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1.
Artigo em Inglês | MEDLINE | ID: mdl-32004424

RESUMO

OBJECTIVE: Little is known regarding what difference in functional performance measures are significant in individuals with chronic medical disease. We examined the important differences in gait speed in adults with radiographic knee osteoarthritis. METHODS: Functional performance was measured by gait speed using 20-meter and 400-meter walk tests performed at self-selected usual pace among adults with radiographic knee osteoarthritis participating in the Osteoarthritis Initiative at baseline and two years later. Both distribution-based methods and anchor-based methods used to calculate the important differences in gait speed. Anchor-based methods used chair stand rate and self-reported function to estimate gait speed differences related to physical function. RESULTS: We included 2527 participants with radiographic knee osteoarthritis. Distribution-based important difference estimates for 20-meter walk ranged from 4.1 to 6.4 meters/minute and 400-meter walk estimates ranged from 2.9 to 6.5 meters/minute. Prevalent (cross-sectional) anchor-based estimates for 20-meter walk ranged from 5.4 to 6.9 meters/minute and for 400-meter walk ranged from 3.0 to 6.9 meters/minute. Longitudinal anchor-based estimates were deemed unreliable. Combining distribution-based with prevalent anchor-based methods showed an important gait speed difference for 20-meter walk is between 4.1 and 6.9 meters/minute and for 400-meter walk is between 2.9 and 6.9 meters/minute. CONCLUSION: Our results found the important difference in gait speed for 20-meter walk and 400-meter walk are consistent with important difference estimates for older adult populations. These findings can provide benchmarks for assessing and understanding functional performance outcomes when comparing exposure groups and can be used in designing future studies targeting adults with radiographic knee osteoarthritis.

2.
Cell Commun Signal ; 18(1): 27, 2020 Feb 17.
Artigo em Inglês | MEDLINE | ID: mdl-32066462

RESUMO

BACKGROUND: Excessive light exposure is a detrimental environmental factor that plays a critical role in the pathogenesis of retinal degeneration. However, the mechanism of light-induced death of retina/photoreceptor cells remains unclear. The mammalian/mechanistic target of rapamycin (mTOR) and Poly (ADP-ribose) polymerase-1 (PARP-1) have become the primary targets for treating many neurodegenerative disorders. The aim of this study was to elucidate the mechanisms underlying light-induced photoreceptor cell death and whether the neuroprotective effects of mTOR and PARP-1 inhibition against death are mediated through apoptosis-inducing factor (AIF). METHODS: Propidium iodide (PI)/Hoechst staining, lentiviral-mediated short hairpin RNA (shRNA), Western blot analysis, cellular fraction separation, plasmid transient transfection, laser confocal microscopy, a mice model, electroretinography (ERG), and hematoxylin-eosin (H & E) staining were employed to explore the mechanisms by which rapamycin/3-Aminobenzamide (3AB) exert neuroprotective effects of mTOR/PARP-1 inhibition in light-injured retinas. RESULTS: A parthanatos-like death mechanism was evaluated in light-injured 661 W cells that are an immortalized photoreceptor-like cell line that exhibit cellular and biochemical feature characteristics of cone photoreceptor cells. The death process featured over-activation of PARP-1 and AIF nuclear translocation. Either PARP-1 or AIF knockdown played a significantly protective role for light-damaged photoreceptors. More importantly, crosstalk was observed between mTOR and PARP-1 signaling and mTOR could have regulated parthanatos via the intermediate factor sirtuin 1 (SIRT1). The parthanatos-like injury was also verified in vivo, wherein either PARP-1 or mTOR inhibition provided significant neuroprotection against light-induced injury, which is evinced by both structural and functional retinal analysis. Overall, these results elucidate the mTOR-regulated parthanatos death mechanism in light-injured photoreceptors/retinas and may facilitate the development of novel neuroprotective therapies for retinal degeneration diseases. CONCLUSIONS: Our results demonstrate that inhibition of the mTOR/PARP-1 axis exerts protective effects on photoreceptors against visible-light-induced parthanatos. These protective effects are conducted by regulating the downstream factors of AIF, while mTOR possibly interacts with PARP-1 via SIRT1 to regulate parthanatos. Video Abstract Schematic diagram of mTOR interacting with PARP-1 to regulate visible light-induced parthanatos. Increased ROS caused by light exposure penetrates the nuclear membrane and causes nuclear DNA strand breaks. PARP-1 detects DNA breaks and synthesizes PAR polymers to initiate the DNA repair system that consumes a large amount of cellular NAD+. Over-production of PAR polymers prompts the release of AIF from the mitochondria and translocation to the nucleus, which leads to parthanatos. Activated mTOR may interact with PARP-1 via SIRT1 to regulate visible light-induced parthanatos.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32023074

RESUMO

Hippocampal network oscillations at gamma frequency band (γ oscillation, 20-80Hz) are synchronized synaptic activities generated by the interactions between the excitatory and inhibitory interneurons, and are associated with higher brain function such as learning and memory. Despite extensive studies about the modulation of intracellular kinases on synaptic transmission and plasticity, little is known about the effects of these kinases on γ oscillations. In this study, we examined the effects of several critical intracellular kinases such as cyclic-AMP-dependent protein kinase (PKA), protein protein kinase B (PKB)/Akt, protein kinase C (PKC), extracellular-regulated protein kinases (ERK) and AMP-activated protein kinase (AMPK), known to regulate synaptic transmission, on hippocam pal γ oscillations in vitro. We found that AMPK inhibitor but not PKA, PKC or ERK inhibitor, strongly enhanced the power of γ oscillation (γ power) and that Akt inhibitor weakly increased γ power. Western blot analysis confirmed that AMPK inhibitor reduced the expression of p-AMPK but not total AMPK. By using slice whole-cell voltage clamp technique, we found that AMPK inhibitor increased the frequency but not amplitude of spontaneous inhibitory postsynaptic currents (sIPSC) and had no effect on either frequency or amplitude of spontaneous excitatory postsynaptic currents (sEPSC). Therefore, AMPK activation negatively modulates hippocampal γ oscillation via modulation of the inhibitory neurons.

4.
Life Sci ; : 117360, 2020 Jan 27.
Artigo em Inglês | MEDLINE | ID: mdl-32001269

RESUMO

AIMS: Progesterone receptor membrane component 1 (PGRMC1) has been reported to mediate the neuroprotective effect of progesterone, but the exact mechanism has not been elucidated. Therefore, the purpose of this study was to investigate the signalling pathway downstream of PGRMC1 in progesterone-induced neuroprotection. Recognition of the mechanism of progesterone opens novel perspectives for the treatment of diseases of the nervous system. MAIN METHODS: The PGRMC1 protein level was knocked down in rat primary cortical neurons, and Aß25-35 was used to establish an Alzheimer's disease cell model. The neuroprotective effect of progesterone was assessed by Hoechst 33258 staining and a cell counting kit-8 (CCK-8) assay. Then, proteomic and bioinformatic methods were used to analyse the proteins altered in response to PGRMC1 silencing to identify target proteins and signalling pathways involved in PGRMC1-mediated progesterone-induced neuroprotection. These findings were further verified by using signalling pathway inhibitors and western blotting. KEY FINDINGS: The neuroprotective effect of progesterone was significantly attenuated with PGRMC1 silencing. The expression of many proteins in the Ras signalling pathway was significantly changed in response to PGRMC1 silencing. FTI-277 inhibited progesterone-induced neuroprotection. Progesterone increased the expression of total Ras and Grb2. SIGNIFICANCE: These findings provide new perspectives for understanding the mechanism of and role of PGRMC1 in progesterone-induced neuroprotection. The Ras signalling pathway is the signalling pathway downstream of PGRMC1 in the mediation of progesterone-induced neuroprotection.

5.
Artigo em Inglês | MEDLINE | ID: mdl-32013005

RESUMO

To investigate the effect of 1800 MHz electromagnetic radiation (EMR) on apoptosis, we exposed NIH/3T3 cells at 1800 MHz with a specific absorption rate (SAR) of 2 W/kg intermittently for 12, 24, 36, and 48 h. After exposure, Cell Counting Kit-8 (CCK-8) and flow cytometry were used to detect cell viability and apoptosis; the expression of p53, a molecule with the key role in apoptosis, was measured by real-time qPCR, western blot, and immunofluorescence; and images of the structure of the mitochondria, directly reflecting apoptosis, were captured by electron microscopy. The results showed that the viability of cells in the 12, 36, and 48 h exposure groups significantly decreased compared with the sham groups; after 48 h of exposure, the percentage of late apoptotic cells in the exposure group was significantly higher. Real-time qPCR results showed that p53 mRNA in the 48 h exposure group was 1.4-fold of that in the sham group; significant differences of p53 protein fluorescence expression were observed between the exposure groups and the sham groups after 24 h and 48 h. The mitochondrial swelling and vesicular morphology were found in the electron microscopy images after 48 h exposure. These findings demonstrated 1800 MHz, SAR 2 W/kg EMR for 48 h may cause apoptosis in NIH/3T3 cells and that this apoptosis might be attributed to mitochondrial damage and upregulation of p53 expression.

6.
ACS Nano ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32027482

RESUMO

Although emerging evidence suggests that the pathogenesis of Parkinson's disease (PD) is closely related to the aggregation of alpha-synuclein (α-syn) in the midbrain, the clearance of α-syn remains an unmet clinical need. Here, we develop a simple and efficient strategy for fabricating the α-syn nanoscavenger for PD via a reprecipitation self-assembly procedure. The curcumin analogue-based nanoscavenger (NanoCA) is engineered to be capable of a controlled-release property to stimulate nuclear translocation of the major autophagy regulator, transcription factor EB (TFEB), triggering both autophagy and calcium-dependent exosome secretion for the clearance of α-syn. Pretreatment of NanoCA protects cell lines and primary neurons from MPP+-induced neurotoxicity. More importantly, a rapid arousal intranasal delivery system (RA-IDDS) was designed and applied for the brain-targeted delivery of NanoCA, which affords robust neuroprotection against behavioral deficits and promotes clearance of monomer, oligomer, and aggregates of α-syn in the midbrain of an MPTP mouse model of PD. Our findings provide a clinically translatable therapeutic strategy aimed at neuroprotection and disease modification in PD.

7.
Stem Cells Dev ; 2020 Jan 17.
Artigo em Inglês | MEDLINE | ID: mdl-31950873

RESUMO

Mechanically stretched skeletal muscle undergoes dramatic shifts in structure, mass and function. In vitro tensile strain models have demonstrated that myogenic progenitor cells including satellite cells and myoblasts are highly mechanosensitive cells, and respond to mechanical strain in a wide variety of aspects. However, the experimental results from different researchers and labs are not always in support of each other. Moreover, some specific molecules or signaling pathways were reported to play distinct roles in stretched myogenic cells, according to the statements of different studies. The purpose of this review is to integrate the researches conducting in vitro culture of satellite cells or myoblasts and exploring their mechano-responses using in vitro stretching models apparatus. These responses will be categorized into several groups, such as activation, proliferation, myogenic differentiation, cellular damage or apoptosis, properties of plasma membrane, transdifferentiation, reorientation, function, etc. Besides In addition, detailed experimental designs like culturing conditions and straining regimens will be displayed and compared, in order to interprete interpret some contradictory statements in different studies. Furthermore, the currently known interconnections among some mechanosensitive pathways will be pictured to give a better understanding about the complex regulations of myogenic cell responses to mechanical stretch. Hopefully, by summarizing the published studies about mechano-responses of myogenic progenitor cells, future directions and perspectives would be made clearer to researchers in this field.

8.
Mil Med Res ; 7(1): 1, 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31928528

RESUMO

Heat stroke (HS) is a fatal disease caused by thermal damage in the body, and it has a very high mortality rate. In 2015, the People's Liberation Army Professional Committee of Critical Care Medicine published the first expert consensus on HS in China, Expert consensus on standardized diagnosis and treatment for heat stroke. With an increased understanding of HS and new issues that emerged during the HS treatment in China in recent years, the 2015 consensus no longer meet the requirements for HS prevention and treatment. It is necessary to update the consensus to include the latest research evidence and establish a new consensus that has broader coverage, is more practical and is more in line with China's national conditions. This new expert consensus includes new concept of HS, recommendations for laboratory tests and auxiliary examinations, new understanding of diagnosis and differential diagnosis, On-site emergency treatment and In-hospital treatment, translocation of HS patients and prevention of HS.

9.
Parasite ; 27: 1, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31908266

RESUMO

Three cyst-forming Sarcocystis species have been identified in horsemeat; however, there exists considerable confusion concerning their relationships. Here, 74% (34/46) of the examined tissue samples from horses contained sarcocysts based on examination by light microscopy (LM), and the organism was identified as Sarcocystis bertrami based on cyst structure. The S. bertrami cysts were microscopic (up to 6750 µm in length) and exhibited a striated wall with 2.0-5.1 µm villar protrusions (vps) under LM. Transmission electron microscopy (TEM) observations showed that the vps were tightly packed, similar to "type 11c". Four genetic markers (18S, 28S, ITS1 and the mitochondrial cox1 gene) of S. bertrami were sequenced and analyzed. The 28S and ITS1 sequences are the first records for Sarcocystis in horses. The newly obtained sequences of the 18S and cox1 genes both shared the highest similarities with those of S. bertrami and S. fayeri obtained from horses. Phylogenetic analysis based on the 18S, 28S and cox1 sequences revealed that S. bertrami and S. fayeri formed an independent clade within a group comprising Sarcocystis spp. from ruminants and pigs. Therefore, S. bertrami and S. fayeri are considered to represent the same species of Sarcocystis in horses, and S. fayeri is a junior synonym of Sarcocystis bertrami.

10.
J Cell Mol Med ; 2020 Jan 13.
Artigo em Inglês | MEDLINE | ID: mdl-31930653

RESUMO

Cancer is a major health problem worldwide. An increasing number of researchers are studying the diagnosis, therapy and mechanisms underlying the development and progression of cancer. The study of noncoding RNA has attracted a lot of attention in recent years. It was found that frequent alterations of miRNA expression not only have various functions in cancer but also that miRNAs can act as clinical markers of diagnosis, stage and progression of cancer. MiR-212 is an important example of miRNAs involved in cancer. According to recent studies, miR-212 may serve as an oncogene or tumour suppressor by influencing different targets or pathways during the oncogenesis and the development and metastasis of cancer. Its deregulation may serve as a marker for the diagnosis or prognosis of cancer. In addition, it was recently reported that miR-212 was related to the sensitivity or resistance of cancer cells to chemotherapy or radiotherapy. Here, we summarize the current understanding of miR-212 functions in cancer by describing the relevant signalling pathways and targets. The role of miR-212 as a biomarker and its therapeutic potential in cancer is also described. The aim of this review was to identify new methods for the diagnosis and treatment of human cancers.

11.
Cell Stress Chaperones ; 25(1): 163-172, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31898286

RESUMO

α-Mangostin (MAN) is a bioactive compound isolated from the inedible pericarp of a tropical fruit mangosteen (Garcinia mangostana Linn). It exhibits notable therapeutic potentials on lung cancers, but the underlying mechanisms are still largely unknown. This study was designed to further explore the mechanisms involved in cytotoxicity of MAN on A549 cells. Apoptosis and cell cycle distribution were analyzed by flow cytometry methods. The fluorescent probes DCFH-DA and JC-1 were used to assess the intracellular reactive oxidative species (ROS) and mitochondrial membrane potential statuses, respectively. The regulation of MAN on relevant pathways was investigated by immunoblotting assays. The results obtained indicated that MAN caused significant apoptosis and cell cycle arrest in A549 cells, which eventually resulted in inhibition on cell proliferation in vitro. All these phenomena were synchronized with escalated oxidative stress and downregulation of nicotinamide phosphoribosyltransferase/nicotinamide adenine dinucleotide (NAMPT/NAD). Supplementation with nicotinamide mononucleotide (NMN) and N-acetylcysteine (NAC) efficiently eased MAN-induced ROS accumulation, and potently antagonized MAN-elicited apoptosis and cell cycle arrest. The pro-apoptotic effect of MAN was further confirmed by increased expressions of cleaved caspase 3, 6, 7, and 9, and its effect on cell cycle progression was validated by the altered expressions of p-p38, p-p53, CDK4, and cyclin D1. The immunoblotting assays also demonstrated that NAC/NMN effectively restored these molecular changes elicited by MAN treatment. Collectively, this study revealed a unique anti-tumor mechanism of MAN by provoking ROS production through downregulation of NAMPT/NAD signaling and further validated MAN as a potential therapeutic reagent for lung cancer treatment.

12.
Dig Dis Sci ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31960204

RESUMO

BACKGROUND: Long noncoding RNAs (lncRNAs) have been shown to play pivotal role in pathogenesis and prognosis of cancers. Identification of novel clinical biomarkers in advanced stage colorectal cancer (CRC) is warranted. AIMS: To identify potential lncRNAs associated with progression of stage III/IV CRC and illuminate regulatory mechanisms. METHODS: Differentially expressed lncRNAs, mRNAs and miRNAs (DElncRNAs, DEmRNAs, and DEmiRNAs) were extracted between stage III/IV CRC and normal tissues. We used DEGs to construct a ceRNA network and analyzed correlations between key lncRNAs and overall survivals (OS) of stage III/IV CRC patients. Weighted gene co-expression network analysis (WGCNA) was applied to a pivotal lncRNA. We conducted functional enrichment analysis on target genes and constructed lncRNA-TF-mRNA network by overlapping mRNAs co-expressed with the key lncRNA and target genes of transcriptional factors (TFs). RESULTS: A total of 26 DElncRNAs, 398 DEmiRNAs, 2155 DEmRNAs were identified. A ceRNA network was constructed with 16 lncRNAs, 20 miRNAs, and 59 mRNAs, in which MFI2-AS1 exhibited promising diagnostic efficiency. (AUC was 0.938.) MFI2-AS1 was negatively correlated to OS of stage III/IV CRC patients (P value < 0.05). KEGG analysis showed potential mRNA targets of MFI2-AS1 mainly involved in cell cycle and cytokine-cytokine receptor interaction. We identified 17 potential TFs of MFI2-AS1 and built a lncRNA-TF-mRNA network. CONCLUSION: Our study provides novel insights into lncRNAs associated regulatory networks and reveals a promising lncRNA biomarker, MFI2-AS1, as an independent prognostic indicator and potential therapeutic target for CRC.

13.
J Cell Biochem ; 121(3): 2385-2393, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31646666

RESUMO

BACKGROUND: Breast cancer (BC) is a common malignant tumor and its incidence and mortality rates are ranked first among female cancers. So far, there has been no effective biomarkers for BC prognosis. METHODS: The DNA methylation data of BC was downloaded from The Cancer Genome Atlas (TCGA), Gene Expression Omnibus, and Functional ANnoTation of The Mammalian Genome databases. The RNA-Seq data and clinical information of patients were downloaded from TCGA. R packages edgeR and minfi were used for differentially methylated genes (DMGs) screening. Then, the DMGs were collected for gene ontology and Kyoto Encyclopedia of Genes and Genomes analysis by the online tool database for annotation, visualization and integrated discovery (DAVID) and Reactome. Cox regression analysis was used to screen candidate differentially methylated sites (DMSs) for BC prognosis. Logrank test was used to explore the correlation between DMSs and survival time. Correlation analysis was used to investigate the correlation between DNA methylation and gene expression. RESULTS: We identified 276 DMGs which contained 1454 DMSs in those three datasets. Also, six DMGs that contained seven DMSs were identified by Cox regression analysis. Interestingly, their expression levels were negatively correlated with the DNA methylation level and not affected by age, subtypes, or tumor stages. CONCLUSIONS: We proposed that these seven differentially DNA methylation sites can be used as a novel prognostic biomarker for BC area under curve (AUC) = 0.74), which may facilitate research and benefit the clinical treatment of BC.

14.
Cell Signal ; 66: 109436, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31654716

RESUMO

BACKGROUND: Severe acute pancreatitis (SAP) is associated with high morbidity and mortality. Bone marrow mesenchymal stem cells (BMSCs) have shown obvious protective effect on SAP. However, little is known about the underlying mechanism. The objective of this study is to unravel the role and regulatory mechanism of miR-181a-5p in BMSCs-mediated pancreatic repair. METHODS: BMSCs were isolated from Sprague-Dawley rats and characterized by flow cytometry and Oil Red O staining. Sodium taurocholate- and caerulein-induced models were used as SAP models in vivo and in vitro, respectively. Pancreatic injury were evaluated by H&E and histopathological analysis, as well as by measuring levels of amylase, lipase and cytokines. qRT-PCR and western blotting were performed to detect the level of miR-181a-5p and the protein levels of PTEN/Akt, respectively. ELISA was conducted to detect the levels of TNF-α, IL-1ß, IL-6, angiopoietin, IL-4, IL-10 and TGF-ß1. The apoptotic rate of AR42J cells was quantitated by concurrent staining with Annexin-V-FITC and PI. RESULTS: BMSCs significantly attenuated pancreatic injury in SAP rats by reducing inflammatory infiltration and necrosis, and this effect was abolished by CXCR4 agonist AMD3100. ADM3100 exhibited more severe pancreatic injury and decreased miR-181a-5p levels in the pancreas and serum compared to SAP group. Overexpression of miR-181a-5p in BMSCs (BMSCs-miR-181a-5p) markedly potentiated the protective effect of BMSCs by reducing histological damage and levels of amylase and lipase. Moreover, BMSCs-miR-181a-5p dramatically reduced levels of angiopoietin, TNF-α, IL-1ß and IL-6, but induced the levels of IL-4 and IL-10. In caerulein-treated AR42J cells, co-culturing of BMSCs-miR-181a-5p alleviated caerulein-induced increase of amylase and lipase, and apoptosis via PTEN/Akt/TGF-ß1 signaling. CONCLUSION: BMSCs alleviate SAP and reduce inflammatory responses and apoptosis by secreting miR-181a-5p to target PTEN/Akt/TGF-ß1 signaling. Hence, BMSCs-miR-181a-5p could serve as potential therapeutic target for SAP.

15.
Ann Rheum Dis ; 79(1): 132-140, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31662318

RESUMO

OBJECTIVES: Diverse evidence including clinical, genetic and microbiome studies support a major role of the gut microbiome in the common immune-mediated arthropathy, ankylosing spondylitis (AS). We set out to (1) further define the key microbial characteristics driving disease, and (2) examine the effects of tumour necrosis factor-inhibitor (TNFi) therapy upon the microbiome. METHODS: The stools from a case-control cohort of 250 Han-Chinese subjects underwent shotgun metagenomic sequencing. All subjects were genotyped using the Illumina CoreExome SNP microarray. RESULTS: Previous reports of gut dysbiosis in AS were reconfirmed and several notable bacterial species and functional categories were differentially abundant. TNFi therapy was correlated with a restoration the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. Enrichment of bacterial peptides homologous to HLA-B27-presented epitopes was observed in the stools of patients with AS, suggesting that either HLA-B27 fails to clear these or that they are involved in driving HLA-B27-associated immune reactions. TNFi therapy largely restored the perturbed microbiome observed in untreated AS cases to that of healthy controls, including several important bacterial species that have been previously associated with AS and other related diseases. TNFi therapy of patients with AS was also associated with a reduction of potentially arthritogenic bacterial peptides, relative to untreated patients. CONCLUSION: These findings emphasise the key role that the gut microbiome plays in driving the pathogenesis of AS and highlight potential therapeutic and/or preventative targets.

16.
Int J Biometeorol ; 64(1): 139-144, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31754771

RESUMO

Limited evidence was seen as the association between fine particulate matter (PM2.5) and physician visits for allergic rhinitis (AR), especially in countries with extreme air pollution exposure. This paper addressed the issues about the association between PM2.5 and daily outpatient visits for AR among individuals residing in Beijing, China. Data on daily outpatient visits for AR obtained from Beijing Medical Claim Data for Employees and daily PM2.5 concentrations available from US embassy reports were linked by date from January 1, 2010, to June 30, 2012. A time-series analysis was conducted with a generalized additive Poisson model to assess the association between PM2.5 and AR, adjusting for daily average temperature, relative humidity, day of the week, calendar time, and public holiday. Totally, 229,685 outpatient visits for AR were included in the analysis. The daily mean (SD) concentration of PM2.5 was 99.5 (75.3) µg/m3 during the study period. We found that a 10-µg/m3 increase in PM2.5 content was associated with a 0.47% (95% CI: 0.39% to 0.55%) increase in the number of outpatient visits on the same day. Furthermore, results from subgroup analyses suggested that the association was consistently significant among the groups of different ages (< 65 years and ≥ 65 years) and gender. However, this study failed to find a statistically significant association in the autumn season but found significant positive associations during the spring and summer seasons (P for interaction < 0.001). This study indicated a possible association between PM2.5 and AR outpatients, which may benefit further researches in studying PM2.5 and its influence on diseases in a real and seriously air-polluted context.


Assuntos
Poluentes Atmosféricos , Poluição do Ar , Rinite Alérgica , Pequim , China , Humanos , Pacientes Ambulatoriais , Material Particulado
17.
Fish Shellfish Immunol ; 97: 571-580, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-31669280

RESUMO

NK-lysins, a type of broad-spectrum antimicrobial peptide (AMP), act as an essential effector of innate defense against microbial attack in higher vertebrates and so in fish. The present study delineates the structural and functional characterization of NK-lysin from yellow catfish (Pelteobagrus fulvidrac) (Pelteobagrus fulvidraco). PfNK-lysin encodes a 153-residue peptide, which displays the hallmark features of other known NK-lysins with the ordered array of six well-conserved cysteine residues and five-exon/four-intron structure. It was found to be ubiquitous in tissues, being detected most abundantly in gill and head kidney. In vivo exposure to stimuli (LPS, PolyI:C, and Edwardsiella ictaluri) induced PfNK-lysin expression in head kidney and spleen. Synthetic PfNK-lysin-derived peptide exhibited in vitro bactericidal potency against both Gram-positive and Gram-negative bacteria, with the highest inhibitory effect on pathogen Edwardsiella ictaluri. Fluorescence microscopy and scanning electron microscopy further confirmed its capacity to cause damage to the bacterial plasma membrane. Taken together, these data suggest that PfNK-lysin might participate in antimicrobial defense of yellow catfish by membrane-disruptive action.

18.
Front Med (Lausanne) ; 6: 271, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31824954

RESUMO

Background: Ankylosing spondylitis (AS) is a rheumatic inflammatory disease with unknown etiology, and fatigue is one of the main systemic symptoms of AS. The aim of the current study was to explore the mechanism of AS-associated fatigue (ASF) from multiple aspects, including neuropsychological changes. Method: A total of 120 AS patients and 78 age- and sex-matched healthy individuals were recruited into the study. Fatigue was assessed by the fatigue item of the Bath Ankylosing Spondylitis Disease Activity Index (BASDAI) and the Multidimensional Assessment of Fatigue (MAF) scale. Anxiety and depression were assessed by the Hospital Anxiety and Depression Scale (HADS). The cortical thickness and subcortical gray matter volume were assessed using a Philips Achieva 3.0 T TX MRI scanner. Result: Of the 120 AS patients, 103 (85.8%) reported varying degrees of fatigue. Among these fatigue cases, 33 (32.0%) were in the severe fatigue group (BASDAI-Fatigue ≥ 5), and 70 patients (68.0%) were considered to be in the mild fatigue group (BASDAI-Fatigue > 0 but <5). The BASDAI, ASDAS-CRP, HAD-A, and HAD-D scores of AS patients in the severe fatigue group were all significantly higher than those of patients in the mild fatigue and non-fatigue groups (all, P < 0.05). The structural equation model suggested that AS activity triggered the occurrence of fatigue by inducing psychological change. Finally, head MRI imaging found that the left thalamus volume in AS patients with severe fatigue was significantly larger than that in non-fatigue AS patients and healthy controls (both, P < 0.05). Conclusion: The study revealed neuropsychological factors involved in fatigue in AS.

19.
Int Ophthalmol ; 2019 Dec 04.
Artigo em Inglês | MEDLINE | ID: mdl-31802371

RESUMO

PURPOSE: To analyze the protective effect of PARP inhibitors on light-damaged retina and explore its possible mechanism from the perspective of ciliopathy. METHODS: A systematic review of the literature was performed to investigate the protection of PARP inhibition on light-damaged cilia. PubMed database was retrieved to find the relevant studies and 119 literatures were involved in the review. RESULTS: In retina, the outer segment of photoreceptor is regarded as a special type of primary cilium, so various retinal diseases actually belong to a type of ciliopathy. The retina is the only central nervous tissue exposed to light, but poly (ADP-ribose) polymerase (PARP), as a nuclear enzyme repairing DNA breaks, is overactivated during the light-induced DNA damage, and is involved in the cell death cascade. Studies show that both ATR and phosphorylated Akt colocalize with cilium and play an important role in regulating ciliary function. PARP may function at ATR or PI3K/Akt signal to exert protective effect on cilia. CONCLUSION: PARP inhibitors may protect the cilia/OS of photoreceptor during light-induced damage, which the possible mechanism may be involved in the activation of ATR and PI3K/Akt signal.

20.
Environ Pollut ; 258: 113673, 2019 Nov 27.
Artigo em Inglês | MEDLINE | ID: mdl-31862581

RESUMO

Endocrine disrupting chemicals (EDCs) are common pollutants in coastal waters. To investigate the estrogen risk of EDCs in the coastal areas of Japan, the Japanese common goby, which is a commonly observed species in these waters, was used as the target fish. Plasma 17ß-estradiol (E2) and vitellogenin (VTG) levels were analyzed and the gonads of fish collected from the Taira River (northern Nagasaki, reference site), Nagasaki Port, and two sites in Tokyo Bay were observed. Abnormal levels (>150 ng/mL, p < 0.05) of plasma VTG and high levels of plasma E2 were detected in the fish from Nagasaki Port and Tokyo Bay, whereas the levels of both were low in the fish from the Taira River. The target EDCs, including natural estrogen [estrone (E1), and E2] and alkylphenols [4-t-octylphenol (4-t-OP), 4-nonylphenol (4-NP), and bisphenol-A (BPA)] in water samples were quantified using gas chromatography tandem mass spectrometry (GC/MS/MS), respectively. It was observed that the E2-equivalent (EEQ) in Nagasaki Port and Tokyo Bay, which was calculated from the actual EDC measurement value, were almost 20- and 150-fold higher, respectively, than that at the reference site (Taira River, 0.021 ng/L). The EEQs mostly comprised natural estrogen in the sampling sites, although there was some influence of alkylphenols. There was an association between the EEQ and the E2 in environmental water, suggesting a high estrogen risk in Japan coastal waters. Moreover, the results indicated that abnormal VTG synthesis was induced by environmental estrogen (EE) pollution in Nagasaki Port and Tokyo Bay.

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