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61.
Platelets have diverse roles in immune processes in addition to their key functions in haemostasis and thrombosis. Some studies imply that platelets may be possibly related to the immune tolerance induction. However, the role of platelets in the development of immune tolerance is not fully understood. The purpose of this study was to investigate the role of platelets in the development of regulatory mechanisms responsible for cutaneous inflammation using a mouse model of low zone tolerance (LZT). Mice were treated with 2,4,6‐trinitro‐1‐chlorobenzene (TNCB) 8 times every other day for tolerance induction with administration of anti‐platelet antibody or control antibody during the tolerance induction phase every 3 days. After the treatment for the tolerance induction, mice were sensitized and then challenged with TNCB. The contact hypersensitivity (CHS) was significantly decreased at 24 hours after challenge in the mice with LZT than in those without LZT. Platelet depletion via administration of anti‐platelet antibody reversed the inhibition of CHS and reduced the frequency of Foxp3+ Tregs in the inflamed skin and draining lymph nodes in mice with LZT. In addition, repeated low‐dose skin exposure resulted in elevated plasma levels of transforming growth factor (TGF)‐β1. Interestingly, platelet depletion reduced plasma TGF‐β1 levels of mice with LZT. Furthermore, the CHS response was reduced by administration of recombinant TGF‐β1 during platelet depletion in mice with LZT. Administration of anti‐TGF‐β antibody reversed the inhibition of the CHS responses. These results suggest that platelets are involved in the induction of immune tolerance via the release of TGF‐β1. 相似文献
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Peyman Sardari Nia Jean H.T. Daemen Jos G. Maessen 《The Journal of thoracic and cardiovascular surgery》2019,157(4):1567-1574
Objectives
The aim of this study was to develop a high-fidelity minimally invasive mitral valve surgery (MIMVS) simulator.Methods
The process of industrial serial design was applied based on pre-set requirements, acquired by interviewing experienced mitral surgeons. A thoracic torso with endoscopic and robotic access and disposable silicone mitral valve apparatus with a feedback system was developed. The feedback system was based on 4 cameras around the silicone valve and an edge detection algorithm to calculate suture depth and width. Validity of simulator measurements was assessed by comparing simulator-generated values with measurements done manually on 3-dimensional reconstructed micro-computed tomography scan of the same sutures. Independent surgeons tested the simulator between 2014 and 2018, whereupon an evaluation was done through a questionnaire.Results
The feedback system was able to provide width and depth measurements, which were subsequently scored by comparison to pre-set target values. Depth did not significantly differ between simulator and micro-computed tomography scan measurements (P = .139). Width differed significantly (P = .001), whereupon a significant regression equation was found (P < .0001) to calibrate the simulator. After calibration, no significant difference was found (P = .865). In total, 99 surgeons tested the simulator and more than agreed with the statements that the simulator is a good method for training MIMVS, and that the mitral valve and suture placement looked and felt realistic.Conclusions
We successfully developed a high-fidelity MIMVS simulator for endoscopic and robotic approaches. The simulator provides a platform to train skills in an objective and reproducible manner. Future studies are needed to provide evidence for its application in training surgeons. 相似文献65.
Shuangchun Liu Fei Wu Zongzhou Wu Ying Li Shujie Zhang Ning Yu 《Experimental dermatology》2019,28(3):233-239
Skin injury can trigger formation of new lesions in psoriasis (Koebner phenomenon). The mechanisms through which injury exacerbates psoriasis are unclear. During wound repair, epidermal keratinocytes are activated and produce abundant IL‐36γ, further promoting the skin inflammation. IL‐17A is the cornerstone cytokine in the pathogenesis of psoriasis. We sought to investigate the effects of IL‐17A on injury‐induced keratinocyte activation and IL‐36γ production. Here, we demonstrated that dsRNA released from necrotic keratinocytes induced the expression of IL‐36γ. Silencing of TLR3 by siRNA decreased the IL‐36γ induction by necrotic keratinocyte supernatant. Co‐stimulation with dsRNA and IL‐17A synergistically increased the expression of IL‐36γ and other proinflammatory mediators (CCL20, CXCL8, DEFB4 and LCN2) in keratinocytes. The synergistic effects were not dependent on TLR3 upregulation, TNF receptor signalling and mRNA stabilization. Co‐stimulation with dsRNA and IL‐17A resulted in an accumulation of IκBζ. The synergistic upregulation of IL‐36γ and proinflammatory mediators were inhibited by IκBζ siRNA. Co‐stimulation with IL‐17A and poly(I:C) markedly activated the p38 MAPK and NF‐κB pathway, compared with poly(I:C). Blockade of p38 MAPK and NF‐κB suppressed dsRNA/IL‐17A–mediated IκBζ and IL‐36γ induction. These findings demonstrated that IL‐17A synergistically enhanced the dsRNA‐mediated IL‐36γ production through a p38 MAPK‐, NF‐κB–, and IκBζ‐dependent mechanism. 相似文献
66.
Alicia Julibert Maria del Mar Bibiloni Josep A. Tur 《Nutrition, metabolism, and cardiovascular diseases : NMCD》2019,29(9):887-905
Background and aimsThe metabolic syndrome (MetS) is a cluster of coexisting cardiovascular risk factors. The role of specific dietary fats was reemphasized by dietary recommendations. This systematic review aims to assess evidence for the effect of dietary fat intake on MetS occurrence and reversion in adults.Methods and ResultsThe MEDLINE database was used to search the existing literature. We included observational studies that analyzed dietary fat intake in adults with MetS and clinical trials that compared the effects of different dietary fat diets on MetS and/or its components. Thirty articles were selected (14 observational and 16 clinical trials), and we included information of dietary fat and fatty acids as well as MetS, body mass index, cholesterol, hypertension, and diabetes in adults. SFA intake was found to be positively associated with MetS components. Most of the observational reviewed studies found beneficial associations between MUFA and PUFA (including n-3 and n-6 subtypes) intake and MetS components. Clinical trials also supported the benefits of MUFA- or PUFA-enriched diets (including low-fat diets) in reducing MetS.ConclusionsThe effects of dietary SFAs on MetS will be influenced by other specific nutrients. Replacement of SFA by MUFA and PUFA has been associated with a decrease in MetS. Dietary recommendations should emphasize on different qualities of fat intake, not only to reduce total fat intake, to obtain health benefits in adults. 相似文献
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《Saudi Journal of Ophthalmology》2019,33(2):153-158
PurposeParaoxonases (PON) are calcium bound enzymes offering protection against oxidative stress by working as endogenous free-radical scavenging molecules. Oxidative stress has been implicated in pathophysiology of many diseases including cataract. Lens opacity is an age related disorder which is a principal cause of blindness in Pakistani population. Relationship of PON2 and PON3 polymorphism with genetic predisposition for incidence of cataract has not been investigated till date. Objective of the current study was to explore possible association between PON2 and PON3 polymorphism with incidence of cataract in local population.MethodsOur study design comprised of fifty-one cataractous and fifty-nine healthy individuals. Identification of single nucleotide polymorphism (SNP) at positions (C311S and G148A) for PON2 and C133A for PON3 was conducted using restriction fragment length polymorphism (RFLP).ResultsStatistical analysis revealed significant association of PON2 G148 allele with incidence of cataract. GG allele was found to be higher in cataract patients as compared to control (p < 0.001) suggesting distribution of PON2 G148A genotype and allele frequency is linked with cataractogenesis. There was no noticeable association between PON2 C311S and PON3 C133A. Significant difference was observed in distribution of 311CS/148A combined genotype with highest frequency in control individuals (88.89%), while 311S/148G combined genotypes showed the highest frequencies among the cataract patients (71.42%).ConclusionOur data suggests mutation at G148A might be related with incidence of cataract in studied population. 相似文献
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The pituitary tumor-transforming gene 1 (PTTG1), also known as Securin, is considered an oncogene. This study aimed to investigate the role of PTTG1 in clear cell renal cell carcinoma (ccRCC) using in silico bioinformatics approaches. A pan-cancer analysis using The Cancer Genome Atlas (TCGA) data indicated that among all cancer types copy number amplification of PTTG1 gene was most frequently found in ccRCC. However, amplification of PTTG1 gene copy number did not correlate with the increase of mRNA level in ccRCC, and did not predict the patients' overall survival. Instead, ccRCC was correlated with overexpression of PTTG1 mRNA, and its expression level was stage-dependent increased in cancer patients. An outlier analysis using the Oncomine database suggested that PTTG1 mRNA expression served as a good biomarker for ccRCC. Pathway analysis for upregulated genes enriched in PTTG1-high expressing ccRCC patients found that PTTG1 overexpression was associated with mitotic defects. Mining drug sensitivity data using the Cancer Therapeutics Response Portal (CTRP) discovered that PTTG1-high expressing ccRCC cell lines were susceptible to a Rac1 (Ras-related C3 botulinum toxin substrate 1) inhibitor NSC23766. Therefore, this study provides an in silico insight into the role of PTTG1 in ccRCC, and repurposes the Rac1 inhibitor NSC23766 for treating PTTG1-high expressing ccRCC. 相似文献