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1.
BMC Cancer ; 19(1): 920, 2019 Sep 14.
Artigo em Inglês | MEDLINE | ID: mdl-31521128

RESUMO

BACKGROUND: Tumor-infiltrating immune cells are present in various malignant tumors, but their clinical significance in gastric cancer (GC) remains unclear. This study aimed to investigate the prognostic significance of tumor-infiltrating lymphocytes (TILs) and tumor-associated macrophages (TAMs). METHODS: Using a prospective database containing 401 cases of GC, we evaluated TIL (cluster of differentiation 8 (CD8) expression) and TAM (cluster of differentiation 68 (CD68) expression) statuses via immunohistochemical staining. RESULTS: Compared with CD8+ TIL-negative cases (n = 196, 48.6%), CD8+ TIL-positive cases (n = 205, 51.1%) showed significantly better recurrence-free survival (RFS) [log-rank p<0.001; multivariate HR: 0.372; 95% confidence interval (CI): 0.239-0.579, p<0.001]. In contrast, compared with CD68+ TAM-negative cases (n = 217, 54.1%), CD68+ TAM-positive cases (n = 184, 45.9%) had significantly poor RFS [log-rank p<0.001; multivariate HR: 2.182; 95% CI: 1.435-3.318, p<0.001]. Thus, patients with a positive CD8+ TIL and negative CD68+ TAM status exhibited significantly increased RFS. Multivariate analysis demonstrated that CD8+ TILs and CD68+ TAMs may serve as independent prognostic markers for RFS. Incorporating CD8+ TIL and CD68+ TAM statuses into the AJCC TNM system generated a predictive model with better predictive accuracy for RFS. More importantly, patients with a positive TIL and negative TAM status showed a tendency of improved RFS after postoperative adjuvant chemotherapy (PAC). Similar results were obtained by overall survival (OS) analysis. CONCLUSIONS: CD8+ TIL and CD68+ TAM statuses were identified as independent prognostic factors that may be integrated into the current TNM staging system to refine risk stratification and to better predict the survival benefit from PAC in patients with GC. TRIAL REGISTRATION: The current controlled trial was registered at ClinicalTrials.gov (ID: NCT02327481 ) on December 30, 2014.

2.
J Agric Food Chem ; 67(30): 8348-8360, 2019 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-31304751

RESUMO

We have recently demonstrated that tau hyperphosphorylation causes diabetic synaptic neurodegeneration of retinal ganglion cells (RGCs), which might be the earliest affair during the pathogenesis of diabetic retinopathy (DR). Thus, there is a pressing need to seek therapeutic agents possessing neuroprotective effects against tau hyperphosphorylation in RGCs for arresting the progression of DR. Here, using a well-characterized diabetes model of db/db mouse, we discovered that topical ocular application of 10 mg/kg/day of ginsenoside Rg1 (GRg1), one of the major active ingredients extracted from Panax ginseng and Panax notoginseng, ameliorated hyperphosphorylated tau-triggered RGCs synaptic neurodegeneration in diabetic mice. The neuroprotective effects of GRg1 on diabetic retinae were abrogated when retinal IRS-1 or Akt was suppressed by intravitreal injection with si-IRS-1 or topically coadministered with a specific inhibitor of Akt, respectively. However, selective repression of retinal GSK3ß by intravitreal administration of si-GSK3ß rescued the neuroprotective properties of GRg1 when Akt was inactivated. Therefore, the present study showed for the first time that GRg1 can prevent hyperphosphorylated tau-induced synaptic neurodegeneration of RGCs via activation of IRS-1/Akt/GSK3ß signaling in the early phase of DR. Moreover, our data clarify the potential therapeutic significance of GRg1 for neuroprotective intervention strategies of DR.


Assuntos
Retinopatia Diabética/tratamento farmacológico , Ginsenosídeos/administração & dosagem , Glicogênio Sintase Quinase 3 beta/metabolismo , Proteínas Substratos do Receptor de Insulina/metabolismo , Fármacos Neuroprotetores/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/metabolismo , Células Ganglionares da Retina/efeitos dos fármacos , Proteínas tau/metabolismo , Animais , Retinopatia Diabética/genética , Retinopatia Diabética/metabolismo , Glicogênio Sintase Quinase 3 beta/genética , Humanos , Proteínas Substratos do Receptor de Insulina/genética , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Degeneração Neural/tratamento farmacológico , Degeneração Neural/genética , Degeneração Neural/metabolismo , Panax notoginseng/química , Fosforilação , Extratos Vegetais/administração & dosagem , Proteínas Proto-Oncogênicas c-akt/genética , Retina/patologia , Células Ganglionares da Retina/metabolismo , Transdução de Sinais/efeitos dos fármacos , Proteínas tau/genética
3.
Bioorg Med Chem ; 27(15): 3299-3306, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31204226

RESUMO

Gastrodia elata is a famous traditional Chinese herb with medicinal and edible application. In this study, nine polybenzyls (1-9), including six new ones (2-5, 7 and 9), were isolated from the EtOAc extract of G. elata. Five compounds 1, 3, 4, 6 and 8 were found to activate melatonin receptors. Especially, compound 1 showed agonistic effects on MT1 and MT2 receptors with EC50 values of 237 and 244 µM. For better understanding their structure-activity relationships (SARs), ten polybenzyl analogs were further synthesized and assayed for their activities on melatonin receptors. Preliminary SARs study suggested that two para-hydroxy groups were the key pharmacophore for maintaining activity. Molecular docking simulations verified that compound 1 could strongly interact with MT2 receptor by bonding to Phe 118, Gly 121, His 208, Try 294 and Ala 297 residues.

4.
J Agric Food Chem ; 67(24): 6765-6772, 2019 Jun 19.
Artigo em Inglês | MEDLINE | ID: mdl-31180676

RESUMO

One unusual resveratrol tetramer, paeonilactiflorol (1), and 14 known compounds (2-15) were isolated from peony seeds ( Paeonia lactiflora) under the guidance of bioassay. Paeonilactiflorol (1) was determined by extensive HRESIMS, UV, IR, 1D and 2D NMR spectroscopic analyses. Most of the stilbenes showed obvious inhibition on PTP1B and α-glucosidase, superior to the monoterpene glycosides. Especially, the stilbene tetramer (1) and trimer (8) exhibited high activity inhibiting both PTP1B with IC50 values of 27.23 and 27.81 µM and α-glucosidase with IC50 values of 13.57 and 14.39 µM. Two trans-dimers (4 and 5) also showed dipeptidyl peptidase-4 (DPPIV) inhibitory activity (55.35% and 61.26%, 500 µM) in addition to PTP1B and α-glucosidase. Enzyme kinetic study indicated that the types of inhibition on PTP1B were noncompetitive for 3 and 5 and mixed for 8 and 10. Quantitative analysis suggested that the stilbene trimers 8 (23.17 ± 0.36 mg/g) and 10 (15.24 ± 0.25 mg/g) were the main contents in peony seeds and should be responsible for the antidiabetic effects. This investigation supports the therapeutic potential of peony seeds in the treatment of diabetes with stilbenes as the active constituents.


Assuntos
Inibidores da Dipeptidil Peptidase IV/química , Inibidores de Glicosídeo Hidrolases/química , Hipoglicemiantes/química , Paeonia/química , Extratos Vegetais/química , Proteína Tirosina Fosfatase não Receptora Tipo 1/antagonistas & inibidores , Estilbenos/química , Dipeptidil Peptidase 4/química , Inibidores da Dipeptidil Peptidase IV/isolamento & purificação , Inibidores de Glicosídeo Hidrolases/isolamento & purificação , Hipoglicemiantes/isolamento & purificação , Estrutura Molecular , Extratos Vegetais/isolamento & purificação , Proteína Tirosina Fosfatase não Receptora Tipo 1/química , Sementes/química , Estilbenos/isolamento & purificação , alfa-Glucosidases/química
5.
Phytochemistry ; 164: 228-235, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31181354

RESUMO

Terminthia paniculata (Sanyeqi) is widely used for treating inflammation and rheumatic arthritis in the folk areas of Yunnan province, China. Its total extract was first revealed with xanthine oxidase (XO) inhibitory activity in vitro and anti-hyperuricemic effect in vivo. Bioassay-guided separation on Fr. A5 yielded six chalcone-flavonone heterodimers, termipaniculatones A-F. Their structures were elucidated based on extensive spectroscopic analyses involving HRESIMS, 1D and 2D NMR, UV, IR and [α]D, and the absolute configuration of termipaniculatone F was verified by ECD calculation. Termipaniculatones A and E showed obvious XO inhibitory activity with IC50 values of 55.6 and 89.5 µM, respectively, which took effects via a mix-type mode. A molecular modeling study revealed that termipaniculatone A was well located into the active site of XO by interacting with Glu802, Arg880, Thr1010 and Val1011 residues. Termipaniculatone A showed anti-hyperuricemic effects by decreasing serum uric acid levels and inhibiting XO activity in both serum and liver on potassium oxonate (PO)-induced hyperuricemia mice, and anti-inflammatory activity through alleviating paw swelling on monosodium urate (MSU)-induced mice, at the concentration of 20 mg/kg. This is the first time to reveal the anti-hyperuricemic and anti-acute gouty arthritis potency of T. paniculata and the characteristic biflavonoids as active constituents, which provides valuable information for searching new XO inhibitors from natural sources.


Assuntos
Anacardiaceae/química , Anti-Inflamatórios não Esteroides/farmacologia , Artrite Gotosa/tratamento farmacológico , Inibidores Enzimáticos/farmacologia , Hiperuricemia/tratamento farmacológico , Animais , Anti-Inflamatórios não Esteroides/química , Anti-Inflamatórios não Esteroides/isolamento & purificação , Artrite Gotosa/induzido quimicamente , Artrite Gotosa/metabolismo , Chalcona/química , Chalcona/isolamento & purificação , Chalcona/farmacologia , Relação Dose-Resposta a Droga , Edema/induzido quimicamente , Edema/tratamento farmacológico , Inibidores Enzimáticos/química , Inibidores Enzimáticos/isolamento & purificação , Flavanonas/química , Flavanonas/isolamento & purificação , Flavanonas/farmacologia , Hiperuricemia/induzido quimicamente , Hiperuricemia/metabolismo , Inflamação/induzido quimicamente , Inflamação/tratamento farmacológico , Inflamação/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos , Estrutura Molecular , Ácido Oxônico/antagonistas & inibidores , Relação Estrutura-Atividade , Ácido Úrico/antagonistas & inibidores , Xantina Oxidase/antagonistas & inibidores , Xantina Oxidase/metabolismo
6.
Nat Prod Bioprospect ; 2019 Apr 29.
Artigo em Inglês | MEDLINE | ID: mdl-31037617

RESUMO

Mentha haplocalyx (Mentha canadensis) is widely used as a medicinal plant in traditional Chinese medicine, and the extracts of its aerial parts are found to significantly inhibit the activity of α-glucosidase with an IC50 value of 21.0 µg/mL. Bioactivity-guided isolation of the extracts afforded two new compounds (1 and 2), together with 23 known ones (3-25). Their structures were established by extensive spectroscopic analyses (1D and 2D NMR, MS, IR and UV). Compounds 1-17 and 21-25 were evaluated for their α-glucosidase inhibitory activities. Compound 11 was the most active ones with an IC50 values of 83.4 µM. These results verify the α-glucosidase inhibitory activity of M. haplocalyx (M. canadensis) and specify its active compounds for the first time.

7.
World J Gastroenterol ; 25(13): 1618-1627, 2019 Apr 07.
Artigo em Inglês | MEDLINE | ID: mdl-30983821

RESUMO

BACKGROUND: Chronic radiation proctitis (CRP) is a complication which occurs in 1%-5% of patients who undergo radiotherapy for pelvic malignancies. Although a wide range of therapeutic modalities are available, there is no literature to date showing any particularly appropriate therapeutic modality for each disease stage. Argon plasma coagulation (APC) is currently recommended as the first-choice treatment for hemorrhagic CRP, however, its indication based on long-term follow-up is still unclear. On the hypothesis that the long-term efficacy and safety of APC are not fully understood, we reviewed APC treatment for patients with hemorrhagic CRP from a single center. AIM: To assess the long-term efficacy and safety of APC for hemorrhagic CRP. METHODS: This is a retrospective study of consecutive patients treated with APC for hemorrhagic CRP from January 2013 to October 2017. Demographics, clinical variables, and typical endoscopic features were recorded independently. Success was defined as either cessation of bleeding or only occasional traces of bloody stools with no further treatments for at least 12 mo after the last APC treatment. We performed univariate and multivariate analyses to identify factors associated with success and risk factors for fistulas. RESULTS: Forty-five patients with a median follow-up period of 24 mo (range: 12-67 mo) were enrolled. Fifteen (33.3%) patients required blood transfusion before APC. Successful treatment with APC was achieved in 31 (68.9%) patients. The mean number of APC sessions was 1.3 (1-3). Multivariate analysis showed that APC failure was independently associated with telangiectasias present on more than 50% of the surface area [odds ratio (OR) = 6.53, 95% confidence interval (CI): 1.09-39.19, P = 0.04] and ulcerated area greater than 1 cm2 (OR = 8.15, 95%CI: 1.63-40.88, P = 0.01). Six (13.3%) patients had severe complications involving rectal fistulation. The only factor significantly associated with severe complications was ulcerated area greater than 1 cm2 (P = 0.035). CONCLUSION: The long-term efficacy of APC for hemorrhagic CRP is uncertain in patients with telangiectasias present on > 50% of the surface area and ulceration > 1 cm2.


Assuntos
Coagulação com Plasma de Argônio/efeitos adversos , Hemorragia Gastrointestinal/cirurgia , Complicações Pós-Operatórias/epidemiologia , Proctite/cirurgia , Lesões por Radiação/cirurgia , Telangiectasia/cirurgia , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Seguimentos , Hemorragia Gastrointestinal/etiologia , Humanos , Mucosa Intestinal/irrigação sanguínea , Mucosa Intestinal/patologia , Mucosa Intestinal/efeitos da radiação , Mucosa Intestinal/cirurgia , Masculino , Pessoa de Meia-Idade , Neoplasias Pélvicas/radioterapia , Complicações Pós-Operatórias/etiologia , Proctite/etiologia , Proctite/patologia , Lesões por Radiação/etiologia , Lesões por Radiação/patologia , Reto/irrigação sanguínea , Reto/patologia , Reto/efeitos da radiação , Reto/cirurgia , Estudos Retrospectivos , Fatores de Risco , Telangiectasia/etiologia , Telangiectasia/patologia , Resultado do Tratamento
8.
J Ethnopharmacol ; 232: 39-46, 2019 Mar 25.
Artigo em Inglês | MEDLINE | ID: mdl-30543912

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Traditional Chinese medicines (TCMs) are fascinating sources for natural drug candidates. Uncaria rhynchophylla (Gouteng) is a famous TCM used for alleviating central nervous system (CNS) disorders, while its antidepressant constituents are still disputed. AIM OF THE STUDY: The present study was designed to assess the antidepressant property of U. rhynchophylla and characterize the active constituents targeting melatonin receptors which are closely related to CNS diseases. MATERIALS AND METHODS: The total extract and each fraction of U. rhynchophylla were extensively assessed for their agonistic activity on melatonin receptors in vitro. The following bioassay-guided fractionation yielded the active constituents, whose activity was confirmed by dose-dependent bioassay and antagonistic experiment on HEK293 cells. Their antidepressant effects were evaluated on forced swimming test (FST), tail suspension test (TST) and open-field test (OFT) mice models in vivo. Their metabolic profiles in mice plasma were analyzed by LCMS-IT-TOF. RESULTS: The stems and hooks of U. rhynchophylla were revealed with agonistic activity on melatonin receptors (MT1 and MT2). Under the guidance of bioassay, two flavanols, catechin and epicatechin were obtained and showed obviously activity agitating MT1 (EC50 = 25.8 and 156.1 µM) and MT2 (EC50 = 47.3 and 208.8 µM) receptors. The agonistic activity of catechin on melatonin receptors can be antagonized by luzindole at the concentrations of 1.57-100 µM. Catechin could significantly reduce the immobility time in both FST and TST mice models at doses of 80 and 40 mg/kg, without obvious effect on locomotor activity in OFT mice model. Five phase II (M1-M5) and one phase I (M6) metabolites of catechin were detected in mice plasma after intragastric (i.g.) administration. CONCLUSION: Catechin is a potent antidepressant candidate from U. rhynchophylla by targeting melatonin receptors. The main metabolic pathways of catechin in mice plasma are glucuronidation (M3) and methylated glucuronidation (M4 and M5). This study provides valuable information for understanding the antidepressant potency of Gouteng and its active constituents.


Assuntos
Antidepressivos/uso terapêutico , Catecóis/uso terapêutico , Depressão/tratamento farmacológico , Extratos Vegetais/uso terapêutico , Receptor MT1 de Melatonina/agonistas , Receptor MT2 de Melatonina/agonistas , Uncaria , Animais , Antidepressivos/farmacologia , Catecóis/farmacologia , Células HEK293 , Humanos , Locomoção/efeitos dos fármacos , Masculino , Camundongos , Fitoterapia , Extratos Vegetais/farmacologia , Caules de Planta , Receptor MT1 de Melatonina/genética , Receptor MT2 de Melatonina/genética
9.
Zhongguo Zhong Yao Za Zhi ; 43(20): 4104-4110, 2018 Oct.
Artigo em Chinês | MEDLINE | ID: mdl-30486538

RESUMO

This paper aimed to study the six chemical components of Polygoni Multiflori Radix (gallic acid, quercetin, luteolin, kaempferol, resveratrol, apigenin). By the established pregnane X receptor (human pregnant X receptor, PXR) CYP3A4 mediated drug induced rapid screening technique, the effect of chemical components on the cell activity was detected by MTS cell method, and the value of IC50 was calculated. The dual luciferase reporter system was used to co-transfect PXR reporter gene expression vector containing transcriptional regulation and CYP3A4 with HepG2 cells, with 10 µmol·L⁻¹ rifampicin (RIF) as a positive control, and 10 µmol·L⁻¹ of ketoconazole (TKZ) as negative control. Gallic acid, quercetin, luteolin, kaempferol, apigenin, resveratrol(5, 10, 20 µmol·L⁻¹) were used to incubate for 24 h, and the luciferase activity was detected. The results showed that when plasmid pcDNA3.1 was co-transfected with pGL4.17-CYP3A4, gallic acid and resveratrol had an inhibitory effect on the regulation of CYP3A4, and quercetin, luteolin, kaempferol had an inductive effect on CYP3A4; when pcDNA3.14-PXR was co-transfected with pGL4.17-CYP3A4, quercetin, luteolin, kaempferol, apigenin, resveratrol had an inductive effect. To sum up, the 6 reported liver injury components had inhibitory or activating effects on CYP3A4. After PXR plasmid was involved, 5 components had an inductive effect on CYP3A4, and the inductive effects of 2 components were significantly different. In this experiment, we found that 2 kinds of potential liver injury components in Polygoni Multiflori Radix had been induced by CYP3A4, which was achieved through PXR regulation. It suggested that attention shall be paid to potential drug interactions when combined with Polygoni Multiflori Radix, so as to improve the safety and efficacy.

10.
J Cancer ; 9(18): 3263-3268, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30271485

RESUMO

Purpose: To investigate the difference in treatment plan quality of volumetric modulated arc treatment (VMAT) for esophageal carcinoma with flattening filter beam (FF) and flattening filter free beam (FFF). Material and methods: A total of fifty-six treatment plans were generated for twenty eight esophageal carcinoma patients with flattening filter beam and flattening filter free beam, using same optimal parameters. The homogeneity index (HI) and conformal index (CI) of targets, and some special points on Dose-Volume Histogram (DVH) curves were used to compare the plan quality. The coverage volumes of 45 Gy, 30 Gy and 20 Gy outside targets (V45Gy, V30Gy and V20Gy ) were used to compare the targets peripheral dose. The MU numbers, measured delivery time and averaged dose rates were used to evaluate the delivery efficiency of treatment plans. Results: A significant decreasing in peripheral dose around targets was found using FFF beams while the dose distributions in targets were equivalent to the plans with FF beams. V45Gy, V30Gy and V20Gy were decreased by 6.46%, 88.18% and 4.40%, respectively. A significant increase in MUs and decrease in treatment time were also found in delivery test. The average MUs was increased by 21.83% and the average treatment time was reduced by down to 11.9%. Conclusions: For esophageal carcinoma, the research showed that the treatment plans with FFF beams could get comparable dose distribution in targets and could significantly reduce the peripheral dose around targets compared to the plans with FF beams.

11.
Asian J Androl ; 2018 Sep 07.
Artigo em Inglês | MEDLINE | ID: mdl-30198493

RESUMO

While it is known that spermatogonial stem cells (SSCs) initiate the production of male germ cells, the mechanisms of SSC self-renewal, proliferation, and differentiation remain poorly understood. We have previously identified Strawberry Notch 1 (SBNO1), a vertebrate strawberry notch family protein, in the proteome profile for mouse SSC maturation and differentiation, revealing SBNO1 is associated with neonatal testicular development. To explore further the location and function of SBNO1 in the testes, we performed Sbno1 gene knockdown in mice to study the effects of SBNO1 on neonatal testicular and SSC development. Our results revealed that SBNO1 is required for neonatal testicular and SSC development in mice. Particularly, in vitro Sbno1 gene knockdown with morpholino oligonucleotides caused a reduction of SSCs and inactivation of the noncanonical Wnt pathway, through Jun N-terminal kinases. Our study suggests SBNO1 maintains SSCs by promoting the noncanonical Wnt pathway.

12.
Eur J Med Chem ; 156: 381-393, 2018 Aug 05.
Artigo em Inglês | MEDLINE | ID: mdl-30015074

RESUMO

Depression is associated with high mortality and morbidity rates worldwide. By our random screening, it was first revealed that 23 magnolol derivatives were synthesized followed by in vitro and in vivo evaluation of their antidepressive potential. Compound 7c was found to be the most promising compound, with EC50 values of 396.5 and 383.0 µM agitating on MT1 and MT2 receptors, respectively. Additionally, we carried out in vivo experiments to confirm the efficacy and safety of compound 7c; the compound was found to be orally bioavailable and highly effective, leading to a significant reduction of immobility time in a mouse model of depression (forced swimming test and tail suspension test); the acting mechanism was explored by determining its effect on the levels of monoamine neurotransmitters and their metabolites in different mice brain regions; the acute toxicity study showed that the 50% lethal dose (LD50) of 7c was higher than 2000 mg/kg, p. o. A total of 25 metabolites of 7c were identified, including 5 metabolites in phase I and 20 metabolites in phase II. Altogether, these results indicate that magnolol derivative 7c is a promising lead compound for the development of a new chemical class of antidepressant drugs.


Assuntos
Antidepressivos/química , Antidepressivos/uso terapêutico , Compostos de Bifenilo/química , Compostos de Bifenilo/uso terapêutico , Depressão/tratamento farmacológico , Lignanas/química , Lignanas/uso terapêutico , Receptor MT1 de Melatonina/agonistas , Receptor MT2 de Melatonina/agonistas , Animais , Antidepressivos/síntese química , Antidepressivos/farmacologia , Compostos de Bifenilo/síntese química , Compostos de Bifenilo/farmacologia , Encéfalo/metabolismo , Depressão/metabolismo , Feminino , Células HEK293 , Elevação dos Membros Posteriores , Humanos , Lignanas/síntese química , Lignanas/farmacologia , Masculino , Camundongos , Ratos Sprague-Dawley , Receptor MT1 de Melatonina/metabolismo , Receptor MT2 de Melatonina/metabolismo
13.
Int Immunopharmacol ; 62: 203-211, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-30015240

RESUMO

Monocytes recruited and adhering to the inflamed arteries are crucial for atherosclerosis development. Here, we report the role of zinc (Zn2+) homeostasis in monocyte adhesion and recruitment. By comparing the expression levels of Zn2+ transporters between non-adhering and adhering monocytes, we found that the Zn2+ importer ZIP8 was specifically upregulated in monocytes adhering to the aortas ex-vivo. Although the overexpression of ZIP8 increased the absorption of Zn2+, Fe2+ and Cd2+ in monocytes, only Zn2+ supplementation was demonstrated capable of promoting the adhesion of monocytes to endothelial monolayers in vitro. In addition, we confirmed the role of ZIP8-dependent Zn2+ influx in promoting monocyte adhesion to the aortas ex-vivo. More importantly, the enforced expression of ZIP8 increased monocyte adhesion and recruitment to the nascent atherosclerotic lesions in ApoE-/- mice. Overall, our results suggest that the Zn2+ influx in monocytes regulated by ZIP8 is a novel factor determining their adhesion and recruitment to atherosclerotic lesions, and that targeting ZIP8 or Zn2+ homeostasis may represent a novel strategy to interfere these activities.

14.
J Ethnopharmacol ; 224: 283-289, 2018 Oct 05.
Artigo em Inglês | MEDLINE | ID: mdl-29890315

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Artemisia capillaris (Yin-Chen) is a famous traditional Chinese medicine (TCM) for treating acute and chronic hepatitis in China. Enynes are one type of characteristic constituents in this herb, while their anti-hepatitis B virus (anti-HBV) properties have not been systemically investigated. AIM OF THE STUDY: This study is to reveal the active part of A. capillaris, and systemically investigate the enynes and their anti-HBV activity. MATERIALS AND METHODS: The total extract and each fraction of A. capillaris were assayed for the anti-HBV activity to reveal the active part. Bioassay-guided fractionation using various chromatographic techniques yielded the enynes, whose structures were elucidated by spectroscopic analyses and ECD calculations. The anti-HBV properties inhibiting HBsAg and HBeAg secretions and HBV DNA replication were evaluated on HepG 2.2.15 cell line in vitro. RESULTS: ACT-2 and ACT-3 was revealed to be the respective active and toxic part of A. capillaris. Twelve enynes (1-12) involving four new ones (1-4) and two unusual enyne analogs (13-14) were isolated from the active part (ACT-2). All the isolates were assayed for their anti-HBV activity, and the preliminary structure-activity relationships were summarized based on the structural features. In particular, compound 4 could significantly inhibit the secretions of HBsAg and HBeAg, and HBV DNA replication with IC50 values of 197.2 (SI > 5.1), 48.7 (SI > 20.5) and 9.8 (SI > 102) µM. CONCLUSIONS: Enynes are responsible for the anti-HBV effects of A. capillaris. Hydroxyl and glycosyl groups are preferable for maintaining activity. This is the first time to systematically investigate the anti-HBV activity of enynes in A. capillaris, which provides valuable information for understanding the ethnopharmacological application of Yin-Chen.


Assuntos
Alquinos/farmacologia , Antivirais/farmacologia , Artemisia , Vírus da Hepatite B/efeitos dos fármacos , Extratos Vegetais/farmacologia , Alquinos/análise , Antivirais/análise , Replicação do DNA/efeitos dos fármacos , DNA Viral/efeitos dos fármacos , Células Hep G2 , Antígenos de Superfície da Hepatite B/imunologia , Antígenos E da Hepatite B/imunologia , Vírus da Hepatite B/genética , Vírus da Hepatite B/imunologia , Vírus da Hepatite B/fisiologia , Humanos , Medicina Tradicional Chinesa , Compostos Fitoquímicos/análise , Compostos Fitoquímicos/farmacologia , Componentes Aéreos da Planta/química , Extratos Vegetais/análise , Replicação Viral/efeitos dos fármacos
15.
Eur Radiol ; 28(10): 4048-4052, 2018 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-29666992

RESUMO

OBJECTIVES: To evaluate the safety and efficiency of computed tomography (CT)-guided medical adhesive, α-cyanoacrylate, for preoperative localisation of pulmonary ground-glass opacity (GGO) used for guiding the video-assisted thoracoscopic surgical (VATS) excision METHODS: The procedure was performed on 188 consecutive patients with solitary GGO (pure GGO = 90 cases; mixed GGO = 98 cases) prior to the thoracoscopic procedure. The complications and efficacy of this method were analysed. The resected GGO was analysed pathologically. RESULTS: The mean duration of the procedure was 16.3 ± 5.2 min. The preoperative localisation was 100% successful. All GGOs were successfully resected by VATS. Asymptomatic pneumothorax was developed in 16/188 patients (8.5%) and mild pulmonary haemorrhage occurred in 15 cases (7.9%) post-localisation. None of the patients required any further treatment for the complications. CONCLUSION: Preoperative localisation using CT-guided medical adhesive, α-cyanoacrylate, is a safe and short-duration procedure, with high accuracy and success rates with respect to VATS resection of GGO. KEY POINTS: • Preoperative localisation is crucial for successful resection of GGO by VATS. • Preoperative adhesive localisation provides an up to 100% successful localisation rate with few complications. • Preoperative adhesive localisation enabled VATS resection in 100% of the GGO. • Preoperative adhesive localisation is safe and effective for VATS resection of GGO.

16.
Int Urol Nephrol ; 50(9): 1679-1685, 2018 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-29651697

RESUMO

BACKGROUND: Chronic kidney disease (CKD) is very common now and is associated with high overall and cardiovascular mortality. Numerous studies have reported that abdominal obesity is a risk factor for cardiovascular mortality. We investigated the link between sagittal abdominal diameter (SAD) and Framingham risk score in non-dialysis CKD patients. METHODS: In a cross-sectional study, we enrolled 307 prevalent non-dialysis CKD patients (175 males, aged 50.7 ± 17.04 years). SAD and Framingham risk score were measured. RESULTS: Framingham cardiovascular disease risk score was independently predicted by SAD (P < 0.01), GFR (P < 0.01) and diabetic history (P < 0.05). Adjusted R2 of the model was 0.178. SAD could be independently predicted by BMI (P < 0.01), diabetic history (P < 0.01), GFR (P < 0.01) and age (P < 0.01). Adjusted R2 of the model was 0.409. Using receiver operating characteristic (ROC) curve, a cutoff SAD value of 16.55 cm was determined with sensitivity of 63.7%, specificity of 58.3%. CONCLUSION: Elevated SAD is significantly associated with increased Framingham risk score in non-dialysis CKD patients. SAD can be predicted by patients' BMI, diabetic history, renal function and age. Further investigation is needed to explore the potential benefits of central obesity lowering therapy in this patient group.

18.
Fitoterapia ; 128: 57-65, 2018 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-29641985

RESUMO

Ten new (1-10) and ten known (11-20) diterpenoids involving ent-atisane, ent-seco-atisane, ent-kaurane and ent-seco-kaurane types were isolated from Sapium insigne under the guidance of LCMS-IT-TOF analyses. Their structures were characterized by extensive spectroscopic analyses (HRESIMS, UV, IR, 1D and 2D NMR). A putative biosynthetic pathway was proposed for ent-seco-atisane diterpenoids. Their inhibitory activities on α-glucosidase in vitro were tested for the first time. Compound 4 showed moderate inhibitory effect on α-glucosidase with an IC50 value of 0.34 mM via a noncompetitive inhibition mechanism (Ki = 0.27 mM). The preliminary structure-activity relationships of the ent-atisane diterpenoids inhibiting α-glucosidase were discussed.


Assuntos
Diterpenos/isolamento & purificação , Sapium/química , alfa-Glucosidases/isolamento & purificação , Cromatografia Líquida , Inibidores de Glicosídeo Hidrolases , Estrutura Molecular , Caules de Planta/química , Relação Estrutura-Atividade , Espectrometria de Massas em Tandem
19.
Zhongguo Zhong Yao Za Zhi ; 43(2): 377-384, 2018 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-29552858

RESUMO

This study aimed to investigate the effect and mechanism of ophiopogonin D (OP-D) on Ang Ⅱ-induced HUVECs apoptosis, in order to provide a reliable basis for the safety and efficacy of traditional Chinese medicines. The effect of Ang Ⅱ on survival and total proteins content of HUVECs were measured by MTT and Western blotting. The effect of OP-D on Ang Ⅱ-induced lactate dehydrogenase (LDH) release rate in HUVECs was measured by enzyme standard instrument. The effects of OP-D and 11,12-EET on phosphorylation of JNK/c-Jun induced by Ang Ⅱ were measured by Western blot and RT-PCR with the help of JNK specific inhibitor SP600125 and CYP450 isozymes selective inhibitor 6-(2-propargyloxyphenyl) hexanoic acid (PPOH). The cell apoptosis was assayed by flow cytometry. According to the results, different doses of Ang Ⅱ had no significant effect on cell survival; treatment with Ang Ⅱ at 1×10⁻6 mol·L⁻¹ could increase the release of LDH (P<0.001), improve the JNK and c-Jun phosphorylation levels(P<0.01, P<0.001), increase the expression of caspase-3(P<0.01), and promote the apoptosis of HUVECs(P<0.001). The phosphorylation of JNK and c-Jun could be inhibited by the pre-treatment with SP600125, 11,12-EET and OP-D. Pre-treatment with OP-D could significantly reduce the release of LDH induced by Ang Ⅱ stimulation, decrease the expression of caspase-3, and diminish the apoptosis of cells. The protective effect of OP-D was suppressed, when being pretreated with PPOH. The experimental results showed that the apoptosis of HUVECs induced by Ang Ⅱ may be associated with JNK/c-Jun signaling pathway. OP-D-mediated CYP2J2 expression increased 11,12-EET levels, and could remarkably resist Ang Ⅱ-induced injury and apoptosis of cells, which is associated with the maintenance of endothelium homeostasis.

20.
Int J Ophthalmol ; 11(1): 31-35, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29375987

RESUMO

AIM: To study the genes responsible for retinitis pigmentosa. METHODS: A total of 15 Chinese families with retinitis pigmentosa, containing 94 sporadically afflicted cases, were recruited. The targeted sequences were captured using the Target_Eye_365_V3 chip and sequenced using the BGISEQ-500 sequencer, according to the manufacturer's instructions. Data were aligned to UCSC Genome Browser build hg19, using the Burroughs Wheeler Aligner MEM algorithm. Local realignment was performed with the Genome Analysis Toolkit (GATK v.3.3.0) IndelRealigner, and variants were called with the Genome Analysis Toolkit Haplotypecaller, without any use of imputation. Variants were filtered against a panel derived from 1000 Genomes Project, 1000G_ASN, ESP6500, ExAC and dbSNP138. In all members of Family ONE and Family TWO with available DNA samples, the genetic variant was validated using Sanger sequencing. RESULTS: A novel, pathogenic variant of retinitis pigmentosa, c.357_358delAA (p.Ser119SerfsX5) was identified in PRPF31 in 2 of 15 autosomal-dominant retinitis pigmentosa (ADRP) families, as well as in one, sporadic case. Sanger sequencing was performed upon probands, as well as upon other family members. This novel, pathogenic genotype co-segregated with retinitis pigmentosa phenotype in these two families. CONCLUSION: ADRP is a subtype of retinitis pigmentosa, defined by its genotype, which accounts for 20%-40% of the retinitis pigmentosa patients. Our study thus expands the spectrum of PRPF31 mutations known to occur in ADRP, and provides further demonstration of the applicability of the BGISEQ500 sequencer for genomics research.

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