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1.
J Hazard Mater ; 390: 122146, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-32007861

RESUMO

Peroxymonosulfate (PMS) activation by heterogeneous catalysts has been widely investigated to remove organic contaminants. Nevertheless, the technology is restricted to the bench-scale batch system. For practical applications, a supported catalyst design based on a reactor configuration with catalyst recovery is the need for future development. In this study, Mn3O4 nanodots-g-C3N4 nanosheets (Mn3O4/CNNS) composites were prepared via a facile hydrothermal method. The micro-structures and compositions of composites were investigated by a series of characterization methods. It was found that the Mn3O4 nanodots (5-10 nm) were distributed uniformly over the CNNS. When the added amount of CNNS was 150 mg during the synthesis process, a composite named as Mn3O4/CNNS-150 was obtained, which exhibited the best performance on PMS activation for 4-chlorophenol (4-CP) removal. The Mn3O4/CNNS-150@PTFE membrane was synthesized by facile vacuum filtration. The catalytic membrane was applied in filtration experiments for the degradation of different contaminants. The stability tests revealed excellent stability of the catalytic membrane. The redox circles of Mn(IV)/Mn(III)/Mn(II) on the Mn3O4 surface were the main source of activated PMS and a possible activation mechanism in the reaction system was provided. This study is of great significance for the development of novel catalytic membranes with PMS activation.

2.
Chemistry ; 2020 Jan 09.
Artigo em Inglês | MEDLINE | ID: mdl-31919969

RESUMO

Controlled synthesis of metal-organic framework (MOF)-based materials with multiple levels of porous structures across different length scales is of great interest in various applications while it still remains challenging. Most of the current strategies are time consuming and labor intensive, and not readily scaled-up. In this work, we introduce a straightforward one-pot fabrication strategy to prepare robust and flexible hierarchically macro-meso-micro porous HKUST-1/polyvinylidene fluoride (PVDF) composite via solvent evaporation, in which MOF crystallization and polymer precipitation are combined together. The effect of MOF precursor and polymer initial amount on the morphology of final composite was thoroughly studied. The interaction between MOF and polymer during the evaporation process is the key factor, which would limit mobility of the polymer chains and cause instability in the MOF growth, thus endowing the composite with hierarchically macro-meso-micro porous structure. This "all-in-one" porous structure could enhance the mass transport property of molecules within the composite. The obtained HKUST-1/PVDF composite showed an enhanced CO 2 adsorption rate constant of 0.821 min -1 (298 K, 1 bar), which was 3.5 times higher than that of the pristine MOF. In addition, the composite showed an equivalent gas adsorption capacity under all the tested pressures and greatly improved water stability.

3.
Sci Rep ; 10(1): 795, 2020 Jan 21.
Artigo em Inglês | MEDLINE | ID: mdl-31964955

RESUMO

Moderate-severe pain after surgical procedures is associated with decreased quality of life and increased costs. This study aimed to identify the incidence and predictive factors of moderate-severe postoperative pain within 48 hours following video-assisted thoracoscopic surgery (VATS) in a tertiary hospital. A retrospective cohort analysis was performed using medical records of adult patients who underwent VATS between January 2015 and December 2016. Logistic regression was performed to identify predictive factors for moderate-severe pain (visual analogue scale, VAS ≥ 4) within 24 hours and within 48 hours postoperatively. Of the 1164 participants, the incidence of moderate-severe pain was 12.7% within the first 24 hours and 15.6% within the first 48 hours after surgery. In multivariable analysis, the independent risk factors related to moderate-severe pain within 24 hours after surgery were younger age, increased body mass index, preoperative pain within 1 month and history of smoking. The risk factors for moderate-severe acute pain within 48 hours were almost the same, except that the number of chest tubes were also included. Moderate-severe postoperative pain following VATS is not rare, and presence of several risk factors deserves more aggressive pain management strategies perioperatively.

4.
J Cell Mol Med ; 24(2): 1700-1712, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31782248

RESUMO

Circular RNAs are a class of widespread and diverse endogenous RNAs that may regulate gene expression in various diseases, but their regulation and function in hypertensive renal injury remain unclear. In this study, we generated ribosomal-depleted RNA sequencing data from normal mouse kidneys and from injured mouse kidneys induced by deoxycorticosterone acetate-salt hypertension and identified at least 4900 circRNA candidates. A total of 124 of these circRNAs were differentially expressed between the normal and injured kidneys. Furthermore, we characterized one abundant circRNA, termed circNr1h4, which is derived from the Nr1h4 gene and significantly down-regulated in the injured kidneys. RNA sequencing data and qPCR analysis also showed many microRNAs and mRNAs, including miR-155-5p and fatty acid reductase 1 (Far1), were differentially expressed between the normal and injured kidney and related to circNr1h4. In vitro, the silencing of circNr1h4 or overexpression of miR-155-5p significantly decreased Far1 levels and increased reactive oxygen species. Mechanistic investigations indicated that circNr1h4 acts as a competing endogenous RNA for miR-155-5p, leading to regulation of its target gene Far1. Our study provides novel insight into the molecular mechanisms underlying kidney injury in hypertension, which will be required to develop therapeutic strategies of targeting circRNAs for hypertensive kidney injury.

5.
J Ethnopharmacol ; 249: 112432, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31790818

RESUMO

ETHNOPHARMACOLOGICAL RELEVANCE: In traditional Chinese medicine (TCM) theory, depression is considered to be "liver qi stagnation", and relieving "liver qi stagnation" is regarded as an effective method for treating depression. Xiaoyao San (XYS) is a well-known TCM formula for the treatment of depression by relieving "liver qi stagnation". This formula consists of Radix Paeoniae Alba (Paeonia lactiflora Pall.), Radix Bupleuri (Bupleurum chinense DC.), Poria (Poria cocos (Schw.) Wolf), Rhizoma Atractylodis Macrocephalae (Atractylodes macrocephala Koidz.), Radix Angelicae Sinensis (Angelica sinensis (Oliv.) Diels), Radix Glycyrrhizae (Glycyrrhiza uralensis Fisch.), Rhizoma Zingiberis Recens (Zingiber officinale Roscoe) and Herba Menthae Haplocalycis (Mentha haplocalyx Briq.). AIM OF THE STUDY: Several studies have suggested that depression is associated with liver injury. XYS was a well-known TCM formula for the treatment of depression and liver stagnancy. However, it was still unknown whether the antidepressant effect of XYS is related to the pharmacological activity of hepatoprotection. The aim of this study was to elucidate the potential link between the antidepressant and hepatoprotective effect of XYS. MATERIALS AND METHODS: A depression rat model was established by the CUMS (chronic unpredictable mild stress) procedure. The antidepressant effect of XYS was assessed by the behavioral indicators, and the hepatoprotective effect of XYS was evaluated through biochemical assays. 1H-NMR and LC/MS-based liver metabolomics were performed to discover key metabolic pathways involved in the antidepressant and hepatoprotective effects of XYS. Further, the key pathway was validated using commercial kits. RESULTS: The results demonstrated that XYS pretreatment could significantly improve the depressive symptom induced by CUMS. More importantly, the results demonstrated that liver injury was observed in the CUMS model rats, and XYS had a hepatoprotective effect by reducing the activities of AST and ALT in serum, increasing the levels of SOD and GSH-Px and reducing the contents of MDA, IL-6, and IL-1ß in the liver. In addition, the NMR and LC/MS-based metabolomics results indicated that XYS improved 23 of the 35 perturbed potential liver biomarkers that were induced by CUMS. Among them, 9 biomarkers were significantly correlated with both depression and liver pathology, according to Pearson correlation analysis. Metabolic pathway analyses of these 9 biomarkers showed that glutamine and glutamate metabolism were the most important metabolic pathways. Furthermore, to verify glutamine and glutamate metabolism, the levels of glutamine and glutamate, and the activity of glutamine synthetase (GS) and glutaminase (GLS) were quantitatively determined in the liver by commercial kits, and these results were consistent with the metabolomics results. CONCLUSIONS: XYS could significantly improve the depressive and liver injury symptoms induced by CUMS. The metabolomics results indicate that the regulation of glutamine and glutamate metabolism to maintain the balance of ammonia and promote energy metabolism is a potential junction between the antidepressant and hepatoprotective effects of XYS.

8.
Medicine (Baltimore) ; 98(42): e17597, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31626136

RESUMO

Hyperuricemia has received increasing attention as a major public health problem. This study aims to investigate the risk factors for hyperuricemia and to explore the relationship between changes in biochemical variables and incident hyperuricemia.A cross-sectional and subsequently prospective study was performed among adults who took their health checkups at Zhejiang University Hospital. The participants who were free of hyperuricemia at baseline received annual follow-up examinations during a 6-year period. Cox proportional hazards regression analyses were conducted to calculate the risks for incident hyperuricemia.Of the 9238 participants enrolled, 1704 (18.4%) were diagnosed as hyperuricemia. During 21,757 person-years of follow-up, 1492 incident hyperuricemia cases were identified. The incidence of hyperuricemia was 68.58 cases per 1000 person-year of follow-up in the overall participants. The prevalence and the incidence of hyperuricemia increased greatly in female older than 50 years. High levels of BMI, SBP, FPG, TG, LDL-C, ALT, BUN, and creatinine increased the risk of hyperuricemia. Suffering fatty liver also increased the risk of hyperuricemia. Subjects with increasing DBP, TG, BUN, creatinine, or decreasing HDL-C were more likely to incident hyperuricemia.This study revealed that the change of diastolic blood pressure (DBP), serum triglycerides (TG), blood urea nitrogen (BUN), creatinine, and high-density lipoprotein cholesterol (HDL-C) level were independently associated with incident hyperuricemia.


Assuntos
HDL-Colesterol/sangue , LDL-Colesterol/sangue , Creatinina/sangue , Hiperuricemia/etiologia , Triglicerídeos/sangue , Ácido Úrico/sangue , Adulto , Biomarcadores/sangue , Pressão Sanguínea/fisiologia , Nitrogênio da Ureia Sanguínea , Índice de Massa Corporal , China/epidemiologia , Estudos Transversais , Feminino , Seguimentos , Humanos , Hiperuricemia/sangue , Hiperuricemia/epidemiologia , Incidência , Masculino , Pessoa de Meia-Idade , Prevalência , Prognóstico , Estudos Prospectivos , Fatores de Risco , Fatores de Tempo
9.
Food Res Int ; 125: 108624, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31554059

RESUMO

The dried and aged pericarps of Citri Reticulatae are condiments and medicinal products in southeast and eastern Asia for hundreds of years, among which Pericarpium Citri Reticulatae 'Chachiensis' (PCR-C) is the premium one with obvious health benefits. In order to explore the microbiota in PCR-C and their relationship with the chemical components during aging, culture-independent methods were applied to investigate PCR-C microbiota for the first time. Here in different PCR-C samples, 16S rRNA gene amplicon sequencing revealed common central bacterial community, which were absent or only accounted for small proportion in fresh pericarps or jute bag controls. Bacillus and Lactococcus were the top two dominant genera in PCR-C with acidic pH (4.06-4.51) and low moisture (11.48%-19.13%). Several OTUs were found to closely relate with specific compositions in essential oils and phenolics, such as d-limonene and nobiletin, which contributed to PCR-C flavor and quality. As the first study to reveal the central bacterial communities in PCR-C, it provides new insights to improve the quality and aging process of traditional Pericarpium Citri Reticulatae, and lays foundation for functional characterization of the microbes within.

10.
Front Pharmacol ; 10: 192, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30894817

RESUMO

Angelicae Sinensis Radix (AS), a well-known herb in traditional Chinese medicine (TCM), has been wildly used for replenishing the blood and promoting circulation, in Asia for thousands of years. It has been confirmed that AS also possesses the pharmacological activity of anti-depression. At the same time, recent studies suggested that depression is associated with anemia, and depression could be ameliorated via modulating the blood system. However, it is still unknown whether the anti-depression effect of AS is related to its pharmacological activity of modulating the blood system. In the current study, hematological examination and metabonomic techniques were performed to explore potential anti-depression mechanisms of AS, related to the function of modulating the blood system in a chronic unpredictable mild stress (CUMS) model. The results demonstrated that AS could significantly improve CUMS-induced depressive symptom, hematological anomalies, and hypoxia symptoms. The analysis of metabonomics demonstrated that 26 potential biomarkers in depression could be regulated by the administration of AS. Among them, eight biomarkers participate in the metabolic pathways of amino acid and sphingolipid, and energy metabolism could also be regulated in an anemia model through the administration of AS, as reported in previous literatures. Further results proved that AS modulated energy metabolism in depression through the inhibition of the expression of pyruvate dehydrogenase lipoamide kinase isozyme 1 (PDK-1) and lactate dehydrogenase A (LDHA). These results suggested that the modulation of the blood system was involved in the anti-depression effect of AS. The mechanism may be associated with the promotion of the body's energy metabolism, the stabilization of cell membranes, the promotion of serum protein synthesis, and the enhancement of immunity.

11.
PLoS One ; 14(3): e0213800, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30865707

RESUMO

[This corrects the article DOI: 10.1371/journal.pone.0156145.].

12.
J Cell Mol Med ; 23(3): 2020-2031, 2019 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-30585412

RESUMO

Peroxisomes play a central role in lipid metabolism. We previously demonstrated that Pex11a deficiency impairs peroxisome abundance and fatty acid ß-oxidation and results in hepatic triglyceride accumulation. The role of Pex11a in dyslipidaemia and obesity is investigated here with Pex11a knockout mice (Pex11a-/- ). Metabolic phenotypes including tissue weight, glucose tolerance, insulin sensitivity, cholesterol levels, fatty acid profile, oxygen consumption, physical activity were assessed in wild-type (WT) and Pex11a-/- fed with a high-fat diet. Molecular changes and peroxisome abundance in adipose tissue were evaluated through qRT-PCR, Western blotting, and Immunofluorescence. Pex11a-/- showed increased fat mass, decreased skeletal muscle, higher cholesterol levels, and more severely impaired glucose and insulin tolerance. Pex11a-/- consumed less oxygen, indicating a decrease in fatty acid oxidation, which is consistent with the accumulation of very long- and long-chain fatty acids. Adipose palmitic acid (C16:0) levels were elevated in Pex11a-/- , which may be because of dramatically increased fatty acid synthase mRNA and protein levels. Furthermore, Pex11a deficiency increased ventricle size and macrophage infiltration, which are related to the reduced physical activity. These data demonstrate that Pex11a deficiency impairs physical activity and energy expenditure, decreases fatty acid ß-oxidation, increases de novo lipogenesis and results in dyslipidaemia and obesity.

13.
Sci Rep ; 8(1): 17320, 2018 11 23.
Artigo em Inglês | MEDLINE | ID: mdl-30470771

RESUMO

Sialic acid (Sia) residues on cell surface are critical for myriad cellular events such as immunity and inflammation. We herein reported the use of abiotic Sia to raise the thresholds of inflammatory cell responses. Identified from a panel of structurally diversified Sia analogs via a cell inflammation assay, Sia-2, with N-butyryl moiety at C-5, markedly lowered LPS-stimulated NF-κB activity in macrophages. Further analysis shows that Sia-2 attenuates phosphorylation of IκB and Erk1/2/p38/JNK, critical for NF-κB signaling and MAPK signaling, and lowers gene transcription of proinflammatory interleukin-6. These results support the use of abiotic Sia as promising agents to modulate cell surface Sia-pertinent cell signaling.


Assuntos
Anti-Inflamatórios/farmacologia , Regulação da Expressão Gênica/efeitos dos fármacos , Inflamação/prevenção & controle , Macrófagos/efeitos dos fármacos , Proteínas Quinases Ativadas por Mitógeno/antagonistas & inibidores , NF-kappa B/antagonistas & inibidores , Ácidos Siálicos/farmacologia , Animais , Inflamação/metabolismo , Inflamação/patologia , Interleucina-6/genética , Interleucina-6/metabolismo , Macrófagos/imunologia , Macrófagos/metabolismo , Macrófagos/patologia , Camundongos , Fosforilação , Células RAW 264.7 , Transdução de Sinais , Estresse Fisiológico
14.
Angew Chem Int Ed Engl ; 57(51): 16638-16642, 2018 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-30375138

RESUMO

For decades, researchers have endeavored to develop a general automated system to synthesize oligosaccharides that is comparable to the preparation of oligonucleotides and oligopeptides by commercially available machines. Inspired by the success of automated oligosaccharide synthesis through chemical glycosylation, a fully automated system is reported for oligosaccharides synthesis through enzymatic glycosylation in aqueous solution. The designed system is based on the use of a thermosensitive polymer and a commercially available peptide synthesizer. This study represents a proof-of-concept demonstration that the enzymatic synthesis of oligosaccharides can be achieved in an automated manner using a commercially available peptide synthesizer.


Assuntos
Glicosiltransferases/metabolismo , Oligossacarídeos/biossíntese , Peptídeos/metabolismo , Automação , Glicosilação , Glicosiltransferases/química , Estrutura Molecular , Oligossacarídeos/química , Peptídeos/química
15.
Angew Chem Int Ed Engl ; 57(30): 9268-9273, 2018 07 20.
Artigo em Inglês | MEDLINE | ID: mdl-29732660

RESUMO

O Mannosylation is a vital protein modification involved in brain and muscle development whereas the biological relevance of O-mannosyl glycans has remained largely unknown owing to the lack of structurally defined glycoforms. An efficient scaffold synthesis/enzymatic extension (SSEE) strategy was developed to prepare such structures by combining gram-scale convergent chemical syntheses of three scaffolds and strictly controlled sequential enzymatic extension catalyzed by glycosyltransferases. In total, 45 O-mannosyl glycans were obtained, covering the majority of identified mammalian structures. Subsequent glycan microarray analysis revealed fine specificities of glycan-binding proteins and specific antisera.


Assuntos
Glicosiltransferases/metabolismo , Manose/biossíntese , Polissacarídeos/biossíntese , Configuração de Carboidratos , Manose/química , Polissacarídeos/química
16.
Sci Rep ; 7(1): 17737, 2017 12 18.
Artigo em Inglês | MEDLINE | ID: mdl-29255279

RESUMO

Kidney biopsy is considered the golden criterion for diagnosing the etiology of kidney disease but accompanied by non-negligible complications. We explored the possibility of using urinary microRNA (miRNA) as a non-invasive biomarker for hypertensive kidney injury. We assessed differential miRNA expressions in the kidneys and urine of hypertensive mice with kidney injury induced by deoxycorticosterone acetate (DOCA)-salt compared to the controls. DOCA-salt treatment significantly increased renal tubular lesions from day 2 and mRNA expression of fibrosis-related genes from day 4 compared to the controls, respectively. Urinary albumin and N-acetyl-beta-D-glucosaminidase was significantly increased on day 8 compared to the controls. Array results showed that 20 out of 585 miRNAs were highly expressed in the kidneys and significantly increased on day 8 compared to the controls, including miR-21, miR-146b, miR-155 and miR-132, which were confirmed by real-time polymerase chain reaction and were significantly higher from day 4. The miR-21/creatinine in the urine from day 4 was significantly higher than that of the controls and was detected earlier than urinary albumin. In conclusion, we have identified urinary miR-21 that correlates with histopathological lesions and functional markers of kidney damage to facilitate a potential noninvasive detection for hypertensive kidney injury.


Assuntos
Fibrose/genética , Hipertensão Renal/genética , MicroRNAs/genética , Acetilglucosaminidase/análise , Acetilglucosaminidase/urina , Lesão Renal Aguda/patologia , Animais , Biomarcadores/metabolismo , Biomarcadores/urina , Creatinina/análise , Creatinina/urina , Desoxicorticosterona/metabolismo , Fibrose/metabolismo , Hipertensão/metabolismo , Hipertensão Renal/metabolismo , Rim/lesões , Rim/metabolismo , Túbulos Renais/metabolismo , Masculino , Camundongos , Camundongos Endogâmicos C57BL , MicroRNAs/fisiologia , Sistema Urinário/metabolismo
17.
Undersea Hyperb Med ; 44(3): 235-242, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28779580

RESUMO

OBJECTIVE: To explore the effect and mechanism of hyperbaric oxygen (HBO2) therapy of open tibial fractures in rabbits after transient seawater immersion. METHODS: Forty-eight (48) New Zealand rabbits were randomly and averagely divided into an HBO2 therapy group (Group A) and a control group (Group B). All rabbits were subjected to unilateral open tibial fractures, while immersed in artificial seawater (20-22 °C) for three hours prior to debridement and external fixation. Group A was treated with HBO2 at 2 atmospheres absolute (ATA) for 50 minutes once daily for two weeks; Group B received postoperative routine treatments only. The fracture zone in each group was compared by radiological, histological and immunohistochemical examinations. RESULTS: In Group A, bony callus and mature osteocytes without infiltration of inflammatory cells were observed in the fracture zone. Vascular endothelial growth factor (VEGF) was expressed mainly in the cytoplasm of osteoblasts, chondrocytes and osteocytes, and exhibited significant changes at different time points. The gray value of bony callus in Group A was 190.58 ± 7.52; that of Group B was 144 ± 8.11. Difference between the groups was statistically significant (P ⟨ 0.01). The content of malondialdehyde (MDA) in Group A was significantly lower than Group B (P ⟨ 0.01), and the activity of superoxide dismutase (SOD) in Group A was higher than Group B (P ⟨ 0.01) at four weeks. There were no significant differences in MDA content and SOD activity between groups at eight and 12 weeks. CONCLUSIONS: HBO2 treatment of open tibial fractures in seawater can reduce the inflammatory reaction and reperfusion injury, and promote osteocytic proliferation and fracture healing.


Assuntos
Consolidação da Fratura/fisiologia , Fraturas Expostas/terapia , Oxigenação Hiperbárica , Fraturas da Tíbia/terapia , Animais , Pressão Atmosférica , Desbridamento , Feminino , Fixação de Fratura/métodos , Fraturas Expostas/diagnóstico por imagem , Fraturas Expostas/metabolismo , Imersão , Masculino , Malondialdeído/metabolismo , Coelhos , Distribuição Aleatória , Traumatismo por Reperfusão/prevenção & controle , Água do Mar , Superóxido Dismutase/metabolismo , Fraturas da Tíbia/diagnóstico por imagem , Fraturas da Tíbia/metabolismo , Fatores de Tempo , Fator A de Crescimento do Endotélio Vascular/metabolismo
18.
Carbohydr Res ; 438: 39-43, 2017 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-27960098

RESUMO

The enzymatic synthesis of biologically important and structurally unique human P1PK blood group type P1 pentasaccharide antigen is described. This synthesis features a three-step sequential one-pot multienzyme (OPME) glycosylation for the stepwise enzymatic chain elongation of readily available lactoside acceptor with cheap and commercially available galactose and N-acetylglucosamine as donor precursors. This enzymatic synthesis provides an operationally simple approach to access P1 pentasaccharide and its structurally related Gb3 and P1 trisaccharide epitopes.


Assuntos
Acetilglucosamina/química , Antígenos de Grupos Sanguíneos/química , Galactose/química , Glicosiltransferases/metabolismo , Oligossacarídeos/síntese química , Glicosilação , Humanos
19.
Hypoxia (Auckl) ; 4: 81-90, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27800510

RESUMO

Glycosaminoglycan hyaluronan (HA), a major constituent of the endothelial glycocalyx, helps to maintain vascular integrity. Preconditioning the heart with volatile anesthetic agents protects against ischemia/reperfusion injury. We investigated a possible protective effect of sevoflurane on the glycocalyx, especially on HA. The effect of pre-ischemic treatment with sevoflurane (15 minutes at 2% vol/vol gas) on shedding of HA was evaluated in 28 isolated, beating guinea pig hearts, subjected to warm ischemia (20 minutes at 37°C) followed by reperfusion (40 minutes), half with and half without preconditioning by sevoflurane. HA concentration was measured in the coronary effluent. Over the last 20 minutes of reperfusion hydroxyethyl starch (1 g%) was continuously infused and the epicardial transudate collected over the last 5 minutes for measuring the colloid extravasation. Additional hearts were fixed by perfusion after the end of reperfusion for immunohistology and electron microscopy. Sevoflurane did not significantly affect post-ischemic oxidative stress, but strongly inhibited shedding of HA during the whole period, surprisingly even prior to ischemia. Immunohistology demonstrated that heparan sulfates and SDC1 of the glycocalyx were also preserved by sevoflurane. Electron microscopy revealed shedding of glycocalyx caused by ischemia and a mostly intact glycocalyx in hearts exposed to sevoflurane. Coronary vascular permeability of the colloid hydroxyethyl starch was significantly decreased by sevoflurane vs the control. We conclude that application of sevoflurane preserves the coronary endothelial glycocalyx, especially HA, sustaining the vascular barrier against ischemic damage. This may explain beneficial effects associated with clinical use of volatile anesthetics against ischemia/reperfusion injury.

20.
PLoS One ; 11(5): e0156145, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-27203692

RESUMO

Androgen receptor (AR) signaling is crucial to the development and homeostasis of the prostate gland, and its dysregulation mediates common prostate pathologies. The mechanisms whereby AR regulates growth suppression and differentiation of luminal epithelial cells in the prostate gland and proliferation of malignant versions of these cells have been investigated in human and rodent adult prostate. However, the cellular stress response of human prostate epithelial cells is not well understood, though it is central to prostate health and pathology. Here, we report that androgen sensitizes HPr-1AR and RWPE-AR human prostate epithelial cells to cell stress agents and apoptotic cell death. Although 5α-dihydrotestosterone (DHT) treatment alone did not induce cell death, co-treatment of HPr-1AR cells with DHT and an apoptosis inducer, such as staurosporine (STS), TNFt, or hydrogen peroxide, synergistically increased cell death in comparison to treatment with each apoptosis inducer by itself. We found that the synergy between DHT and apoptosis inducer led to activation of the intrinsic/mitochondrial apoptotic pathway, which is supported by robust cleavage activation of caspase-9 and caspase-3. Further, the dramatic depolarization of the mitochondrial membrane potential that we observed upon co-treatment with DHT and STS is consistent with increased mitochondrial outer membrane permeabilization (MOMP) in the pro-apoptotic mechanism. Interestingly, the synergy between DHT and apoptosis inducer was abolished by AR antagonists and inhibitors of transcription and protein synthesis, suggesting that AR mediates pro-apoptotic synergy through transcriptional regulation of MOMP genes. Expression analysis revealed that pro-apoptotic genes (BCL2L11/BIM and AIFM2) were DHT-induced, whereas pro-survival genes (BCL2L1/BCL-XL and MCL1) were DHT-repressed. Hence, we propose that the net effect of these AR-mediated expression changes shifts the balance of BCL2-family proteins, such that androgen signaling sensitizes mitochondria to apoptotic signaling, thus rendering HPr-1AR more vulnerable to cell death signals. Our study offers insight into AR-mediated regulation of prostate epithelial cell death signaling.


Assuntos
Androgênios/farmacologia , Apoptose/efeitos dos fármacos , Células Epiteliais/citologia , Células Epiteliais/efeitos dos fármacos , Próstata/citologia , Receptores Androgênicos/metabolismo , Linhagem Celular , Di-Hidrotestosterona/farmacologia , Células Epiteliais/metabolismo , Humanos , Immunoblotting , Masculino , Transdução de Sinais/efeitos dos fármacos , Estaurosporina/farmacologia
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