A Novel Insight into the Role of Entry Tears in Type B Aortic Dissection: Pressure Measurements in an in Vitro Model

2017 ◽  
Vol 40 (10) ◽  
pp. 563-574 ◽  
Author(s):  
Stefania Marconi ◽  
Ettore Lanzarone ◽  
Hector De Beaufort ◽  
Michele Conti ◽  
Santi Trimarchi ◽  
...  
Keyword(s):  
False Lumen ◽  
Patient Characteristics ◽  
Acute Type ◽  
Type B ◽  
Type B Dissection ◽  
Vitro Model ◽  
Insight Into

Introduction Predicting aortic growth in acute type B dissection is fundamental in planning interventions. Several factors are considered to be growth predictors in the literature and, among them, size and location of entry tears have been recognized to particularly influence the false lumen pressure. In this study, we develop an in vitro setting to analyze the actual impact of size and location of the entry tears on false lumen pressure, in the absence of other confounding factors such as the deformability of the aortic wall. Methods We formalize some indexes that synthetically describe the false lumen pressure with respect to the true lumen pressure. Then, we experimentally derive their values in several configurations of the in vitro setting, and we look for trends in the indexes with respect to the size and location of entry tears. Results: Results show that the tears have a relevant impact on the false lumen pressure, but that their size and location alone are not enough to explain the phenomena observed in vivo. Conclusions To predict the behavior of acute type B dissection, we therefore recommend not limiting to size and location, as many effects may derive from the interactions between these parameters and other patient characteristics.

scholarly journals Role of the C5a-C5a receptor axis in the inflammatory responses of the lungs after experimental polytrauma and hemorrhagic shock

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Shinjini Chakraborty ◽  
Veronika Eva Winkelmann ◽  
Sonja Braumüller ◽  
Annette Palmer ◽  
Anke Schultze ◽  
...  
Keyword(s):  
Hemorrhagic Shock ◽  
Inflammatory Responses ◽  
Experimental Models ◽  
Lung Damage ◽  
C5a Receptor ◽  
Cytokine Levels ◽  
Vitro Model

AbstractSingular blockade of C5a in experimental models of sepsis is known to confer protection by rescuing lethality and decreasing pro-inflammatory responses. However, the role of inhibiting C5a has not been evaluated in the context of sterile systemic inflammatory responses, like polytrauma and hemorrhagic shock (PT + HS). In our presented study, a novel and highly specific C5a L-aptamer, NoxD21, was used to block C5a activity in an experimental murine model of PT + HS. The aim of the study was to assess early modulation of inflammatory responses and lung damage 4 h after PT + HS induction. NoxD21-treated PT + HS mice displayed greater polymorphonuclear cell recruitment in the lung, increased pro-inflammatory cytokine levels in the bronchoalveolar lavage fluids (BALF) and reduced myeloperoxidase levels within the lung tissue. An in vitro model of the alveolar-capillary barrier was established to confirm these in vivo observations. Treatment with a polytrauma cocktail induced barrier damage only after 16 h, and NoxD21 treatment in vitro did not rescue this effect. Furthermore, to test the exact role of both the cognate receptors of C5a (C5aR1 and C5aR2), experimental PT + HS was induced in C5aR1 knockout (C5aR1 KO) and C5aR2 KO mice. Following 4 h of PT + HS, C5aR2 KO mice had significantly reduced IL-6 and IL-17 levels in the BALF without significant lung damage, and both, C5aR1 KO and C5aR2 KO PT + HS animals displayed reduced MPO levels within the lungs. In conclusion, the C5aR2 could be a putative driver of early local inflammatory responses in the lung after PT + HS.

scholarly journals Dissemination of Rat Cytomegalovirus through Infected Granulocytes and Monocytes In Vitro and In Vivo

2003 ◽  
Vol 77 (20) ◽  
pp. 11274-11278 ◽  
Author(s):  
B. W. A. van der Strate ◽  
J. L. Hillebrands ◽  
S. S. Lycklama à Nijeholt ◽  
L. Beljaars ◽  
C. A. Bruggeman ◽  
...  
Keyword(s):  
Intravenous Injection ◽  
Systemic Infection ◽  
Insight Into

ABSTRACT The role of leukocytes in the in vivo dissemination of cytomegalovirus was studied in this experiment. Rat cytomegalovirus (RCMV) could be transferred to rat granulocytes and monocytes by cocultivation with RCMV-infected fibroblasts in vitro. Intravenous injection of purified infected granulocytes or monocytes resulted in a systemic infection in rats, indicating that our model is a powerful tool to gain further insight into CMV dissemination and the development of new antivirals.

scholarly journals Histone H3K23-specific acetylation by MORF is coupled to H3K14 acylation

2019 ◽  
Vol 10 (1) ◽  
Author(s):  
Brianna J. Klein ◽  
Suk Min Jang ◽  
Catherine Lachance ◽  
Wenyi Mi ◽  
Jie Lyu ◽  
...  
Keyword(s):  
Posttranslational Modification ◽  
Memory Impairment ◽  
Target Genes ◽  
Epigenetic Mark ◽  
Mechanistic Insight ◽  
Genomic Analyses ◽  
Insight Into

Abstract Acetylation of histone H3K23 has emerged as an essential posttranslational modification associated with cancer and learning and memory impairment, yet our understanding of this epigenetic mark remains insufficient. Here, we identify the native MORF complex as a histone H3K23-specific acetyltransferase and elucidate its mechanism of action. The acetyltransferase function of the catalytic MORF subunit is positively regulated by the DPF domain of MORF (MORFDPF). The crystal structure of MORFDPF in complex with crotonylated H3K14 peptide provides mechanistic insight into selectivity of this epigenetic reader and its ability to recognize both histone and DNA. ChIP data reveal the role of MORFDPF in MORF-dependent H3K23 acetylation of target genes. Mass spectrometry, biochemical and genomic analyses show co-existence of the H3K23ac and H3K14ac modifications in vitro and co-occupancy of the MORF complex, H3K23ac, and H3K14ac at specific loci in vivo. Our findings suggest a model in which interaction of MORFDPF with acylated H3K14 promotes acetylation of H3K23 by the native MORF complex to activate transcription.

scholarly journals Chronic Microcystin-LR Exposure Induces Hepatocarcinogenesis via Increased Gankyrin in Vitro and in Vivo

2018 ◽  
Vol 49 (4) ◽  
pp. 1420-1430 ◽  
Author(s):  
Lixiong He ◽  
Yujing Huang ◽  
Qiaonan Guo ◽  
Hui Zeng ◽  
Chuanfen Zheng ◽  
...  
Keyword(s):  
Low Dose ◽  
Soft Agar ◽  
Tumor Formation ◽  
Sprague Dawley ◽  
Sprague Dawley Rats ◽  
L02 Cells ◽  
Insight Into

Background/Aims: Our recent study indicated that the serum microcystin-LR (MC-LR) level is positively linked to the risk of human hepatocellular carcinoma (HCC). Gankyrin is over-expressed in cancers and mediates oncogenesis; however, whether MC-LR induces tumor formation and the role of gankyrin in this process is unclear. Methods: We induced malignant transformation of L02 liver cells via 35 passages with exposure to 1, 10, or 100 nM MC-LR. Wound healing, plate and soft agar colony counts, and nude mice tumor formation were used to evaluate the tumorigenic phenotype of MC-LR-treated cells. Silencing gankyrin was used to confirm its function. We established a 35-week MC-LR exposure rat model by twice weekly intraperitoneal injection with 10 μg/kg body weight. In addition, 96 HCC patients were tested for tumor tissue gankyrin expression and serum MC-LR levels. Results: Chronic low-dose MC-LR exposure increased proliferation, mobility, clone and tumor formation abilities of L02 cells as a result of gankyrin activation, while silencing gankyrin inhibited the carcinogenic phenotype of MC-LR-treated cells. MC-LR also induced neoplastic liver lesions in Sprague-Dawley rats due to up-regulated gankyrin. Furthermore, a trend of increased gankyrin was observed in humans exposed to MC-LR. Conclusion: These results suggest that MC-LR induces hepatocarcinogenesis in vitro and in vivo by increasing gankyrin levels, providing new insight into MC-LR carcinogenicity studies.

scholarly journals Role of LecA and LecB Lectins in Pseudomonas aeruginosa-Induced Lung Injury and Effect of Carbohydrate Ligands

2009 ◽  
Vol 77 (5) ◽  
pp. 2065-2075 ◽  
Author(s):  
Chanez Chemani ◽  
Anne Imberty ◽  
Sophie de Bentzmann ◽  
Maud Pierre ◽  
Michaela Wimmerová ◽  
...  
Keyword(s):  
Pseudomonas Aeruginosa ◽  
Acute Lung Injury ◽  
Lung Injury ◽  
Parental Strain ◽  
A549 Cells ◽  
Carbohydrate Ligands ◽  
Vitro Model

ABSTRACT Pseudomonas aeruginosa is a frequently encountered pathogen that is involved in acute and chronic lung infections. Lectin-mediated bacterium-cell recognition and adhesion are critical steps in initiating P. aeruginosa pathogenesis. This study was designed to evaluate the contributions of LecA and LecB to the pathogenesis of P. aeruginosa-mediated acute lung injury. Using an in vitro model with A549 cells and an experimental in vivo murine model of acute lung injury, we compared the parental strain to lecA and lecB mutants. The effects of both LecA- and Lec B-specific lectin-inhibiting carbohydrates (α-methyl-galactoside and α-methyl-fucoside, respectively) were evaluated. In vitro, the parental strain was associated with increased cytotoxicity and adhesion on A549 cells compared to the lecA and lecB mutants. In vivo, the P. aeruginosa-induced increase in alveolar barrier permeability was reduced with both mutants. The bacterial burden and dissemination were decreased for both mutants compared with the parental strain. Coadministration of specific lectin inhibitors markedly reduced lung injury and mortality. Our results demonstrate that there is a relationship between lectins and the pathogenicity of P. aeruginosa. Inhibition of the lectins by specific carbohydrates may provide new therapeutic perspectives.

Unravelling some mysteries of porcine respiratory and reproductive syndrome virus (PRRSV) infections: new insights from modelling studies

2009 ◽  
Vol 2009 ◽  
pp. 30-30
Author(s):  
A Doeschl-Wilson ◽  
I Kyriazakis ◽  
L Galina-Pantoja
Keyword(s):  
Immune Response ◽  
Host Immune Response ◽  
Growing Pigs ◽  
Modelling Studies ◽  
Porcine Respiratory ◽  
Insight Into

Porcine reproductive and respiratory syndrome (PRRS) is an endemic pig disease in most European countries, causing respiratory distress, fever and growth reductions in growing pigs and increased litter mortality in sows. The disease is characterised by exceptionally long-term viral persistence within the host, a weak innate host immune response and delayed adaptive host immune response, and large between animal variation in the immune response (Murtaugh et al., 2004). Although numerous in-vitro and in-vivo studies produced valid insight into the fine details of the virus dynamics and its interaction with the host’s immune response, several fundamental questions concerning the role of diverse immune components and host genetics remain unanswered. In this study mathematical models were developed to investigate the role of diverse processes caused by the virus or the immune response on the infection characteristics.

scholarly journals The Role of False Lumen Size in Prediction of In-Hospital Complications After Acute Type B Aortic Dissection

2008 ◽  
Vol 52 (14) ◽  
pp. 1170-1176 ◽  
Author(s):  
Chih-Ping Chang ◽  
Juhn-Cherng Liu ◽  
Ying-Ming Liou ◽  
Shih-Sheng Chang ◽  
Jan-Yow Chen
Keyword(s):  
Aortic Dissection ◽  
False Lumen ◽  
Acute Type ◽  
Type B ◽  
Type B Aortic Dissection

scholarly journals Emerging era of microneedle array for pharmaceutical and biomedical applications: recent advances and toxicological perspectives

2021 ◽  
Vol 7 (1) ◽  
Author(s):  
Shailesh Dugam ◽  
Rahul Tade ◽  
Rani Dhole ◽  
Sopan Nangare
Keyword(s):  
Biomedical Applications ◽  
Microneedle Array ◽  
Bioavailability Enhancement ◽  
Main Text ◽  
The Past ◽  
Recent Advancement ◽  
Insight Into

Abstract Background Microneedles (MNs) are the utmost unique, efficient, and minimally invasive inventions in the pharmaceutical field. Over the past decades, many scientists around the globe have reported MNs cautious because of their superb future in distinct areas. Concerning the wise use of MNs herein, we deal in depth with the present applications of MNs in drug delivery. Main text The present review comprises various fabrication materials and methods used for MN synthesis. The article also noted the distinctive advantages of these MNs, which holds huge potential for pharmaceutical and biomedical applications. The role of MNs in serving as a platform to treat various ailments has been explained accompanied by unusual approaches. The review also inculcates the pharmacokinetics of MNs, which includes permeation, absorption, and bioavailability enhancement. Besides this, the in vitro/in vivo toxicity, biosafety, and marketed product of MNs have been reviewed. We have also discussed the clinical trials and patents on the pharmaceutical applications of MNs in brief. Conclusion To sum up, this article gives insight into the MNs and provides a recent advancement in MNs, which pave the pathway for future pharmaceutical and biomedical applications. Graphical abstract Pharmaceutical and biomedical applications of MNs

scholarly journals MicroRNA Signature in Alcoholic Liver Disease

2012 ◽  
Vol 2012 ◽  
pp. 1-6 ◽  
Author(s):  
Shashi Bala ◽  
Gyongyi Szabo
Keyword(s):  
Liver Disease ◽  
Alcoholic Liver Disease ◽  
Current Knowledge ◽  
Isolated Hepatocytes ◽  
Tnf Alpha ◽  
Insight Into ◽  
Global Health Problem

Alcoholic liver disease (ALD) is a major global health problem. Chronic alcohol use results in inflammation and fatty liver, and in some cases, it leads to fibrosis and cirrhosis or hepatocellular carcinoma. Increased proinflammatory cytokines, particularly TNF alpha, play a central role in the pathogenesis of ALD. TNF alpha is tightly regulated at transcriptional and posttranscriptional levels. Recently, microRNAs (miRNAs) have been shown to modulate gene functions. The role of miRNAs in ALD is getting attention, and recent studies suggest that alcohol modulates miRNAs. Recently, we showed that alcohol induces miR-155 expression both in vitro (RAW 264.7 macrophage) and in vivo (Kupffer cells, KCs of alcohol-fed mice). Induction of miR-155 contributed to increased TNF alpha production and to the sensitization of KCs to produce more TNF alpha in response to LPS. In this paper, we summarize the current knowledge of miRNAs in ALD and also report increased expression of miR-155 and miR-132 in the total liver as well as in isolated hepatocytes and KCs of alcohol-fed mice. Our novel finding of the alcohol-induced increase of miRNAs in hepatocytes and KCs after alcohol feeding provides further insight into the evolving knowledge regarding the role of miRNAs in ALD.

scholarly journals An Insight into Anti-Inflammatory Activities and Inflammation Related Diseases of Anthocyanins: A Review of Both In Vivo and In Vitro Investigations

2021 ◽  
Vol 22 (20) ◽  
pp. 11076
Author(s):  
Zilong Ma ◽  
Bin Du ◽  
Jun Li ◽  
Yuedong Yang ◽  
Fengmei Zhu
Keyword(s):  
Fruits And Vegetables ◽  
Food Ingredients ◽  
Inflammatory Mechanism ◽  
Clear Insight ◽  
Anti Oxidant ◽  
Anti Inflammatory ◽  
Insight Into

Anthocyanin is a type of flavonoid pigment widely present in fruits and vegetables. It can not only be used as natural pigment, but also has a variety of health functions, for instance, anti-oxidant, anti-inflammatory, anti-tumor, and neuroprotective activities. Persistent proinflammatory status is a major factor in the development, progression, and complications of chronic diseases. Not surprisingly, there are thus many food ingredients that can potentially affect inflammation related diseases and many studies have shown that anthocyanins play an important role in inflammatory pathways. In this paper, the inflammation related diseases (such as, obesity, diabetes, cardiovascular disease, and cancer) of anthocyanins are introduced, and the anti-inflammatory effect of anthocyanins is emphatically introduced. Moreover, the anti-inflammatory mechanism of anthocyanins is elaborated from the aspects of NF-κB, toll like receptor, MAPKs, NO, and ROS and the main efficacy of anthocyanins in inflammation and related diseases is determined. In conclusion, this review aims to get a clear insight into the role of anthocyanins in inflammation related diseases.

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