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1.
Environ Toxicol ; 2019 Sep 30.
Artigo em Inglês | MEDLINE | ID: mdl-31566298

RESUMO

Galangin, a natural flavonol, has anti-inflammatory and antioxidative potential. However, the cytoprotective effects of galangin against oxidative-induced aging in human fibroblasts have not been well studied. IGF-1 signaling pathway is associated with the control of aging and longevity in human. The goal of this study was to investigate the effects of galangin on human skin fibroblast HS68 cells under H2 O2 exposure to induce aging. In this study, we demonstrate that galangin could decrease the levels of pro-inflammatory proteins and enhanced collagen formation through promoting the IGF-1R pathway. Furthermore, aging markers such as senescence-associated ß-galactosidase p53, p21Cip1/WAF1 , and p16INK4A were upregulated under H2 O2 exposure and galangin could reverse its effects. Taken together, these data indicated that anti-inflammatory and antiaging activities of galangin may be mediated through the IGF-1R signaling pathway. These findings may provide the evidence for galangin to develop as an antiwrinkle product on human skin.

2.
Future Oncol ; 15(30): 3503-3511, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31580147

RESUMO

Aim: To investigate the risk factors for developing osteonecrosis of jaw (ONJ) in advanced cancer patients with bone metastases underwent zoledronic acid (ZA) treatment. Materials & methods: Univariate and multivariate logistic regression analyses were performed to investigate factors associated with developing ONJ in advanced cancer patients. Results: A total of 2214 advanced cancer patients were included. Univariate and multivariate logistic regression analyses for risk factors associated with ONJ were older age (≥66 years, hazards ratio [HR]: 3.21; p = 0.007), anemia (HR: 3.29; p = 0.006) and duration of ZA exposure (between 1 and 2 years, HR: 3.91, p = 0.01; ≥2 years, HR: 8.07, p < 0.001), respectively. Conclusion: Patients with older age, anemia and/or more than 1 year of ZA treatment are at high risk of developing ONJ.

3.
J Cell Mol Med ; 2019 Oct 27.
Artigo em Inglês | MEDLINE | ID: mdl-31657123

RESUMO

Radiation-induced lung injury (RILI) is the major complication of thoracic radiation therapy, and no effective treatment is available. This study explored the role of high-mobility group box 1 (HMGB1) in acute RILI and the therapeutic effect of glycyrrhizin, an inhibitor of HMGB1, on RILI. C57BL/6 mice received a 20 Gy dose of X-ray radiation to the whole thorax with or without administration of glycyrrhizin. Severe lung inflammation was present 12 weeks after irradiation, although only a mild change was noted at 2 weeks and could be alleviated by administration of glycyrrhizin. Glycyrrhizin decreased the plasma concentrations of HMGB1 and sRAGE as well as TNF-α, IL-1ß and IL-6 levels in the bronchoalveolar lavage fluid (BALF). The expression of RAGE was decreased while that of TLR4 was significantly increased at 12 weeks, but not 2 weeks, after irradiation in mouse lung tissue. In vitro, the expression of TLR4 increased in RAW 264.7 cells after conditioning with the supernatant from the irradiated MLE-12 cells containing HMGB1 but showed no change when conditioned medium without HMGB1 was used. However, conditioned culture had no effect on RAGE expression in RAW 264.7 cells. Glycyrrhizin also inhibited the related downstream transcription factors of HMGB/TLR4, such as NF-κB, JNK and ERK1/2, in lung tissue and RAW 264.7 cells when TLR4 was activated. In conclusion, the HMGB1/TLR4 pathway mediates RILI and can be mitigated by glycyrrhizin.

4.
Cell Cycle ; : 1-12, 2019 Oct 22.
Artigo em Inglês | MEDLINE | ID: mdl-31640472

RESUMO

To identify the mechanism and functions of IRX1 in heart failure (HF) and provide evidence for new therapies. Bioinformatic analysis was performed to select target genes in HF cells compared to normal groups. Experimental rats were treated in a controllable manner to explore how IRX1 methylation accounted for this disease in vivo. Cardiac ultrasonic and morphologic examinations were conducted to test the mouse heart and evaluate the degree of cardiac impairment at in the level of organization. GSEA analysis revealed the relative enrichment of functions. Immunofluorescent assays, western blotting and qRT-PCR were used to determine the DNA methylation and expression levels. IRX1 was hypermethylated in heart failure and identified as a target gene by bioinformatic analysis. Transverse aortic constriction (TAC) induced heart failure in rats, while 5-aza-2'-deoxycytidine (5-Aza) alleviated heart failure in rats according to medical cardiac indexes. Western blotting and qRT-PCR revealed that a conspicuous difference in the expression of IRX1 and CXCL14 between HF and normal cardiac cells. As a result of gene methylation, left ventricular hypertrophy and cardiac fibrosis is usually accompanied by heart failure. Moreover, is the results implied that the demethylation of IRX1 improves heart failure in vivo and in vitro. IRX1 methylation induced damaged cardiac function and even heart failure, which has important implications for HF treatment and diagnosis.

5.
Molecules ; 24(17)2019 Aug 28.
Artigo em Inglês | MEDLINE | ID: mdl-31466370

RESUMO

The vibrational spectrum of ice II was investigated using the CASTEP code based on first-principles density functional theory (DFT). Based on good agreement with inelastic neutron scattering (INS), infrared (IR), and Raman experimental data, we discuss the translation, libration, bending, and stretching band using normal modes analysis method. In the translation band, we found that the four-bond and two-bond molecular vibration modes constitute three main peaks in accordance with INS ranging from 117 to 318 cm-1. We also discovered that the lower frequencies are cluster vibrations that may overlap with acoustic phonons. Whale et al. found in ice XV that some intramolecular vibrational modes include many isolated-molecule stretches of only one O-H bond, whereas the other O-H bond does not vibrate. This phenomenon is very common in ice II, and we attribute it to local tetrahedral deformation. The pathway of combining normal mode analysis with experimental spectra leads to scientific assignments.

6.
Brain Res Bull ; 153: 143-149, 2019 Aug 16.
Artigo em Inglês | MEDLINE | ID: mdl-31425730

RESUMO

Cranioplasty is a challenge to neurosurgeons, especially considering protection of intracranial contents. In recent years, material choice for cranioplasty is still controversial, which brings complexity to this seemingly straightforward procedure. PEEK, a tough, rigid, biocompatible material, has been used more recently in cranioplasty to provide better protection. The aim of this review is to summarize the outcome of research conducted on the material for cranioplasty applications. We also reviewed the comparison of PEEK with several common materials in previous articles. This is also the most complete data review article at present. In addition, the combination of nano-materials and PEEK is also a hotspot of research, so we have made a careful review of this aspect. We also summarized our own experience, telling about the future prospects of PEEK in the field of clinical cranioplasty should be highlighted. Improving the bioactivity, porosity, thinning, biocompatibility, antibacterial ability, integration and cost reduction of PEEK implants without affecting their mechanical properties is a major challenge.

7.
Angew Chem Int Ed Engl ; 58(36): 12540-12544, 2019 Sep 02.
Artigo em Inglês | MEDLINE | ID: mdl-31318124

RESUMO

Highly active and durable electrocatalysts for the oxygen evolution reaction (OER) is greatly desired. Iridium oxide/graphitic carbon nitride (IrO2 /GCN) heterostructures are designed with low-coordinate IrO2 nanoparticles (NPs) confined on superhydrophilic highly stable GCN nanosheets for efficient acidic OER. The GCN nanosheets not only ensure the homogeneous distribution and confinement of IrO2 NPs but also endows the heterostructured catalyst system with a superhydrophilic surface, which can maximize the exposure of active sites and promotes mass diffusion. The coordination number of Ir atoms is decreased owing to the strong interaction between IrO2 and GCN, leading to lattice strain and increment of electron density around Ir sites and hence modulating the attachment between the catalyst and reaction intermediates. The optimized IrO2 /GCN heterostructure delivers not only by far the highest mass activity among the reported IrO2 -based catalysts but also decent durability.

8.
Breast J ; 25(6): 1134-1142, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31286612

RESUMO

In this study, we attempted to assess the efficacy of upfront brain radiotherapy (RT) in breast cancer (BC) patients with brain metastases (BM). Medical records of 111 consecutive BC patients treated with WBRT or SRS between August 2009 and November 2017 in single center were retrospectively reviewed. Eighty patients received upfront brain RT after BM diagnosis and 31 had delayed RT. The median age at BM was 54 years (22-77), with median KPS 80 (50-90). The molecular BC subtypes of Luminal A, Luminal B, triple-negative and HER2 overexpression were 16, 47, 27, and 19, respectively, with 2 unknown. Of them, 83 received WBRT after BM and 28 SRS. Median overall survival (OS) was significantly related to Breast-GPA, as following: 6.5, 9.9, 14.4, and 24.5 months in 0-1.0, 1.5-2.0, 2.5-3.0, and 3.5-4.0 subgroups, respectively (P = 0.007). Univariate and multivariate analysis showed that KPS ≤70, infratentorial involvement, extracranial metastases, and no continuing systemic therapy were independent risk factors for OS. In the whole group, no significant difference in OS was found between upfront or delayed RT. For Breast-GPA 0-2.0 subgroup, upfront RT was associated with increased median OS (3.3 vs 9.8 months, P = 0.04). In GPA 2.5-4.0 subgroup, the median OS for upfront and delayed RT was 13.8 and 16.5 months, respectively (P = 0.58). In conclusion, BCBM patients with better KPS, systemic therapy, without infratentorial involvement and extracranial metastases are associated with better OS. Patients with Breast-GPA 0-2.0 might benefit from upfront brain RT.

9.
Radiat Oncol ; 14(1): 115, 2019 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-31266510

RESUMO

PURPOSE: To investigate the efficacy and toxicity of concurrent radiation therapy (RT) and paclitaxel in the treatment of unresectable locoregionally recurrent breast cancer (RBC) after mastectomy as primary treatment. METHODS: This was a prospective monocentric study of 51 patients (pts) diagnosed with unresectable locoregionally RBC after mastectomy and treated between 2008 and 2012. Radiotherapy (RT) was delivered at 60 Gy in 30 treatment fractions to recurrent sites. Chemotherapy was weekly paclitaxel of 50 mg/m2 for 5 weeks. All pts. underwent clinical examination, CT or PET/CT every 3 months in first 2 years and then every 6 months. Tumor response was evaluated clinically and by CT using the RECIST criteria. Toxicity was assessed weekly during RT by the NCI common toxicity criteria (version 3.0). RESULTS: Fifty-one pts. with 61 recurrent sites were studied. The median age was 49 years. Sites of RBC were chest wall in 20 patients (32.8%), supraclavicular in 19 (31.1%), axilla in 11 (18.0%), and internal mammary lymph nodes in the remaining 11 (18.0%). RBC presented as single in 25 pts., multiple in 20 pts. and diffuse growth in 6 pts. Clinical response was observed in 47 pts. (92.2%), with 36 (70.6%) complete and 11 (21.6%) partial responses. Two patients (3.9%) presented with stable disease and 2 progressive disease. The cumulative local progression-free survival rate was 62.8% at 2 year and 53.0% at 5 years after treatment. No grade 4 toxicity was observed. Grade 3 radiation dermatitis and leukocytopenia were observed in 10 (19.6%) and 12 (23.5%) pts., respectively. One patient experienced grade 2 pneumonitis. CONCLUSIONS: Concurrent RT and weekly paclitaxel could be an effective therapeutic option for unresectable locoregionally recurrent breast cancer after mastectomy with an acceptable toxicity profile.

10.
Radiat Oncol ; 14(1): 128, 2019 Jul 17.
Artigo em Inglês | MEDLINE | ID: mdl-31315683

RESUMO

BACKGROUND: Lacking quantitative evaluations of clinicopathological features and the risk factors for loco-regional recurrence (LRR) in gastric cancer after D2 gastrectomy, we aimed to develop a competing risk nomogram to identify the risk predictors for initial LRR. METHODS: We retrospectively analysed 1105 patients who underwent radical gastrectomy with D2 resection for stage I-III gastric cancer. A nomogram predicting initial LRR of gastric cancer was conducted based on Fine and Grey's competing risk analysis. The predictive accuracy and discriminative ability of the model were determined using the concordance index (C-index) and calibration curve. Decision tree analysis was performed for patient grouping. RESULTS: At a median follow-up of 28.4 months, 274 patients developed 373 first recurrence events (local, regional, and distant disease). The median recurrence-free survival (RFS) was 16.7 months. Multivariate competing risk analysis showed that age (SHR, 1.72; 95% CI, 1.10-2.83, p = 0.031), CEA (SHR, 1.94; 95% CI, 1.09-3.46, p = 0.024), pT4 (SHR, 2.77; 95% CI, 1.01-7.57, p = 0.047), lymph node metastasis (SHR 1.92, 95% CI: 1.09-3.38, p = 0.024) and LVI (SHR, 1.84; 95% CI, 1.06-3.20, p = 0.028) were independent risk factors for LRR (all p < 0.05). The nomogram incorporating these factors achieved good agreement between prediction and actual observation with a concordance index of 0.738 (95% CI, 0.767 to 0.709). In a subgroup analysis of node-positive patients, pN3b was associated with increased peritoneal and distant metastasis (p = 0.048). The para-aortic lymph nodes were the most frequent sites (n = 71) of LRR, and among them, the 16a2 and 16b1 nodes exhibited even more prevalence (90.1 and 81.7%). CONCLUSIONS: Adjuvant radiotherapy might be recommended in gastric cancer patients ≥65 years old or those with pN+, pT4, LVI, or increased CEA levels, particularly in high-risk or pN1-3a patients. The competing risk nomograms may be considered as convenient and individualized predictive tools for LRR in gastric cancer after D2 gastrectomy. It is also recommended that the clinical target volume (CTV) include 16a2 and 16b1 regions of para-aortic lymph nodes.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31252687

RESUMO

BACKGROUND: The prevalence of lead poisoning in children under the age of six years living in Lancaster County, Pennsylvania continues to be greater than the state-wide prevalence for this age group. This study aims to determine the factors that contribute to the high lead poisoning rates. METHODS: For this qualitative study, the researchers recruited a convenience sample of professionals providing healthcare and social welfare services in the county. Researchers conducted in-depth interviews with participants. The research team audio recorded, transcribed verbatim, and analyzed each interview using NVivo 12 software. RESULTS: The 16 interviewed participants identified factors that contribute to high lead poisoning rates including knowledge levels, housing status, and competing interests. Specifically, low knowledge levels, renting as opposed to home ownership, and having competing interests seemed to minimize the attention directed towards preventing lead poisoning. The experts offered recommendations to address the high lead poisoning rates including increasing lead knowledge levels of both community members and landlords, through creating and distributing health promotion material, enacting policies to empower renters, and systematically collaborating to streamline lead poisoning related information and services. CONCLUSIONS: Findings provide insights to factors that Lancaster can address to achieve a decrease in lead poisoning rates. This study provides information that can be utilized by public health professionals to develop appropriate interventions.

12.
Macromol Rapid Commun ; 40(15): e1900182, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-31087721

RESUMO

The aggregate morphologies of 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene (BODIPY) main chain supramolecular polymer amphiphiles (SPA) are tunable by a fine balance of different non-covalent interactions. When the BODIPY segments and sodium cholate are mixed in aqueous solution, they form SPA by electrostatic attraction and hydrogen-bonds. This SPA displays helical nanowires' morphology. After the third component dimeric ß-cyclodextrin (ß-CD-C) is added, the hydrogen bonds between the cholate are substituted by the host-guest interaction between cholate and ß-CD-C. Therefore, these SPA transform their aggregate morphologies into nanosheets' architecture. Therefore, a simple and effective way to regulate self-assembly by non-covalent forces is developed. This supramolecular method may provide an effective way to prepare various nanostructures in aqueous solution and show promising application in the future.

13.
Se Pu ; 37(4): 454-461, 2019 Apr 08.
Artigo em Chinês | MEDLINE | ID: mdl-30977351

RESUMO

In order to improve the hydrothermal deoxygenation of organic acids as well as to reduce the cost, we prepared a Cu-Ce/γ-Al2O3 catalyst to study the hydrothermal deoxygenation of stearic acid in the absence of H2. The Brunauer-Emmett-Teller surface area and X-ray diffraction pattern suggest that both CuO and CeO2 exist in the Cu-Ce/γ-Al2O3 catalyst. The crystals of Cu-Ce/γ-Al2O3 were more stable compared with those of the Cu/γ-Al2O3 catalyst after 12 h of hydrothermal liquefaction at 300℃, thereby indicating a better thermal stability of the former. The presence of Cu-Ce/γ-Al2O3 catalyst could greatly improve the conversion of stearic acid (94.71%) and the yield of hydrocarbon (81.41%). A preliminary analysis of the mechanism suggests that decarboxylation is the main step in the deoxygenation during the hydrothermal liquefaction of stearic acid. The addition of Cu/γ-Al2O3 and Cu-Ce/γ-Al2O3 decreased the yield of n-heptadecane and increased the yield of n-octadecane. Besides, the yields of n-paraffins increased drastically from 0.45% to 49.72% along the series from n-nonane to n-hexadecane. Thus, the cracking reactions could be improved in the presence of Cu-Ce/γ-Al2O3, suggesting that it is an efficient deoxygenation catalyst in the hydrothermal liquefaction of organic acid. In addition, the Cu-Ce/γ-Al2O3 catalyst could help in removing the carbonyl groups, and this effectively reduced the amounts of aldehydes and ketones in the bio-oil.


Assuntos
Óleos Vegetais/química , Polifenóis/química , Ácidos Esteáricos/química , Óxido de Alumínio , Catálise , Cério , Cobre
14.
Int J Biol Sci ; 15(4): 738-748, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30906206

RESUMO

Ubiquitin-specific protease 17 (USP17), a novel member of deubiquitinase, is reported to play essential roles in several solid tumors. However, the expression and function of USP17 in breast cancer tumorigenesis remains ambiguity. Here we found that the mRNA level of USP17 was lower in breast cancer tissues than normal tissues. Meanwhile, higher USP17 level was detected in normal epithelial cell MCF-10A and a less-malignant cell MCF-7 than malignant cell line MDA-MB-231. Inhibition of USP17 in MCF7 cells enhanced tumorigenesis and tumor growth while overexpression of USP17 in malignant MDA-MB-231 cells reduced its tumorigenesis and growth ability in vitro and in vivo. Further study revealed that USP17 interacted with and deubiquitinated Asparaginyl endopeptidase (AEP), resulting in decreased protein levels of AEP. Moreover, knockdown of AEP inhibited breast cancer tumorigenesis and growth in vitro and in vivo through the inactivation of ERK signaling. Taken together, our works indicate that USP17 deubiquitinates AEP, down-regulates its protein level, and inhibits breast cancer tumorigenesis through disturbing ERK signaling. Thus, our data suggests that USP17 is a potential tumor suppressor in breast cancer and AEP is a promising target in breast cancer therapy.

15.
J Clin Lab Anal ; 33(5): e22874, 2019 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30843267

RESUMO

BACKGROUND: Kawasaki disease is a childhood systemic vasculitis that causes coronary artery abnormalities. The etiology remains unknown and there are no specific diagnostic tests. Circular non-coding RNAs are a special class of endogenous RNAs that display some characteristics of an ideal biomarker. However, few studies have examined the expression of circRNAs in the serum of Kawasaki disease (KD) patients. The aim of this study was to identify circRNAs in the serum that can serve as potential biomarkers for KD diagnosis. METHODS: The cases were children diagnosed with KD (n = 56). The controls comprised healthy children (n = 56). Blood was collected from the patients before and after intravenous immunoglobulin therapy, and from the healthy controls. Levels of circANRIL and hsa_circ_0123996 in the serum were measured by quantitative reverse transcription PCR. Then, the potential relationship between serum circRNA levels and patients' biochemical parameter levels was investigated. Receiver operating characteristic curves were constructed for evaluating the diagnostic value of these circRNAs. RESULTS: The serum levels of circANRIL were lower in patients with KD before therapy than in the controls, but became higher in the patients after therapy than before therapy. The serum levels of hsa_circ_0123996 were higher in patients with KD before therapy than in healthy controls. CONCLUSION: Our study indicated that the circANRIL and hsa_circ_0123996 levels in the serum of patients with KD were significantly different from those in healthy individuals. circANRIL and hsa_circ_0123996 may become potential biomarkers for early KD diagnosis.

16.
Sensors (Basel) ; 19(5)2019 Mar 12.
Artigo em Inglês | MEDLINE | ID: mdl-30871039

RESUMO

In this paper, a microscale high-frequency ultrasonic transducer was prepared by combining traditional planar ultrasonic phased-array technology and micro processing technology. The piezoelectric ceramic material PZT was used as the functional material of the transducer. The number of the arrays was 72, the width of each array was 50 µm, the pitch of each array was 70 µm, and the length of each array was 3 mm. The PZT chip was finely ground to a thickness of 130 µm and could reach a frequency of 10 MHz. The experimental platform of micron-scale precision was set up for a beam-forming lateral sound field test and imaging experiment to validate the theoretical analysis. The echo imaging test showed that a mold with a feature size of about 400 µm could be imaged well.

17.
Nat Cell Biol ; 21(4): 476-486, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30858581

RESUMO

The capacity of cells to alter bioenergetics in response to the demands of various biological processes is essential for normal physiology. The coordination of energy sensing and production with highly energy-demanding cellular processes, such as cell division, is poorly understood. Here, we show that a cell cycle-dependent mitochondrial Ca2+ transient connects energy sensing to mitochondrial activity for mitotic progression. The mitochondrial Ca2+ uniporter (MCU) mediates a rapid mitochondrial Ca2+ transient during mitosis. Inhibition of mitochondrial Ca2+ transients via MCU depletion causes spindle checkpoint-dependent mitotic delay. Cellular ATP levels drop during early mitosis, and the mitochondrial Ca2+ transients boost mitochondrial respiration to restore energy homeostasis. This is achieved through mitosis-specific MCU phosphorylation and activation by the mitochondrial translocation of energy sensor AMP-activated protein kinase (AMPK). Our results establish a critical role for AMPK- and MCU-dependent mitochondrial Ca2+ signalling in mitosis and reveal a mechanism of mitochondrial metabolic adaptation to acute cellular energy stress.


Assuntos
Proteínas Quinases Ativadas por AMP/metabolismo , Canais de Cálcio/fisiologia , Cálcio/metabolismo , Mitocôndrias/metabolismo , Mitose , Trifosfato de Adenosina/biossíntese , Animais , Canais de Cálcio/genética , Linhagem Celular , Células Cultivadas , Células HeLa , Humanos , Camundongos Endogâmicos C57BL , Microtúbulos/metabolismo , Mitocôndrias/enzimologia
18.
Pharmacotherapy ; 39(1): 67-76, 2019 01.
Artigo em Inglês | MEDLINE | ID: mdl-30537010

RESUMO

BACKGROUND: There are limited markers that could facilitate individualized tacrolimus treatment in the early posttransplantation period. Genetic factors have been found to play critical roles in determining tacrolimus pharmacokinetics. OBJECTIVE: We aimed to examine the association of donor and recipient Toll-like receptor (TLR) polymorphisms with tacrolimus elimination and the potential mechanism for TLR gene polymorphism-mediated tacrolimus metabolism. METHODS: Two independent cohorts including 297 patients receiving liver transplantation (LT) were enrolled in this study (cohort A was composed of 200 patients; cohort B included 97 patients and served as a validation set). Toll-like receptors polymorphisms were genotyped using TaqMan single nucleotide polymorphisms (SNPs) assays. The protein expressions were detected by Western blotting. The metabolism assay was used to quantify tacrolimus elimination. The activity of nuclear factor-kB (NF-kB) was evaluated by luciferase reporter assay. RESULTS: Tacrolimus dose-adjusted trough blood concentrations (C/D) ratios were significantly lower for donor TLR9 rs352139 AG/GG carriers than AA carriers at weeks 1, 2, and 3 after LT. In multivariate analysis, donor and recipient CYP3A5 rs776746 and donor TLR9 rs352139 were independent predictors of tacrolimus C/D ratios in the early period after transplantation in both cohorts. When investigating the combined effects of donor CYP3A5 rs776746 and donor TLR9 rs352139 genotypes, the C/D ratios were remarkably significant at all time points during the first month after LT within the four groups. Furthermore, CYP3A5 mRNA expression in liver tissue was significantly higher for AG/GG patients than AA carriers after LT. In addition, we demonstrated that the TLR9 rs352139 genetic variant promotes tacrolimus metabolism of liver cells via upregulation of CYP3A5, which is dependent on the repression of NF-κB/pregnane X receptor (PXR) signaling. CONCLUSIONS: Donor TLR9 rs352139 genetic variant facilitated tacrolimus elimination during the early stage after LT in Chinese patients, which might be related to the upregulation of CYP3A5 enzyme via the NF-kB/PXR signaling pathway.

19.
J Ethnopharmacol ; 229: 180-189, 2019 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-30336305

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: Zanthoxylum bungeanum Maxim. (ZBM), a Chinese herb medicine and food additive, has been shown to have broad-spectrum beneficial effects. However, the anticancer activities of its seed have not been reported. AIM OF THE STUDY: for the first time investigated the anti-proliferation activity of seed oil of ZBM (ZBSO) on melanoma A375 cells as well as the underlying mechanisms. MATERIALS AND METHODS: The chemical composition of ZBSO was analyzed by Ultra Performance Liquid Chromatography. A375 cells exposure at different concentrations of ZBSO to examine the selectivity versus normal skin cells, invasion, apoptosis and cell cycle arrest. Furthermore, transcriptome analysis was employed to investigate potential anticancer mechanisms of ZBSO. RESULTS: Major compounds of ZBSO were identified and unsaturated fatty acid made up the major compound. ZBSO-treated A375 cells showed more typical apoptotic morphologic features than normal cells. ZBSO can significantly inhibit invasion and proliferation of A375 cells by G1 phase arrest and induction of apoptosis. Transcriptome analysis showed that ZBSO may affect cell cycle and MAPK signaling pathway of A375 cells. CONCLUSION: ZBSO possessed anticancer activities that were selectively effective to A375 cells. This study support the hypothesis that ZBSO is a capable candidate for anti-melanoma agent, and provide new insights for future work on investigating the utilization of ZBSO in malignant melanoma treatment.


Assuntos
Antineoplásicos Fitogênicos/farmacologia , Óleos Vegetais/farmacologia , Zanthoxylum , Apoptose/efeitos dos fármacos , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Humanos , Melanoma/tratamento farmacológico , Sementes
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