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1.
Ruth?Huizinga Karim?L?Kreft Sabina?Onderwater Joke?G?Boonstra Ruud?Brands Rogier?Q?Hintzen Jon?D?Laman
Background
Alkaline phosphatase (AP) is a ubiquitously expressed enzyme which can neutralize endotoxin as well as adenosine triphosphate (ATP), an endogenous danger signal released during brain injury. In this study we assessed a potential therapeutic role for AP in inhibiting neuroinflammation using three complementary approaches.Methods
Mice were immunized to induce experimental autoimmune encephalomyelitis (EAE) and treated with AP for seven days during different phases of disease. In addition, serological assays to determine AP activity, endotoxin levels and endotoxin-reactive antibodies were performed in a cohort of multiple sclerosis (MS) patients and controls. Finally, the expression of AP and related enzymes CD39 and CD73 was investigated in brain tissue from MS patients and control subjects.Results
AP administration during the priming phase, but not during later stages, of EAE significantly reduced neurological signs. This was accompanied by reduced proliferation of splenocytes to the immunogen, myelin oligodendrocyte glycoprotein peptide. In MS patients, AP activity and isoenzyme distribution were similar to controls. Although endotoxin-reactive IgM was reduced in primary-progressive MS patients, plasma endotoxin levels were not different between groups. Finally, unlike AP and CD73, CD39 was highly upregulated on microglia in white matter lesions of patients with MS.Conclusions
Our findings demonstrate that: 1) pre-symptomatic AP treatment reduces neurological signs of EAE; 2) MS patients do not have altered circulating levels of AP or endotoxin; and 3) the expression of the AP-like enzyme CD39 is increased on microglia in white matter lesions of MS patients.2.
Altaf A. Kondkar Nikhil B. Edward Hatem Kalantan Abdullah S. Al-Kharashi Saleh Altuwaijri Gamal Mohamed Tahira Sultan Taif A. Azad Khaled K. Abu-Amero 《Journal of negative results in biomedicine》2017,16(1):3
Background
To investigate whether polymorphism rs540782 on chromsome 1, in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene, is a risk factor for primary open angle glaucoma (POAG).Method
The study genotyped 92 unrelated POAG cases and 95 control subjects from Saudi Arabia using Taq-Man® assay.Results
The genotype frequency distribution did not deviate significantly from the Hardy-Weinberg equilibrium (p?>?0.05). Overall, both the genotype and allele frequencies were not significantly different between cases and controls. The minor ‘C’ allele frequency was 49.4%, which was comparable to the Japanese population and higher than the Indian and Afro-Caribbean populations. Similarly, no significant association was found between genotypes and systemic diseases and health awareness/behavior domain variables. Importantly, glaucoma specific indices, such as intraocular pressure, cup/disc ratio and number of anti-glaucoma medication, also showed no statistically significant effect of genotypes within POAG cases.Conclusion
Polymorphism rs540782 is not a risk factor for POAG in the Saudi cohort.3.
4.
Background
P-glycoprotein (P-gp) and breast cancer resistance protein (BCRP) play a critical role in keeping neurotoxic substances from entering the brain. We and others have previously reported an impact of inflammation on the regulation of adult blood–brain barrier (BBB) efflux transporters. However, studies in children have not been done. From the pediatric clinical perspective, it is important to understand how the central nervous system (CNS) and BBB drug efflux transporters differ in childhood from those of adults under normal and inflammatory conditions. Therefore, we examined and compared the regulation of P-gp and BCRP expression and transport activity in young and adult BBB and investigated the molecular mechanisms underlying inflammatory responses.Methods
Rats at postnatal day (P) P21 and P84, corresponding to the juvenile and adult stages of human brain maturation, respectively, were treated with endothelin-1 (ET-1) given by the intracerebroventricular (icv) route. Twenty-four hours later, we measured P-gp and BCRP protein expression in isolated brain capillary by immunoblotting as well as by transport activity in vivo by measuring the unbound drug partitioning coefficient of the brain (Kp,uu,brain) of known efflux transporter substrates administered intravenously. Glial activation was measured by immunohistochemistry. The release of cytokines/chemokines (interleukins-1α, 1-β (IL-1β), -6 (IL-6), -10 (IL-10), monocyte chemoattractant protein (MCP-1/CCL2), fractalkine and tissue inhibitor of metalloproteinases-1 (TIMP-1)) were simultaneously measured in brain and serum samples using the Agilent Technology cytokine microarray.Results
We found that juvenile and adult BBBs exhibited similar P-gp and BCRP transport activities in the normal physiological conditions. However, long-term exposure of the juvenile brain to low-dose of ET-1 did not change BBB P-gp transport activity but tended to decrease BCRP transport activity in the juvenile brain, while a significant increase of the activity of both transporters was evidenced at the BBB in the adult brain. Moreover, juvenile and adult brain showed differences in their expression profiles of cytokines and chemokines mediated by ET-1.Conclusions
BBB transporter activity during neuroinflammation differs between the juvenile and adult brains. These findings emphasize the importance of considering differential P-gp and BCRP transport regulation mechanisms between adult and juvenile BBB in the context of neuroinflammation.5.
Taif A. Azad Nikhil B. Edward Altaf A. Kondkar Hatem Kalantan Saleh Altuwaijri Tahira Sultan Faisal A. Al-Mobarak Saleh A. Al-Obeidan Khaled K. Abu-Amero 《Journal of negative results in biomedicine》2017,16(1):12
Background
To investigate the association between polymorphism rs547984, located in close proximity to the Zona Pellucida Glycoprotein 4 (ZP4) gene on human chromosome 1q43 and primary open angle glaucoma (POAG).Method
Polymorphism rs547984 was genotyped using Taq-Man® assay in 185 subjects comprising of 90 unrelated POAG cases and 95 controls of Saudi origin.Results
Association analysis between cases and controls revealed no significant genotype distribution under additive (p = 0.356), dominant (p = 0.517) and recessive (p = 0.309) models. Besides, the allele frequency distribution was also found to be non-significant (p = 0.70). The minor “A” allele frequency was found to be 0.49 and 0.50 among POAG cases and controls, respectively. In addition, specific clinical indices used to assess severity of glaucoma such as intraocular pressure (IOP), cup/disc ratio and number of anti-glaucoma medication also did not show any significant genotype distribution in POAG cases.Conclusion
Polymorphism rs547984 is neither associated with any clinical indices important for POAG such as IOP and cup/disc ratio nor is a risk factor for POAG in the Saudi cohort.6.
John C. Moring Alan L. Peterson Kathryn E. Kanzler 《International journal of behavioral medicine》2018,25(3):312-321
Purpose
Acoustic trauma is more prevalent in military settings, especially among individuals with combat-related military occupational specialties. Gunfire, improvised explosive devices, and mortar explosions are a few examples that may cause hearing degradation and tinnitus. It is possible that the same events that are associated with auditory problems can cause traumatic brain injury (TBI) and posttraumatic stress disorder (PTSD).Method
This paper reviews the distinct and overlapping symptoms of tinnitus, TBI, and PTSD, and how these disorders interact to synergistically promote negative outcomes.Results
Tinnitus may serve as a significant contributor to symptoms of TBI and PTSD. Therefore, tinnitus subtypes could be identified as physiologically or psychologically based, or both.Conclusions
Additional research is warranted to determine the common and unique symptoms and associated neurological pathways of tinnitus, TBI, and PTSD. Brief treatment recommendations are provided, including a multidisciplinary approach for the physical and psychological distress associated with tinnitus.7.
Zahida Taibi-Djennah Marie-France Martin-Eauclaire Fatima Laraba-Djebari 《Inflammation research》2018,67(10):863-877
Objective
Kaliotoxin2 (KTX2) is a highly selective blocker of voltage-dependent potassium channels Kv1.3 containing 37 amino acid residues. It is purified from Androctonus australis scorpion venom. The binding of KTX2 to its targets is able to alter the neuronal excitability leading to neurological disorders, accompanied by an inflammatory response. In brain, activation of insulin receptor signaling pathway by insulin induces current suppression and concomitant tyrosine phosphorylation of Kv1.3 channel. The aim of this study is to evaluate the effect of insulin injected by i.c.v. route on the neuro-pathophysiological and systemic disorders induced by KTX2.Materials and methods
Tissue damage, inflammatory response and oxidative stress biomarkers were assessed in NMRI mice at 24 h after co-injection of KTX2 and insulin by intracerebroventricular route.Results
Obtained results revealed that the central administration of insulin prevents cerebral cortex injury, brain edema and blood–brain barrier alteration induced by KTX2, these are accompanied by significant decrease of systemic disorders including serum cytokines, inflammatory and oxidative stress markers and tissue damage.Conclusion
These results indicate that insulin is able to reduce neuro-immunological effects and systemic disorders induced by KTX2. The neuroprotective effect of insulin may be due to its crucial role in the regulation of inflammation response and its properties to modulate the activity of Kv1.3 channels in brain.8.
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.9.
Hong Wang Mingqiang Hua Shukang Wang Jie Yu Chen Chen Xueyun Zhao Chen Zhang Chaoqin Zhong Ruiqing Wang Na He Ming Hou Daoxin Ma 《Inflammation research》2017,66(3):249-258
Background
Though the pathogenesis of AML is still unknown, accumulating evidence revealed that immune response plays a vital part in it. NLRP3 inflammasome as a component of immune system has been found related to several cancers. The single nucleotide polymorphisms (SNPs) of NLRP3 inflammasome genes may be related to pathogenesis and prognosis of AML.Methods and results
We determined polymorphisms of NLRP3 (rs35829419), CARD8 (rs2043211), IL-1β (rs16944), IL-18 (rs1946518) and NF-κB ?94 ins/del ATTG in de novo AML patients to find out whether they play roles in the susceptibility and severity of AML. In our study, 383 AML cases and 300 randomly selected healthy individuals were examined for the polymorphisms and expression of NLRP3 genes. IL-1β (rs16944) polymorphism in different risk AML subgroups was found statistically different, with more GA genotype in favorable-risk cytogenetics group. We also demonstrated that the bone marrow blasts of patients carrying IL-18 (rs1946518) GG or GT genotype were higher than patients of TT genotype. IL-18 plasma level of patients with IL-18 (rs1946518) GT or TT genotype was higher than GG genotype. Moreover, the GT genotype of IL-18 (rs1946518) led to statistically poorer AML-specific survival.Conclusion
IL-1β (rs16944) and IL-18 (rs1946518) may be served as potential predictors for AML.10.
Isabelle C. C. dos Santos Julieta Genre Diego Marques Ananília M. G. da Silva Jéssica C. dos Santos Jéssica N. G. de Araújo Victor H. R. Duarte Angel Carracedo Maria Torres-Español Gisele Bastos Carlos C. de Oliveira Ramos André D. Luchessi Vivian N. Silbiger 《BMC medical genetics》2017,18(1):140
Background
Thyroid cancer is a common malignant disease of the endocrine system with increasing incidence rates over the last few decades. In this study, we sought to analyze the possible association of 45 single nucleotide polymorphisms (SNPs) with thyroid cancer in a population from Rio Grande do Norte, Brazil.Methods
Based on histological analysis by a pathologist, 80 normal thyroid specimens of tissue adjacent to thyroid tumors were obtained from the biobank at the Laboratory of Pathology of Liga Norte Riograndense Contra o Câncer, Natal, RN. Patient samples were then genotyped using the MassARRAY platform (Sequenon, Inc) followed by statistical analysis employing the SNPassoc package in R program. The genotypic frequencies of all 45 SNPs obtained from the International HapMap Project database and based on data from the ancestral populations of European and African origin were used to compose the control study group.Results
In our study, the following 9 SNPs showed significant differences in their frequency when comparing the study and control groups: rs3744962, rs258107, rs1461855, rs4075022, rs9943744, rs4075570, rs2356508, rs17485896, and rs2651339. Furthermore, the SNPs rs374492 C/T and rs258107 C/T were associated with a relative risk for thyroid carcinoma of 3.78 (p?=?6.27?×?10e?5) and 2.91 (p?=?8.27?×?10e?5), respectively, after Bonferroni’s correction for multiple comparisons.Conclusions
These nine polymorphisms could be potential biomarkers of predisposition to thyroid carcinoma in the population from Rio Grande do Norte. However, complementary studies including a control group with samples obtained from healthy subjects in Rio Grande do Norte state, should be conducted to confirm these results.11.
Hong Song Lei Chen RuiQi Gao Iordachescu Ilie Mihaita Bogdan Jian Yang Shuliang Wang Wentian Dong Wenxiang Quan Weimin Dang Xin Yu 《BMC medical informatics and decision making》2017,17(3):166
Background
Schizophrenia is a kind of serious mental illness. Due to the lack of an objective physiological data supporting and a unified data analysis method, doctors can only rely on the subjective experience of the data to distinguish normal people and patients, which easily lead to misdiagnosis. In recent years, functional Near-Infrared Spectroscopy (fNIRS) has been widely used in clinical diagnosis, it can get the hemoglobin concentration through the variation of optical intensity.Methods
Firstly, the prefrontal brain networks were constructed based on oxy-Hb signals from 52-channel fNIRS data of schizophrenia and healthy controls. Then, Complex Brain Network Analysis (CBNA) was used to extract features from the prefrontal brain networks. Finally, a classier based on Support Vector Machine (SVM) is designed and trained to discriminate schizophrenia from healthy controls. We recruited a sample which contains 34 healthy controls and 42 schizophrenia patients to do the one-back memory task. The hemoglobin response was measured in the prefrontal cortex during the task using a 52-channel fNIRS system.Results
The experimental results indicate that the proposed method can achieve a satisfactory classification with the accuracy of 85.5%, 92.8% for schizophrenia samples and 76.5% for healthy controls. Also, our results suggested that fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.Conclusions
Our results suggested that, using the appropriate classification method, fNIRS has the potential capacity to be an effective objective biomarker for the diagnosis of schizophrenia.12.
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.13.
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.14.
Shahanas Chathoth Mona H. Ismail Chittibabu Vatte Cyril Cyrus Zhara Al Ali Khandaker Ahtesham Ahmed Sadananda Acharya Aisha Mohammed Al Barqi Amein Al Ali 《BMC medical genetics》2018,19(1):203
Background
Obesity is one of the main causes of morbidity and mortality worldwide. More than 120 genes have been shown to be associated with obesity related phenotypes. The aim of this study was to determine the effect of selected genetic polymorphisms in Uncoupling protein 1 (UCP1) and Niemann-Pick C1 (NPC1) genes in an obese population in Saudi Arabia.Methods
The genotypes of rs1800592, rs10011540 and rs3811791 (UCP1 gene) and rs1805081 and rs1805082 (NPC1 gene) were determined in a total of 492 subjects using TaqMan chemistry by Real-time PCR. In addition, capillary sequencing assay was performed to identify two specific polymorphisms viz., rs45539933 (exon 2) and rs2270565 (exon 5) of UCP1 gene.Results
A significant association of UCP1 polymorphisms rs1800592 [OR, 1.52 (1.10–2.08); p?=?0.009] was observed in the obese cohort after adjusting with age, sex and type 2 diabetes. Further BMI based stratification revealed that this association was inconsistent with both moderate and extreme obese cohort. A significant association of UCP1 polymorphisms rs3811791 was observed only in the moderate-obese cohort [OR?=?2.89 (1.33–6.25); p?=?0.007] but not in the extreme-obese cohort indicating an overlying genetic complexity between moderate-obesity and extreme-obesity. The risk allele frequencies, which were higher in moderate-obese cohort, had abnormal HDL, LDL and triglyceride levels.Conclusion
The rs1800592 and rs3811791 of UCP1 gene are associated with obesity in general and in the moderate-obese group in particular. The associated UCP1 polymorphisms in the moderate-obese group may regulate the impaired energy metabolism which plays a significant role in the initial stages of obesity.15.
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.16.
Doortje W. Dekens Petrus J. W. Naudé Jan N. Keijser Ate S. Boerema Peter P. De Deyn Ulrich L. M. Eisel 《Journal of neuroinflammation》2018,15(1):330
Background
Lipocalin 2 (Lcn2) is an acute-phase protein implicated in multiple neurodegenerative conditions. Interestingly, both neuroprotective and neurodegenerative effects have been described for Lcn2. Increased Lcn2 levels were found in human post-mortem Alzheimer (AD) brain tissue, and in vitro studies indicated that Lcn2 aggravates amyloid-β-induced toxicity. However, the role of Lcn2 has not been studied in an in vivo AD model. Therefore, in the current study, the effects of Lcn2 were studied in the J20 mouse model of AD.Methods
J20 mice and Lcn2-deficient J20 (J20xLcn2 KO) mice were compared at the behavioral and neuropathological level.Results
J20xLcn2 KO and J20 mice presented equally strong AD-like behavioral changes, cognitive impairment, plaque load, and glial activation. Interestingly, hippocampal iron accumulation was significantly decreased in J20xLcn2 KO mice as compared to J20 mice.Conclusions
Lcn2 contributes to AD-like brain iron dysregulation, and future research should further explore the importance of Lcn2 in AD.17.
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.18.
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.19.
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.20.
Xiujian Xu Liang Zhang Xinchun Ye Qi Hao Tao Zhang Guiyun Cui Ming Yu 《Inflammation research》2018,67(1):57-65