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1.
J Pharm Biomed Anal ; 177: 112869, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31539714

RESUMO

A rapid, sensitive, selective, and accurate UPLC-MS/MS method was developed and fully validated for the simultaneous determination of quercitrin, phloridzin, quercetin, and phloretin in rat plasma after oral administration of Malus hupehensis (Pamp.) Rehd extracts. The pharmacokinetic parameters of oral phloridzin monomer and phloridzin in the extract were also compared. Plasma samples were processed with a simple protein precipitation technique using methanol, followed by chromatographic separation using a Sun Fire ™C18 column. Bergenin was used an internal standard (IS). A 15.0 min linear gradient elution was used at a flow rate of 0.8 mL/min with a mobile phase of 0.1% formic acid in water and acetonitrile. The analytes and IS were detected using negative ion electrospray ionization in multiple reaction monitoring mode. The developed method exhibited good linearity (r ≥ 0.9911), and the lower limits of quantification ranged from 0.2 to 0.8 ng/mL for the four analytes. Intra-day and inter-day precision were both less than 8.5% and were within the acceptable limits. Matrix effect and recovery efficiency of all analytes were found to be >76.2% and >71.4%, respectively. Stability results showed that the analytes were stable at all conditions. Additionally, the carry-over effect and dilution effect were within the acceptance range. The developed method was successfully applied to a pharmacokinetic study of four analytes in rats after oral administration of Malus hupehensis (Pamp.) Rehd. extracts.

2.
J Pharm Biomed Anal ; 177: 112855, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31561061

RESUMO

FSH plays a key role in the function of the reproductive system of human beings and is widely used both diagnostically and therapeutically in reproductive medicine. With the growing incidence of infertility, the demand for FSH pharmaceutical products is increasing. For this reason, the quality control process for FSH products is becoming more stringent. An accurate determination of bioactivity is crucial for the safety and efficacy of recombinant human follicle stimulating hormone (rhFSH). Up to now, in-vivo bioassay based on FSH-induced increases in rat ovarian weight has been the only method widely accepted by different pharmacopoeias. However this method has such drawbacks as the complex procedures, long assay period and high variability. Here, we established a reporter gene assay (RGA) based on the CHO-K1-FSHR-CRE-Luc cell line that stably expresses human follicle stimulating hormone receptor (hFSHR), as well as a luciferase reporter under the control of cyclic adenosine monophosphate (cAMP) response elements (CRES). Our study showed that our new assay not only has good dose-dependent responsiveness to rhFSH, but it also performs excellently in terms of specificity, precision, linearity, and simplicity compared with in-vivo rat bioassays. These results implied that this robust reporter gene assay may be a viable supplement to the animal in-vivo bioassay and may be employed in potency determination of rhFSH pharmaceutical products.

3.
J Cell Biochem ; 121(1): 723-734, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31452248

RESUMO

With the extensive use of dexmedetomidine (Dex) in the surgical resection of tumours for its potent sedative and analgesic properties, its effects on various properties of tumours have received increased attention. The study described herein aimed to investigate the effects of Dex on glioma cells in the presence or absence of cisplatin (DDP). Glioma U251 and U87MG cells were treated with different doses (1-50 nM) of Dex for 12 hours, then recultured in a Dex-free medium. In addition, Dex was added to U251 and U87MG cells 12 hours before or simultaneously with a 12-hour DDP treatment. Treatment with Dex increased the viability of both cell lines; this effect continued for at least 24 hours after Dex was removed. A cell invasion assay indicated that Dex inhibited cell invasion at 50 nM, but not at 10 nM. Western blot analysis showed that Dex increased the expression of phosphorylated extracellular-signal-regulated kinase 1/2, phosphoitide 3-kinase and p-AKT, but decreased ROCK protein levels at a dose of 50 nM. Intracellular Ca 2+ concentration was decreased by Dex in a dose-dependent manner. DDP toxicity was attenuated by 10 nM Dex added either before or with DDP treatment. However, pretreatment with 50 nM Dex instead enhanced the toxicity of DDP. Single-dose treatment with Dex did not significantly change glioma volume in nude mice, but changed the expression of Ki67 and matrix metalloproteinase-3 in the tumour. In conclusion, this study provides evidence of the regulatory effects of Dex on proliferation, invasion and chemosensitivity of glioma cells, and outlines potential mechanisms for these effects.

4.
J Biomed Mater Res B Appl Biomater ; 108(1): 128-142, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30912286

RESUMO

Endowing the conduit with conductivity has been an effective way to stimulate nerve growth and functional recovery. Here, conducting polyaniline (PANi) was used to construct a conductive guidance by coating on the surface of microtubes inserted in a three-dimensional zein nerve conduit to study the repairing efficacy on peripheral nerve injury. PANi nanoparticles with a size of 20-30 nm were synthesized and coated on the surface of microtubes through layer-by-layer deposition. Then, conduits including microtubes with and without PANi coating were implanted into rats to bridge a 10-mm sciatic nerve defect and autograft as the control group. After 2 months, the conduit with PANicoating improved the recovery of proximal compound muscle action potential significantly in the regenerated nerve compared to the conduit without PANi coating, which was not inferior to the autograft group. However, the repairing efficacy was changed reversely at the fourth month postimplantation. PANi coating fragmented to form debris within or around the regenerated nerves while microtubes seem to degrade completely as observed by H&E staining. In vitro degradation experiment confirmed this process. The PANi nanoparticles could induce cytotoxicity and reactive oxygen species (ROS) generation of both NIH 3T3 cells and macrophage cell line RAW 264.7. These in vitro and in vivo results implied that the nondegradable PANi may occupy the regeneration space and stimulate the inflammatory response in later implantation in vivo. While there was no such risk if the PANi coating keeps in an intact film. © 2019 Wiley Periodicals, Inc. J Biomed Mater Res Part B: Appl Biomater 108B:128-142, 2020.

5.
J Environ Sci (China) ; 87: 250-259, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791498

RESUMO

Water-uptakes of pure sodium carbonate (Na2CO3), pure ß-alanine and internally mixed ß-alanine/Na2CO3 aerosol particles with different mole ratios are first monitored using attenuated total reflectance Fourier transform infrared spectroscopy (ATR-FTIR) technique. For pure Na2CO3 aerosol particles, combining the absorptions at 877 and 1422 cm-1 with abrupt water loss shows the efflorescence relative humidity (ERH) of 62.9%-51.9%. Upon humidifying, solid Na2CO3 firstly absorbs water to from Na2CO3·H2O crystal at 72.0% RH and then deliquesces at 84.5% RH (DRH). As for pure ß-alanine particles, the crystallization takes place in the range of 42.4%-33.2% RH and becomes droplets at ~88.2% RH. When ß-alanine is mixed with Na2CO3 at various mole ratios, it shows no efflorescence of Na2CO3 when ß-alanine to Na2CO3 mole ratio (OIR) is 2:1. For 1:1 and 1:2 ß-alanine/Na2CO3 aerosols, the ERHs of Na2CO3 are 51.8%-42.3% and 57.1%-42.3%, respectively. While ß-alanine crystal appears from 62.7% RH for 2:1 and 59.4% RH for both 1:1 and 1:2 particles and lasts to driest state. On hydration, the DRH is 44.7%-75.2% for Na2CO3 with the OIR of 1:1 and 44.7%-69.0% for 1:2 mixture, and those of ß-alanine are 74.8% for 2:1 mixture and 68.9% for two others. After the first dehumidification-humidification, all the water contents decrease despite of constituent fraction. And at ~92% RH, the remaining water contents are 92%, 89% and 82% at ~92% RH, corresponding to OIR of 2:1, 1:1 and 1:2 mixed system, respectively.

6.
Biomed Pharmacother ; 121: 109596, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31731193

RESUMO

Vasoactive intestinal peptide (VIP) is a neuropeptide that exerts anti-inflammatory functions. We have reported that VIP mediated by lentivirus attenuates acute lung injury (ALI) in lipopolysaccharide (LPS)-induced murine model. However, the exact role of VIP in uncontrolled inflammation during ALI is largely unknown. Accumulating evidence indicates that the NLRP3 inflammasome has a critical role during ALI. In this study, we investigated the effects of VIP on the activation of NLRP3 inflammasome during the development of ALI in mice. Seven days after the intratracheal injection of VIP-lentivirus, a murine ALI model was induced by intratracheal injection of LPS. VIP-lentivirus significantly reduced the expression of NLRP3 inflammasome components in lung tissue, including NLRP3, pro-caspase-1, pro-IL-1ß, and pro-IL-18. VIP-lentivirus also inhibited the formation of caspase-1 p10 and the maturation of IL-1ß and IL-18. In vitro, exogenous VIP pre-treatment inhibited the priming of NLRP3 inflammasome in murine primary peritoneal macrophages, indicated by down-regulation of expression of NLRP3 inflammasome components. VIP pre-treatment effectively prevented the LPS-induced degradation of I-κB and the synthesis of the downstream of NF-κB, including TNF-α and IL-17A. Furthermore, VIP pre-treatment pronouncedly suppressed the autoproteolysis of caspase-1 and the secretion of IL-1ß and IL-18 induced by LPS plus ATP in macrophages. In addition, VIP inhibited the generation of reactive oxygen species in macrophages by decreasing NOX1 and NOX2 expression. These findings illustrate one mechanism that VIP attenuates ALI induced by LPS through inhibiting the activation of the NLRP3 inflammasome and encourage further studies assessing the therapeutic potential of VIP to ALI.

7.
Sci Rep ; 9(1): 18002, 2019 Nov 29.
Artigo em Inglês | MEDLINE | ID: mdl-31784669

RESUMO

It is known that the day-night shift-rotation has a negative impact on the immune system. The underlying mechanism remains to be further investigated. Probiotics have regulatory effects on immune functions. This study aims to investigate the role of probiotic ingestion in preventing the DEC205+ dendritic cell (decDC) dysfunction in day-night shift-engaging nurses. In this study, blood samples were collected from day-night shift-rotating nurses who took or did not take yogurt (containing C. Butyricum) during the night shift (NS). decDC functions were evaluated with pertinent immunological approaches. We observed that the immune tolerogenic functions and interleukin (IL)-10 expression were impaired in decDCs of nurses after NS. HDAC11 was detected in decDCs that was markedly up regulated after NS. The HDAC11 levels were negatively correlated with the immune tolerogenic functions in decDCs. Ingestion of probiotic-containing yogurt during NS efficiently suppressed Bmal1 and HDAC11 levels as well as up regulated the immune regulatory functions in decDCs. In conclusion, NS has a negative impact on decDC immune tolerogenic functions, which can be prevented by ingesting probiotics-containing yogurt during NS.

8.
Cancer Nurs ; 2019 Nov 18.
Artigo em Inglês | MEDLINE | ID: mdl-31789938

RESUMO

BACKGROUND: The experiences of teenagers with cancer are related to falling ill, receiving treatment, and the way they exist in the world. The understanding of the meaning of teenagers coexisting with cancer must be placed in the social context with the teenagers at the core. OBJECTIVE: By using an interpretive ethnographic research method, this study applied the body perception view of Merleau-Ponty to how teenagers with cancer understand self through the body in a social and cultural context. METHODS: Participant observation and individual semistructured interviews of 18 teenagers diagnosed with cancer were conducted over a 20-month period. RESULTS: The illness experience of teenagers undergoing chemotherapy was described as self-integration. Five themes emerged: boundary ambiguity of body, medical equipment as part of the body, confined body space, from self-dissociation toward self-integration, and healing power formed by self and others. CONCLUSION: In the face of the adjustments of body disorder, the teenagers with cancer initiated motility of the body, self-displacement, and integration in order to regain control of the body. IMPLICATIONS FOR PRACTICE: The provision of correct disease knowledge to strengthen teenagers' understanding and their sense of mastery of their bodies throughout the participation in their cancer treatment is essential. Discussions on making decisions, self-management, and social identification are related to the relationship between body and self as well as between healthcare and otherness. Providing culture and social sensitivity support systems and resources to teenagers and families can strengthen them to face the disease and promote positive healing.

9.
Phytomedicine ; 66: 153130, 2019 Oct 30.
Artigo em Inglês | MEDLINE | ID: mdl-31790897

RESUMO

BACKGROUND: Non-alcoholic fatty liver disease (NAFLD) is the most prevalent form of chronic liver diseases. Cyclocarya paliurus (C. paliurus), an edible and medicinal plant in Chinese folk, has been demonstrated to ameliorate diabetes, obesity and lipid metabolism disorders. However, its effects on NAFLD and its potential molecular mechanism have not been clearly expounded. PURPOSE: The present study was designed to explore the therapeutic potential of triterpenic acids-enriched fraction from C. paliurus (CPT), as well as its underlying mechanism in vivo and in vitro models of NAFLD. METHODS: The metabolic effects and possible molecular mechanism of CPT were examined using HepG2 cells and primary hepatocytes (isolated from C57BL/6 J mice) models of fatty liver induced by palmitic acid (PA) and a high fat diet mouse model. RESULTS: In high fat diet-induced C57BL/6 J mice, CPT significantly reduced liver weight index, serum alanine transaminase (ALT), aspartate transaminase (AST), triacylglycerol (TG), total cholesterol (TC) and hepatic TG, TC levels. Moreover, CPT dramatically decreased the contents of blood glucose, insulin, and insulin resistance (HOMA-IR) index. Meanwhile, CPT significantly increased the tyrosine phosphorylation level of IRS and the uptake of 2-deoxyglucose (2DG) in PA-induced HepG2 cells and primary hepatocytes fatty liver models. Furthermore, in PA-induced HepG2 cells and primary hepatocytes, CPT significantly decreased the number of lipid droplets and intracellular TG content. In addition, mechanism investigation showed that CPT increased the phosphorylation of phosphoinositide 3-kinase (PI3K), protein kinase B (Akt) and glycogen synthase-3ß (GSK3ß) in vivo and in vitro models, which were abrogated by PI3K inhibitor LY294002 in vitro models. CONCLUSION: These findings indicate that CPT may exert the therapeutic effects on NAFLD via regulating PI3K/Akt/GSK3ß pathway.

10.
Adv Mater ; : e1905399, 2019 Dec 05.
Artigo em Inglês | MEDLINE | ID: mdl-31803996

RESUMO

The emulation of human sensation, perception, and action processes has become a major challenge for bioinspired intelligent robotics, interactive human-machine interfacing, and advanced prosthetics. Reflex actions, enabled through reflex arcs, are important for human and higher animals to respond to stimuli from environment without the brain processing and survive the risks of nature. An artificial reflex arc system that emulates the functions of the reflex arc simplifies the complex circuit design needed for "central-control-only" processes and becomes a basic electronic component in an intelligent soft robotics system. An artificial somatic reflex arc that enables the actuation of electrochemical actuators in response to the stimulation of tactile pressures is reported. Only if the detected pressure by the pressure sensor is above the stimulus threshold, the metal-organic-framework-based threshold controlling unit (TCU) can be activated and triggers the electrochemical actuators to complete the motion. Such responding mechanism mimics the all-or-none law in the human nervous system. As a proof of concept, the artificial somatic reflex arc is successfully integrated into a robot to mimic the infant grasp reflex. This work provides a unique and simplifying strategy for developing intelligent soft robotics, next-generation human-machine interfaces, and neuroprosthetics.

11.
Drug Des Devel Ther ; 13: 3657-3667, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31695333

RESUMO

Background: Diabetic nephropathy (DN) is a common complication of diabetes mellitus (DM) and also a major cause of end-stage renal disease (ESRD). Olmesartan medoxomil (OM) is an angiotensin II receptor blocker (ARB) and has been shown to exhibit renoprotective effects on a streptozotocin (STZ)-induced diabetic rat model. Yet, whether OM affects DN progression and renal injury in db/db mice, a type 2 diabetic murine model, has not been established. Methods: Wild-type (n = 15) and db/db mice (n = 15) were treated with control saline or OM via oral gavage. The physiological and biochemical parameters were evaluated and histological examinations of kidney specimens were performed. Results: Compared with saline-treated db/db mice, db/db mice administered with OM showed ameliorated diabetic physiological and biochemical parameters. In addition, OM decreased urinary albumin excretion and plasma creatinine level in db/db mice. Moreover, histologically, OM reduced glomerular hypertrophy and injury, and also ameliorated tubular injury, thus suggesting that OM improves renal function and minimizes renal pathological deterioration in db/db mice. Conclusion: Our study reveals a beneficial role of OM in ameliorating DN in db/db mice, which is associated with its renoprotective function.

12.
Artigo em Inglês | MEDLINE | ID: mdl-31698049

RESUMO

OBJECTIVE: This network meta-analysis compared treatment via laparoscopy (LP), hysteroscopy (HP), combined laparoscopy with hysteroscopy (LH), and vaginal repair (VR) for reducing intermittent abnormal uterine bleeding and caesarean scar defect (CSD) diverticulum depth in patients with CSD. DATA SOURCES: Electronic databases (PubMed, EMBASE, CENTRAL, MEDLINE, ClinicalTrials.gov, Chinese Biomedical Literature Database, and China National Knowledge Integrated) were searched for articles published through June 13, 2018. METHODS OF STUDY SELECTION: The search included randomized controlled trials (RCTs) and observational studies of surgical treatment for CSD. Standardized mean difference (SMD) and 95% confidence intervals (CI) were reported. Randomized controlled trials were evaluated by the Cochrane risk-of-bias tool, observational studies by Risk of Bias in Nonrandomized Studies of Intervention (ROBINS-I), and overall evidence quality by grade. Data were analyzed by STATA (version 15.0, StataCorp, College Station, TX, USA) and R software for windows (version 3.5.0, R Core Team, 2018). TABULATION, INTEGRATION, AND RESULTS: Ten studies (n = 858; 4 RCTs and 6 observational studies) were included. Patients who underwent uterine diverticulum resection by LH had a shorter duration of abnormal uterine bleeding than that by HP (SMD = 1.36, 95% CI, 0.37 to 2.36, p = .007) and VR (SMD = 1.58, 95% CI, 0.97 to 2.19, p < .0001). Laparoscopy with hysteroscopy reduced the CSD diverticulum depth more than VR (SMD = 1.57, 95% CI, 0.54 to 2.61, p = .003). There was no significant difference in efficacy among the surgical procedures. CONCLUSION: Laparoscopy with hysteroscopy reduced intermittent abnormal uterine bleeding and scar depth more than the other surgical interventions. Larger clinical trials are warranted to verify this analysis.

13.
Artigo em Inglês | MEDLINE | ID: mdl-31715575

RESUMO

Heart diseases alter the rhythmic behaviors of cardiac electrical activity. Recent advances in sensing technology bring the ease to acquire space-time electrical activity of the heart such as vectorcardiogram (VCG) signals. Recurrence analysis of successive heartbeats is conducive to detect the disease-altered cardiac activities. However, conventional recurrence analysis is more concerned about homogeneous recurrences, and overlook heterogeneous types of recurrence variations in VCG signals (i.e., in terms of state properties and state transition dynamics). This paper presents a new framework of heterogeneous recurrence analysis for the characterization and modeling of disease-altered spatiotemporal patterns in multi-channel cardiac signals. Experimental results show that the proposed approach yields an accuracy of 96.9%, a sensitivity of 95.0%, and a specificity of 98.7% for the identification of myocardial infarctions. The proposed method of heterogeneous recurrence analysis shows strong potential to be further extended for the analysis of other physiological signals such as electroencephalogram (EEG) and electromyography (EMG) signals towards medical decision making.

14.
Leukemia ; 2019 Nov 12.
Artigo em Inglês | MEDLINE | ID: mdl-31719677

RESUMO

Myelodysplastic syndromes (MDS) are characterized by ineffective hematopoiesis and cytopenias due to uncontrolled programmed cell death. The presence of pro-inflammatory cytokines and constitutive activation of innate immunity signals in MDS cells suggest inflammatory cell death, such as necroptosis, may be responsible for disease phenotype. We evaluated 64 bone marrow samples from 55 patients with MDS or chronic myelomonocytic leukemia (CMML) obtained prior to (n = 46) or after (n = 18) therapy with hypomethylating agents (HMAs). RNA from sorted bone marrow CD34+ cells was isolated and subject to amplification and RNA-Seq. Compared with healthy controls, expression levels of MLKL (CMML: 2.09 log2FC, p = 0.0013; MDS: 1.89 log2FC, p = 0.003), but not RIPK1 or RIPK3, were significantly upregulated. Higher expression levels of MLKL were associated with lower hemoglobin levels at diagnosis (-0.19 log2FC per 1 g/dL increase of Hgb, p = 0.03). Significant reduction in MLKL levels was observed after HMA therapy (-1.06 log2FC, p = 0.05) particularly among nonresponders (-2.89 log2FC, p = 0.06). Higher RIPK1 expression was associated with shorter survival (HR 1.92, 95% CI 1.00-3.67, p = 0.049 by Cox proportional hazards). This data provides further support for a role of necroptosis in MDS, and potentially response to HMAs and prognosis. This data also indicate that RIPK1/RIPK3/MLKL are potential therapeutic targets in MDS.

15.
Hua Xi Kou Qiang Yi Xue Za Zhi ; 37(5): 509-515, 2019 Oct 01.
Artigo em Chinês | MEDLINE | ID: mdl-31721499

RESUMO

OBJECTIVE: To investigate the effect of circular RNA hsa_circ_0002203 on the malignant biological behavior of oral squamous cell carcinoma (OSCC) cell lines. METHODS: Forty patients with oral squamous cell carcinoma were included. Real-time fluorescent polymerase chain reaction (PCR) was used to detect the expression level of circular RNA hsa_circ_0002203 in OSCC and corresponding adjacent tissues, OSCC cell lines, and human oral keratinocytes (HOK). SCC15 and CAL27 cells were transfected with lenti-virus. The expression level of circular RNA hsa_circ_0002203 was detected by real-time fluorescent PCR. Cell proliferation was detected by cell counting assay (CCK-8). Cell migration and invasion ability was detected by scratch assay and Transwell migration and invasion assay. Apoptosis level was detected by flow cytometry. The expression of corresponding protein was detected by Western blot. Murine tumor formation experiments were performed to observe the effect of hsa_circ_0002203 on the tumorigenesis of SCC15 cells in vivo. RESULTS: The expression of circular RNA hsa_circ_0002203 in OSCC tissues was lower than that in adjacent tissues (P<0.01), and the expression in OSCC cell lines was lower than that in HOK (P<0.001). Hsa_circ_0002203 expression increased after the lentiviral infection of SCC15 and CAL27. The proliferation, migration, and invasion of SCC15 and CAL27 reduced, and apoptosis level was promoted. The tumor volume, weight decreased, and growth rate of nude mice decreased. CONCLUSIONS: The low expression of circular RNA hsa_circ_0002203 in oral squamous cell carcinoma can enhance the proliferation, migration, and invasion of cancer cells and inhibit tumor cell apoptosis.


Assuntos
Carcinoma de Células Escamosas , Neoplasias Bucais , Animais , Apoptose , Linhagem Celular Tumoral , Proliferação de Células , Humanos , Camundongos , Camundongos Nus , RNA
16.
Stem Cell Res Ther ; 10(1): 327, 2019 Nov 19.
Artigo em Inglês | MEDLINE | ID: mdl-31744536

RESUMO

Stem cells are considered the fundamental underpinnings of tissue biology. The stem cell microenvironment provides factors and elements that play significant roles in controlling the cell fate direction. The bone marrow is an important environment for functional hematopoietic stem cells in adults. Remarkable progress has been achieved in the area of hematopoietic stem cell fate modulation based on the recognition of biochemical factors provided by bone marrow niches. In this review, we focus on emerging evidence that hematopoietic stem cell fate is altered in response to a variety of microenvironmental physical cues, such as geometric properties, matrix stiffness, and mechanical forces. Based on knowledge of these biophysical cues, recent developments in harnessing hematopoietic stem cell niches ex vivo are also discussed. A comprehensive understanding of cell microenvironments helps provide mechanistic insights into pathophysiological mechanisms and underlies biomaterial-based hematopoietic stem cell engineering.

17.
Mol Med Rep ; 2019 Nov 05.
Artigo em Inglês | MEDLINE | ID: mdl-31746415

RESUMO

Individual differences in the response to fentanyl, which may be caused by different concentrations of the drug in the central nervous system, can complicate analgesic treatment. It has been reported that the organic anion transporting polypeptide (OATP) at the blood­brain barrier (BBB) in Sprague­Dawley rats may serve an important role in the transport of fentanyl across the BBB. However, whether human OATP can transport fentanyl has thus far not been reported. The present study aimed to establish a 293 cell line stably overexpressing OATP1A2, and to determine whether OATP1A2 is able to transport fentanyl across the plasma membrane. Initially, 293 cells were transfected with an OATP1A2­expressing plasmid (referred to as 293­OATP1A2 cells), and single colonies were selected and characterized following geneticin treatment. Subsequently, reverse transcription­quantitative polymerase chain reaction and western blot analyses were conducted to verify the transfection efficiency. Furthermore, treatment of 293­OATP1A2 cells with different concentrations of fexofenadine (FEX) and fentanyl was performed to investigate the transport function of OATP1A2 in 293 cells. FEX and fentanyl uptake experiments were also performed with naringenin, an inhibitor of OATP1A2. The results indicated that FEX and fentanyl uptake was significantly increased in 293­OATP1A2 cells compared with that in the control­transfected cells. The 293­OATP1A2­mediated uptake of FEX at concentration of 100 nM FEX was ~10­fold higher than that of 293­VC cells. The 293­OATP1A2­mediated uptake of fentanyl (100 nM) was 5.1­fold higher compared with that in 293­VC cells. In 293­OATP1A2 cells, the uptake of FEX without OATP1A2 inhibitor naringenin (100 µg/ml) was 2.8­fold higher compared with that in the presence of naringenin, and the uptake of fentanyl without naringenin was 7.3­fold higher compared with that in the presence of naringenin (100 µg/ml). In conclusion, 293 cells that overexpressed OATP1A2 were successfully constructed, and OATP1A2 was revealed to mediate fentanyl uptake in the cultured cells.

18.
Free Radic Biol Med ; 2019 Nov 08.
Artigo em Inglês | MEDLINE | ID: mdl-31711983

RESUMO

Inflammation and oxidative stress contribute to the progression of acute lung injury (ALI). Galectin-1 (Gal-1) has important anti-inflammatory properties in renal ischemia-reperfusion injury, arthritis, uveitis, and hepatitis. However, whether Gal-1 could protect against ALI is still poorly elucidated. The current study aimed to investigate the protective effects of Gal-1 against lipopolysaccharide (LPS)-induced ALI and the underlying mechanisms. Accordingly, we found that pretreatment with Gal-1 attenuated the lung tissue injury induced by LPS, with the recovery of lung function, protecting against the production of pro-inflammatory cytokines and oxidative stress. We also confirmed the therapeutic potential of Gal-1 on the survival rate of LPS-challenged mice. In vitro studies demonstrated the protective effects of exogenous Gal-1 through downregulating pro-inflammatory cytokines release and oxidative stress in primary macrophages challenged by LPS. In addition, Gal-1 suppressed TXNIP-NLRP3 inflammasome activation in ALI mice and LPS-treated primary macrophages partly through directly binding to the NLRP3 protein. Gal-1 alleviated LPS-induced lung injury via activation of Nrf-2, which may be associated with AMPK phosphorylation. Collectively, our experimental results firstly provided the support that Gal-1 effectively protected against LPS-induced ALI via suppression of inflammation response and oxidative stress, which were largely dependent on the upregulation of the Nrf2 pathway via phosphorylation of AMPK. These results suggest that Gal-1 could be a valuable therapeutic candidate in the treatment of ALI.

19.
Artigo em Inglês | MEDLINE | ID: mdl-31740206

RESUMO

Acute myocardial infarction (MI) is a major cause of death worldwide. Although timely and successful reperfusion could reduce myocardial ischemia injury, limit infarct size, and improve ventricular dysfunction and reduce acute mortality, restoring blood flow might also lead to unwanted myocardial ischemic-reperfusion (I/R) injury. Pre-clinical studies have demonstrated that multiple approaches are capable of attenuating the myocardial I/R injury. However, there is still no effective therapy for preventing myocardial I/R injury for the clinical setting. It is known that myocardial I/R injury could induce cardiac autonomic imbalance with over-activated sympathetic tone and reduced vagal activity, in turn, contributing to pathogenesis of myocardial I/R injury. Cumulative evidence shows that the enhancement of vagal activity, so called vagus nerve stimulation (VNS), is able to reduce injury and promote recovery of injured myocardium. Therefore, VNS might be a potentially novel strategy choice for preventing/attenuating myocardial I/R injury. In this review, we describe the protective role of VNS in myocardial I/R injury and related potential mechanisms. Then, we discuss the challenge and the opportunity of VNS in the treatment of acute myocardial I/R injury.

20.
Brain Behav Immun ; 2019 Oct 25.
Artigo em Inglês | MEDLINE | ID: mdl-31669519

RESUMO

The vicious cycle between the chronicactivationofmicroglia and dopamine neurons degeneration is linked with the progression of Parkinson's disease (PD). Targeting microglialactivationhas proven to be a viable option to develop a disease-modified therapy for PD. Galectin-1, which has been reported to have an anti-neuroinflammation effect was used in the present study to evaluate its therapeutic effects on microglia activation and neuronal degeneration in Parkinson's disease model. It was found that galectin-1 attenuated the inflammatory insult and the apoptosis of SK-N-SH human neuroblastoma cells from conditioned medium of activated microglia induced by Lipopolysaccharides (LPS). Nonetheless, galectin-1 administration (0.5 mg/kg) inhibited the microglia activation, improved the motor deficits in PD mice model induced by MPTP (25 mg/kg weight of mouse, i.p.) and prevented the degeneration of dopaminergic neurons in the substantia nigra. Administration of galectin-1 resulted in p38 and ERK1/2 dephosphorylation followed by IκB/NFκB signaling pathway inhibition. Galectin-1 significantly decreased the secretion of pro-inflammatory cytokines, including interleukin (IL)-1ß, tumor necrosis factor-α (TNF-α), and protein levels of inducible nitric oxide synthase (iNOS) and cyclooxygenase-2 (COX-2). The protective effects and modulation of the MAPK/IκB/NFκB signaling pathway were abolished with ß-D-galactose which blocked the carbohydrate-recognition domain of galectin-1. The present study demonstrated that galectin-1 inhibited microglia activation and ameliorated neurodegenerative process in PD model by modulating MAPK/IκB/NFκB axis through its carbohydrate-recognition domain.

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