgesia, as evidenced by the significant decrease in PWMT and PWTL (p < 0.01), and the significant increase in oxidative stress and inflammation evidenced by up-regulations of malondialdehyde, 3-nitrotyrosine, interleukin-1ß and tumour necrosis factor-α (p < 0.01) in spinal dorsal horn and matrix metalloproteinase-9 (MMP-9) activity (p < 0.01) in dorsal root ganglion, as well as a decrease in manganese superoxide -dismutase activity (p < 0.01) compared with control and -incision groups. All these results mentioned above were markedly reversed by pre-treatment with BA (p < 0.01) compared with RIH group. These findings demonstrated that BA can effectively attenuate RIH, which associates with potentially inhibiting oxidative stress and subsequently down-regulating MMP-9-related pro-inflammatory cyokines in spinal dorsal horn.


Assuntos
Hiperalgesia/induzido quimicamente , Hiperalgesia/tratamento farmacológico , Inflamação/tratamento farmacológico , Estresse Oxidativo/efeitos dos fármacos , Remifentanil/antagonistas & inibidores , Corno Dorsal da Medula Espinal/efeitos dos fármacos , Triterpenos/farmacologia , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Interações Medicamentosas , Gânglios Espinais/efeitos dos fármacos , Gânglios Espinais/metabolismo , Gânglios Espinais/patologia , Hiperalgesia/metabolismo , Inflamação/metabolismo , Inflamação/patologia , Interleucina-1beta/metabolismo , Masculino , Dor Pós-Operatória/tratamento farmacológico , Triterpenos Pentacíclicos , Distribuição Aleatória , Ratos , Ratos Sprague-Dawley , Remifentanil/toxicidade , Corno Dorsal da Medula Espinal/metabolismo , Corno Dorsal da Medula Espinal/patologia , Superóxido Dismutase/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Tirosina/análogos & derivados , Tirosina/metabolismo , Ácido Betulínico
8.
Int J Mol Sci ; 19(5)2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29693643

RESUMO

To investigate the roles and explore the altered expression of microRNAs (miRNAs) and mRNAs in chicken embryos in response to Newcastle disease virus (NDV) infection, deep sequencing was performed. Then, a conjoint analysis of small RNA-seq and mRNA-seq was performed to screen interactional miRNA⁻mRNA pairs during NDV infection. In total, 15 and 17 up- and downregulated miRNAs were identified that potentially targeted 4279 and 6080 mRNAs in NDV-infected chicken embryonic tissues, respectively; in addition, 595 upregulated and 480 downregulated mRNAs were identified. The conjoint analysis of the obtained data identified 1069 miRNA⁻mRNA pairs. Among these pairs, 130 pairs were related to immune or inflammatory responses. The relationship between gga-miR-203a and its target transglutaminase 2 (TGM2) was confirmed using a dual-luciferase reporter system and a real time quantitative polymerase chain reaction (RT-qPCR) assay. Overall, the discovery of miRNAs, mRNAs, and their potential pairing relationships, which may be involved in the regulation of NDV infection, will facilitate our understanding of the complex regulatory relationship between the host and the virus.


Assuntos
MicroRNAs/genética , Doença de Newcastle/genética , RNA Mensageiro/genética , Vísceras/metabolismo , Animais , Embrião de Galinha , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Células HEK293 , Humanos , MicroRNAs/metabolismo , Doença de Newcastle/metabolismo , Doença de Newcastle/virologia , Vírus da Doença de Newcastle/patogenicidade , Proteína 2 Glutamina gama-Glutamiltransferase , RNA Mensageiro/metabolismo , Transcriptoma , Transglutaminases/genética , Transglutaminases/metabolismo , Vísceras/virologia
9.
Molecules ; 23(11)2018 Nov 15.
Artigo em Inglês | MEDLINE | ID: mdl-30445733

RESUMO

Super-paramagnetic iron oxide nanoparticles (SPIONs)/gelatin (gel)/polyvinyl alcohol (PVA) nanoparticles were designed and synthesized by the co-precipitation method and further modified with gel and PVA. These nanoparticles were used for the removal of Cu(II) and Zn(II) from aqueous solutions. The adsorbents were rich in different functional groups for chemisorption and showed effective adsorption properties. The adsorption of Cu(II) and Zn(II) on the SPIONs/gel and SPIONs/gel/PVA materials were investigated with respect to pH, adsorption kinetics, and adsorption isotherms. The adsorption data was fitted to the Langmuir, Freundlich, and Sips models at the optimum pH 5.2 (±0.2) over 60 min; SPIONs/gel showed maximum adsorption capacities of 47.594 mg/g and 40.559 mg/g for Cu(II) and Zn(II); SPIONs/gel/PVA showed those of 56.051 mg/g and 40.865 mg/g, respectively. The experimental data fitted the pseudo-second-order model, indicating that the process followed chemical monolayer adsorption. In addition, the SPIONs/gel/PVA showed better stability and Cu(II) adsorption efficiency than SPIONs/gel.


Assuntos
Cobre/química , Íons/química , Compostos de Ferro/química , Nanopartículas de Magnetita/química , Álcool de Polivinil/química , Zinco/química , Adsorção , Cinética , Nanopartículas de Magnetita/ultraestrutura , Soluções , Espectroscopia de Infravermelho com Transformada de Fourier , Difração de Raios X
10.
Fish Shellfish Immunol ; 52: 167-78, 2016 05.
Artigo em Inglês | MEDLINE | ID: mdl-26997199

RESUMO

Galectins are a family of endogenous lectins with ß-galactosides affinity, playing significant roles in the innate immunity of vertebrates and invertebrates. In this report, a new galectin-9 cDNA was identified and characterized in large yellow croaker Larimichthys crocea (designated as LcGal-9). The complete cDNA sequence of LcGal-9 was 1795 bp, with an open reading frame (ORF) of 1032 bp encoding 343 amino acids. The putative LcGal-9 protein contained two carbohydrate recognition domains (CRDs) connected by a linker peptide, with each carrying two conserved ß-galactoside binding motifs H-NPR and WG-EE-, and it possessed neither a signal peptide nor a transmembrane domain. LcGal-9 protein shared 43-74% identity with galectin-9 sequences from other species. The qRT-PCR analysis revealed that LcGal-9 mRNA was constitutively expressed in all tissues examined, predominately expressed in liver, spleen, gill, kidney, head-kidney and intestine. Western blot analysis showed that LcGal-9 protein was highly expressed in liver, spleen, intestine, kidney, head-kidney, skin, gill, and heart, but not detected in muscle and plasma. LcGal-9 mRNA transcripts were induced by poly I:C in the liver (from 6 h to 48 h), spleen (at 12 h) and head-kidney (at 12 h and 24 h). In contrast, Vibrio parahaemolyticus caused a significant down-regulation in these three tissues, except for in spleen of 48 h and head-kidney of 3 h. Post-infection with Cryptocaryon irritans, the transcripts were dramatically up-regulated in gill, skin, spleen and head-kidney during initial infection period, while significant down-regulation afterward was also observed both in spleen and head-kidney. The recombinant LcGal-9 (named as rLcGal-9) purified from Escherichia coli BL21 (DE3) demonstrated hemagglutination against human, rabbit and L. crocea in a Ca(2+)-independent manner, which was inhibited by α-Lactose and LPS. The results of bacterial agglutination assays showed that rLcGal-9 was able to agglutinate Gram-negative bacteria V. alginolyticus and Aeromonas hydrophila in a Ca(2+)-independent manner. By immunohistochemistry assay, significant increases of LcGal-9 protein appeared in the spleen stimulated with poly I:C (for 12 h) and V. parahaemolyticus (for 48 h) compared with the control. Based on the collective data, LcGal-9 might play an important role in innate immune responses, especially defense against Gram-negative bacteria in L. crocea.


Assuntos
Infecções por Cilióforos/veterinária , Galectinas/genética , Galectinas/metabolismo , Regulação da Expressão Gênica/genética , Perciformes , Vibrioses/veterinária , Sequência de Aminoácidos , Animais , Sequência de Bases , Cilióforos/fisiologia , Infecções por Cilióforos/genética , Infecções por Cilióforos/imunologia , Infecções por Cilióforos/microbiologia , Proteínas de Peixes/química , Proteínas de Peixes/genética , Proteínas de Peixes/metabolismo , Galectinas/química , Poli I-C/farmacologia , Vibrioses/genética , Vibrioses/imunologia , Vibrioses/microbiologia , Vibrio parahaemolyticus/fisiologia
11.
Zhong Yao Cai ; 39(8): 1800-2, 2016 Aug.
Artigo em Chinês | MEDLINE | ID: mdl-30204387

RESUMO

Objective: To identify the main chemical constituents and to determine the content in Feifukang mistura. Methods: HPLC-MS technique was used to profile and identify the chemical constituents by comparing the retention time,MS data with the reference standard. The content determination of all the chemical constituents were carried on a HPLC system. Results: Five compounds were separated from Feifukang mistura,which were identified as neomangiferin,mangiferin,calycosin-7-O-glucoside,calycosin,and schizandrol A. The standard curves of them showed good linearity on the range of 2. 08 ~ 104. 0 µg/m L,2. 00 ~ 100. 0 µg/m L,2. 00 ~ 100. 0µg/m L,2. 09 ~ 104. 5 µg/m L,and 1. 98 ~ 99. 0 µg/m L,respectively. The average recoveries were all in the range of 91. 3 ~ 103. 8%. Conclusion: The methods of chemical constituents identification and content determination were established,which may offer better revealing the material basis and controlling quality of Feifukang mistura.

12.
J Cell Mol Med ; 19(5): 1103-13, 2015 May.
Artigo em Inglês | MEDLINE | ID: mdl-25704671

RESUMO

Pulmonary fibrosis (PF) is a disease with an unknown cause and a poor prognosis. In this study, we aimed to explore the pathogenesis of PF and the mechanism of sulindac in attenuating bleomycin (BLM)-induced PF. The rat PF model was induced by BLM and verified through histological studies and hydroxyproline assay. The severity of BLM-induced PF in rats and other effects, such as the extent of the wet lung to bw ratios, thickening of alveolar interval or collagen deposition, was obviously ameliorated in sulindac-treated rat lungs compared with BLM-induced lungs. Sulindac also reversed the epithelial mesenchymal transition (EMT) and inhibited the PF process by restoring the levels of E-cadherin and α-smooth muscle actin (SMA) in A549 cells. Our results further demonstrated that the above effects of sulindac might be related to regulating of interferon gamma (IFN-γ) expression, which further affects signal transducers and activators of transcription 3 (STAT3) and phosphorylated STAT3 (p-STAT3) levels. Moreover, higher miR-21 levels with the decreased E-cadherin and increased α-SMA expressions were found in transforming growth factor-ß1-treated A549 cells, which can be reversed by sulindac. Collectively, our results demonstrate that by decreasing IFN-γ-induced STAT3/p-STAT3 expression to down-regulate miR-21, sulindac could significantly reverse EMT in A549 cells and prevent BLM-induced PF.


Assuntos
Pulmão/efeitos dos fármacos , MicroRNAs/genética , Fibrose Pulmonar/prevenção & controle , Fator de Transcrição STAT3/metabolismo , Sulindaco/farmacologia , Actinas/metabolismo , Animais , Anti-Inflamatórios não Esteroides/farmacologia , Bleomicina , Western Blotting , Caderinas/metabolismo , Linhagem Celular Tumoral , Transição Epitelial-Mesenquimal/efeitos dos fármacos , Feminino , Expressão Gênica/efeitos dos fármacos , Humanos , Interferon gama/metabolismo , Pulmão/metabolismo , Pulmão/patologia , Microscopia de Fluorescência , Fibrose Pulmonar/induzido quimicamente , Fibrose Pulmonar/genética , Ratos Sprague-Dawley , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Transdução de Sinais/efeitos dos fármacos
13.
Tumour Biol ; 36(6): 4819-24, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25631750

RESUMO

Lung cancer is the leading cause of cancer-related death worldwide. Transforming growth factor-ß receptor II (TGF-ßRII) plays an important role in the regulation of proliferation and progression in cancer. Statins have been documented to exhibit anticancer and cancer chemopreventive properties. However, the effects and mechanisms of simvastatin on the development of lung cancer are still unclear. In the present study, quiescent A549 cells were treated in vitro with fetal bovine serum (FBS) in the presence or absence of simvastatin. MTT, Western blot, and real-time qPCR were used to detect cell viability, activation of ERK, and expression of TGF-ßRII at the protein and RNA level. Our results demonstrated that simvastatin inhibited activation of ERK, downregulated expression of TGF-ßRII, and suppressed A549 cell proliferation. Furthermore, the effects of simvastatin can be reversed by farnesyl pyrophosphate (FPP). Therefore, these results suggest that simvastatin may inhibit A549 cell proliferation and downregulate TGF-ßRII expression by inhibiting activation of ERK. Our findings may advance the current understanding of the effects of simvastatin on cancer progression and contribute to the study of cancer treatment.


Assuntos
MAP Quinases Reguladas por Sinal Extracelular/biossíntese , Neoplasias Pulmonares/tratamento farmacológico , Proteínas Serina-Treonina Quinases/biossíntese , Receptores de Fatores de Crescimento Transformadores beta/biossíntese , Sinvastatina/administração & dosagem , Linhagem Celular Tumoral , Proliferação de Células/efeitos dos fármacos , Sobrevivência Celular/efeitos dos fármacos , MAP Quinases Reguladas por Sinal Extracelular/genética , Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos , Humanos , Neoplasias Pulmonares/genética , Neoplasias Pulmonares/patologia , Fosfatos de Poli-Isoprenil/administração & dosagem , Proteínas Serina-Treonina Quinases/genética , Receptor do Fator de Crescimento Transformador beta Tipo II , Receptores de Fatores de Crescimento Transformadores beta/genética , Sesquiterpenos/administração & dosagem
14.
Am J Emerg Med ; 33(1): 50-5, 2015 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-25453476

RESUMO

BACKGROUND: Previous meta-analyses have shown that ultrasound guidance is an effective technique for radial artery catheterization. However, these reports neglected to include several non-English language studies. Therefore, an updated meta-analysis including more eligible studies was performed to assess the effectiveness of ultrasound-guided radial artery catheterization. METHODS: Eligible studies were identified by systematically searching PubMed, EMBASE, Wanfang, and China National Knowledge Infrastructure literature databases. The outcome measure was the rate of first-attempt success. Two investigators identified the randomized controlled trials (RCTs) for inclusion and independently extracted data from these RCTs. The quality of the included studies was evaluated using the Jadad score. The relative risk (RR) for dichotomous outcomes and the 95% confidence intervals (CIs) were calculated and pooled using a random-effects model. RESULTS: Eleven RCTs involving 803 patients met the inclusion criteria. Ultrasound-guided radial artery catheterization was generally associated with a 47% improvement, as compared with the palpation technique, in terms of the rate of first-attempt success (RR, 1.47; 95% CI, 1.22-1.76; P < .0001). Specifically, the ultrasound-guided technique significantly improved the rate of first-attempt success for adult (RR, 1.39; 95% CI, 1.13-1.72; P = .002) and pediatric (RR, 1.68; 95% CI, 1.15-2.47; P = .008) patients. CONCLUSIONS: Adult and pediatric patients benefited from ultrasound-guided radial artery catheterization in terms of the rate of first-attempt success. Given the potential bias and significant heterogeneity of the available data in the present study, further investigation is required to confirm the present findings and to identify other effects of the ultrasound-guided technique.


Assuntos
Cateterismo Periférico/métodos , Artéria Radial , Ultrassonografia de Intervenção , Humanos
15.
Molecules ; 20(9): 17469-82, 2015 Sep 18.
Artigo em Inglês | MEDLINE | ID: mdl-26393571

RESUMO

In an attempt to find a new class antibacterial agents, a series of biscoumarins (1-4) and dihydropyrans (5-13) were successfully prepared. The molecular structures of four representative compounds, that is, 4, 5, 8 and 12 were confirmed by single crystal X-ray diffraction study. These synthesized compounds were screened for their antibacterial activity in vitro against Staphylococcus aureus (S. aureus ATCC 29213), methicillin-resistant S. aureus (MRSA XJ 75302), vancomycin-intermediate S. aureus (Mu50 ATCC 700699), USA 300 (Los Angeles County clone, LAC), Staphylococcus epidermidis (S. epidermidis ATCC 14990), methicillin-resistant S. epidermidis (MRSE XJ 75284) and Escherichia coli (E. coli ATCC 25922). Additionally, there are two classical intramolecular O-H···O hydrogen bonds (HBs) in biscoumarins 1-4 and the corresponding HB energies were further performed with the density functional theory (DFT) [B3LYP/6-31G*] method.


Assuntos
Antibacterianos/síntese química , Cumarínicos/farmacologia , Piranos/farmacologia , Antibacterianos/farmacologia , Cumarínicos/síntese química , Cristalografia por Raios X , Ligação de Hidrogênio , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Estrutura Molecular , Piranos/síntese química , Staphylococcus aureus/efeitos dos fármacos , Staphylococcus epidermidis/efeitos dos fármacos
16.
BMC Complement Altern Med ; 14: 80, 2014 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-24580804

RESUMO

BACKGROUND: Dai Huang Fu Zi Tang (DHFZT), an oriental herbal formula, has long been used clinically in treatment of intestinal obstruction, acute pancreatitis, cholecystalgia and chronic diarrhea for thousands of years. Recent studies have demonstrated that DHFZT can reduce intestinal pathological injury and the concentration of enterogenous endotoxin in an animal model. But the underlying mechanism has not been fully elucidated. METHODS: SD male rats in adult were used to model HS and treated with DHFZT. The serum concentration of endotoxin were analyzed by dynamic turbidimetric method. In addition, the blood flow of small intestine were measured using laser speckle technique. Phosphorylated vasodilator-stimulated phosphoprotein (p-VASP) and zonula occludens (ZO)-1 protein, intestinal fatty acid binding protein (IFABP) were measured by Western Blotting, RT-PCR, ELISA respectively. RESULTS: Present study showed that DHFZT markedly elevated the blood flow of small intestine, protected the intestinal barrier function by up-regulating the expression of ZO-1 protein and down-regulating expression of p-VASP, and notely decreased serum concentration of IFABP and endotoxin in HS. CONCLUSIONS: These results reveal that DHFZT improves intestinal blood flow, protects the intestinal barrier function, and ameliorates intestinal endotoxaemia in rats with HS.


Assuntos
Moléculas de Adesão Celular/metabolismo , Medicamentos de Ervas Chinesas/farmacologia , Intestinos/irrigação sanguínea , Intestinos/efeitos dos fármacos , Proteínas dos Microfilamentos/metabolismo , Fosfoproteínas/metabolismo , Fluxo Sanguíneo Regional/efeitos dos fármacos , Choque Hemorrágico/tratamento farmacológico , Choque Hemorrágico/metabolismo , Proteína da Zônula de Oclusão-1/metabolismo , Animais , Modelos Animais de Doenças , Mucosa Intestinal/metabolismo , Masculino , Ratos , Ratos Sprague-Dawley
17.
Front Cardiovasc Med ; 11: 1266195, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38385135

RESUMO

Pulsed field ablation (PFA) is a new treatment for atrial fibrillation (AF), and its selective ablation characteristics give it a significant advantage in treatment. In previous cellular and animal experiments, we have demonstrated that biphasic asymmetric pulses can be used to ablate myocardial tissue. However, small-scale clinical trials are needed to test whether this approach is safe and feasible before extensive clinical trials can be performed. Therefore, the purpose of this experiment is to determine the safety and feasibility of biphasic asymmetric pulses in patients with AF and is to lay the foundation for a larger clinical trial. Ablation was performed in 10 patients with AF using biphasic asymmetric pulses. Voltage mapping was performed before and after PFA operation to help us detect the change in the electrical voltage of the pulmonary veins (PV). 3-Dimensional mapping system showed continuous low potential in the ablation site, and pulmonary vein isolation (PVI) was achieved in all four PV of the patients. There were no recurrences, PV stenosis, or other serious adverse events during the 12 months follow-up. The results suggest that PFA using biphasic asymmetric waveforms for patients with AF is safe, durable, and effective and that a larger clinical trial could begin. Clinical Trial Registration: https://www.chictr.org.cn/, identifier, ChiCTR2100051894.

18.
Adv Healthc Mater ; : e2401005, 2024 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-38663447

RESUMO

In chronic wound management, efficacious handling of exudate and bacterial infections stands as a paramount challenge. Here a novel biomimetic fabric, inspired by the natural transpiration mechanisms in plants, is introduced. Uniquely, the fabric combines a commercial polyethylene terephthalate (PET) fabric with asymmetrically grown 1D rutile titanium dioxide (TiO2) micro/nanostructures, emulating critical plant features: hierarchically porous networks and hydrophilic water conduction channels. This structure endows the fabric with exceptional antigravity wicking-evaporation performance, evidenced by a 780% one-way transport capability and a 0.75 g h-1 water evaporation rate, which significantly surpasses that of conventional moisture-wicking textiles. Moreover, the incorporated 1D rutile TiO2 micro/nanostructures present solar-light induced antibacterial activity, crucial for disrupting and eradicating wound biofilms. The biomimetic transpiration fabric is employed to drain exudate and eradicate biofilms in Staphylococcus aureus (S. aureus)-infected wounds, demonstrating a much faster infection eradication capability compared to clinically common ciprofloxacin irrigation. These findings illuminate the path for developing high-performance, textile-based wound dressings, offering efficient clinical platforms to combat biofilms associated with chronic wounds.

19.
Adv Biol (Weinh) ; : e2300514, 2024 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-38217312

RESUMO

Obesity (OB) is a prevalent metabolic disorder. With the advancement of the economy, the prevention and treatment of obesity is a big problem for the global community. The methods to lose weight include exercise, diet, medicine, and surgery. Compared with other methods, diet regulation is safer and more effective. Hawthorn fruit has the effect of reducing weight, but the mechanism of effectiveness are not clear. In this study, obesity model rats are used to conduct scientific pharmacological research on hawthorn flavonoids. Hawthorn flavonoids can effectively improve the body weight, lipid accumulation, and lipid levels of obese rats. The contents of the colon of rats are analyzed using 16S rDNA sequencing technology. The intestinal microflora in obese rats changed significantly after flavonoids treatment, and they tended to be the control group. Based on liquid chromatography-mass spectrometry, serum metabolomics showed that the metabolites in the serum changed significantly, after hawthorn flavonoids treatment. Hawthorn flavonoids are especially involved in the biological processes of grade bile acid biosynthesis, histidine metabolism, and lipid metabolism. Pearson correlation analysis showed that the disorder of intestinal microorganisms is connected to changes in serum metabolites. These findings give a new idea about how hawthorn flavonoids help with obesity.

20.
Zhongguo Yi Xue Ke Xue Yuan Xue Bao ; 35(2): 190-8, 2013 Apr.
Artigo em Chinês | MEDLINE | ID: mdl-23643009

RESUMO

OBJECTIVE: To investigate the changes of gene expression file in transitional cell carcinoma of bladder after hepatocyte cell adhesion molecule(hepaCAM) overexpression. METHODS: Affymetrix Human Genome U133 Plus 2.0 Array was used to investigate the changes of gene expression profile between adenovirus-green fluorescent protein(GFP) -hepaCAM group and GFP group in transitional cell carcinoma of bladder EJ cells.Significant Analysis of Microarray(SAM) was used to screen the differentially expressed genes, DAVID software was used to conduct gene ontology analysis and wikiPathway analysis based on the differentially expressed genes. Reverse transcription-polymerase chain reaction and Western blot were applied to verify microarray data. RESULTS: Compared with the GFP group, a total of 2469 genes were up-regulated or down-regulated by more than 2 times in the GFP-hepaCAM group. Among these genes, 1602 genes were up-regulated and 867 were down-regulated.Most of the differentially expressed genes were involved in the function of cell proliferation and cell cycle regulation. The mRNA expressions of nibrin, liver kinase B1, and cyclin D1 detected by reverse transcription-polymerase chain reaction in three different bladder cancer cell lines were consistent with the microarray data.The protein expressions of nibrin and liver kinase B1 in these three cell lines measured by Western blot were consistent with the mRNA expression. CONCLUSIONS: HepaCAM can alter the gene expression profile of bladder cancer EJ cells. The well-known anti-tumor effect of hepaCAM may be mediated by regulating the gene expression via multiple pathways.


Assuntos
Carcinoma de Células de Transição/patologia , Genes Supressores de Tumor/fisiologia , Proteínas/fisiologia , Neoplasias da Bexiga Urinária/patologia , Quinases Proteína-Quinases Ativadas por AMP , Carcinoma de Células de Transição/genética , Proteínas de Ciclo Celular/metabolismo , Linhagem Celular Tumoral , Ciclina D1/metabolismo , Perfilação da Expressão Gênica , Regulação Neoplásica da Expressão Gênica , Humanos , Proteínas Nucleares/metabolismo , Proteínas Serina-Treonina Quinases/metabolismo , Proteínas/genética , Neoplasias da Bexiga Urinária/genética
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