Your browser doesn't support javascript.
Mostrar: 20 | 50 | 100
Resultados 1 - 20 de 2.106
Filtrar
1.
Ann Neurol ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31916277

RESUMO

OBJECTIVE: Aging is a major risk factor for numerous neurological disorders and the mechanisms underlying brain aging remain elusive. Recent animal studies demonstrated tight relationship between impairment of glymphatic pathway, meningeal lymphatic vessels and aging. However, the relationship in human brain remains uncertain. METHODS: In this observational cohort study, patients underwent MRI before and at multiple time points after intrathecal administration of contrast agent. Head T1-Weighted Imaging was performed to assess function of glymphatic pathway and head high-resolution T2-Fluid Attenuated Inversion Recovery to visualize putative meningeal lymphatic vessels (pMLVs). We measured the signal unit ratio (SUR) of 6 locations in glymphatic pathway and pMLVs, defined percentage change in SUR from baseline to 39 hour as the clearance of glymphatic pathway and pMLVs, and then analyzed their relationships with aging. RESULTS: In all patients (n = 35), the SUR of glymphatic pathway and pMLVs changed significantly after intrathecal injection of contrast agent. The clearance of both glymphatic pathway and pMLVs were related to aging (all p <0.05). The clearance of pMLVs was significantly related to the clearance of the glymphatic pathway (all p <0.05), and the clearance of glymphatic pathway was significantly faster in patients with early filling of pMLVs than those with late filling (all p <0.05). INTERPRETATION: We revealed that both glymphatic pathway and pMLVs might be impaired in aging human brain, through the novel clinically-available method to simultaneously visualize their clearance. Our findings also support that in humans, pMLVs are the downstream of the glymphatic pathway. This article is protected by copyright. All rights reserved.

2.
Talanta ; 209: 120436, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31892062

RESUMO

pH regulates the function of many organelles and plays a pivotal role in requiring multitud cellular behaviors. Compared with single fluorescent probes, ratio fluorescent probes have higher sensitivity and immunity to interference. Herein, a novel Janus ratio nanoprobe was developed for intracellular pH detection. Modified rhodamine B probe and fluorescein isothiocyanate (FITC) were individually encapsulated in the independent hemispheres of Janus microparticles fabricated via Pickering emulsion. Moreover, it exhibits a satasified ratiometric detection of pH compared to the previous core-shell structure and organic small molecule probe. Accordingly, the Janus nanoprobe possesses many important features as an attractive sensor, including high anti-jamming capability, excellent stability, good reversibility and low cytotoxicity. Variations of the two fluorescence intensities (Fgreen/Fred) resulted in a ratiometric pH fluorescent sensor, which can respond to wide range of pH values from 3 to 8. To be more specific, with a single excitation wavelength of 488 nm, there are dual emission bands centered at 538 nm and 590 nm. Also the Janus nanoprobe displays a excellent linear relationship in the physiologically relevant pH range of 4.0-6.0. Consequently, detecting of pH and imaging was successfully achieved in living cells, which provides a simple and reliable method for detecting intracelluar pH and other similar substances.

3.
J Environ Sci (China) ; 89: 252-263, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31892397

RESUMO

Plants constitute a major element of constructed wetlands (CWs). In this study, a coupled system comprising an integrated vertical flow CW (IVCW) and a microbial fuel cell (MFC) for swine wastewater treatment was developed to research the effects of macrophytes commonly employed in CWs, Canna indica, Acorus calamus, and Ipomoea aquatica, on decontamination and electricity production in the system. Because of the different root types and amounts of oxygen released by the roots, the rates of chemical oxygen demand (COD) and ammonium nitrogen (NH4+-N) removal from the swine wastewater differed as well. In the unplanted, Canna indica, Acorus calamus, and Ipomoea aquatica systems, the COD removal rates were 80.20%, 88.07%, 84.70%, and 82.20%, respectively, and the NH4+-N removal rates were 49.96%, 75.02%, 70.25%, and 68.47%, respectively. The decontamination capability of the Canna indica system was better than those of the other systems. The average output voltages were 520±42, 715±20, 660±27, and 752±26mV for the unplanted, Canna indica, Acorus calamus, and Ipomoea aquatica systems, respectively, and the maximum power densities were 0.2230, 0.4136, 0.3614, and 0.4964W/m3, respectively. Ipomoea aquatica had the largest effect on bioelectricity generation promotion. In addition, electrochemically active bacteria, Geobacter and Desulfuromonas, were detected in the anodic biofilm by high-throughput sequencing analysis, and Comamonas (Proteobacteria), which is widely found in MFCs, was also detected in the anodic biofilm. These results confirmed the important role of plants in IVCW-MFCs.

4.
Postgrad Med ; : 1-7, 2020 Jan 03.
Artigo em Inglês | MEDLINE | ID: mdl-31900004

RESUMO

Objective: To characterize the influence of relative wall thickness (RWT) on Cornell, Sokolow-Lyon and Peguero-Lo Presti voltages and elucidate its potential impacts on their diagnostic accuracy for LVH in a large general Chinese population.Methods: A total of 10,614 permanent residents aged ≥ 35 years were recruited for this study. All the participants were subjected to ECG and echocardiogram during the same visit. Multivariate linear and logistic regression analyzes were conducted to assess the influence of RWT on the voltages and their diagnostic performance for LVH detection.Results: A distinct correlation was identified between RWT and Cornell and Peguero-Lo Presti voltages following adjustments for age, gender and left ventricular mass (LVM) (ß = 0.675 and 1.342, respectively; Ps < 0.001). Besides, subjects with RWT > 0.42 exhibited higher rates of LVH diagnosed by Cornell (OR = 1.78, 95% CI: 1.45-2.20), Sokolow-Lyon (OR = 1.30, 95% CI: 1.08-1.56), and Peguero-Lo Presti voltage (OR = 1.48, 95% CI: 1.29-1.70) after adjustments for age, gender and echocardiographic LVH. Furthermore, concentric remodeling or concentric hypertrophy displayed higher rates of LVH diagnoses via Cornell and Peguero-Lo Presti voltage criteria, as compared with normal geometry or eccentric hypertrophy, respectively (all Ps < 0.05), findings of which were independent of age, gender and LVMI.Conclusion: Echocardiographic RWT was independently correlated with electrocardiographic voltage measures of LVH, which influenced their positive rates and contributed to poor diagnostic performance.

5.
J Exp Bot ; 2020 Jan 04.
Artigo em Inglês | MEDLINE | ID: mdl-31900491

RESUMO

Plants have to cope with various environmental stress factors which significantly impact plant physiology and secondary metabolism. Individual stresses, such as low temperature, are known to activate plant volatile compounds as a defense. However, less is known about the effect of multiple stresses on plant volatile formation. Here, the effect of dual stresses (wounding and low temperature) on volatile compounds in tea (Camellia sinensis) plants and the underlying signalling mechanisms were investigated. Indole, an insect-resistance volatile, was maintained at a higher content and for a longer time under dual stresses compared to wounding alone. CsMYC2a, a jasmonate responsive transcription factor, was the major regulator of CsTSB2, a gene encoding a tryptophan synthase ß-subunit essential for indole synthesis. During the recovery phase after tea wounding, low temperature helped to maintain a higher JA level. Further study showed that CsICE2 interacted directly with CsJAZ2 to relieve inhibition of CsMYC2a, thereby promoting the JA biosynthesis and downstream expression of the responsive gene CsTSB2 ultimately enhancing the indole biosynthesis. These findings shed light on the role of low temperature in promoting plant damage responses and improve knowledge of the molecular mechanisms by which multiple stresses coordinately regulate plant responses to the biotic and abiotic environment.

7.
Artigo em Inglês | MEDLINE | ID: mdl-31924743

RESUMO

Inactivating mutations in the copper transporter Atp7b result in Wilson's disease. The Atp7b -/- mouse develops hallmarks of Wilson's disease. The activity of several nuclear receptors decreased in Atp7b -/- mice, and nuclear receptors are critical for maintaining metabolic homeostasis. Therefore, we anticipated that Atp7b -/- mice would exhibit altered progression of diet-induced obesity, fatty liver, and insulin resistance. Following 10 wk on a chow or Western-type diet (40% kcal fat), parameters of glucose and lipid homeostasis were measured. Hepatic metabolites were measured by liquid chromatography-mass spectrometry and correlated with transcriptomic data. Atp7b -/- mice fed a chow diet presented with blunted body-weight gain over time, had lower fat mass, and were more glucose tolerant than wild type (WT) littermate controls. On the Western diet, Atp7b -/- mice exhibited reduced body weight, adiposity, and hepatic steatosis compared with WT controls. Atp7b -/- mice fed either diet were more insulin sensitive than WT controls; however, fasted Atp7b -/- mice exhibited hypoglycemia after administration of insulin due to an impaired glucose counterregulatory response, as evidenced by reduced hepatic glucose production. Coupling gene expression with metabolomic analyses, we observed striking changes in hepatic metabolic profiles in Atp7b -/- mice, including increases in glycolytic intermediates and components of the tricarboxylic acid cycle. In addition, the active phosphorylated form of AMP kinase was significantly increased in Atp7b -/- mice relative to WT controls. Alterations in hepatic metabolic profiles and nuclear receptor signaling were associated with improved glucose tolerance and insulin sensitivity as well as with impaired fasting glucose production in Atp7b -/- mice.

8.
Respir Res ; 21(1): 1, 2020 Jan 02.
Artigo em Inglês | MEDLINE | ID: mdl-31898493

RESUMO

OBJECTIVE: To observe the efficacy of recombinant human granulocyte-macrophage colony-stimulating factor (rhGM-CSF) for pulmonary alveolar proteinosis (PAP). MATERIALS AND METHODS: A total of 55 patients with PAP were screened at Shanghai Pulmonary Hospital between May 2014 and May 2018. Among these, 42 were diagnosed with idiopathic PAP, 24 were included in this study, 20 were treated for 6 months, and 17 were followed up for additional 6 months. All patients received a subcutaneous injection of 75µg/d GM-CSF qd for 1 month. The therapeutic dose was adjusted according to the changes in the lesions of chest CT. If the lesions were absorbed, subcutaneous injections of 75µg/d GM- CSF qd and 75µg/d GM-CSF qod were given for 2 and 3 months, otherwise, the dose was increased to 150µg/d GM-CSF qd and 150µg/d qod for 2 and 3 months, respectively. All cases were treated once a day in the first 3 months and once every other day in the last 3 months. The total course of treatment was 6 months. After withdrawal, the patients were followed up for another 6 months. The deadline of follow up was September 30, 2019. RESULTS: Twenty patients completed the treatment and efficacy evaluation. One patient was completely cured, 16 cases improved, three cases were noneffective. After 1-month evaluation, 12 patients received an increased dose (150µg) from the second month of treatment. Seventeen patients completed the 12-month follow-up, among which fourteen improved. CT showed the lesions were slightly increased in three cases. Economic burden was the following: RMB 7324-15,190 Yuan were required for the 6-month treatment course, which is significantly lower compared to other treatment methods. CONCLUSION: Subcutaneous injection of rhGM-CSF at low dose (75µg-150µg /d) is effective treatment for patients with idiopathic PAP. TRIAL REGISTRATION: NCT01983657. Registered 16 April 2013.

9.
Semin Cancer Biol ; 2020 Jan 11.
Artigo em Inglês | MEDLINE | ID: mdl-31935456

RESUMO

Scavenger receptor class B type I (SR-BI) protein is an integral membrane glycoprotein. SR-BI is emerging as a multifunctional protein, which regulates autophagy, efferocytosis, cell survival and inflammation. It is well known that SR-BI plays a critical role in lipoprotein metabolism by mediating cholesteryl esters selective uptake and the bi-directional flux of free cholesterol. Recently, SR-BI has also been identified as a potential marker for cancer diagnosis, prognosis, or even a treatment target. Natural products are a promising source for the discovery of new drug leads. Multiple natural products were identified to regulate SR-BI protein expression. There are still a number of challenges in modulating SR-BI expression in cancer and in using natural products for modulation of such protein expression. In this review, our purpose is to discuss the relationship between SR-BI protein and cancer, and the molecular mechanisms regulating SR-BI expression, as well as to provide an overview of natural products that regulate SR-BI expression.

10.
Medicine (Baltimore) ; 99(1): e18616, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31895817

RESUMO

To evaluate the qualitative image quality and quantitative apparent diffusion coefficient (ADC) value of reduced field-of view (rFOV) and full field-of-view (fFOV) diffusion-weighted imaging (DWI) sequences at 3.0 T in patients with gastric cancer.Fifty-three patients (37 males, 16 females; mean age, 63.3 ±â€Š10.3 years) with 60 lesions with gastric cancer who underwent magnetic resonance (MR) scans, including both rFOV-DWI and fFOV-DWI, were retrospectively analyzed. Two observers subjectively evaluated image quality for both the fFOV-DWI and rFOV-DWI sequences regarding the anatomic details, distortion, lesion conspicuity, artifacts, and overall image quality. The mean ADC values of gastric cancer were calculated. The Wilcoxon test and paired samples t test were used. Interobserver agreement was assessed using kappa statistics.The mean scores based on the 2 observers demonstrated significant differences in image quality in terms of anatomic details, distortion, lesion conspicuity, artifacts and overall image quality at both b values between rFOV-DWI and fFOV-DWI (P < .05) in the whole gastric area. rFOV-DWI yielded significantly better scores in image quality at b = 800 seconds/mm (P < .05) in patients with esophagogastric junction cancers, but there were no significant differences in the gastric corpus and gastric antrum region. The mean tumor ADC values of rFOV-DWI were significantly lower than those of fFOV-DWI (1.237 ±â€Š0.228 × 10-3 mm/second vs 1.683 ±â€Š0.322 × 10-3 mm/second, P < .001).rFOV-DWI yielded significantly better image quality (anatomic details, distortion, lesion conspicuity, artifacts, overall image quality) and more accurate ADC measurements than fFOV-DWI did.


Assuntos
Imagem de Difusão por Ressonância Magnética/métodos , Neoplasias Gástricas/diagnóstico por imagem , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos
11.
Microb Drug Resist ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31951499

RESUMO

Although vancomycin heteroresistance exists in enterococci, it is not easily detected using routine methods and the mechanism is not clearly understood. In this study, we characterized the molecular mechanism underlying vancomycin heteroresistance in a clinical vanM-type Enterococcus faecium strain. The original E. faecium isolate, hVREm7, was susceptible to vancomycin by broth microdilution and Etest. However, vancomycin-resistant subcolonies were present within the Etest zone of inhibition. Three passages of hVREm7 were carried out to eliminate the possibility of contamination. hVREm7 and three resistant variants were selected to study the heteroresistance mechanism. Sequence analysis revealed that all four strains contained an unaltered vanM cluster. Southern blot analysis showed that vanM was present both chromosomally and extrachromosomally in the three variants, but only extrachromosomally in hVREm7. The size of the vanM-bearing extrachromosomal DNA fragments in the three variants was larger than that in hVREm7, indicating a variation of vanM gene amplification in the variants. Consistently, vanM copy number and expression level were increased in variant strain VREm7-1. These results suggest that partial or complete amplification/transfer of the vanM gene cluster by an as-yet-unidentified mechanism leads to increased copy number and augmented expression of the vanM gene, which contribute to the transformation of vancomycin-heteroresistant E. faecium into high-level vancomycin-resistant variants.

12.
BMC Nephrol ; 21(1): 13, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31931741

RESUMO

BACKGROUND: The long-term predictive ability of acute kidney injury (AKI) classification based on "Kidney Disease: Improving Global Outcomes"(KDIGO) AKI diagnosis criteria has not been clinically validated in diffuse proliferative lupus nephritis (DPLN) patients with AKI. Our objective was to assess the long-term predictive value of KDIGO AKI classification in DPLN patients with AKI. METHODS: Retrospective cohort study was conducted by reviewing medical records of biopsy-proven DPLN patients with AKI from the First Affiliated Hospital of Wenzhou Medical University between Jan 1, 2000 and Dec 31, 2014. Multivariate Cox regression and survival analysis were performed. RESULTS: One hundred sixty-seven DPLN patients were enrolled,82(49%) patients were normal renal function (No AKI), 40(24%) patients entered AKI-1 stage (AKI-1), 26(16%) patients entered AKI-2 stage (AKI-2) and 19(16%) patients entered AKI-3 stage (AKI-3). The mean follow-up of all patients was 5.1 ± 3.8 years. The patient survival without ESRD of all patients was 86% at 5 years and 79% at 10 years. The patient survival rate without ESRD at 10 yr was 94.5% for No AKI patients, 81.8% for AKI-1 patients, 44.9% for AKI-2 patients and 14.6% for AKI-3 patients. The area under the ROC curve for KDIGO AKI classification to predict the primary end point was 0.83 (95% CI: 0.73-0.93) (P < 0.001). In Cox regression analysis, AKI stage was independently associated with primary endpoint, with an adjusted hazard ratio (HR) of 3.8(95% CI 2.1-6.7, P < 0.001). CONCLUSION: Severity of AKI based on KDIGO AKI category was associated with progression to ESRD in DPLN patients. Analytical data also confirmed the good discriminative power of the KDIGO AKI classification system for predicting long-term prognosis of DPLN patients with AKI.

13.
Aging (Albany NY) ; 12(1): 844-865, 2020 Jan 12.
Artigo em Inglês | MEDLINE | ID: mdl-31929114

RESUMO

Postoperative delirium (POD) is a common complication following surgery and anesthesia (Surgery/Anesthesia). Mitochondrial dysfunction, which is demonstrated by energy deficits and excessively activated oxidative stress, has been reported to contribute to POD. The dynamic balance between mitochondrial fusion and fission processes is critical in regulating mitochondrial function. However, the impact of Surgery/Anesthesia on mitochondrial fusion/fission dynamics remains unclear. Here, we evaluate the effects of laparotomy under 1.4% isoflurane anesthesia for 2 hours on mitochondrial fission/fusion dynamics in the brain of aged mice. Mice in Surgery/Anesthesia group showed unbalanced fission/fusion dynamics, with decreased DISC1 expression and increased expression of Drp1 and Mfn2 in the mitochondrial fraction, leading to excessive mitochondrial fission and disturbed mitochondrial morphogenesis in the hippocampus and prefrontal cortex. In addition, surgical mice presented mitochondrial dysfunction, demonstrated by abnormally activated oxidative stress (increased ROS level, decreased SOD level) and energy deficits (decreased levels of ATP and MMP). Surgery/Anesthesia also decreased the expression of neuronal/synaptic plasticity-related proteins such as PSD-95 and BDNF. Furthermore, Surgery/Anesthesia induced delirium-like behavior in aged mice. In conclusion, Surgery/Anesthesia disturbed mitochondrial fission/fusion dynamics and then impaired mitochondrial function in the brain of aged mice; these effects may be involved in the underlying mechanism of POD.

14.
Arch Pharm Res ; 2020 Jan 19.
Artigo em Inglês | MEDLINE | ID: mdl-31956964

RESUMO

Glioma is the most common type of primary brain tumor, and it has a high mortality rate. Currently, there are only a few therapeutic approaches for gliomas, and their effects are unsatisfactory. Therefore, uncovering the pathogenesis and exploring more therapeutic strategies for the treatment of gliomas are urgently needed to overcome the ongoing challenges. Cellular redox imbalance has been shown to be associated with the initiation and progression of gliomas. Among reactive oxygen species (ROS), hydrogen peroxide (H2O2) is considered the most suitable for redox signaling and is a potential candidate as a key molecule that determines the fate of cancer cells. In this review, we discuss the potential cellular and molecular roles of H2O2 in gliomagenesis and explore the potential implications of H2O2 in radiotherapy and chemotherapy and in the ongoing challenges of current glioma treatment. Moreover, we evaluate H2O2 as a potential redox sensor and potential driver molecule of nanocatalytic therapeutic strategies for glioma treatment.

15.
Helicobacter ; : e12679, 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958193

RESUMO

BACKGROUNDS: Due to the decreasing eradication rate of Helicobacter pylori, some novel alternatives have been developed, such as bismuth-containing quadruple therapy and non-bismuth-containing quadruple therapy (sequential and concomitant treatment). Little is known about whether a success rate above 90% can be achieved with these regimens in Chinese children. METHODS: In this prospective, open, comparative cross-sectional study, we recruited treatment-naïve children (aged between 6 and 18 years) with H pylori infection. The patients were assigned either standard triple therapy, sequential therapy, bismuth-based quadruple therapy, or concomitant therapy at the discretion of the prescribing physician. H pylori infection was evaluated at least 4 weeks after the completion of the treatment. A negative urea breath test (UBT) indicated successful eradication. The primary endpoint was the eradication frequency of H pylori in the full analysis set (FAS), which included all children who received at least one dose of the treatment and with available follow-up data. RESULTS: Between September 2017 and December 2018, 228 patients were finally included in the FAS analyses. The eradication rates were 74.1% for standard triple therapy (43/58, [95% CI: 62.8%-85.5%]), 69.5% for sequential therapy (41/59, [95% CI: 57.8%-81.2%]), 89.8% for bismuth-based quadruple therapy (53/59, [95% CI: 82.1%-97.5%]), and 84.6% for concomitant therapy (44/52, [95% CI: 74.8%-94.4%]). Bismuth-based therapy was superior to triple therapy, while sequential therapy and concomitant therapy were not superior to triple therapy. The frequency of adverse events was 12.1% (7/58) in standard triple therapy, 6.8% (4/59) in sequential therapy, 15.3% (9/59) in bismuth-based therapy, and 15.4% (8/52) in concomitant therapy. The rate of adverse events was similar among the four groups. CONCLUSION: Bismuth quadruple therapy can achieve an eradication rate of 89.8% as first-line treatment and is safe and well tolerated. Bismuth could be a promising alternative as a first-line regimen in Chinese children.

16.
J Environ Sci (China) ; 87: 39-48, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791512

RESUMO

Carbon-silica materials with hierarchical pores consisting of micropores and mesopores were prepared by introducing nanocarbon microspheres derived from biomass sugar into silica gel channels in a hydrothermal environment. The physicochemical properties of the materials were characterized by nitrogen physical adsorption (BET), scanning electron microscopy (SEM), and thermogravimetric (TG), and the adsorption properties of various organic waste gases were investigated. The results showed that microporous carbon materials were introduced successfully into the silica gel channels, thus showing the high adsorption capacity of activated carbon in high humidity organic waste gas, and the high stability and mechanical strength of the silica gel. The dynamic adsorption behavior confirmed that the carbon-silica material had excellent adsorption capacity for different volatile organic compounds (VOCs). Furthermore, the carbon-silica material exhibited excellent desorption characteristics: adsorbed toluene was completely desorbed at 150°C, thereby showing superior regeneration characteristics. Both features were attributed to the formation of hierarchical pores.


Assuntos
Modelos Químicos , Compostos Orgânicos Voláteis/química , Adsorção , Biomassa , Carvão Vegetal , Umidade , Interações Hidrofóbicas e Hidrofílicas , Microesferas , Porosidade , Dióxido de Silício/química , Tolueno/química
17.
Pharm Biol ; 58(1): 60-63, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31868554

RESUMO

Context: 23-Hydroxybetulinic acid (23-HBA), a major active constituent of Pulsatilla chinensis (Bunge) Regel (Ranunculaceae), exhibits potential antitumor activity. Its metabolism, however, has not yet been studied.Objective: This study focuses on the metabolism of 23-HBA in vitro by human liver microsomes.Materials and methods: The metabolic kinetics of 23-HBA (0.5-100 µM) and the effects of selective CYP450 (CYP1A2, CYP2C9, CYP2C19, CYP2D6, and CYP3A4) inhibitors on metabolism of 23-HBA were evaluated in human liver microsomes incubation system and then determined by LC-MS method. The Michaelis-Menten parameters Km and Vmax were initially estimated by analysing Lineweaver-Burk plot. The clearance (CLint) was also calculated.Results: The Vmax, Km, and CLint of 23-HBA were 256.41 ± 11.20 pmol/min/mg, 11.10 ± 1.07 µM, and 23.10 ± 1.32 µL/min/mg, respectively. The metabolism of 23-HBA was significantly inhibited by furafylline (0.05 µM, p < 0.01) and ketoconazole (0.02 µM, p < 0.05). Ticlopidine (1.3 µM, p < 0.05) could inhibit the metabolism of 23-HBA, while the other inhibitors (sulfaphenazole and quinidine) showed nonsignificant inhibition on the metabolism of 23-HBA.Discussion and conclusions: This is the first investigation of the metabolism of 23-HBA in human liver microsomes. The in vitro study indicates that CYP1A2 and CYP3A4 are mainly involved in the metabolism of 23-HBA. Special attention should be given to the pharmacokinetic and clinical outcomes when 23-HBA was co-administrated with other compounds mainly undergoing CYP1A2/CYP3A4-mediated metabolism. Further studies are needed to evaluate the significance of this interaction and strengthen the understanding of traditional Chinese medicine.

18.
J Cell Physiol ; 235(2): 1197-1208, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31270811

RESUMO

Chemotherapy is the first-line treatment option for patients with lung cancer. However, therapeutic resistance occurs through an incompletely understood mechanism. Our research wants to investigate the influence of Caveolin-1 (Cav-1) on the therapeutic sensitivity of lung cancer in vitro. Results in this study demonstrated that Cav-1 levels were markedly inhibited in A549 lung cancer cells after exposure to cisplatin. Knockdown of caveolin further enhanced cisplatin-triggered cancer death in A549 cells. The functional investigation demonstrated that Cav-1 inhibition amplified the mitochondrial stress signaling induced by cisplatin, as evidenced by the mitochondrial reactive oxygen species burst, cellular metabolic disruption, mitochondrial membrane potential reduction, and mitochondrial caspase-9-related apoptosis activation. At the molecular level, cav-1 augmented cisplatin-mediated mitochondrial damage by inhibiting Parkin-related mitochondrial autophagy. Mitophagy activation effectively attenuated the promotive impact of Cav-1 knockdown on mitochondrial damage and cell death. Furthermore, our data indicated that Cav-1 affected Parkin-related mitophagy by activating the Rho-associated coiled-coil kinase 1 (ROCK1) pathway; inhibition of the ROCK1 axis prevented cav-1 knockdown-mediated cell death and mitochondrial damage. Taken together, our results provide ample data illuminate the necessary action exerted by Cav-1 on affecting cisplatin-related therapeutic resistance. Silencing of Cav-1 inhibited Parkin-related mitophagy, thus amplifying cisplatin-mediated mitochondrial apoptotic signaling. This finding identifies the Cav-1/ROCK1/Parkin/mitophagy axis as a potential target to overcome cisplatin-related resistance in lung cancer cells.

19.
J Cell Biochem ; 121(1): 651-660, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31407409

RESUMO

Idiopathic pulmonary fibrosis (IPF), a chronic, progressive and irreversible disease, needs long-term treatment. Bicyclol was found to play a great role in pulmonary fibrosis, and the present study is to explore how bicyclol affects IPF with the involvement of microRNA-455-3p (miR-455-3p) and Bax. Bleomycin (BLM) was used to induce the IPF model in Sprague-Dawley rats to detect the expression of miR-455-3p, Bax, and B-cell lymphoma factor 2 (Bcl-2). Moreover, to further investigate the mechanisms of bicyclol, the BLM-induced fibrotic cell model was used after the lung epithelial cells HPAEpiC received miR-455-3p knockout treatment. The rats were then treated with vehicle and bicyclol, respectively. The apoptosis of fibrotic cells and Bax/Bcl-2 were identified. Inhibition function of bicyclol was optimal at a dose of 150 mg/kg. Bicyclol inhibited cell apoptosis and reduced Bax/Bcl-2 expression in rats. miR-455-3p could potentially bind to Bax gene. Bicyclol reduced the levels of methylenedioxyamphetamine, superoxide dismutase, and glutathione in rat lung tissue, inhibited the apoptosis of rats with IPF and upregulated miR-455-3p expression. In vitro studies showed that bicyclol significantly promoted miR-455-3p expression in HPAEpiC fibrosis. Bicyclol inhibited fibrosis-induced apoptosis of HPAEpiC in alveolar epithelial cells through promoting miR-455-3p, which inhibited Bax expression in IPF. Bicyclol may suppress the apoptosis of alveolar epithelial cells by upregulating miR-455-3p. This study laid a theoretical foundation for further understanding of IPF and searching for new molecular therapeutic targets.

20.
Artigo em Inglês | MEDLINE | ID: mdl-31820593

RESUMO

Patients undergoing cardiac valve replacement may experience cardiovascular adverse events during the preoperative period before anesthesia. The study was to compare the preemptive anti-stress response effects of oxycodone versus sufentanil for patients undergoing cardiac valve replacement. Ninety-four patients were enrolled and assigned to group Oxy, group Suf and group NS. Patients in group Oxy were administrated with oxycodone 0.1 mg/kg, group Suf received sufentanil 0.1 µg/kg and group NS were given equivalent volume of normal saline. The primary outcomes included serum levels of cortisol, norepinephrine, and adrenaline. The secondary outcomes involved bispectral index value and the observer's assessment of awareness/sedation grade, levels of mean arterial pressure, heart rate, and the adverse reactions. Compared to group NS, the serum levels of cortisol at T1 to T5 (P < .05), and levels of norepinephrine and adrenaline at T3 to T5 (P < .05) in group Oxy and Suf were lower. The bispectral index value and observer's assessment of awareness/sedation grade T1 to T2 (P < .05) in group Suf were lower than those in group Oxy and NS. Compared with group NS, the levels of mean arterial pressure and heart rate in group Oxy and Suf at T3 to T5 (P < .05) were lower. The incidence of coughing was significantly higher in group Suf (23.3%), but not in group NS (6.7%), than that in group Oxy (3.3%). The preemptive analgesia of oxycodone may be used to inhibit the stress response, without leading to excessive sedation and respiratory depression, which may also help to stabilize hemodynamics during preoperative period.

SELEÇÃO DE REFERÊNCIAS
DETALHE DA PESQUISA