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1.
Ruozhi Zhao Khuong Le Mohammed H. Moghadasian Garry X. Shen 《Inflammation research》2017,66(9):783-792
Objective and design
To determine the requirement of plasminogen activator inhibitor-1-knockout (PAI-1) for monocyte adhesion in animals and cells under diabetic conditions.Methods and subjects
Monocyte adhesion assay, enzyme-linked immunosorbent assay, and Western blotting were used in analyzing samples from PAI-1-knockout (PAI-1-KO) mice or cultured human umbilical vein endothelial cells (HUVEC).Treatments
Diabetes in PAI-1-KO and wild-type mice was induced by intraperitoneal injection of streptozotocin (STZ). HUVEC was transfected with short interference RNA (siRNA) against PAI-1, tumor necrosis factor-α (TNFα), or toll-like receptor (TLR4), and then was treated with glycated low-density lipoproteins (glyLDL).Results
The adhesion of monocytes to aortic intima was reduced in PAI-1-KO mice, which was associated with decreased levels of TNFα and monocyte chemotactic protein-1 (MCP-1) in plasma and cardiovascular tissue, and increased abundances of urokinase plasminogen activator (uPA) and uPA receptor (uPAR) in cardiovascular tissue compared to wild-type mice. Significant reductions in monocyte adhesion, inflammatory, and fibrinolytic regulators were detected in cardiovascular tissue or plasma in diabetic PAI-1-KO mice compared to wild-type diabetic mice. Transfection of PAI-1, TNFα or TLR4 siRNA to HUVEC inhibited glyLDL-induced monocyte adhesion to EC. PAI-1 siRNA inhibited the abundances of TLR4 and TNFα in EC.Conclusion
The findings suggest that PAI-1 is required for diabetes-induced monocyte adhesion via interactions with uPA/uPAR, and it also regulates TLR4 and TNFα expression in vascular EC. Inhibition of PAI-1 potentially reduces vascular inflammation under diabetic condition.2.
Introduction
Histaminergic status can modify adipose tissue (AT) development: histamine-free mice exhibit visceral obesity, and treatments with H3-antagonists reduce body weight gain. However, direct histamine effects on AT remain poorly documented: it has been observed that histamine stimulates lipolysis in rodent adipocytes when its oxidation by amine oxidases (AOs) is blocked by inhibitors such as semicarbazide.Objective
The aim of this work was to study the influence of AOC3 gene invalidation, encoding for semicarbazide-sensitive AO (SSAO), on histamine oxidation and on histamine lipolytic activity in AT.Materials and methods
Expression of AOC- and MAO-encoding genes was determined by real-type PCR in wild-type (WT) and SSAO-deficient (AOC3-KO) mice. Lipolysis was assessed by glycerol release in isolated adipocytes and AO activity by substrate-induced hydrogen peroxide formation in kidney, ileum and AT.Results
The expression levels of the genes encoding AOC1, AOC2 or MAOA and MAOB were not modified in the AT of AOC3-KO mice. In WT mice, histamine oxidation was lower than that of the reference SSAO-substrate benzylamine in AT, but not in ileum. The order of magnitude regarding benzylamine oxidation was AT > ileum >> kidney. In AOC3-KO mice, benzylamine oxidation was abolished in all tissues, while histamine oxidation was abolished in AT but not in ileum. Histamine was inactive on lipolysis in WT but stimulated lipolysis in fat cells from AOC3-KO mice, without reaching the maximal intensity of beta-adrenergic stimulation.Conclusion
Histamine was mainly oxidized by diamine oxidase (AOC1 product) in intestine, but by SSAO (AOC3 product) in AT. When protected from its oxidation by SSAO in AT, histamine moderately activated lipolysis in adipocytes in AOC3-KO mice.3.
Background
Cordyceps sinensis has been used for centuries in China as one of the most valued herbal medicine and tonic food. Paecilomyces hepiali, a fungal strain isolated from natural C. sinensis, has been used widely as a substitute of C. sinensis in medicine and health food. P. hepiali has been reported to have various pharmaceutical benefits, including triglyceride-lowing activity. However, its effects on triglyceride metabolism in adipocytes remain unknown. The purpose of the present study was to evaluate the effect of P. hepiali mycelia on adipocyte lipolysis and to clarify the underlying mechanisms.Methods
The fully differentiated 3T3-L1 adipocytes were treated with methanol extract of Paecilomyces hepiali mycelia (PHME). Contents of glycerol released into the culture medium and intracellular triglyceride were measured as indices of lipolysis using glycerol assay kit and Oil red O staining, respectively. Then, effects of PHME on the main lipases or kinases involved in lipolysis regulation were investigated. Protein expression of adipose triglyceride lipase (ATGL) and perilipin, as well as phosphorylation of hormone-sensitive lipase (HSL), AMP-activated protein kinase (AMPK), and mitogen-activated protein kinases (MAPKs) were determined by western blotting. Moreover, nucleosides, important constituents of PHME, were analyzed using high performance liquid chromatography (HPLC).Results
Treatment with PHME led to a significant increase in glycerol release thereby reduced intracellular triglyceride accumulation in fully differentiated adipocytes. PHME upregulated protein kinase (PK) A-mediated phosphorylation of HSL at serine residues of 563 and 660. Meanwhile, PHME treatment also upregulated phosphorylation of extracellular signal-regulated kinase (ERK), and downregulated the protein level of perilipin. Pretreatment with the PKA inhibitor, H89, blunted the PHME-induced lipolysis and the phosphorylation of HSL (Ser 563 and 660). Moreover, pretreatment with ERK inhibitor, PD98059, weakened the PHME-caused glycerol release and downregulation of perilipin expression. HPLC analysis indicated there were adenosine, cordycepin, uridine and vernine in PHME.Conclusions
Our results showed that PHME significantly induced lipolysis in 3T3-L1 adipocytes, which is mainly mediated by activation of HSL through PKA pathway and by downregulation of perilipin through activation of ERK pathway.4.
Objective
RBL-2H3 cells express Toll-like receptors, including TLR4. This study aims to assess various aspects of the TLR4 pathway.Methods
RBL-2H3 cells were indirectly stained for cell surface TLR4, 25 CD14 and intracellular MyD88 proteins and analysed through flow cytometry for single-colour staining.Results
While TLR4-receptors are expressed in RBL-2H3 cells, associated elements involved in the signaling pathway, CD14 and MyD88, are not.Conclusion
Care should be taken if RBL-2H3 cells are used to study aspects of the innate immune system in mast cells.5.
Background
Adiponectin, a protein hormone produced by adipose tissues, exhibits anti-inflammatory functions in various models. This study was investigated the effects of adiponectin on dextran sodium sulfate (DSS)-colonic injury, inflammation, apoptosis, and intestinal barrier dysfunction in Caco-2 cell and mice.Materials and methods
The results showed that DSS caused inflammatory response and intestinal barrier dysfunction in vitro and in vivo. Adiponectin injection alleviated colonic injury and rectal bleeding in mice. Meanwhile, adiponectin downregulated colonic IL-1β and TNF-α expressions and regulated apoptosis relative genes to attenuate DSS-induced colonic inflammation and apoptosis. Adiponectin markedly reduced serum lipopolysaccharide concentration, a biomarker for intestinal integrity, and enhanced colonic expression of tight junctions (ZO-1 and occludin). The in vitro data further demonstrated that adiponectin alleviated DSS-induced proinflammatory cytokines production and the increased permeability in Caco-2 cells.Conclusion
Adiponectin plays a beneficial role in DSS-induced inflammation via alleviating apoptosis and improving intestinal barrier integrity.6.
Nicolas Degand Justine Dautremer Benoît Pilmis Agnès Ferroni Fanny Lanternier Julie Bruneau Olivier Hermine Stéphane Blanche Xavier Nassif Olivier Lortholary Marc Lecuit 《Journal of clinical immunology》2017,37(7):727-731
?
Helicobacter bilis is a commensal bacterium causing chronic hepatitis and colitis in mice. In humans, enterohepatic Helicobacter spp. are associated with chronic hepatobiliary diseases.Purpose
We aimed at understanding the microbial etiology in a patient with X-linked agammaglobulinemia presenting with suppurative cholangitis.Methods
16S rDNA PCR directly performed on a liver biopsy retrieved DNA of H. bilis.Results
Clinical outcome resulted in the normalization of clinical and biological parameters under antibiotic treatment by a combination of ceftriaxone, metronidazole, and doxycyclin followed by a 2-week treatment with moxifloxacin and a 2-month treatment with azithromycin.Conclusion
In conclusion, these data suggest a specific clinical and microbiological approach in patients with humoral deficiency in order to detect H. bilis hepatobiliary diseases.7.
Background
Turkey, with a Muslim population of officially over 99 %, is one of the few secular states in the Muslim world. Although state institutions are not based on Islamic juridical and ethical norms, the latter play a significant role in defining people’s attitudes towards controversial issues in the modern world, especially when backed by opinions of Muslim scholars living in Turkey. Accordingly, opinions of Muslim scholars undoubtedly have an important effect on bioethical decisions made by institutions and individuals.Objective(s)
To explore the ethical positions of Muslim scholars living in Turkey and their arguments used in the ethical assessment of embryonic stem cell research; to discuss the biological-moral tensions arising in medical research on human embryos.Design
Qualitative study.Setting
Muslim scholars located in different parts of Turkey.Methods
Qualitative method, involving the collection of opinions of various scholars, by means of 15 individual semi-structured interviews, evaluated using thematic qualitative analysis.Results
Positions regarding embryonic stem cell research differ among Muslim scholars in Turkey. On the other hand, even where positions are similar, they are often supported by different arguments.Conclusion
Despite the heterogeneity of the arguments presented, the dominant position considers embryonic stem cell research as morally acceptable.8.
Kneginja Richter Lukas Peter Stefanie Kellner Thomas Hillemacher 《Somnologie - Schlafforschung und Schlafmedizin》2018,22(3):194-198
Background
Millions of people share a bed with their partner. Sleep und relationship could possibly influence each other.Objectives
To identify and discuss connections between relationship and sleep quality.Methods
Review of the literature in electronic databases.Results
Conflict and violence in relationships lead to decreases in both partners’ sleep quality. Constructive approaches to resolving conflicts is necessary for good sleep, and vice versa. Women prefer partners with sleep-wake rhythms matching their own and report higher relationship satisfactions when the couple’s chronotypes are compatible.Conclusions
Sleep and circadian rhythms play important roles in relationships. When treating insomnia, the relationship and the partner’s sleep should be taken into account.9.
Maria Lavinia Bartolucci Ida Marini Francesco Bortolotti Daniela Impellizzeri Rosanna Di Paola Giuseppe Bruschetta Rosalia Crupi Marco Portelli Angela Militi Giacomo Oteri Emanuela Esposito Salvatore Cuzzocrea 《Inflammation research》2018,67(10):891-901
Objective and design
Temporomandibular disorder (TMD) is a common painful condition in the temporomandibular joint (TMJ). Joint inflammation is believed to be a chief cause of pain in patients with TMD, through the release of pro-inflammatory cytokines that induce peripheral sensitization of nerve terminals followed by microglial stimulation.Materials and subject
TMJ was induced in rats with the injection of complete Freund’s adjuvant (CFA) emulsion into the left TMJ capsule.Treatment
The present study would assess the effects of micronized palmitoylethanolamide (m-PEA) on glial activation and trigeminal hypersensitivity.Methods
Ten mg/kg m-PEA or corresponding vehicle was administered 1 h after CFA and mechanical allodynia and edema were evaluated at 24 and 72 h after CFA injection.Results
CFA-injected animals showed TMJ edema and ipsilateral mechanical allodynia accompanied by a robust growth in GFAP protein-positive satellite glial cells and activation of resident macrophages in the TG. Moreover, m-PEA administration significantly reduced the degree of TMJ damage and pain, macrophage activation in TG and up-regulation of Iba1.Conclusions
The results confirm that m-PEA could represent a novel approach for monitoring pain during trigeminal nerve sensitization.10.
Alessandra Bitto Daniela Giuliani Giovanni Pallio Natasha Irrera Eleonora Vandini Fabrizio Canalini Davide Zaffe Alessandra Ottani Letteria Minutoli Mariagrazia Rinaldi Salvatore Guarini Francesco Squadrito Domenica Altavilla 《Inflammation research》2017,66(5):389-398
Objective and design
Alzheimer’s disease (AD) is associated with amyloid plaques (Aβ) and hyperphosphorylated tau protein tangles in the brain. We investigated the possible neuroprotective role of flavocoxid, a dual inhibitor of cyclooxygenases-1/2 (COX-1/2) and 5-Lipoxygenase (5-LOX), in triple-transgenic (3xTg-AD) mice.Subjects
Mice were 3 months at the beginning of the study.Treatment
Animals received once daily for 3-month saline solution or flavocoxid (20 mg/kg/ip).Methods
Morris water maze was used to assess learning and memory. Histology was performed to evidence Aβ plaques and neuronal loss, while inflammatory proteins were determined by western blot analysis.Results
Saline-treated 3xTg-AD mice showed an impairment in spatial learning and memory (assessed at 6 months of age), and increased expression of inflammatory and apoptotic molecules. Treatment of 3xTg-AD mice with flavocoxid reduced: (1) learning and memory loss; (2) the increased eicosanoid production and the phosphorylation level of amyloid precursor protein (APP-pThr668), Aβ 1–42, p-tau (pThr181), pERK, and the activation of the NLRP3 inflammasome; (3) Aβ plaques; and (4) neuronal loss, compared to saline-treated animals.Conclusions
Pharmacological blockade of both COX-1/2 and 5-LOX was able to counteract the progression of AD by targeting pathophysiological mechanisms up- and downstream of Aβ and tau.11.
Background
The Digestive Diseases Week (DDW) is the major meeting for presentation of research in gastroenterology. The acceptance of an abstract for presentation at this meeting is the most important determinant of subsequent full publication. We wished to examine the determinants of abstract acceptance for this meeting.Methods
A cross-sectional study was performed, based on abstracts submitted to the DDW. All 17,205 abstracts submitted from 1992 to 1995 were reviewed for acceptance, country of origin and research type (controlled clinical trials (CCT), other clinical research (OCR), basic science (BSS)). A random sub-sample (n = 1,000) was further evaluated for formal abstract quality, statistical significance of study results and sample size.Results
326 CCT, 455 OCR and 219 BSS abstracts were evaluated in detail. Abstracts from N/W Europe (OR 0.4, 95% CI 0.3–0.6), S/E Europe (OR 0.4, 95% CI 0.2–0.6) and non-Western countries (OR 0.3, 95% CI 0.2–0.5) were less likely to be accepted than North-American contributions when controlling for research type. In addition, the OR for the acceptance for studies with negative results as compared to those with positive results was 0.4 (95% CI 0.3–0.7). A high abstract quality score was also weakly associated with acceptance rates (OR 1.4, 95% CI 1.0–2.0).Conclusions
North-American contributions and reports with statistically positive results have higher acceptance rates at the AGA. Formal abstract quality was also predictive for acceptance.12.
Giasemi Koutouzi Behrooz Nasihatkton Monika Danielak-Nowak Henrik Leonhardt Mårten Falkenberg Fredrik Kahl 《BMC medical imaging》2018,18(1):42
Background
A crucial step in image fusion for intraoperative guidance during endovascular procedures is the registration of preoperative computed tomography angiography (CTA) with intraoperative Cone Beam CT (CBCT). Automatic tools for image registration facilitate the 3D image guidance workflow. However their performance is not always satisfactory. The aim of this study is to assess the accuracy of a new fully automatic, feature-based algorithm for 3D3D registration of CTA to CBCT.Methods
The feature-based algorithm was tested on clinical image datasets from 14 patients undergoing complex endovascular aortic repair. Deviations in Euclidian distances between vascular as well as bony landmarks were measured and compared to an intensity-based, normalized mutual information algorithm.Results
The results for the feature-based algorithm showed that the median 3D registration error between the anatomical landmarks of CBCT and CT images was less than 3 mm. The feature-based algorithm showed significantly better accuracy compared to the intensity-based algorithm (p?<?0.001).Conclusion
A feature-based algorithm for 3D image registration is presented.13.
Background
Studies have shown that sleep quality is negatively affected by perfectionism. Moreover, partner- or relationship-oriented perfectionism negatively influences relationship quality.Objective
This paper aims to investigate the association of general perfectionism with sleep quality and relationship quality.Materials and methods
A study assessing perfectionism, sleep quality, and relationship quality was performed via analyzing online questionnaires completed by 489 German adults from the general population.Results
Participants with impaired sleep showed a higher level of maladaptive perfectionism (concern over mistakes and doubts, parental expectations, and criticism) than participants with good sleep, whereby the severity of sleep problems was not determining. Relationship quality is affected by perfectionism. However, this association is mediated by sleep quality.Conclusion
Perfectionism is associated with worse sleep quality but not with worse relationship quality when sleep quality is integrated into the model as a mediator.14.
Background
SNOMED CT is the most comprehensive medical terminology. However, its use for intelligent services based on formal reasoning is questionable.Methods
The analysis of the structure of SNOMED CT is based on the formal top-level ontology DOLCE.Results
The analysis revealed several ontological and knowledge-engineering errors, the most important are errors in the hierarchy (mostly from an ontological point of view, but also regarding medical aspects) and the mixing of subsumption relations with other types (mostly 'part of').Conclusion
The found errors impede formal reasoning. The paper presents a possible way to correct these problems.15.
Background
In our previous study, we revealed that MEG3 was a tumor suppressor gene in retinoblastoma and inhibited proliferation of retinoblastoma cells by regulating the activity of the Wnt/β-catenin pathway. Here, we further explored the mechanism of MEG3 inactivation in retinoblastoma.Methods
MSP and qRT-PCR were performed to detect the methylation status of MEG3 promoter and levels of MEG3 expression, respective. To further explore relationship between MEG3 expression and epigenetic modifications, 5-Aza-CdR was used to interfere with DNA methylation. In addition, we evaluated proliferation, apoptosis and the expression of β-catenin via CCK-8, flow cytometric analysis and western blot analysis, respective.Results
Hypermethylation of MEG3 promoter was observed more frequently in retinoblastoma tissues and was highly associated with low MEG3 expression and poor survival of retinoblastoma patients. We also provided evidence demonstrating that hypermethylation of MEG3 promoter depressed MEG3 expression, promoted proliferation, inhibited apoptosis and increased β-catenin expression of retinoblastoma cells in vitro.Conclusions
Our present study indicates that promoter silencing by hypermethylation may account for the loss of MEG3 expression and predict poor prognosis.16.
Maísa Mota Antunes Alan Moreira Araújo Ariane Barros Diniz Rafaela Vaz Sousa Pereira Débora Moreira Alvarenga Bruna Araújo David Renata Monti Rocha Maria Alice Freitas Lopes Sarah Cozzer Marchesi Brenda Naemi Nakagaki Érika Carvalho Pedro Elias Marques Bernhard Ryffel Valérie Quesniaux Rodrigo Guabiraba Brito José Carlos Alves Filho Denise Carmona Cara Rafael Machado Rezende Gustavo Batista Menezes 《Inflammation research》2018,67(1):77-88
Objective and design
The aim of this study was to investigate the contribution of IL-33/ST2 axis in the onset and progression of acute liver injury using a mice model of drug-induced liver injury (DILI).Material and treatments
DILI was induced by overdose administration of acetaminophen (APAP) by oral gavage in wild-type BALB/c, ST2-deficient mice and in different bone marrow chimeras. Neutrophils were depleted by anti-Ly6G and macrophages with clodronate liposomes (CLL).Methods
Blood and liver were collected for biochemical, immunologic and genetic analyses. Mice were imaged by confocal intravital microscopy and liver non-parenchymal cells and hepatocytes were isolated for flow cytometry, genetic and immunofluorescence studies.Results
Acetaminophen overdose caused a massive necrosis and accumulation of immune cells within the liver, concomitantly with IL-33 and chemokine release. Liver non-parenchymal cells were the major sensors for IL-33, and amongst them, neutrophils were the major players in amplification of the inflammatory response triggered by IL-33/ST2 signalling pathway.Conclusion
Blockage of IL-33/ST2 axis reduces APAP-mediated organ injury by dampening liver chemokine release and activation of resident and infiltrating liver non-parenchymal cells.17.
18.
H. G. Schwelberger 《Inflammation research》2010,59(2):219-221
Objective
To evaluate the evidence regarding the disease concept of histamine intolerance as a state of inadequate histamine inactivation.Methods
Keyword-based systematic screening of the scientific literature and of public websites focusing on diagnostic and therapeutic procedures.Results
Histamine intolerance is commonly diagnosed based solely on subjective reporting of symptoms instead of following systematic diagnostic procedures based on objective laboratory and physical parameters. The only effective long-term therapy is avoidance of histamine-containing food.Conclusions
The concept of histamine intolerance as a metabolic disease is in need of more experimental and clinical evidence and affected patients will benefit from a clear, evidence-based diagnostic and therapeutic regime.19.
Rachel Hamias Assaf Rudich George Greenberg Gabriel Szendro Talya Wolak 《Inflammation research》2018,67(3):265-275
Objective and design
Evaluating the pro-/anti-inflammatory activity of the C-terminal cleavage product of osteopontin in comparison to angiotensin 1–7.Material and subjects
Human coronary endothelial cells (hcEC) treated with conditioned media from human U937 macrophages.Treatment
Macrophages were (pre)treated with C-terminal, full-length or N-terminal osteopontin (OPN-C, OPN-FL, OPN-N, respectively), angiotensin II, angiotensin 1–7 or TNF-α. OPN-C modulatory capacity was compared to that of Ang1–7 in inhibiting subsequent Ag II, OPN-FL or OPN-N-induced macrophage-mediated endothelial inflammation.Methods
Protein expression of NFκB, IκB, vCAM-1 and iCAM-1 was assessed using western blot. Promotor activation by NFκB was also assessed by dual-luciferase reporter assay.Results
Conditioned media of macrophages treated with OPN-C induced hcECs’ NfκB activation to a lower degree than OPN-FL or OPN-N. Priming of macrophages with angiotensin 1–7 attenuated the endothelial pro-inflammatory effect induced by subsequent exposure of the macrophages to angiotensin II, OPN-FL or OPN-N. This was evidenced by both NfκB activation and vCAM and iCAM expression. In contrast, priming macrophages with OPN-C did not significantly attenuate the subsequent response to the pro-inflammatory cytokines.Conclusions
OPN-C induces lower macrophage-induced endothelial inflammation compared to OPN-FL or OPN-N, but unlike angiotensin 1–7, fails to prevent endothelial inflammation induced by subsequent pro-inflammatory macrophage stimulation.20.
Kai Xu Liuxi Chen Lingyun Fu Shaofang Xu Hongying Fan Qianqian Gao You Xu Wei Wang 《International journal of behavioral medicine》2016,23(4):458-463