Histone deacetylases 3 (HDAC3) modulates the acetylation state of histone and non‐histone proteins and could be a powerful regulator of the inflammatory process in stroke. Inflammasome activation is ...a ubiquitous but poorly understood consequence of acute ischemic stroke. Here, we investigated the potential contributions of HDAC3 to inflammasome activation in primary cultured microglia and experimental stroke models. In this study, we documented that HDAC3 expression was increased in microglia of mouse experimental stroke model. Intraperitoneal injection of RGFP966 (a selective inhibitor of HDAC3) decreased infarct size and alleviated neurological deficits after the onset of middle cerebral artery occlusion (MCAO). In vitro data indicated that LPS stimulation evoked a time‐dependent increase of HDAC3 and absent in melanoma 2 (AIM2) inflammasome in primary cultured microglia. Interestingly, AIM2 was subjected to spatiotemporal regulation by RGFP966. The ability of RGFP966 to inhibit the AIM2 inflammasome was confirmed in an experimental mouse model of stroke. As expected, AIM2 knockout mice also demonstrated significant resistance to ischemia injury compared with their wild‐type littermates. RGFP966 failed to exhibit extra protective effects in AIM2−/− stroke mice. Furthermore, we found that RGFP966 enhanced STAT1 acetylation and subsequently attenuated STAT1 phosphorylation, which may at least partially contributed to the negative regulation of AIM2 by RGFP966. Together, we initially found that RGFP966 alleviated the inflammatory response and protected against ischemic stroke by regulating the AIM2 inflammasome.
•A framework for integrating cross-efficiency and meta-frontier analysis is developed.•Technology gap of different frontiers is measured in the cross-evaluation perspective.•Different inefficient ...reasons are obtained by aggregating and decomposing cross efficiency.•Cross-evaluation strategy is constructed to ensure the stability of the optimal solution.
Efficiency overestimation and technology heterogeneity are important factors that affect the use of data envelopment analysis. This paper introduces a meta-frontier analysis framework into a cross-efficiency method to develop a new efficiency evaluation method. This method can be used to calculate, aggregate, and decompose the cross efficiencies relative to the meta-frontier and group-frontier. Then the technology gap between these frontiers can be measured and more detailed information regarding the inefficiency of decision-making units can be obtained. This enables decision makers to improve efficiency in a targeted manner. Subsequently, the non-uniqueness of the optimal solution is discussed for the new method, and the cross-evaluation strategy is introduced to ensure the stability of the optimal solution. Finally, two examples are presented to illustrate the effectiveness of this method.
Planar cell polarity (PCP) signalling specifies the orientation of epithelial cells and regulates directional beating of motile cilia of multiciliated epithelial cells. Clinically, defects in cilia ...function are associated with nasopharyngeal symptoms. The polarity of the nasopharyngeal epithelium is poorly understood. Here, we demonstrated PCP in the nasopharyngeal epithelium. Multiciliated cells (MCCs) were uniformly aligned with their long axis parallel to the tissue axis of the nasopharynx (NP). In addition, PCP proteins exhibited an asymmetrical localisation between adjacent cells. Motile cilia were uniformly aligned in the same direction within both individual cells and neighbouring cells, which manifested as cilial polarity in MCCs. Mutation of Vangl2, a mammalian homologue of the Drosophila PCP gene, resulted in significant disruption of the orientation of epithelial cells. Finally, keratin‐5‐positive basal cells constantly replenished the luminal ciliated cells; the new dynamic ciliated cells were also oriented parallel to the tissue axis. These results indicate a role for the PCP pathway in the uniform orientation of dynamically replenished epithelial cells in the NP.
Planar cell polarity (PCP) signalling specifies the orientation of epithelial cells and regulates directional beating of motile cilia of multiciliated epithelial cells. Clinically, defects in cilia function are associated with nasopharyngeal symptoms. Here, we present that PCP governs the alignment of the nasopharyngeal epithelium. Our findings provide a complete understanding of PCP in the nasopharyngeal epithelium and reveal novel structural features which are likely crucial within diseases of the nasopharynx.
The existing studies on environmental efficiency evaluation generally have the problem of efficiency overestimation. To solve this problem, a new data envelopment analysis (DEA) cross‐efficiency ...approach with undesirable outputs is developed to evaluate environmental efficiency from the perspectives of both self‐evaluation and peer evaluation. Then, three new evaluation strategies, namely, economic development strategy, environmental protection strategy, and win–win strategy, are proposed to reflect the needs of decision makers under different policy objectives. The proposed cross‐efficiency approach with different evaluation strategies not only realizes the cross evaluation of environmental efficiency, but also guarantees the relative uniqueness of the optimal solution on the basis of the preferences of decision makers. Combining the metafrontier DEA approach and DEA window analysis, a new cross‐efficiency analytical framework is constructed to gradually analyse the influences of policy objectives, technology heterogeneity, and dynamic correlation on the environmental efficiency. Subsequently, the environmental efficiency of China's economic development during 2006–2015 is in‐depth analysed on the basis of the proposed analytical framework, and some interesting conclusions, and some useful suggestions are obtained.
Selecting suitable internal reference genes is an important prerequisite for the application of quantitative real-time PCR (qRT-PCR). However, no systematic studies have been conducted on reference ...genes in luffa. In this study, seven reference genes were selected, and their expression levels in luffa plants exposed to various simulated abiotic stresses i.e., cold, drought, heat, salt, H
O
, and abscisic acid (ABA) treatments were analyzed by qRT-PCR. The stability of the reference gene expression levels was validated using the geNorm, NormFinder, BestKeeper, and RefFinder algorithms. The results indicated that EF-1α was the most stably expressed and suitable reference gene overall and for the heat, cold, and ABA treatments. Additionally, UBQ expression was stable following the salt treatment, whereas TUB was identified as a suitable reference gene for H
O
and drought treatments. The reliability of the selected reference genes was verified by analyzing the expression of copper/zinc superoxide dismutase (Cu/Zn-SOD) gene in luffa. When the most unstable reference genes were used for data normalizations, the resulting expression patterns had obvious biases when compared with the expression patterns for the most ideal reference genes used alone or combined. These results will be conducive to more accurate quantification of gene expression levels in luffa.
A nanocage coupling effect from a redox Ru
-Pd
metal-organic cage (MOC-16) is demonstrated for efficient photochemical H
production by virtue of redox-guest modulation of the photo-induced electron ...transfer (PET) process. Through coupling with photoredox cycle of MOC-16, tetrathiafulvalene (TTF) guests act as electron relay mediator to improve the overall electron transfer efficiency in the host-guest system in a long-time scale, leading to significant promotion of visible-light driven H
evolution. By contrast, the presence of larger TTF-derivatives in bulk solution without host-guest interactions results in interference with PET process of MOC-16, leading to inefficient H
evolution. Such interaction provides an example to understand the interplay between the redox-active nanocage and guest for optimization of redox events and photocatalytic activities in a confined chemical nanoenvironment.
Concurrent non-alcoholic fatty liver disease (NAFLD) is common in patients with chronic HBV infection. But the impact of fatty liver on the histologic progression of HBV infection remains ...controversial. Consecutive HBV-infected patients who underwent liver biopsy between 2016 and 2021 were included. Alcohol consumption and other types of viral hepatitis were excluded. All biopsies were scored for grading and staging by Scheuer's score, and the steatosis was scored as an estimate of the percentage of liver parenchyma replaced by fat. Logistic regression analyses were applied to assess the associated factors for significant liver inflammation (G greater than or equal to 2), significant fibrosis (S greater than or equal to 2) and advanced fibrosis (S greater than or equal to 3). Among the 871 HBV-infected patients, hepatic steatosis was prevalent in 255 patients (29.28%). Significant liver inflammation was present in 461 patients (52.93%). Significant fibrosis was observed in 527 patients (60.51%), while advanced liver fibrosis was observed in 171 patients (19.63%). Patients with concomitant NAFLD were more likely to have significant liver inflammation and advanced fibrosis. Fatty liver was an independent risk factor for significant liver inflammation (OR: 2.117, 95% CI: 1.500-2.988), but it could not predict the development of fibrosis. Especially, in HBV-infected patients with persistent normal ALT (immune tolerant and inactive carrier phase), the presence of significant liver inflammation was higher in NAFLD than those without NAFLD. The prevalence of advanced liver fibrosis was higher in NAFLD than non-NAFLD only in the immune tolerant phase, while NAFLD did not increase fibrosis burden in other stages of HBV infection. We developed a predictive model for significant liver inflammation with the area under receiver operating characteristic curve (AUROC) of 0.825, and a model for significant fibrosis with the AUROC of 0.760. NAFLD is independently associated with significant liver inflammation, and increases the burden of advanced liver fibrosis in HBV-infected patients. The influence of NAFLD on the degree of liver inflammation and fibrosis is different in distinct clinical phases of chronic HBV infection.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
Little research regarding genotypes and clopidogrel response related to acute ischemic stroke has been published. This study was conducted to investigate whether the polymorphisms of receptors or ...enzymes involved in the metabolic process of clopidogrel affect clopidogrel response and prognosis related to acute stroke.
A total of 259 patients with acute ischemic stroke were enrolled in this study; all received follow-up evaluations 3 and 6 months after clopidogrel treatment. CYP2C19, CYP3A4, and P2Y12 were screened. The adenosine diphosphate-induced platelet aggregation test, the National Institutes of Health Stroke Scale (NIHSS), and the modified Rankin Scale (mRS) were used, and blood vascular events were evaluated.
The difference before and after clopidogrel treatment on adenosine diphosphate-induced platelet aggregation was significantly smaller in patients carrying 1 or 2 CYP2C19 loss-of-function alleles (*2, *3) compared with patients carrying none. Patients with none had better outcomes than patients with CYP2C19 loss-of-function alleles, as demonstrated by NIHSS and mRS scores at 3 and 6 months after treatment. Regression analysis showed that CYP2C19 was an independent predictor of clopidogrel resistance.
CYP2C19 genotypes had significant impact on clopidogrel response and prognosis of patients with stroke. Clinical Trial Registration Information- URL: http://www.chictr.org/. Unique Identifier: ChiCTR-OCH-12002681.
Chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS) is a poorly understood disease. Accumulating evidence suggests that autoimmune dysfunction is involved in the development of CP/CPPS. ...Interleukin‐17 (IL‐17) is associated with the occurrence and development of several chronic autoimmune inflammatory diseases. However, the molecular mechanisms underlying the role of IL‐17 in CP/CPPS are not clear. We confirmed that IL‐17 was increased in the prostate tissues of experimental autoimmune prostatitis (EAP) mice. Corresponding to the increase of IL‐17, neutrophil infiltration and the levels of CXCL1 and CXCL2 (CXC chemokine ligands 1 and 2) were also increased in the prostate of EAP. Treatment of EAP mice with an IL‐17‐neutralizing monoclonal antibody (mAb) decreased the number of infiltrated neutrophils and CXCL1 and CXCL2 levels. Depletion of neutrophils using anti‐Ly6G antibodies ameliorated the inflammatory changes and hyperalgesia caused by EAP. Fucoidan, a could potent inhibitor of neutrophil migration, also ameliorate the manifestations of EAP. Our findings suggested that IL‐17 promoted the production of CXCL1 and CXCL2, which triggered neutrophil chemotaxis to prostate tissues. Fucoidan might be a potential drug for the treatment of EAP via the effective inhibition of neutrophil infiltration.
There is an urgent need to discover more sensitive and specific biomarkers to improve early diagnosis and screen high-risk patients for pancreatic ductal adenocarcinoma (PDAC). Pancreatic juice is an ...ideal specimen for PDAC biomarkers discovery, because it is an exceptionally rich source of proteins released from pancreatic cancer cells.
To identify novel potential biomarkers for PDAC from pancreatic juice, we carried out difference gel electrophoresis (DIGE) and tandem mass spectrometry (MS/MS) to compare the pancreatic juice profiling from 9 PDAC patients and 9 cancer-free controls. Of the identified differently expressed proteins, three up-regulated proteins in pancreatic cancer juice, matrix metalloproteinase-9 (MMP-9), oncogene DJ1 (DJ-1) and alpha-1B-glycoprotein precursor (A1BG), were selected for validation by Western blot and immunohistochemistry. Serum MMP-9 levels were also detected by enzyme linked immunosorbent assay (ELISA).
Fourteen proteins were up-regulated and ten proteins were down-regulated in cancerous pancreatic juice compared with cancer-free controls. Increased MMP-9, DJ-1 and A1BG expression in cancerous pancreatic juice were confirmed by Western blot. Immunohistochemical study showed MMP-9, DJ-1 and A1BG positively expressed in 82.4%, 72.5% and 86.3% of pancreatic cancer tissues, significantly higher than that in normal pancreas tissues. Up-regulation of DJ-1 was associated with better differentiation (p < 0.05). Serum MMP-9 levels were significantly higher in PDAC (255.14 ng/ml) than those in chronic pancreatitis (210.22 ng/ml, p = 0.009) and healthy control (203.77 ng/ml, p = 0.027).
The present proteome analysis revealed MMP-9, DJ-1 and A1BG proteins as elevated in pancreatic juice from PDAC, which suggest their further utility in PDAC diagnosis and screening. This is the first time A1BG was identified as a potential biomarker in pancreatic cancer associated samples. The measurement of serum MMP-9 might be clinically useful for PDAC diagnosis.
Celotno besedilo
Dostopno za:
DOBA, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
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