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51.
Bleomycin is a well-recognized antineoplastic drug. However, pulmonary fibrosis (PF) is considered to be the principal drawback that greatly limits its use. Here, we sought to investigate ability of the neurokinin receptor 1 blocker, aprepitant, to prevent PF caused by bleomycin. Male adult Wistar rat groups were given a single intratracheal injection of bleomycin, either alone or in combination with aprepitant therapy for 3 or 14 days. Collagen deposition and a rise in transforming growth factor beta (TGF-β) immunoreactivity in lung tissue serve as evidence of bleomycin-induced PF. The serum levels of lactate dehydrogenase, alkaline phosphatase, and total antioxidant improved after aprepitant therapy.Additionally, it reduced the protein expressions of interferon alpha, tumor necrosis factor alpha, and lung lipid peroxidation. Moreover, aprepitant treatment led to an increase in the antioxidant indices glutathione, glutathione peroxidase, and catalase. Aprepitant is postulated to protect against bleomycin-induced PF by decreasing TGF-β, phosphorylating Smad3, and increasing interleukin 37, an anti-fibrotic cytokine, and G Protein-coupled Receptor Kinase 2. Aprepitant for 14 days considerably exceeded aprepitant for 3 days in terms of improving lung damage and having an anti-fibrotic impact. In conclusion, aprepitant treatment for 14 days may be used as an adjuvant to bleomycin therapy to prevent PF, mostly through inhibiting the TGF-/p-Smad3 fibrotic pathway. 相似文献
53.
《The British journal of oral & maxillofacial surgery》2022,60(4):507-512
This study assessed whether preoperative class III patients could recreate their facial difference based on a profile photograph. Twenty class III pre-surgery bimaxillary orthognathic patients used CASSOS (SoftEnable Technology Ltd.) to manipulate a distorted soft tissue image of them until they felt it resembled their current soft tissue profile. Patients were able to move their upper lip and lower chin backward and forwards, as well as the lower chin up and down. Differences in the mean absolute distance between the patient-perceived position of the upper lip (Labrale superious) and chin (Pogonion) and the actual position of their upper lip and chin were measured on two occasions. Intra-patient reproducibility was found to be excellent (ICC 0.93 to 0.98). All differences were statistically significantly greater than 3mm, and would be clinically significant. Patients were better at re-creating their AP chin position rather than their AP upper lip and vertical chin positions. Approximately half of patients undergoing surgical correction of their class III skeletal pattern were unable to correctly identify their pre-surgical facial profile. Given the lack of awareness of their profile, this questions the validity of using profile planning for informed consent. 相似文献
54.
《Brain stimulation》2019,12(6):1526-1536
BackgroundEvidence suggests that repetitive transcranial magnetic stimulation (rTMS), a non-invasive neuromodulation technique, alters resting brain activity. Despite anecdotal evidence that rTMS effects wear off, there are no reports of longitudinal studies, even in humans, mapping the therapeutic duration of rTMS effects.ObjectiveHere, we investigated the longitudinal effects of repeated low-intensity rTMS (LI-rTMS) on healthy rodent resting-state networks (RSNs) using resting-state functional MRI (rs-fMRI) and on sensorimotor cortical neurometabolite levels using proton magnetic resonance spectroscopy (MRS).MethodsSprague-Dawley rats received 10 min LI-rTMS daily for 15 days (10 Hz or 1 Hz stimulation, n = 9 per group). MRI data were acquired at baseline, after seven days and after 14 days of daily stimulation and at two more timepoints up to three weeks post-cessation of daily stimulation.Results10 Hz stimulation increased RSN connectivity and GABA, glutamine, and glutamate levels. 1 Hz stimulation had opposite but subtler effects, resulting in decreased RSN connectivity and glutamine levels. The induced changes decreased to baseline levels within seven days following stimulation cessation in the 10 Hz group but were sustained for at least 14 days in the 1 Hz group.ConclusionOverall, our study provides evidence of long-term frequency-specific effects of LI-rTMS. Additionally, the transient connectivity changes following 10 Hz stimulation suggest that current treatment protocols involving this frequency may require ongoing “top-up” stimulation sessions to maintain therapeutic effects. 相似文献
55.
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
56.
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58.
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59.
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
60.
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