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1.
Artigo em Inglês | MEDLINE | ID: mdl-32406007

RESUMO

Long non-coding RNA (lncRNA) plays a pivotal role in the development of myocardial infarction (MI). The aim of this study was to investigate the effects of lncRNA actin filament-associated protein 1 antisense RNA 1 (AFAP1-AS1) on cell cycle, proliferation, and apoptosis. RT-qPCR was used to detect the expression levels of AFAP1-AS1, miR-512-3p, and reticulon 3 (RTN3) in rat model of I/R. The simulated MI environment was constructed. MTT assay and flow cytometry were used to detect changes in cardiomyocyte viability and cell cycle/apoptosis after MI by AFAP1-AS1 silencing or RTN3 silencing. The targeting relationship of miR-512-3p and AFAP1-AS1 and RTN3 in cardiomyocytes was verified by dual luciferase reporter assay. The expression levels of AFAP1-AS1 and RTN3 were significantly upregulated in a rat model of LAD ligation (or MI) ligation, while the expression level of miR-512-3p was significantly reduced. Overexpressed AFAP1-AS1 and RTN3 promoted cardiomyocyte apoptosis and inhibited cardiomyocyte proliferation. MiR-512-3p was a direct target of AFAP1-AS1, and RTN3 was a direct target of miR-512-3p. AFAP1-AS1 promoted the progression of MI by targeting miR-512-3p. AFAP1-AS1 promoted the progression of MI by modulating the miR-512-3p/RTN3 axis. AFAP1-AS1 may be a potential therapy target for MI. Graphical Abstract The role of AFAP1-AS1 in regulating MI injury in vivo. (A) Effect of AFAP1-AS1 in MI injury in vivo. (B) The mRNA level of RTN3 in MI injury in vivo. (C) The protein level of RTN3 in MI injury in vivo. (D) Effect of miR-512-3p in MI model group. (E) TUNEL assay. *P < 0.05, **P < 0.01 vs the sham group; #P < 0.05, ##P < 0.01 vs the MI group.

2.
Sci Total Environ ; 725: 138251, 2020 Apr 01.
Artigo em Inglês | MEDLINE | ID: mdl-32298905

RESUMO

BACKGROUND: Since 2011 human leptospirosis incidence in China has remained steadily low with persistent pockets of notifications reported in communities within the Upper Yangtze River Basin (UYRB) and Pearl River Basin (PRB). To help guide health authorities within these residual areas to identify communities where interventions should be targeted, this study quantified the local effect of socioeconomic and environmental factors on the spatial distribution of leptospirosis incidence and developed predictive maps of leptospirosis incidence for UYRB and PRB. METHODS: Data on all human leptospirosis cases reported during 2005-2016 across the UYRB and PRB regions were geolocated at the county-level and included in the analysis. Bayesian conditional autoregressive (CAR) models with zero-inflated Poisson link for leptospirosis incidence were developed after adjustment of environmental and socioeconomic factors such as precipitation, normalized difference vegetation index (NDVI), modified normalized difference water index (MNDWI), land surface temperature (LST), elevation, slope, land cover, crop production, livestock density, gross domestic product and population density. RESULTS: The relationship of environmental and socioeconomic variables with human leptospirosis incidence varied between both regions. While across UYRB incidence of human leptospirosis was associated with MNDWI and elevation, in PRB human leptospirosis incidence was significantly associated with NDVI, livestock density and land cover. Precipitation was significantly and positively associated with the spatial variation of incidence of leptospirosis in both regions. After accounting for the effect of environmental and socioeconomic factors, the predicted distribution of residual high-incidence county is potentially more widespread both in the UYRB and PRB compared to the observed distribution. In the UYRB, the highest predicted incidence was found along the border of Chongqing and Guizhou towards Sichuan basin and northwest Yunnan. The highest predicted incidence was also identified in counties in the central and lower reaches of the PRB. CONCLUSIONS: This study demonstrated significant geographical heterogeneity in leptospirosis incidence within UYRB and PRB, providing an evidence base for prioritising targeted interventions in counties identified with the highest predicted incidence. Furthermore, environmental drivers of leptospirosis incidence were highly specific to each of the regions, emphasizing the importance of localized control measures. The findings also suggested the need to expand interventional coverage and to support surveillance and diagnostic capacity on the predicted high-risk areas.

3.
Channels (Austin) ; 14(1): 151-162, 2020 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-32290730

RESUMO

Residue Thr1604 in the CaV1.2 channel is a Ca2+/calmodulin dependent protein kinase II (CaMKII) phosphorylation site, and its phosphorylation status maintains the basic activity of the channel. However, the role of CaV1.2 phosphorylation at Thr1604 in myocardial hypertrophy is incompletely understood. Isoproterenol (ISO) was used to induce cardiomyocyte hypertrophy, and autocamtide-2-related inhibitory peptide (AIP) was added as a treatment. Rats in a myocardial hypertrophy development model were subcutaneously injected with ISO for two or three weeks. The heart and left ventricle weights, each of which were normalized to the body weight and cross-sectional area of the myocardial cells, were used to describe the degree of hypertrophy. Protein expression levels were detected by western blotting. CaMKII-induced CaV1.2 (Thr1604) phosphorylation (p-CaV1.2) was assayed by coimmunoprecipitation. The results showed that CaMKII, HDAC, MEF2 C, and atrial natriuretic peptide (ANP) expression was increased in the ISO group and downregulated by AIP treatment in vitro. There was no difference in the expression of these proteins between the ISO 2-week group and the ISO 3-week group in vivo. CaV1.2 channel expression did not change, but p-CaV1.2 expression was increased after ISO stimulation and decreased by AIP. In the rat model, p-CaV1.2 levels and CaMKII activity were much higher in the ISO 3-week group than in the ISO 2-week group. CaMKII-induced CaV1.2 channel phosphorylation at residue Thr1604 may be one of the key features of myocardial hypertrophy and disease development.Abbreviations: CaMKII: Ca2+/calmodulin dependent protein kinase II; p-CaMKII: autophosphorylated Ca2+/calmodulin dependent protein kinase II; CaM: calmodulin; AIP: autocamtide-2-related inhibitory peptide; ECC: excitation-contraction coupling; ISO: isoproterenol; BW: body weight; HW: heart weight; LVW: left ventricle weight; HDAC: histone deacetylase; p-HDAC: phosphorylated histone deacetylase; MEF2C: myocyte-specific enhancer factor 2C; ANP: atrial natriuretic peptide; PKC: protein kinase C.

5.
Med Sci Monit ; 26: e921754, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31988273

RESUMO

BACKGROUND Posterior vertebrectomy with bilateral pedicle approach (BPA) is widely applied in lumber burst fracture (LBF). However, some disadvantages exist, such as a prolonged operation time, extensive soft tissue injury, and excessive blood loss. Posterior vertebrectomy with unilateral pedicle approach (UPA) is a novel technique for decompression of spinal canal. Thus, we explored the potential of UPA to achieve better outcomes than BPA. MATERIAL AND METHODS Of 47 patients who underwent posterior vertebrectomy for LBF, 23 patients were treated with UPA and 24 patients were treated with BPA. Clinical and radiographical outcomes were assessed with a follow-up of more than 24 months. Patients were evaluated before and after surgery according to the following parameter: duration of operation (DO), blood loss volume (BLV), the kyphotic angle (KA), the ratio of the height of anterior vertebral edge, the ratio of the sagittal injury, visual analog scale (VAS), Oswestry Disability Index (ODI), and Frankel scores. RESULTS The follow-up time ranged from 24 to 37 months (average 26.4 months). The UPA group had significantly decreased DO and BLV (P<0.05). The 2 cohorts showed similar performance at 6 months (P>0.05), 12 months (P>0.05), and 24 months (P>0.05) post-surgery, in terms of parameters including KA, the ratio of the vertebral anterior, the ratio of sagittal damage, Frankel scores, ODI, and VAS. CONCLUSIONS UPA and BPA had a similar clinical performance for LBF. However, the shorter DO and lower BLV achieved in the UPA cohort suggested UPA is a better alternative for LBF.

6.
Andrology ; 2020 Jan 18.
Artigo em Inglês | MEDLINE | ID: mdl-31955524

RESUMO

BACKGROUND: Diabetes mellitus-induced erectile dysfunction is a common diabetic complication, and new therapeutics and the pathogenesis of diabetes mellitus-induced erectile dysfunction need to be investigated. OBJECTIVES: The aim was to investigate the pathogenesis of diabetes mellitus-induced erectile dysfunction and the pharmacological mechanism of simvastatin treatment in diabetes mellitus-induced erectile dysfunction model rats. MATERIALS AND METHODS: A total of 86 male Sprague Dawley rats aged 8 weeks old were used in this study. The rats were divided into three groups: control (normal), diabetes mellitus-induced erectile dysfunction (streptozotocin-injected), and diabetes mellitus-induced erectile dysfunction + simvastatin (sim). Each group was subdivided into two subgroups for in vitro and in vivo analyses. A bioinformatics method was used to detect differences in gene expression in the corpus cavernosum between normal and diabetes mellitus-induced erectile dysfunction rats. Erectile function was measured by a cavernous nerve electrostimulation test. Corpus cavernosum fibrosis was assessed by Masson staining and Western blotting. Immunofluorescence and Western blotting were performed to explore the differential expression of autophagy-related genes and the AMPK-SKP2-CARM1 pathway genes in rat cavernous smooth muscle cells and the corpus cavernosum. The autophagosomes of the corpus cavernosum tissue were observed by transmission electron microscopy. RESULTS: Autophagy-related genes and pathways (the AMPK and FoxO pathway) were identified by bioinformatics analysis and confirmed at the protein level. Simvastatin, an AMPK agonist, was used to treat diabetes mellitus-induced erectile dysfunction rats for 8 weeks, demonstrating that erectile function was improved for 80.5% (P < .05) of rats. Corpus cavernosum fibrosis was alleviated (P < .05), and autophagy was further enhanced (P < .05); these results might be partially caused by AMPK-SKP2-CARM1 pathway activation (P < .05). DISCUSSION AND CONCLUSION: Simvastatin could enhance protective autophagy by activating the AMPK-SKP2-CARM1 pathway to improve erectile function in diabetes mellitus-induced erectile dysfunction rats.

7.
Oxid Med Cell Longev ; 2019: 4764071, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31885796

RESUMO

Excessive compression, the main cause of intervertebral disc (IVD) degeneration, affected endogenous repair of the intervertebral disc. Pioglitazone (PGZ) is the agonist of peroxisome proliferator-activated receptor γ, which has been widely used in the treatment of diabetes mellitus. The present study aim at investigating whether pioglitazone has protective effects on compression-mediated cell apoptosis in nucleus pulposus mesenchymal stem cells (NP-MSCs) and further exploring the possible underlying mechanism. Our results indicated that the isolated cells satisfied the criteria of MSC stated by the International Society for Cellular Therapy. Besides, our research revealed that pioglitazone could protect cell viability, cell proliferation of NP-MSCs and alleviated the toxic effects caused by compression. The actin stress fibers was suppressed obviously under compression, and pioglitazone alleviated the adverse outcomes. Pioglitazone exerted protective effects on compression-induced NP-MSCs apoptosis according to annexin V/PI double-staining and TUNEL assays. Pioglitazone suppressed compression-induced NP-MSCs oxidative stress, including decreasing compression-induced overproduction of reactive oxygen species (ROS) and malondialdehyde (MDA), and alleviated compression-induced mitochondrial membrane potential (MMP) decrease. Ultrastructure collapse of the mitochondria exhibited a notable improvement by pioglitazone in compression-induced NP-MSCs according to transmission electron microscopy (TEM). Furthermore, the molecular results showed that pioglitazone significantly decreased the expression of apoptosis-associated proteins, including cyto.cytochrome c, Bax, cleaved caspase-9, and cleaved caspase-3, and promoted Bcl-2 expression. These results indicated that pioglitazone alleviated compression-induced NP-MSCs apoptosis by suppressing oxidative stress and the mitochondrial apoptosis pathway, which may be a valuable candidate for the treatment of IVD degeneration.

8.
Medicine (Baltimore) ; 98(38): e17270, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31568005

RESUMO

BACKGROUND: Atrial septal defect (ASD) is one of the most common congenital heart diseases, with an average of 1.64 per 1000 newborns with the ASD. Empirical studies suggest that surgery should be performed early in the presence of right atrium and or right ventricular enlargement, even for asymptomatic patients. Many surgical procedures can be used to treat ASD. But which method is the best choice remains unclear. This study aims to compare the efficacy and safety of standard median sternotomy, right minithoracotomy, totally thoracoscopic surgery, percutaneous closure, transcutaneous by echocardiography, and transcutaneous by radiotherapy for ASDs in children using Bayesian network meta-analysis (NMA). METHODS: We will perform a comprehensive literature search using PubMed, EMBASE.com, the Cochrane Library, Web of Science, and Chinese Biomedical Literature Database to identify relevant studies from inception to April 2019. Randomized controlled trials, prospective or retrospective cohort studies that reported the efficacy and safety of surgical procedures for the treatment of atrial septal defects will be included. Risk of bias of the included randomized controlled trials and prospective or retrospective cohort studies will be evaluated according to the Cochrane Handbook 5.1.0 and the risk of bias in non-randomized studies of interventions, respectively. A Bayesian NMA will be performed using R 3.4.1. RESULTS: The results of this NMA will be submitted to a peer-reviewed journal for publication. CONCLUSION: This NMA will summarize the direct and indirect evidence to assess the efficacy and safety of different surgical procedures for the treatment of ASDs. ETHICS AND DISSEMINATION: Ethics approval and patient consent are not required as this study is a network meta-analysis based on published trials. PROSPERO REGISTRATION NUMBER: CRD42019130902.


Assuntos
Comunicação Interatrial/cirurgia , Esternotomia , Toracoscopia , Toracotomia , Técnicas de Fechamento de Ferimentos , Criança , Humanos
9.
Cell Death Dis ; 10(10): 751, 2019 Oct 03.
Artigo em Inglês | MEDLINE | ID: mdl-31582722

RESUMO

The molecular mechanism of intervertebral disc degeneration (IVDD) remains unclear. This study aimed to investigate the role of circular RNAs (circRNAs) in the pathogenesis of IVDD. We sued nucleus pulposus (NP) tissues of patients, tert-butyl hydroperoxide (TBHP) stimulated NP cells (NPCs), and IVDD rat model to explore the interaction between circERCC2 and miR-182-5p/SIRT1 axis. The results showed that downregulation of circERCC2 increased the level of miR-182-5p and decreased the level of SIRT1 in degenerative NP tissues in vivo as well as in TBHP-stimulated NPCs in vitro. Treatment of SIRT1-si activated apoptosis and inhibited mitophagy. Moreover, miR-182-5p-si could regulate the mitophagy and the apoptosis of NPCs by targeting SIRT1. The effects of circERCC2 on NPCs and IVDD rat model were mediated by miR-182-5p/SIRT1 axis. In conclusion, this study provides the first evidence that circERCC2 could ameliorate IVDD through miR-182-5p/SIRT1 axis by activating mitophagy and inhibiting apoptosis, and suggests that circERCC2 is a potentially effective therapeutic target for IVDD.

10.
Peptides ; 121: 170122, 2019 11.
Artigo em Inglês | MEDLINE | ID: mdl-31386895

RESUMO

Growth hormone secretagogues (GHS) have been proved to exert protective effects on the cardiovascular system, while their potential beneficial effects on macrophages in atherosclerosis (AS) are rarely been clarified. This study aimed to demonstrate whether hexarelin, a synthetic peptidyl GHS, can suppress AS progression via regulating the function of macrophages. AS was induced by chronic (3 months) feeding with high lipid diet in ApoE-/- mice. Mice were treated either with hexarelin (100 µg/kg s.c., q.d. for 3 months) (AS + Hex group) or saline (AS group). Age-matched C57BL/6 J mice were used as normal controls. AS and related signaling molecules in aortic tissues and RAW264.7 macrophages were identified with variant methods including histological staining, ELISA, western blotting, confocal microscopy and flow cytometry. AS significantly developed in ApoE-/- mice fed with high lipids diet. Hexarelin decreased serum TC, TG and LDL-c, increased serum HDL-c and attenuated the formation of atherosclerotic plaques and neointima compared with the AS group. Hexarelin decreased the aortic expressions of CD68 and LOX-1 which were elevated in the AS group. Hexarelin increased GHSR expression, suppressed ox-LDL uptake and LOX-1 expression and inhibited nuclear factor-kappa B (NF-κB) activation both in the aorta of ApoE-/- mice and in RAW264.7 macrophages. We conclude that hexarelin effectively attenuates AS progression in ApoE-/- mice by modulating circulatory lipids profile and inhibiting macrophage ox-LDL uptake via suppressing the LOX-1-NF-κB signaling pathway. The study supports the perspective of hexarelin as an anti-AS drug.

11.
Environ Res ; 176: 108523, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31203048

RESUMO

BACKGROUND: In the past three decades, the incidence rate of notified leptospirosis cases in China have steeply declined and are now circumscribed to discrete areas in the country. Previous research showed that climate and environmental variation may play an important role in leptospirosis transmission. However, quantitative associations between climate, environmental factors and leptospirosis in the high-risk areas in China, is still poorly understood. OBJECTIVE: To quantify the temporal effects of climate and remotely-sensed physical environmental factors on human leptospirosis in the high-risk counties in China. METHODS: Time series seasonal decomposition was performed to explore the seasonality pattern of leptospirosis incidence in Mengla County, Yunnan and Yilong County, Sichuan for the period 2006-2016. Time series cross-correlation analysis was carried out to examine lagged effects of rainfall, relative humidity, normalized difference vegetation index (NDVI), modified normalized difference water index (MNDWI) and land surface temperature (LST) on leptospirosis. The associations of climatic and physical environment factors with leptospirosis in each county were assessed by using a generalized linear regression model with negative binomial link, adjusted by seasonal components. RESULTS: Leptospirosis incidence in both counties showed strong and unique annual seasonality. Our results show that in Mengla County leptospirosis notifications exhibits a bi-modal temporal pattern while in Yilong County it follows a typical single epidemic curve. After adjusting for seasonality, the final best-fitting model for Mengla County indicated that leptospirosis notifications were significantly associated with present LST values (incidence rate ratio, IRR = 0.857, 95% confidence interval (CI):0.729-0.929) and rainfall at a lag of 6-months (IRR = 0.989; 95% CI: 0.985-0.993). The incidence of leptospirosis in Yilong was associated with rainfall at 1-month lag (IRR = 1.013, 95% CI: 1.003-1.023), LST (3-months lag) (IRR = 1.193, 95% CI: 1.095-1.301), and MNDWI (5-months lag) (IRR = 7.960, 95% CI: 1.241-47.66). CONCLUSIONS: Our study identified lagged effects between leptospirosis incidence and climate and remotely-sensed environmental factors in the two most endemic counties in China. Rainfall in combination with satellite derived physical environment factors provided better insight of the local epidemiology as well as good predictors for leptospirosis outbreak in both counties. This would also be an avenue for the development of leptospirosis early warning systems to support leptospirosis control in China.

12.
Front Plant Sci ; 10: 581, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31130978

RESUMO

Phytolith-occluded carbon (PhytOC) can be preserved in soils or sediments for thousands of years and might be a promising potential mechanism for long-term terrestrial carbon (C) sequestration. As the principal pathway for the return of organic matters to soils, the forest litter layers make a considerable contribution to terrestrial C sequestration. Although previous studies have estimated the phytolith production fluxes in the above-ground vegetations of various terrestrial ecosystems, the storages of phytoliths and PhytOC in litter layers have not been thoroughly investigated, especially in forest ecosystems. Using analytical data of silica, phytoliths, return fluxes and storages of forest litter, this study estimated the phytolith and PhytOC storages in litter layers in different forest types in southern China. The results indicated that the total phytolith storage in forest litter layers in southern China was 24.34 ± 8.72 Tg. Among the different forest types, the phytolith storage in bamboo forest litter layers (15.40 ± 3.40 Tg) was much higher than that in other forests. At the same time, the total PhytOC storage reached up to 2.68 ± 0.96 Tg CO2 in forest litter layers in southern China, of which approximately 60% was contributed by bamboo forest litter layers. Based on the current litter turnover time of different forest types in southern China, a total of 1.01 ± 0.32 Tg of PhytOC per year would be released into soil profiles as a stable C pool during litter decomposition, which would make an important contribution to the global terrestrial long-term biogeochemical C sink. Therefore, the important role of PhytOC storage in forest litter layers should be taken into account in evaluating long-term forest C budgets.

13.
Exp Ther Med ; 17(5): 4183-4189, 2019 May.
Artigo em Inglês | MEDLINE | ID: mdl-31007749

RESUMO

The aim of the present study was to explore the indications for and safety of orthotopic liver transplantation for polycystic liver disease (PLD). Orthotopic liver transplantation in 11 patients with PLD between May 2004 and September 2013 was retrospectively analyzed. Patient epidemiological, clinical and follow-up data were collected. The survival rate was calculated using the Kaplan-Meier method. Over the 10-year period, 11 patients received orthotopic liver transplantation (n=9) and combined liver-kidney transplantation (n=2) for PLD. The recipients' median age was 56 years [(interquartile range (IQR), 52-57 years], and 7 of the patients (63.6%) were classified as having Gigot type II PLD and 4 (36.4%) as having Gigot type III. A total of 8 (72.7%) patients had a severely decreased quality of life (Eastern Cooperative Oncology Group performance status score, ≥3). Only 3 cases (27.3%) were of Class C stage. The mean hospitalization duration was 45.4±15.3 days and the mean length of stay at the intensive care unit was 4.1±1.9 days. The peri-operative mortality was 18.2% and the morbidity was 54.5%. The median follow-up period was 111 months (IQR, 33-132 months). A total of 2 patients died of severe complications after combined liver-kidney transplantation. Furthermore, 1 patient died of ischemia cholangitis during the follow-up period. The actuarial 1-, 5- and 10-year survival rate during the follow-up period was 81.8, 81.8 and 65.5%, respectively. The mean physical component summary score was 87.1±6.9 and the mean mental component summary score was 81.5±6.4. In conclusion, liver transplantation is the only curative procedure for PLD, and the present study indicated that it is relatively and safe and leads to good long-term prognosis and high quality of life. Based on our experience and results, liver transplantation is a primary option for cases of PLD with progressive or advanced symptomatic disease where previous other forms of therapy to palliate symptoms have been insufficient.

14.
J Appl Toxicol ; 39(8): 1096-1107, 2019 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-30907447

RESUMO

Glyphosate-based herbicides have been used worldwide for decades and have been suggested to induce nephrotoxicity, but the underlying mechanism is not yet clear. In this study, we treated a human renal proximal tubule cell line (HK-2) with glyphosate for 24 hours at concentrations of 0, 20, 40 and 60 µm. Glyphosate was found to reduce cell viability and induce apoptosis and oxidative stress in a dose-dependent manner. Because the chemical structures of glyphosate and those of its metabolite AMPA are similar to glycine and glutamate, which are agonists of the N-methyl-d-aspartate receptor (NMDAR), we investigated the potential role of the NMDAR pathway in mediating the proapoptotic effect of glyphosate on proximal tubule cells. We found that NMDAR1 expression, as well as intracellular Ca2+ ([Ca2+ ]i ) and reactive oxygen species (ROS) levels, increased after glyphosate treatment. Blocking NMDAR attenuated glyphosate-induced upregulation of [Ca2+ ]i and ROS levels as well as apoptosis. Meanwhile, inhibition of [Ca2+ ]i reduced glyphosate-induced ROS and apoptosis, and inhibition of ROS alleviated glyphosate-induced apoptosis. In mice exposed to 400 mg/kg glyphosate, the urine low molecular weight protein levels started to increase from day 7. Upregulation of apoptosis and NMDAR1 expression in renal proximal tubule epithelium and an imbalance of oxidant and antioxidative products were observed. These results strongly suggest that activation of the NMDAR1 pathway, together with its downstream [Ca2+ ]i and oxidative stress, is involved in glyphosate-induced renal proximal tubule epithelium apoptosis.

15.
Am J Chin Med ; 47(2): 457-476, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-30834778

RESUMO

Ligustroflavone is one major compound contained in active fraction from Fructus Ligustri Lucidi (the fruit of Ligustrum lucidum), which could regulate parathyroid hormone (PTH) levels and improve calcium balance by acting on calcium-sensing receptors (CaSR). This study aimed to explore the potency of ligustroflavone as a CaSR antagonist and its protective effects against diabetic osteoporosis in mice. LF interacted well with the allosteric site of CaSR shown by molecular docking analysis, increased PTH release of primary parathyroid gland cells and suppressed extracellular calcium influx in HEK-293 cells. The serum level of PTH attained peak value at 2 h and maintained high during the period of 1 h and 3 h than that before treatment in mice after a single dose of LF. Treatment of diabetic mice with LF inhibited the decrease in calcium level of serum and bone and the enhancement in urinary calcium excretion as well as elevated circulating PTH levels. Trabecular bone mineral density and micro-architecture were markedly improved in diabetic mice upon to LF treatment for 8 weeks. LF reduced CaSR mRNA and protein expression in the kidneys of diabetic mice. Taken together, ligustroflavone could transiently increase PTH level and regulate calcium metabolism as well as prevent osteoporosis in diabetic mice, suggesting that ligustroflavone might be an effective antagonist on CaSR.


Assuntos
Apigenina/farmacologia , Complicações do Diabetes/complicações , Glicosídeos/farmacologia , Ligustrum/química , Osteoporose/etiologia , Osteoporose/prevenção & controle , Receptores de Detecção de Cálcio/antagonistas & inibidores , Animais , Apigenina/administração & dosagem , Apigenina/isolamento & purificação , Densidade Óssea/efeitos dos fármacos , Cálcio/metabolismo , Osso Esponjoso/metabolismo , Células Cultivadas , Expressão Gênica/efeitos dos fármacos , Glicosídeos/administração & dosagem , Glicosídeos/isolamento & purificação , Células HEK293 , Humanos , Rim/metabolismo , Masculino , Camundongos Endogâmicos C57BL , Glândulas Paratireoides/citologia , Glândulas Paratireoides/metabolismo , Hormônio Paratireóideo/metabolismo , Receptores de Detecção de Cálcio/genética , Receptores de Detecção de Cálcio/metabolismo , Fatores de Tempo
16.
Arch Toxicol ; 93(4): 965-986, 2019 04.
Artigo em Inglês | MEDLINE | ID: mdl-30796460

RESUMO

Cadmium (Cd), an occupational and environmental pollutant, induces nephrotoxicity by primarily damaging renal proximal tubular cells. In this study, we hypothesized that pyroptosis, a caspase-1-dependent inflammatory programmed cell death mechanism, mediates Cd-induced nephrotoxicity. Human proximal tubular epithelial HK-2 cells were treated with 0-10 µM CdCl2 for 48 h. We found that Cd dose-dependently caused cytotoxicity, which correlated with activation of the NLRP3 inflammasome, increases in the expression and secretion of pro-inflammatory cytokines and upregulation of pyroptosis-related genes in HK-2 cells or/and in kidneys of Cd-treated mice. These effects were significantly abrogated by inhibiting caspase-1 activity with inhibitor YVAD or silencing NLRP3 with siRNA in vitro, suggesting that Cd induces caspase-1- and NLRP3-inflammasome-dependent pyroptosis. Moreover, Cd treatment also activated three branches (ATF6, PERK and IRE-1α) of endoplasmic reticulum stress. Selective inhibition of the IRE-1α/XBP-1s branch by a pharmacological inhibitor STF-083010 or by genetic silencing of XBP-1 significantly attenuated Cd-induced NLRP3 inflammasome activation and pyroptosis. Mechanistically, Cd suppressed deacetylase Sirtuin-1 (SIRT-1) protein expression and activity leading to decrease in physical binding with XBP-1s protein, and thus the accumulation of acetylated XBP-1s levels. Activation of SIRT1 using a pharmacological agonist resveratrol or genetic SIRT1 overexpression significantly abolished Cd-induced activation of the IRE-1α/XBP-1s pathway and the NRLP3 inflammasome as well as pyroptosis, which were counteracted by co-overexpression of both SIRT1 and XBP-1s. Collectively, our findings indicate that SIRT1 activity protects against Cd-induced pyroptosis through deacetylating XBP-1s, and thus inhibiting the IRE-1α/XBP-1s pathway in HK-2 cells. These results provide a novel mechanism for Cd-induced nephrotoxicity.

17.
Sensors (Basel) ; 19(2)2019 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-30669530

RESUMO

Monitoring traffic states from the road is arousing increasing concern from traffic management authorities. To complete the picture of real-time traffic states, novel data sources have been introduced and studied in the transportation community for decades. This paper explores a supplementary and novel data source, Wi-Fi signal data, to extract traffic information through a well-designed system. An IoT (Internet of Things)-based Wi-Fi signal detector consisting of a solar power module, high capacity module, and IoT functioning module was constructed to collect Wi-Fi signal data. On this basis, a filtration and mining algorithm was developed to extract traffic state information (i.e., travel time, traffic volume, and speed). In addition, to evaluate the performance of the proposed system, a practical field test was conducted through the use of the system to monitor traffic states of a major corridor in China. The comparison results with loop data indicated that traffic speed obtained from the system was consistent with that collected from loop detectors. The mean absolute percentage error reached 3.55% in the best case. Furthermore, the preliminary analysis proved the existence of the highly correlated relationship between volumes obtained from the system and from loop detectors. The evaluation confirmed the feasibility of applying Wi-Fi signal data to acquisition of traffic information, indicating that Wi-Fi signal data could be used as a supplementary data source for monitoring real-time traffic states.

18.
Spine (Phila Pa 1976) ; 44(10): E585-E595, 2019 May 15.
Artigo em Inglês | MEDLINE | ID: mdl-30407277

RESUMO

STUDY DESIGN: Experimental study. OBJECTIVE: The purposes of this study were to evaluate whether advanced glycation end-products (AGEs) induce annulus fibrosus (AF) cell apoptosis and further to explore the mechanism by which this process occurs. SUMMARY OF BACKGROUND DATA: Recent studies revealed that AGEs accumulation is considered an important factor in diabetic intervertebral disc (IVD) degeneration. However, the effect of AGEs on intervertebral disc remains unclear. METHODS: AF cells were treated with various concentrations of AGEs for 3 days. Cell viability and cell proliferation were measured by Cell Counting Kit-8 (CCK-8) and 5-ethynyl-2'-deoxyuridine (EdU) incorporation assays, respectively. Cell apoptosis was examined by Annexin V/PI apoptosis detection kit and Hoechst 33342. The expression of apoptosis-related proteins, including Bax, Bcl-2, cytochrome c, caspase-3, and caspase-9, was detected by western blotting. In addition, Bax and Bcl-2 mRNA expression levels were detected by real-time PCR (RT-PCR). Mitochondrial membrane potential (MMP) and intracellular reactive oxygen species (ROS) production of AF cell were examined by 5,5',6,6' -Tetrachloro-1,1',3,3'- tetraethyl-imidacarbocyanine iodide (JC-1) staining and 2',7'-Dichlorodihydrofluorescein diacetate (DCFH-DA) fluorescent probes, respectively. RESULTS: Our results indicated that AGEs had inhibitory effects on AF cell proliferation and induced AF cell apoptosis. The molecular data showed that AGEs significantly up-regulated Bax expression and inhibited Bcl-2 expression. In addition, AGEs increased the release of cytochrome c into the cytosol and enhanced caspase-9 and caspase-3 activation. Moreover, treatment with AGEs resulted in a decrease in MMP and the accumulation of intracellular ROS in AF cells. The antioxidant N-acetyl-L-cysteine (NAC) significantly reversed AGE-induced MMP decrease and AF cell apoptosis. CONCLUSION: These results suggested that AGEs induce rabbit AF cell apoptosis and mitochondrial pathway may be involved in AGEs-mediated cell apoptosis, which may provide a theoretical basis for diabetic IVD degeneration. LEVEL OF EVIDENCE: N/A.


Assuntos
Anel Fibroso , Apoptose/efeitos dos fármacos , Produtos Finais de Glicação Avançada/farmacologia , Mitocôndrias/metabolismo , Animais , Anel Fibroso/citologia , Anel Fibroso/efeitos dos fármacos , Apoptose/fisiologia , Humanos , Mitocôndrias/efeitos dos fármacos , Coelhos , Transdução de Sinais/efeitos dos fármacos
19.
Nanotechnology ; 30(8): 085708, 2019 Feb 22.
Artigo em Inglês | MEDLINE | ID: mdl-30523942

RESUMO

Au doped ZnO nanocomposite films on TiO2 seeding layer (AuZ/T) were fabricated by hydrothermal processing and their photocatalytic performance was investigated. It could be found that the AuZ/T with micrometer(µm)-sized, lying ZnO bulks revealed optimal photocatalytic performance toward methyl orange under simulated sunlight, whose apparent degradation rate constant K app of 1.31 was about 20% higher compared to that of ZnO/TiO2 and 3 times higher compared to that of ZnO. The Au nanoparticles, TiO2 seeding layer and hydrothermal processing time imposed vital influence on the morphology of ZnO nanostructures, which played key roles in the formation of ZnO/TiO2 heterojunction and charge transfer (CT) inside it, as demonstrated by kinetics of transient photoluminescence (PL) decaying. The incorporation of Au nanoparticles not only induced the variations of ZnO crystallinity and reduction of ZnO band gap (E g), but also generated the Schottky heterojunction of metal-semiconductor, which would be beneficial to the CT inside nanocomposite films and separation of photo-generated electron-hole pairs, as verified by the remarkable PL suppression. The mechanism responsible for photocatalysis enhancement, which was resulted from the hybrid effects of Au nanoparticles and the ZnO morphology was discussed in details.

20.
Sci Total Environ ; 650(Pt 1): 97-104, 2019 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-30195134

RESUMO

Previous studies demonstrated that finer soil particles have smaller rates of CO2 emission but larger Q10 values (the proportionate increase in the rate for a warming of 10 °C) than coarser particles. However, it has not been tested whether there is a regular pattern for rates and Q10 for N2O emission (net production) across soil particle size fractions, considering the known positive correlation between soil CO2 and N2O emissions. A short-term incubation study with different soil particle fractions was conducted for soils from a grassland, a forest, an upland (including organic manure (OM) and chemical nitrogen, phosphorus, and potassium fertilizers (NPK) treatments), and a paddy (including manure plus chemical fertilizer (MNPK) and NPK treatments) under a series of increasing and decreasing temperatures between 5 °C and 30 °C with 5 °C intervals. For all the soils, net N2O production per unit mass of soil N was smaller from the silt (2-50 µm) fraction than from the sand (>50 µm) and clay (<2 µm) fractions. In paddy soils, Q10 for net N2O production was highest from the clay fraction. In contrast, Q10 was highest in the sand fraction for the grassland soil. In the upland and paddy soils, the rates of net N2O production were higher in OM or MNPK treatment than in their corresponding NPK treatment, but Q10 values were similar between the manure and NPK treatments. The net N2O production rates positively correlated with CO2 emission across all soil samples, and this was also the case for their Q10 values. Q10 values for net N2O production averaged 8% lower than those for CO2 emissions. In conclusion, the net N2O production rates appear to be the smallest from the silt fraction.

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