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1.
BMC Cardiovasc Disord ; 20(1): 40, 2020 Jan 30.
Artigo em Inglês | MEDLINE | ID: mdl-32000667

RESUMO

BACKGROUND: Endothelial dysfunction may play a key role in non-obstructive coronary artery atherosclerosis. Our study aimed to evaluate the vascular endothelial function and its influencing factors in patients with non-obstructive coronary artery atherosclerosis. METHODS: A total of 131 consecutive patients with non-obstructive coronary artery atherosclerosis were enrolled. Flow-mediated dilatation (FMD) was measured at baseline and 1-year follow-up. Endothelial progenitor cells (EPCs) were counted by staining the fasting venous blood with antibodies against CD34 and vascular endothelial growth factor receptor 2. RESULTS: Systolic blood pressure, pulse pressure and the levels of HbA1c in participants with baseline FMD < 6% (n = 65) were significantly higher than those with baseline FMD ≥ 6% (n = 66). Baseline FMD was negatively associated with EPC counts (r = - 0.199, P < 0.05) and systolic blood pressure (r = - 0.315, P < 0.01). The 1-year FMD was significantly increased compared to the baseline FMD [(9.31 ± 5.62) % vs (7.31 ± 5.26) %, P < 0.001]. Independent predictors of FMD improvement included elevated EPC counts (OR = 1.104, 95% CI: 1.047-1.165, P < 0.001) and decreased levels of serum creatinine (OR = 0.915, 95% CI: 0.843-0.993, P = 0.034). CONCLUSIONS: Family history of premature cardiovascular diseases, hypertension, elevated systolic pressure, and HbA1c > 6.5% are independent risk factors for endothelial dysfunction in non-obstructive atherosclerotic patients. Elevated peripheral blood EPC counts and decreased levels of serum creatinine are independent predictors of endothelial function improvement.

2.
Cell Commun Signal ; 18(1): 17, 2020 Feb 03.
Artigo em Inglês | MEDLINE | ID: mdl-32014008

RESUMO

BACKGROUND: Esophageal squamous cell cancer (ESCC) is one kind of frequent digestive tumor. The inflammatory environment plays an important role in the tumorigenesis and development of ESCC. Cancer stem cells are a small group of tumor cells with stem cell characteristics, which can potentially hinder the tumor management and treatment. METHODS: ELISA was performed to detect the lipopolysaccharide concentration in cancer tissues. qPCR, Western blot, FACS, Immunohistochemistry, Immunofluorescence and Dot blot were applied to detect target genes expression. CCK-8, Colony-formation, Transwell, Sphere and Xenograft were conducted to investigate the function of cells, influenced by risk factors. The survival curve was drawn with the Kaplan-Meier product limit estimator. Nano-hmC-Seal-seq was utilized to detect the downstream target of TET3. ChIP-qPCR was adopted to demonstrate the transcriptional regulation of stem cell-associated genes by HOXB2. RESULTS: Lipopolysaccharide concentration was significantly up-regulated in ESCC. High concentration of lipopolysaccharide stimulation induced the stemness of ESCC cells. TET3 expression was elevated with lipopolysaccharide stimulation via p38/ERK-MAPK pathway in ESCC and negatively correlated with patients' survival. TET3 induced the stemness of ESCC cells. Nano-hmC-Seal-seq showed that TET3 overexpression led to a significant increase in 5hmC levels of HOXB2 gene region, which was thus identified as the downstream target of TET3. The binding of HOXB2 to NANOG and cMYC was verified by ChIP-qPCR. CONCLUSIONS: Lipopolysaccharide served as a tumor promotor in ESCC by inducing cancer cell stemness through the activation of a LPS-TET3-HOXB2 signaling axis, which might provide a novel therapeutic strategy for ESCC. Video Abstract.

3.
Ann Surg Oncol ; 2020 Feb 10.
Artigo em Inglês | MEDLINE | ID: mdl-32040700

RESUMO

BACKGROUND: This meta-analysis aimed to investigate the value of preoperative sarcopenia in predicting complications after esophagectomy. Clinicopathologic characteristics of sarcopenia patients, which may support sarcopenia management, also were studied. METHODS: This study searched for articles describing an association between sarcopenia and short-term outcomes after esophagectomy using PubMed, EMBASE, and the Cochrane Library. Mantel-Haenszel and inverse variance models were used for the meta-analyses of end points. RESULTS: The meta-analysis included 14 studies comprising a total of 2387 patients. Sarcopenia was significantly associated with advanced age (weighted mean difference [WMD], 3.48; 95% confidence interval [CI], 2.22-4.74), lower body mass index (WMD - 2.22; 95% CI - 2.65 to - 1.79), squamous cell carcinoma (odds ratio [OR], 2.78; 95% CI 1.72-4.47), advanced clinical tumor stage (OR 1.65; 95% CI 1.28-2.15), and neoadjuvant therapy (OR 1.87; 95% CI 1.38-2.53). The sarcopenia patients showed lower preoperative albumin levels (WMD - 0.11; 95% CI - 0.19 to - 0.04) than the nonsarcopenia patients. Sarcopenia was significantly predictive of pneumonia (OR 2.58; 95% CI 1.75-3.81) and overall complications (OR 1.52; 95% CI 1.07-2.15) after esophagectomy. The sarcopenia patients also showed nonsignificant increases in the risks of anastomotic leakage (OR 1.29; 95% CI 0.99-1.67), vocal cord palsy (OR 2.03; 95% CI 0.89-4.64), and major complications (≥ Clavien-Dindo grade III; OR 1.30; 95% CI 0.95-1.79) but not increased operation time, blood loss, or mortality. CONCLUSIONS: Preoperative sarcopenia assessment showed considerable potential for predicting postoperative complications for esophageal cancer patients. To realize this potential, more effective diagnostic criteria and severity classifications for sarcopenia are warranted.

4.
Neuroscience ; 429: 203-212, 2020 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-31962145

RESUMO

Soluble N-ethylmaleimide-sensitive factor attachment protein receptors (SNAREs) have been implicated in the trafficking of postsynaptic glutamate receptors, including N-methyl-d-aspartate (NMDA)-subtype glutamate receptors (NMDARs) that are critical for nociceptive plasticity and behavioral sensitization. However, the components of SNAREs complex involved in spinal nociceptive processing remain largely unknown. Here we found that SNAP25, syntaxin4, VAMP2 and Munc18-1 were localized at postsynaptic sites and formed the complex in the superficial lamina of spinal cord dorsal horn of rats. The complex formation between these SNAREs components were accelerated after intraplantar injection of complete Freund's adjuvant (CFA), pharmacological removal of GABAergic inhibition or activation of NMDAR in intact rats. The increased SNAP25/syntaxin4/VAMP2/Munc18-1 interaction facilitated the surface delivery and synaptic accumulation of NMDAR during inflammatory pain. Disruption of the molecular interaction between SNAP25 with its SNARE partners by using a blocking peptide derived from the C-terminus of SNAP25 effectively repressed the surface and synaptic accumulation of GluN2B-containing NMDARs in CFA-injected rats. This peptide also alleviated inflammatory mechanical allodynia and thermal hypersensitivity. These data suggested that SNAREs complex assembly in spinal cord dorsal horn was involved in the inflammatory pain hypersensitivity through promoting NMDAR synaptic trafficking.

5.
J Nurs Manag ; 2020 Jan 20.
Artigo em Inglês | MEDLINE | ID: mdl-31958352

RESUMO

AIM: To develop a hospital-based nursing human capital model for Taiwan. BACKGROUND: Effective nursing management only becomes possible when nurse managers are able to manage and maintain the right equilibrium among human capital components. METHOD: We developed an analytic hierarchy process (AHP) model with 8 dimensions and 31 indicators based on extensive literature review and experts' perceptual assessment. We used expert and purposive sampling and invited 82 nursing professionals to rate the importance of these dimensions and indicators. The AHP process was performed to identify the weightage and prioritize the dimensions and indicators of the nursing human capital. RESULTS: Our analysis showed that, for nursing human capital, health was the most important factor (weight: 34.8%), followed by employee protection (20.4%), work attitude (13.7%), employee stability (10.8%), general nursing training (6.3%), competencies (5.8%), advanced nursing training (4.3%) and clinical nursing experience (3.9%). CONCLUSION AND IMPLICATION FOR NURSING MANAGEMENT: The model would be most useful for nurse administrators in long-range strategic management. Specifically, the model can be used as a reference to form a rating system to analyse nursing human capital. Health promotion programs and employee protection measures targeting nurses could improve nursing human capital in hospitals.

6.
Transbound Emerg Dis ; 2020 Jan 06.
Artigo em Inglês | MEDLINE | ID: mdl-31903722

RESUMO

This study used social network analysis to investigate the indirect contact network between counties through the movement of live pigs through four wholesale live pig markets in Guangdong Province, China. All 14,118 trade records for January and June 2016 were collected from the markets and the patterns of pig trade in these markets analysed. Maps were developed to show the movement pathways. Evaluating the network between source counties was the primary objective of this study. A 1-mode network was developed. Characteristics of the trading network were explored, and the degree, betweenness and closeness were calculated for each source county. Models were developed to compare the impacts of different disease control strategies on the potential magnitude of an epidemic spreading through this network. The results show that pigs from 151 counties were delivered to the four wholesale live pig markets in January and/or June 2016. More batches (truckloads of pigs sourced from one or more piggeries) were traded in these markets in January (8,001) than in June 2016 (6,117). The pigs were predominantly sourced from counties inside Guangdong Province (90%), along with counties in Hunan, Guangxi, Jiangxi, Fujian and Henan provinces. The major source counties (46 in total) contributed 94% of the total batches during the two-month study period. Pigs were sourced from piggeries located 10 to 1,417 km from the markets. The distribution of the nodes' degrees in both January and June indicates a free-scale network property, and the network in January had a higher clustering coefficient (0.54 vs. 0.39) and a shorter average pathway length (1.91 vs. 2.06) than that in June. The most connected counties of the network were in the central, northern and western regions of Guangdong Province. Compared with randomly removing counties from the network, eliminating counties with higher betweenness, degree or closeness resulted in a greater reduction of the magnitude of a potential epidemic. The findings of this study can be used to inform targeted control interventions for disease spread through this live pig market trade network in south China.

7.
J Virol ; 2020 Jan 22.
Artigo em Inglês | MEDLINE | ID: mdl-31969440

RESUMO

The features of HSV-1 strain 129 (H129), including natural neurotropism and anterograde transneuronal trafficking, make it a potential tool for anterograde neural circuitry tracing. Recently anterograde poly-synaptic and mono-synaptic tracers were developed from H129, and have been applied for identification of novel connections and functions of different neural circuitries. However, how H129 viral particles are transported in neurons, especially those of the central nervous system remains unclear. In this study, we constructed recombinant H129 variants with mCherry-labeled capsids and/or GFP-labeled envelopes and infected the cortical neurons to study axonal transport of H129 viral particles. We found that different types of viral particles were unevenly distributed in the nucleus, cytoplasm of the cell body and axon. Most H129 progeny particles were unenveloped capsids and transported as capsids rather than virions in the axon. Notably, capsids acquired envelopes at axonal varicosities and terminals where are the sites forming synapse connected with other neurons. Moreover, viral capsids moved more frequently in the anterograde direction in axons, with an average velocity of 0.62 ± 0.18 µm/s and maximal velocity of 1.80 ± 0.15 µm/s. We also provided evidence that axonal transport of capsids requires the kinesin-1 molecular motor. These findings support that H129-derived tracers mapping neural circuit anterogradely and possibly transsynaptically. These data will guide future modifications and improvements of the H129-based anterograde viral tracers.IMPORTANCE Anterograde transneuronal tracers derived from H129 virus are important tools for mapping neural circuit anatomic and functional connections. It is therefore critical to elucidate the transport pattern of H129 virus within neuron and between neurons. We constructed recombinant H129 variants with genetically encoded fluorescence labeled capsid protein and/or glycoprotein to visualize viral particle movement in neurons. Both electron microscopy and light microscopy data show that H129 capsids and envelopes move separately, and notably capsids are enveloped at axonal varicosity and terminal which are the sites forming synapse to connect with other neurons. Super-resolution microscopy-based colocalization analysis and inhibition of H129 particle movement by inhibitors of molecular motors support that kinesin-1 contributes to the anterograde transport of capsids. These results shed light into mechanisms for anterograde transport of H129-derived tracers' transport in axon, and transmission between neurons via synapses, explaining the anterograde labeling of neural circuits by H129-derived tracers.

8.
Neurochem Int ; 134: 104656, 2020 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-31899197

RESUMO

Neuronal apoptosis is one of the main pathophysiological events in the early brain injury (EBI) post subarachnoid hemorrhage (SAH). Wnt-3a, one of the endogenous wnt ligands crucial in neurogenesis, has been proven to be efficacious in neuroprotection in traumatic brain injury and ischemic stroke. The glycolytic enzyme aldolase C and ribosome biogenesis protein PPAN were revealed to be linked to wnt signaling pathway. The aim of the study was to explore the antiapoptotic effects of intranasal wnt-3a through Frizzled-1 (Frz-1)/aldolase C/PPAN pathway in SAH. Approaches for assessment included SAH grade, Garcia test, brain water content evaluation, rotarod test, Morris water maze test, Western blot, immunofluorescence and transmission electron microscopy. The results showed that wnt-3a improved the neurological scores, brain water content and long-term neurobehavioral functions after SAH. Wnt-3a increased the level of Frz-1, aldolase C, ß-catenin, PPAN and the Bcl-2/Bax ratio; and decreased the level of axin and cleaved caspase-3 (CC-3). The anti-apoptotic effect of wnt-3a was further evidenced by TUNEL staining and subcellular structure imaging. Frz-1 siRNA and aldolase C siRNA offset the effects of wnt-3a; and restoration of aldolase C by aldolase C CRISPR in Frz-1 siRNA preconditioned SAH rats salvaged the level of Frz-1, aldolase C, PPAN and reduced axin and CC-3. In summary, intranasal administration of wnt-3a alleviates neuronal apoptosis through Frz-1/aldolase C/PPAN pathway in the EBI of SAH rats. The feasible intranasal route and the long-lasting neuroprotective property of wnt-3a is of great clinical relevance.

9.
Sichuan Da Xue Xue Bao Yi Xue Ban ; 51(1): 35-41, 2020 Jan.
Artigo em Chinês | MEDLINE | ID: mdl-31950787

RESUMO

Objective: We analyzed the brain structure of schizophrenia patients from multiple perspectives to explore the relationship between the duration of untreated psychosis (DUP) and clinical outcomes. Methods: For 85 patients and 86 controls, clinical symptoms and cognitive function were evaluated, magnetic resonance imaging (MRI) and free surfer analysis were used to extract the cortical indicator, such as brain cortex thickness, surface area, volume, and so on. The patients were divided into four subgroups according to the boundary of March, June and two year due to the distribution and median of DUP. Finally multi-group comparison and correlation analysis for above indicators were analysed. Results: DUP was associated with the surface area of the left insula, parsorbitalis, right hippocampus, superior frontal gyrus, frontal pole, and temporal pole; DUP mainly influenced the cortical thickness of left posterior cingulate gyrus, postcentral gyrus, right lateral occipital cortex, parsopercularis, medial orbitofrontal cortex, and the bilateral precentral gyrus. For cortical volume, DUP significantly affected left postcentral gyrus, right precuneus, lateral occipital cortex, parsopercularis, lingual gyrus, superior temporal gyrus, bilateral cuneus, pericalcarine cortex, precentral gyrus,superior parietal lobule, and insula.The first three months after onset is a critical period for the deterioration of cortical morphology and clinical function. Conclusion: DUP in first-episode schizophrenia is associated with cortical morphological changes of temporal lobe, precentral, orbitofrontal cortex and the majority of medial regions of occipital lobe, it is very important to conduct early intervention for patients.


Assuntos
Córtex Cerebral , Imagem por Ressonância Magnética , Transtornos Psicóticos , Esquizofrenia , Córtex Cerebral/diagnóstico por imagem , Humanos , Transtornos Psicóticos/diagnóstico por imagem , Transtornos Psicóticos/terapia , Esquizofrenia/diagnóstico por imagem , Esquizofrenia/patologia , Lobo Temporal/diagnóstico por imagem , Fatores de Tempo
10.
Medicine (Baltimore) ; 99(4): e18720, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31977861

RESUMO

The methylenetetrahydrofolate reductase (MTHFR) may play a pathological role in polycystic ovary syndrome (PCOS). However, the conclusions of published reports on the relationship between the MTHFR C677T polymorphism and PCOS risk remain controversial.To derive a more precise estimation we performed a metaanalysis based on 22 studies that together included 2405 cases and 2419 controls. PubMed, EMBASE, WanFang and the Chinese National Knowledge Infrastructure databases were used to retrieve articles up to up to October 28, 2019. The crude odds ratios (ORs) with 95% confidence intervals (95% CI) were calculated to evaluate the association.Metaanalysis results showed a significant association between the MTHFR C677T polymorphism and PCOS risk in 3 genetic models (allele model: OR = 1.40, 95% CI = 1.27-1.53; dominant model: OR = 1.47, 95% CI = 1.17-1.85); homozygous model: OR = 1.90, 95% CI = 1.55-2.32). Moreover, significant associations were observed when stratified by ethnicity, source of controls, etiology, and genotype methods.This metaanalysis suggests that the T-allele of the MTHFR C677T polymorphism is associated with an increased risk of PCOS, especially in Asians further studies with larger population sizes are needed to confirm these results.


Assuntos
Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Síndrome do Ovário Policístico/genética , Grupos de Populações Continentais , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Polimorfismo de Nucleotídeo Único
11.
Aging (Albany NY) ; 12(1): 204-223, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31905170

RESUMO

Liver fibrosis biomarker, Type IV collagen, may function as hepatocarcinogenesis niche. However, among the six isoforms, the isoforms providing tumor microenvironment and their regulatory network are still unclarified. Based on bioinformatics analysis of hundreds of HCC transcriptome datasets from public databases, we found that COL4A1/2 expressions were significantly correlated with hepatocarcinogenesis, progression, and prognosis. The expressions of COL4A1/2 were significantly upregulated in the preneoplastic and HCC tissues compared with normal tissues. Moreover, the overexpression of COL4A2 was highly correlated with shorter progression-free survival in HCC patients. Bioinformatics analysis also generates an interactive regulatory network in which COL4A1/2 directly binding to integrin alpha-2/beta-1 initiates a sequentially and complicated signaling transduction, to accelerate cell cycle and promote tumorigenesis. Among those pathways, the PI3K-Akt pathway is significantly enriched in cooperative mutations and correlation analysis. This suggests that the key activated signaling is PI3K-Akt pathway which severing as the centerline linked with other pathways (Wnt and MAPK signaling) and cell behaviors signaling (cell cycle control and cytoskeleton change). Switching extracellular matrix collagen isoform may establish pro-tumorigenic and metastatic niches. The findings of COL4A1/2 and related signaling networks are valuable to be further investigated that may provide druggable targets for HCC intervention.

12.
BMC Vet Res ; 16(1): 23, 2020 Jan 28.
Artigo em Inglês | MEDLINE | ID: mdl-31992293

RESUMO

BACKGROUND: Marek's disease (MD) is caused by the oncogenic Marek's disease virus (MDV), and is a highly contagious avian infection with a complex underlying pathology that involves lymphoproliferative neoplasm formation. MicroRNAs (miRNAs) act as oncogenes or tumor suppressors in most cancers. The gga-miR-155 is downregulated in the MDV-infected chicken tissues or lymphocyte lines, although its exact role in tumorigenesis remains unclear. The aim of this study was to analyze the effects of gga-miR-155 on the proliferation, apoptosis and invasiveness of an MDV-transformed lymphocyte line MSB1 and elucidate the underlying mechanisms. RESULTS: The expression level of gga-miR-155 was manipulated in MSB1 cells using specific mimics and inhibitors. While overexpression of gga-miR-155 increased proliferation, decreased the proportion of G1 phase cells relative to that in S and G2 phases, reduced apoptosis rates and increased invasiveness. However, its downregulation had the opposite effects. Furthermore, gga-miR-155 directly targeted the RORA gene and downregulated its expression in the MSB1 cells. CONCLUSION: The gga-miR-155 promotes the proliferation and invasiveness of the MDV-transformed lymphocyte line MSB1 and inhibits apoptosis by targeting the RORA gene.

13.
Bioorg Chem ; 94: 103413, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31791679

RESUMO

A series of new ferulic acid derivatives were designed, synthesized and evaluated as multi-target inhibitors against Alzheimer's disease. In vitro studies indicated that most compounds showed significant potency to inhibit self-induced ß-amyloid (Aß) aggregation and acetylcholinesterase (AChE), and had good antioxidant activity. Specifically, compound 4g exhibited the potent ability to inhibit cholinesterase (ChE) (IC50, 19.7 nM for hAChE and 0.66 µM for hBuChE) and the good Aß aggregation inhibition (49.2% at 20 µM), and it was also a good antioxidant (1.26 trolox equivalents). Kinetic and molecular modeling studies showed that compound 4g was a mixed-type inhibitor, which could interact simultaneously with the catalytic anionic site (CAS) and the peripheral anionic site (PAS) of AChE. Moreover, compound 4g could remarkably increase PC12 cells viability in hydrogen peroxide-induced oxidative cell damage and Aß-induced cell damage. Finally, compound 4g had good ability to cross the BBB using the PAMPA-BBB assay. These results suggested that compound 4g was a promising multifunctional ChE inhibitor for the further investigation.

14.
Clin Cancer Res ; 26(2): 384-390, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31615934

RESUMO

PURPOSE: To examine whether submucosal saline injection (SSI) can improve traditional endoscopic ultrasound (EUS) accuracy in distinguishing between T1a and T1b stage esophageal squamous cell carcinoma (ESCC). EXPERIMENTAL DESIGN: Patients with T1N0M0 stage ESCC (n = 180) ages 18 to 85 years were enrolled between February 14, 2012 to June 4, 2018 at Sun Yat-sen University Cancer Center (Guangdong, China). They were randomly assigned (1:1) to receive either EUS examination after 3-5 mL SSI or EUS only examination. All the patients were referred to thoracic surgeons to receive endoscopic resection (ER) or esophagectomy 5 to 10 days after EUS examination. Standard EUS criteria were used to preoperatively stage the ESCC cases, and surgical pathology reports after referral were used to postoperatively stage the cases. The primary endpoint was the diagnostic accuracy of T1b staging [defined as the sum of the true positive (T1b) and true negative (T1a) cases divided by the total number of cases]. RESULTS: Among the per-protocol population, the SSI+EUS group (n = 81) was superior to the EUS-only group (n = 85) in terms of the diagnostic accuracy for T1b staging [93.8% (95% confidence interval (CI), 88.6-99.1) vs. 65.9% (95% CI, 55.8-76.0); P < 0.001]. The positive predictive value of SSI+EUS for diagnosing T1b ESCC reached 90.9% (95% CI, 81.1-100), which was significantly superior to that of EUS only [0.576 (0.450-0.702), P = 0.001]. CONCLUSIONS: SSI significantly improves the diagnostic accuracy of EUS in distinguishing between T1a and T1b ESCC, which might help avoid unnecessary esophagectomy and diagnostic ER.

15.
Biochem Biophys Res Commun ; 521(3): 639-645, 2020 Jan 15.
Artigo em Inglês | MEDLINE | ID: mdl-31679693

RESUMO

Obesity and its associated non-alcoholic fatty liver disease (NAFLD) have become epidemic medical problems worldwide; however, the current available therapeutic options are limited. Farnesoid X receptor (FXR) has recently emerged as an attractive target for obesity treatment. Here we demonstrate that isotschimgine (ITG), a constituent in genus Ferula, as a novel FXR agonist with anti-obesity and anti-hepatic steatosis effects. The results showed that ITG activated the FXR transactivity and bound with the ligand binding dormain (LBD) of FXR with gene reporter assays and AlphaScreen assays. In high-fat diet-induced obese (DIO) mice, ITG lowered body weight and fat mass, improved insulin resistance and hepatic steatosis. Mechanistic studies showed that ITG altered the expression levels of FXR downstream genes, lipid synthesis and energy metabolism genes in the liver of mice. Our findings suggest that ITG is a novel FXR agonist and may be a potential therapeutic choice for obesity associated with NAFLD.

16.
J Comput Biol ; 27(1): 69-80, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31424269

RESUMO

This study intended to identify biomarkers for septic cardiomyopathy (SC). Microarray data GSE79962 including 20 SC samples and 11 normal samples were downloaded from the Gene Expression Omnibus database. Differentially expressed genes (DEGs) between SC and control groups were identified, followed with functional enrichment analyses. In addition, the protein-protein interaction (PPI) network and modules were constructed. Finally, a transcription factors (TFs)-microRNA (miRNA)-target gene network was constructed and the potential drugs targeting key DEGs were searched. There were 119 upregulated and 80 downregulated genes in the SC group compared with the control group. The upregulated DEGs were significantly enriched tumor necrosis factor signaling pathway, Jak-signal transducer and activator of transcription (STAT) signaling pathway, hypoxia-inducible transcription factor-1 signaling pathway, chemokine signaling pathway, and cytokine-cytokine receptor interaction. The downregulated genes involved in biological processes of negative regulation of DNA biosynthetic process, and skeletal muscle cell differentiation. CCL2, STAT3, MYC, and SERPINE1 were hub nodes in the PPI network and modules. miR-29 family and miR-30 family were considered as key miRNAs, and TATA, MEF2, and STAT5B were considered as key TFs. SERPINE1 and MYC were also drug target genes. The identified DEGs and pathways may be implicated in the progression of human SC, which may lead to a better understanding of SC pathogenesis.

17.
Plant J ; 101(2): 310-323, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31536657

RESUMO

Seed is vital to the conservation of germplasm and plant biodiversity. Seed dormancy is an adaptive trait in numerous seed-plant species, enabling plants to survive under stressful conditions. Seed dormancy is mainly controlled by abscisic acid (ABA) and gibberellin (GA) and can be classified as primary and secondary seed dormancy. The primary seed dormancy is induced by maternal ABA. Here we found that AtPER1, a seed-specific peroxiredoxin, is involved in enhancing primary seed dormancy. Two loss-of-function atper1 mutants, atper1-1 and atper1-2, displayed suppressed primary seed dormancy accompanied with reduced ABA and increased GA contents in seeds. Furthermore, atper1 mutant seeds were insensitive to abiotic stresses during seed germination. The expression of several ABA catabolism genes (CYP707A1, CYP707A2, and CYP707A3) and GA biosynthesis genes (GA20ox1, GA20ox3, and KAO3) in atper1 mutant seeds was increased compared to wild-type seeds. The suppressed primary seed dormancy of atper1-1 was completely reduced by deletion of CYP707A genes. Furthermore, loss-of-function of AtPER1 cannot enhance the seed germination ratio of aba2-1 or ga1-t, suggesting that AtPER1-enhanced primary seed dormancy is dependent on ABA and GA. Additionally, the level of reactive oxygen species (ROS) in atper1 mutant seeds was significantly higher than that in wild-type seeds. Taken together, our results demonstrate that AtPER1 eliminates ROS to suppress ABA catabolism and GA biosynthesis, and thus improves the primary seed dormancy and make the seeds less sensitive to adverse environmental conditions.

18.
Invest New Drugs ; 38(1): 99-110, 2020 Feb.
Artigo em Inglês | MEDLINE | ID: mdl-30825104

RESUMO

Background Pexidartinib, a novel, orally administered small-molecule tyrosine kinase inhibitor, has strong selectivity against colony-stimulating factor 1 receptor. This phase I, nonrandomized, open-label multiple-dose study evaluated pexidartinib safety and efficacy in Asian patients with symptomatic, advanced solid tumors. Materials and Methods Patients received pexidartinib: cohort 1, 600 mg/d; cohort 2, 1000 mg/d for 2 weeks, then 800 mg/d. Primary objectives assessed pexidartinib safety and tolerability, and determined the recommended phase 2 dose; secondary objectives evaluated efficacy and pharmacokinetic profile. Results All 11 patients (6 males, 5 females; median age 64, range 23-82; cohort 1 n = 3; cohort 2 n = 8) experienced at least one treatment-emergent adverse event; 5 experienced at least one grade ≥ 3 adverse event, most commonly (18%) for each of the following: increased aspartate aminotransferase, blood alkaline phosphatase, gamma-glutamyl transferase, and anemia. Recommended phase 2 dose was 1000 mg/d for 2 weeks and 800 mg/d thereafter. Pexidartinib exposure, area under the plasma concentration-time curve from zero to 8 h (AUC0-8h), and maximum observed plasma concentration (Cmax) increased on days 1 and 15 with increasing pexidartinib doses, and time at Cmax (Tmax) was consistent throughout all doses. Pexidartinib exposure and plasma levels of adiponectin and colony-stimulating factor 1 increased following multiple daily pexidartinib administrations. One patient (13%) with tenosynovial giant cell tumor showed objective tumor response. Conclusions This was the first study to evaluate pexidartinib in Asian patients with advanced solid tumors. Pexidartinib was safe and tolerable in this population at the recommended phase 2 dose previously determined for Western patients (funded by Daiichi Sankyo; clinicaltrials.gov number, NCT02734433).

19.
Spectrochim Acta A Mol Biomol Spectrosc ; 224: 117468, 2020 Jan 05.
Artigo em Inglês | MEDLINE | ID: mdl-31425861

RESUMO

Low-frequency vibrations of l-histidine in a neat solid state and its monohydrochloride monohydrate are both investigated using THz spectroscopy and DFT calculations. The molecular motions in those modes are further quantitatively decomposed into a number of submotions and discussed in terms of their contributions to a mode. The results show significant differences in the averaged contribution percentage of intermolecular motions and the dihedral angle distortions of the imidazole ring between these two crystals. Those phenomena are interpreted from the viewpoint of their hydrogen-bond configurations.

20.
Med Care ; 58(1): 65-69, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31569113

RESUMO

BACKGROUND: Urosepsis is common in older adults with more infections identified as community-acquired as opposed to hospital-acquired. Despite the prevalence of urosepsis and its high mortality rates, very little is known about the care outcomes of older adult patients with community-acquired urosepsis who are admitted to the hospital on a weekend. OBJECTIVES: To determine if a weekend admission was associated with inpatient mortality in older adults admitted to an acute care hospital with a diagnosis of community-acquired urosepsis. METHODS: Data from the State Inpatient Datasets for Florida were merged with data from the American Hospital Association Annual Survey on hospital characteristics for the year 2014. Logistic regression models with a sizable number of patient and hospital controls were used to identify factors associated with inpatient mortality in patients 65 years of age and older with a primary or secondary diagnosis of community-acquired urosepsis. RESULTS: In total 21,904 older adults were admitted to a Florida hospital with a diagnosis of community-acquired urosepsis; 5736 of these patients were admitted on a weekend. In a fully adjusted logistic regression model, weekend admission was associated with a 12% increase in the odds of mortality, and each additional hour of nursing care per patient day was associated with a 2% decrease in the odds of mortality. CONCLUSIONS: Our findings suggest that weekend admission was associated with an increase in the odds of mortality in older adults with community-acquired urosepsis. Small increases in nurse staffing seem to reduce the odds of mortality.

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