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1.
Reprod Sci ; 2020 Jan 01.
Artigo em Inglês | MEDLINE | ID: mdl-32046395

RESUMO

Epithelial-mesenchymal transition (EMT) induced by estrogen contributes to the development of adenomyosis. However, the exact underlying mechanism remains mostly obscure. We hypothesized that a transmembrane glycoprotein neuropilin 1 (NRP1) was critical in the EMT induced by estrogen, accelerating the development of adenomyosis. We firstly investigated the expression pattern of NRP1 in endometrium samples from women with adenomyosis. We found that NRP1 expression was significantly increased in the endometrium of uterine adenomyosis, especially in the ectopic endometrium. To determine the role of NRP1 in the EMT in endometrial cells, we used an NRP1 overexpression retrovirus to up-regulate the NPR1 expression in human endometrial cells (HEC-1-A). Endometrial cells infected with NRP1 retroviruses showed a high expression of NRP1 and exerted a mesenchymal phenotype, characterized by down-regulation of E-cadherin and Occludin, up-regulation of α-SMA and N-cadherin, and enhanced migration. Then, we found that 17ß-estradiol (E2) up-regulated the expression of NRP1 in endometrial cells in a dose-dependent manner, which was eliminated by raloxifene, a selective estrogen receptor inhibitor. Importantly, NRP1 shRNA significantly suppressed the EMT induced by E2 in endometrial cells. And NRP1 shRNA significantly inhibited the phosphorylation of Smad3 and restored the expressions of Slug and Snail1 mRNA. Collectively, these data highlight the possible role of NRP1 in the EMT in the development of adenomyosis and provide a potential therapeutic target for adenomyosis patients.

2.
Meat Sci ; 162: 108043, 2020 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-31911339

RESUMO

In order to study the potential of replacing pork back-fat by sodium alginate solution (sodium alginate/water = 1/29, W/W), the physico-chemical, protein conformation and sensory of frankfurters made with various amounts of pork back-fat and sodium alginate were evaluated. With the increase of sodium alginate solute, the fat and energy was decreased significantly (P < .05). Compared with the control, the cooking yield, emulsion stability, L⁎ and ΔE values were not different significantly (P > .05) when pork back-fat was replaced by 25% and 50%, meanwhile, a decrease of α-helix content accompanied by an increase of ß-sheet, ß-turn and random coil content, more hydrophobic and tyrosine residues became exposed, those implied the hardness was increased. The texture, juiciness and overall acceptance scores were decreased significantly (P < .05) when pork back-fat was replaced beyond 50%. From the above, the use of sodium alginate solution instead of pork back-fat could transform protein structure and lowered fat and energy of frankfurters.

3.
J Agric Food Chem ; 2020 Feb 05.
Artigo em Inglês | MEDLINE | ID: mdl-31976658

RESUMO

Various mycotoxins widely co-exist in agro-products, and their combined effects cause toxicity and potential carcinogenicity to humans and animals. In this work, we developed an economical and sensitive quantum dots (QDs)/QD microbead (QDs/QB)-based multiplex immunochromatographic assay (mICA) for the rapid detection of fumonisin B1 (FB1), zearalenone (ZEN), and ochratoxin A (OTA) without the building-up process of mycotoxin conjugates. QDs and QBs were selected as fluorescent reporters and conjugated with antimycotoxin monoclonal antibodies for improving sensitivity. Furthermore, phage-displayed FB1, ZEN, and OTA mimotope peptide-based soluble and monovalent fusions to maltose-binding protein (MBP) were applied onto the test line of the mICA as the mimetic coating antigen. Under the optimized conditions, the visual detection limits (vLODs) of peptide-MBP-based mICA could be obtained as 0.25 ng/mL for FB1, 3.0 ng/mL for ZEN, and 0.5 ng/mL for OTA within 10 min. The results for spiked real sample detection indicate good accuracy, reproducibility, and practicability. In addition, the proposed mICA was comparable with ultraperformance liquid chromatography coupled to tandem mass spectrometry (UPLC-MS/MS) in terms of reliability in detecting FB1, ZEN, and OTA using natural samples. From the point of promoting commercial production, these time-saving and low-cost peptide-MBP antigens applied in ICA might provide promising potential for promoting productivity and decreasing the cost of production.

4.
Zhongguo Zhong Yao Za Zhi ; 44(17): 3662-3671, 2019 Sep.
Artigo em Chinês | MEDLINE | ID: mdl-31602938

RESUMO

The research on biopharmaceutics classification system of Chinese materia medica( CMMBCS) should be finally implemented to the holistic research level of traditional Chinese medicine compounds,while the overall biopharmaceutical properties of traditional Chinese medicine compounds are not only the sum of solubility and permeability of each component. In this study,Gegen Qinlian Tablets was used as the research object,and the contents of 12 representative components,i.e. puerarin,daidzin,baicalin,daidzein,wogonoside,baicalein,wogonin,glycyrrhizic acid,coptisine hydrochloride,epiberberine,berberine hydrochloride and palmatine hydrochloride,were simultaneously determined by HPLC to obtain the mass weight of each component. The in vitro lipopolysaccharide( LPS)-induced RAW264. 7 cells inflammation model was established to investigate the anti-inflammatory effects of 12 representative components and obtain the efficacy weight of each component. In order to obtain the number of doses and effective permeability coefficient which can represent the overall biopharmaceutical properties of Gegen Qinlian Tablets,mass weight was combined with efficacy weight to integrate the solubility and permeability data of each component determined by typical shake flask method and in situ single pass intestinal perfusion model respectively. The results indicated that Gegen Qinlian Tablets should be categorized Ⅳ drug of the CMMBCS with low solubility and low permeability.


Assuntos
Anti-Inflamatórios/farmacologia , Biofarmácia/classificação , Medicamentos de Ervas Chinesas/classificação , Materia Medica/classificação , Medicamentos de Ervas Chinesas/farmacologia , Comprimidos
5.
J Natl Cancer Inst ; 2019 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-31086947

RESUMO

Background The high cost and insufficient supply of human papillomavirus (HPV) vaccines have slowed the pace of controlling cervical cancer. A phase 3 clinical trial was conducted to evaluate the efficacy, safety and immunogenicity of a novel Escherichia coli-produced bivalent HPV-16/18 vaccine. Methods A multi-centre, randomized, double-blind trial started on November 22, 2012, in China. In total, 7372 eligible women aged 18-45 years were age-stratified and randomly assigned to receiving 3 doses of the test or control (hepatitis E) vaccine at months 0, 1 and 6. Co-primary endpoints included high-grade genital lesions and persistent infection (over 6 months) associated with HPV-16/18. The primary analysis was performed on a per-protocol susceptible population of individuals who were negative for relevant HPV type-specific neutralizing antibodies (at day 0) and DNA (at day 0 through month 7) and who received 3 doses of the vaccine. This report presents data from a pre-specified interim analysis used for regulatory submission. Results In the per-protocol cohort, the efficacies against high-grade genital lesions and persistent infection were 100.0% (95% confidence interval [CI] = 55.6% to 100.0%, 0/3306 in the vaccine group vs. 10/3296 in the control group) and 97.8% (95% CI = 87.1% to 99.9%, 1/3240 vs. 45/3246), respectively. The side effects were mild. No vaccine-related serious adverse events were noted. Robust antibody responses for both types were induced and persisted for at least 42 months. Conclusions The Escherichia coli-produced HPV-16/18 vaccine is well tolerated and highly efficacious against HPV-16/18 associated high-grade genital lesions and persistent infection in women.

6.
Molecules ; 24(10)2019 May 14.
Artigo em Inglês | MEDLINE | ID: mdl-31091775

RESUMO

A chemical investigation on 70% EtOH extract from the bark of Phellodendron chinense Schneid (Rutaceae) led to six new methyl apiofuranosides (1-6), and ten known compounds (7-16). All these compounds were characterized by the basic analysis of the spectroscopic data including extensive 1D-, 2D-NMR (HSQC, HMBC), and high-resolution mass spectrometry, and the absolute configurations were determined by both empirical approaches and NOESY. Inhibitory effects of compounds 1-9 and 11-16 on nitric oxide production were investigated in lipopolysaccharide (LPS)-mediated RAW 264.7 cells, as a result, most of these isolates inhibited nitric oxide (NO) release, and among them 9, 11, and 12 displayed the strongest inhibition on NO release at the concentration of 12.5 µM.


Assuntos
Lipopolissacarídeos/efeitos adversos , Óxido Nítrico/metabolismo , Pentoses/farmacologia , Phellodendron/química , Animais , Camundongos , Estrutura Molecular , Pentoses/química , Casca de Planta/química , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Células RAW 264.7
7.
Nat Prod Res ; : 1-6, 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31030559

RESUMO

Two new sesquiterpenoids, including a kessane-type sesquiterpenoid (1) and one bisabolane derivative (2), together with fourteen known sesquiterpenoids (3-16), were isolated from the roots and rhizomes of Valeriana amurensis. The structures of new compounds were established on the basis of extensive spectroscopic analysis. All isolates were evaluated for their effects on nerve growth factor (NGF)-mediated neurite outgrowth in pheochromocytoma (PC12) cells. As a results, four compounds including 10-12 and 15 showed potent promoting effects at the concentration of 10 µM on NGF-induced neurite outgrowth in PC12 cells with the differentiation rate of 11.84%, 12.21%, 13.77% and 12.16%, respectively.

8.
Invest Ophthalmol Vis Sci ; 60(4): 1265-1274, 2019 03 01.
Artigo em Inglês | MEDLINE | ID: mdl-30924851

RESUMO

Purpose: MicroRNA-182 (miR-182) is abundantly expressed in mammalian retinas; however, the association between miR-182 and retinal function remains unclear. In this study, we explored whether miR-182 contributes to functional decline in retinas using a miR-182 depleted mouse. Methods: Electroretinogram (ERG) amplitudes at different ages were measured in miR-182 knockout (KO) mice. The thickness and lamination of retinas were assessed using a color fundus camera and high-resolution optical coherence tomography. Expression levels of key photoreceptor-specific genes and the miR-183/96/182 cluster (miR-183C) were quantified using quantitative real-time PCR. RNA sequencing and light-induced damage were carried out to observe the changes in the retinal transcriptome and sensitivity to light damage in the miR-182 KO mice. Results: The ERG recording reveals that the ERG response amplitude decreased both at early and later ages when compared with control littermates. The expression of some key photoreceptor-specific genes was down-regulated with deletion of miR-182 in retina. RNA sequencing indicated that some biological processes of visual system were affected, and the numbers of potential target genes of miR-182 were presented in the mouse retina using bioinformatics analysis. The miR-182 KO mice were characterized by progressively losing the outer segment after being treated with light-damage exposure. The thickness and lamination of retina as well as compensatory expression of miR-183C showed no apparent changes in retina of miR-182 KO mice under normal laboratory lighting condition. Conclusions: Our findings provided new insights into the relationship between the miR-182 and retinal development and revealed that miR-182 may play a critical role in maintaining retinal function.


Assuntos
Sequência de Bases , MicroRNAs/genética , Retina/fisiopatologia , Degeneração Retiniana/genética , Deleção de Sequência , Animais , Modelos Animais de Doenças , Eletrorretinografia , Angiofluoresceinografia , Imuno-Histoquímica , Luz/efeitos adversos , Camundongos Endogâmicos C57BL , Camundongos Knockout , Lesões Experimentais por Radiação/genética , Lesões Experimentais por Radiação/fisiopatologia , Reação em Cadeia da Polimerase em Tempo Real , Retina/efeitos da radiação , Degeneração Retiniana/fisiopatologia , Tomografia de Coerência Óptica
9.
Mol Oncol ; 13(2): 246-263, 2019 02.
Artigo em Inglês | MEDLINE | ID: mdl-30372581

RESUMO

Epidermal growth factor receptor (EGFR) is a rational target for cancer therapy, because its overexpression plays an important oncogenic role in a variety of solid tumors; however, EGFR-targeted antibody-drug conjugate (ADC) therapy for esophageal squamous cell carcinoma (ESCC) is exceedingly rare. LR004 is a novel anti-EGFR antibody with the advantages of improved safety and fewer hypersensitivity reactions. It may be of great value as a carrier in ADCs with high binding affinity and internalization ability. Here, we prepared an EGFR-targeting ADC, LR004-VC-MMAE, and evaluated its antitumor activities against ESCC and EGFR-positive cells. LR004 was covalently conjugated with monomethyl auristatin E (MMAE) via a VC linker by antibody interchain disulfide bond reduction. VC-MMAE was conjugated with LR004 with approximately 4.0 MMAE molecules per ADC. LR004-VC-MMAE showed a potent antitumor effect against ESCC and other EGFR-positive cells with IC50 values of nM concentrations in vitro. The in vivo antitumor effects of LR004-VC-MMAE were investigated in ESCC KYSE520 and A431 xenograft nude mice models. Significant activity was seen at 5 mg·kg-1 , and complete tumor regression was observed at 15 mg·kg-1 in the KYSE520 xenograft nude mice after four injections, while the naked antibody LR004 had little effect on inhibiting tumor growth. Similar promising results were obtained in the A431 models. In addition, the tumors also remained responsive to LR004-VC-MMAE for large tumor experiments (tumor volume 400-500 mm3 ). The study results demonstrated that LR004-VC-MMAE could be a potential therapeutic agent for ESCC and other EGFR-expressing malignancies. We also evaluated PK profile of LR004-VC-MMAE ADC in the mice model, which would provide qualitative guiding significance for the further research.


Assuntos
Anticorpos Monoclonais/uso terapêutico , Receptores ErbB/metabolismo , Carcinoma de Células Escamosas do Esôfago/tratamento farmacológico , Imunoconjugados/uso terapêutico , Oligopeptídeos/uso terapêutico , Animais , Anticorpos Monoclonais/química , Anticorpos Monoclonais/farmacocinética , Anticorpos Monoclonais/farmacologia , Morte Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Endocitose/efeitos dos fármacos , Feminino , Humanos , Imunoconjugados/química , Imunoconjugados/farmacocinética , Imunoconjugados/farmacologia , Concentração Inibidora 50 , Camundongos Endogâmicos BALB C , Camundongos Nus , Oligopeptídeos/química , Oligopeptídeos/farmacocinética , Oligopeptídeos/farmacologia , Resultado do Tratamento , Ensaios Antitumorais Modelo de Xenoenxerto
10.
Reprod Fertil Dev ; 31(2): 237-247, 2019 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30017025

RESUMO

Precise regulation of glucose metabolism-related genes is essential for early embryonic development. Although previous research has yielded detailed information on the biochemical processes, little is yet known of the dynamic gene expression profiles in glucose metabolism of preimplantation embryos at a single-cell resolution. In the present study, we performed integrated analysis of single-cell RNA sequencing (scRNA-seq) data of human preimplantation embryos that had been cultured in sequential medium. Different cells in the same embryo have similar gene expression patterns in glucose metabolism. During the switch from the cleavage to morula stage, the expression of glycolysis-related genes, such as glucose transporter genes (solute carrier family 2 (facilitated glucose transporter), member 1 (SLC2A1) and solute carrier family 2 (facilitated glucose transporter), member 3 (SLC2A3) and genes encoding hexokinase, phosphofructokinase, pyruvate kinase and lactate dehydrogenase, is increased. The genes involved in the pentose phosphate pathway are highly expressed at the cleavage stage, generating the reducing power to balance oxidative stress derived from biosynthesis. Expression of the genes involved in the biosynthesis of glycerophospholipids is increased after the morula stage. Nevertheless, the expression of tricarboxylic acid-related genes remains relatively unchanged during the preimplantation stages. In conclusion, we discovered that the gene expression profiles are dynamic according to glucose utilisation in the embryos at different stages, which contributes to our understanding of regulatory mechanisms of glucose metabolism-related genes in human preimplantation embryos.


Assuntos
Blastocisto/metabolismo , Metabolismo dos Carboidratos/genética , Desenvolvimento Embrionário/genética , Regulação da Expressão Gênica no Desenvolvimento , Glucose/metabolismo , Bases de Dados Genéticas , Técnicas de Cultura Embrionária , Transportador de Glucose Tipo 1/genética , Transportador de Glucose Tipo 1/metabolismo , Transportador de Glucose Tipo 3/genética , Transportador de Glucose Tipo 3/metabolismo , Hexoquinase/genética , Hexoquinase/metabolismo , Humanos , L-Lactato Desidrogenase/genética , L-Lactato Desidrogenase/metabolismo , Fosfofrutoquinase-1/genética , Fosfofrutoquinase-1/metabolismo , Piruvato Quinase/genética , Piruvato Quinase/metabolismo , Análise de Sequência de RNA , Transcriptoma
11.
J Geriatr Cardiol ; 15(10): 618-627, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30416510

RESUMO

Background: Growth-differentiation factor-15 (GDF-15) is a promising prognostic biomarker in patients with chronic heart failure (CHF). Comparatively little is known about the value of repeated measurement of GDF-15 with CHF in Chinese Han population. This study sought to identify the clinical value of repeated measurement of GDF-15 in Chinese Han patients with post-myocardial infarction CHF. Methods: In total, 232 consecutive Chinese Han patients with post-myocardial infarction CHF were enrolled prospectively from January 2014 to June 2016.The plasma concentration of GDF-15 was determined on admission and over 12 months. Patients were followed up for all-cause death and a composite outcome of major adverse cardiac events (MACE) included all-cause death, myocardial infarction and first heart failure (HF) re-hospitalization. Association with other clinical variables and adverse outcomes of repeated measurement of GDF-15 was explored. Results: The median baseline GDF-15 level was 2025 ng/L. Baseline GDF-15 was moderately associated with baseline N-terminal pro-B type natriuretic peptide (NT-proBNP) (coefficient 0.561, P < 0.001). During a median follow-up of 20 months, there were 53 deaths and 100MACE. GDF-15 remained an independent predictor of all-cause death (adjusted hazard ratio 1.826 per 1 Ln U, 95% CI: 1.037-8.360; P = 0.037) and MACE (adjusted hazard ratio 2.243 per 1 Ln U, 95% CI: 1.181-1.775; P < 0.001) adjusted for established risk factors. Repeated measurement of GDF-15 was performed in 173 survivals over 12months. Increase of GDF-15 over 12 months was associated with dilatation of left ventricle and acted as an independent predictor of subsequent all-cause death (adjusted HR = 3.164, 95% CI: 1.245-0.041; P = 0.015). In the joint model, GDF-15 was also shown to be a risk factor for all-cause death (HR = 2.749, 95% CI: 1.667-3.831; P < 0.001) and MACE (HR = 2.434, 95% CI: 1.425-3.443; P < 0.001). Conclusions: Repeated measurements of GDF-15 have promising prognostic value of the risk of all-cause death in Chinese Han patients with CHF post-myocardial infarction. GDF-15 may influence the post-myocardial infarction CHF through the path physiological pathway of myocardial remodeling.

12.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4074-4076, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30486533

RESUMO

A new isobenzofuranone derivative has been isolated from Phlomis betonicoides by using various chromatographic techniques, including silica gel, Sephadex LH-20, MCI-gel resin and RP-HPLC. This compound was determined as 5-(3-hydroxypropyl)-2,2-dimethyl-2H-furo[3,4-h]chromen-7(9H)-one (1) by NMR, MS, IR and UV spectroscopic data. Compound 1 showed potent antibacterial activity with an MIC90 value of (58.4 ± 4.2) mg·L⁻¹ for methicillin resistant Staphylococcus aureus (MRSA) strain [levofloxacin as a control with MIC90 value of (52.8±4.6) mg·L⁻¹].


Assuntos
Antibacterianos/farmacologia , Benzofuranos/farmacologia , Staphylococcus aureus Resistente à Meticilina/efeitos dos fármacos , Phlomis/química , Antibacterianos/isolamento & purificação , Benzofuranos/isolamento & purificação , Testes de Sensibilidade Microbiana , Compostos Fitoquímicos/isolamento & purificação , Compostos Fitoquímicos/farmacologia
13.
Kaohsiung J Med Sci ; 34(10): 569-575, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30309485

RESUMO

Hypertrophic cardiomyopathy (HCM) is the most common genetic cardiac disease and is an important cause of sudden death in patients of all ages. The aim of this study was to find out whether Toll-like receptor-4 (TLR4) polymorphism is associated with HCM. To explore the association between TLR4 gene polymorphisms and HCM, 486 HCM patients and 214 healthy controls were enrolled in a case-control study of Chinese Han population. Two single nucleotide polymorphisms (SNPs) in the promoter region of TLR4 gene, -728G > C (rs11536865) and -2081G > A (rs10983755), were genotyped by PCR restriction fragment length polymorphism (PCR-RFLP). The associations between TLR4 SNPs and overall survival (OS) of HCM patients were analyzed by the Kaplan-Meier estimation method and Cox proportional hazards regression analysis. Serum TLR4 level was determined by ELISA. Our results showed that the C allelic frequency of -728G > C and A allelic frequency of -2081G > A were higher in HCM patients than those in controls (P < 0.001). The ratios of genotype frequencies for both SNPs were associated with HCM susceptibility under three genetic models (P < 0.01). Two SNPs were also associated with the OS in HCM patients (P < 0.001). The CC genotype of -728G > C and AA genotype of -2081G > A were associated with poor prognosis of HCM (P < 0.001). Moreover, HCM patients had a higher serum TLR4 level compared with the controls (242.6 pg/ml versus 135.7 pg/ml, P = 0.027). In addition, significant associations were observed between CC genotype of -728G > C or AA genotype of -2081G > A and plasma TLR4 level (P < 0.01). The results of this study indicated that TLR4 polymorphisms may be a genetic susceptibility factor for HCM in the Han Chinese population.


Assuntos
Cardiomiopatia Hipertrófica/genética , Polimorfismo de Nucleotídeo Único/genética , Receptor 4 Toll-Like/genética , Adulto , Cardiomiopatia Hipertrófica/patologia , Estudos de Casos e Controles , Feminino , Frequência do Gene/genética , Genótipo , Humanos , Masculino , Pessoa de Meia-Idade , Prognóstico
14.
Zhongguo Zhong Yao Za Zhi ; 43(11): 2269-2273, 2018 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-29945378

RESUMO

To illustrate the intrinsic dissolution rate(IDR) involved in biopharmaceutics classification system of Chinese materia medica(CMMBCS), investigate the effect of artificial multicomponent environment on IDR of berberine, by using a non-disintegrating disk, and summarize related rules by using the obtained data. Progressive levels design was used to investigate the effects of single component environment (puerarin, baicalin, and glycyrrhizic acid); double-component environment(puerarin+baicalin, puerarin+ glycyrrhizic acid, baicalin+glycyrrhizic acid); and triple-component environment(puerarin+baicalin+glycyrrhizic acid) on IDR of berberine, laying a foundation for further researches on the absorption mechanism of multiple components.


Assuntos
Berberina/química , Medicamentos de Ervas Chinesas/química , Materia Medica , Biofarmácia , Solubilidade
16.
Artigo em Chinês | MEDLINE | ID: mdl-29737735

RESUMO

OBJECTIVES: To investigate the content of pepsin in salivary, and to assess the laryngophargeal lesions based on the reflux founding score (RFS) scale in asymptomatic volunteers, in order to provide a reference for the diagnosis of laryngopharyngeal reflux. METHODS: A total of 91 asymptomatic subjects were recruited in this study. Participants provided a fasting saliva specimen for pepsin measurement using enzyme-linked immunoadsorbent assay, completed the reflux symptom index (RSI) assessment and underwent laryngostroboscopic examination using a rigid endoscope. Their RFS were graded according to the laryngeal findings. RESULTS: The median concentration of pepsin in 91 asymptomatic volunteers was 55.5 µg/L (range 3.53-191.64 µg/L). The mean individuals RSI was 2.24±2.34, and the mean individuals RFS was 5.78±1.74. CONCLUSIONS: Our data demonstrate that certain concentration of pepsin was detected and showed a higher RFS score in asymptomatic volunteers.


Assuntos
Refluxo Laringofaríngeo/diagnóstico , Pepsina A/análise , Saliva/química , Humanos , Laringoscopia , Voluntários
17.
J Nat Prod ; 81(4): 1098-1102, 2018 04 27.
Artigo em Inglês | MEDLINE | ID: mdl-29667821

RESUMO

Nine dimeric acylphloroglucinols, including the new hyperjaponicols A-D (1-4), were isolated from the whole plant of Hypericum japonicum. The new structures were determined by the interpretation of NMR and MS data, and the relative configuration of the known compound, sarothralen C (5), was reassigned via NMR spectroscopic analysis and single-crystal X-ray diffraction data. The inhibitory activities of the isolates against four bacterial strains were evaluated, and compounds 1-4, 6, and 7 exhibited significant antibacterial activity with MIC values of 0.8-3.4 µM. In addition, compound 3 showed moderate lipase inhibitory activity (IC50 8.3 µM).


Assuntos
Antibacterianos/química , Hypericum/química , Floroglucinol/química , Concentração Inibidora 50 , Espectroscopia de Ressonância Magnética/métodos , Difração de Raios X/métodos
18.
Stem Cell Reports ; 10(4): 1267-1281, 2018 04 10.
Artigo em Inglês | MEDLINE | ID: mdl-29526738

RESUMO

Retinitis pigmentosa (RP) is an irreversible, inherited retinopathy in which early-onset nyctalopia is observed. Despite the genetic heterogeneity of RP, RPGR mutations are the most common causes of this disease. Here, we generated induced pluripotent stem cells (iPSCs) from three RP patients with different frameshift mutations in the RPGR gene, which were then differentiated into retinal pigment epithelium (RPE) cells and well-structured retinal organoids possessing electrophysiological properties. We observed significant defects in photoreceptor in terms of morphology, localization, transcriptional profiling, and electrophysiological activity. Furthermore, shorted cilium was found in patient iPSCs, RPE cells, and three-dimensional retinal organoids. CRISPR-Cas9-mediated correction of RPGR mutation rescued photoreceptor structure and electrophysiological property, reversed the observed ciliopathy, and restored gene expression to a level in accordance with that in the control using transcriptome-based analysis. This study recapitulated the pathogenesis of RPGR using patient-specific organoids and achieved targeted gene therapy of RPGR mutations in a dish as proof-of-concept evidence.


Assuntos
Ciliopatias/terapia , Terapia Genética , Células-Tronco Pluripotentes Induzidas/patologia , Organoides/patologia , Células Fotorreceptoras/patologia , Retina/patologia , Retinite Pigmentosa/patologia , Retinite Pigmentosa/terapia , Diferenciação Celular , Ciliopatias/patologia , Ciliopatias/fisiopatologia , Proteínas do Olho/genética , Humanos , Células-Tronco Pluripotentes Induzidas/metabolismo , Mutação/genética , Células Fotorreceptoras/metabolismo , Canais de Potássio/metabolismo , Retinite Pigmentosa/fisiopatologia
19.
J Infect Dev Ctries ; 12(9): 794-798, 2018 09 30.
Artigo em Inglês | MEDLINE | ID: mdl-31999639

RESUMO

INTRODUCTION: Neonates are at high risk of nosocomial infections, especially in developing countries. This study aimed to examine the effectiveness of drug-resistant bacteria (DRB) screening in combination with patient barrier precautions in controlling nosocomial infections in neonatal wards. METHODOLOGY: The clinical data of neonates admitted to the Mianyang Central Hospital, Mianyang, China in 2010 and 2012 were retrospectively analyzed. In 2010, DRB screening was conducted using nasal and anal swabs. In 2012, in addition to the DRB screening, patient barrier precautions were implemented. The barrier precautions were lifted if the patients were negative for the DRB screening. Patients with DRB colonization were further isolated to reduce the risk of nosocomial infection. The rate of nosocomial infections in the two years was compared. RESULTS: A total of 1280 neonates in 2010 and 1504 neonates in 2012 were included in the analysis. No significant difference was noticed between the two years in gestational weeks, age, gender, and birth weight. The rate of nosocomial infections was reduced significantly from 2.34% in 2010 to 1.13% in 2012. CONCLUSIONS: DRB screening in combination with the patient barrier precautions may reduce the risk of nosocomial infection in neonates.

20.
Zhongguo Zhong Yao Za Zhi ; 42(21): 4127-4134, 2017 Nov.
Artigo em Chinês | MEDLINE | ID: mdl-29271150

RESUMO

One of the advantages of biopharmaceutics classification system of Chinese materia medica (CMMBCS) is expanding the classification research level from single ingredient to multi-components of Chinese herb, and from multi-components research to holistic research of the Chinese materia medica. In present paper, the alkaloids of extract of huanglian were chosen as the main research object to explore their change rules in solubility and intestinal permeability of single-component and multi-components, and to determine the biopharmaceutical classification of extract of Huanglian from holistic level. The typical shake-flask method and HPLC were used to detect the solubility of single ingredient of alkaloids from extract of huanglian. The quantitative research of alkaloids in intestinal absorption was measured in single-pass intestinal perfusion experiment while permeability coefficient of extract of huanglian was calculated by self-defined weight coefficient method.


Assuntos
Medicamentos de Ervas Chinesas/química , Materia Medica/classificação , Extratos Vegetais/química , Animais , Biofarmácia , Medicamentos de Ervas Chinesas/classificação , Absorção Intestinal , Extratos Vegetais/classificação
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