1,721,128 research outputs found
Overview of ventilator-induced lung injury mechanisms
No full textPURPOSE OF REVIEW: Mechanical ventilation is the main supportive therapy for patients with acute respiratory distress syndrome. As with any therapy, mechanical ventilation has side effects and may induce lung injury. This review will focus on stretch-dependent activation of alveolar epithelial and endothelial cells and polymorphonuclear leukocytes, and apoptosis/necrosis balance. RECENT FINDINGS: The past year has seen important research in the area of mechanotransduction and lung native immunity, suggesting further mechanisms of lung inflammation and injury in ventilator-induced lung injury. Research in the past year has also stressed the importance of inflammatory response by alveolar cells and role of polymorphonuclear leukocytes in stretch-induced lung injury and has suggested a role for apoptosis in the maintenance of the alveolar epithelium. SUMMARY: The proportion of patients receiving protective ventilatory strategies remains modest. If efforts to minimize the iatrogenic consequences of mechanical ventilation are to succeed, there must be a greater understanding of the signal transduction mechanisms and the development of potential pharmacologic targets to modulate the molecular and cellular effects of lung stretch
Plasma exosomes after PCI in non-diabetic STEMI patients fed barley beta-D-glucan-enriched pasta reduce oxidative stress-induced endothelial cell senescence.
No full textBackground: Endothelial aging delays endothelialization, which increases restenosis risk in acute coronary syndrome with ST segment elevation (STEMI) patients following primary percutaneous coronary intervention (PCI). Normocaloric diet supplemented with barley beta-D-glucan (BBG)-enriched pasta protects the heart, although its significance in releasing exosomes that prevent endothelium aging after PCI is unknown. Methods: In non-diabetic anterior STEMI patients (mean age 57 years, 8 women) who undeerwent PCI, we isolated plasma exosomes (pEXOs) before (T0) and after 3 months (T1) of normocaloric diet supplemented with 100g of pasta containing 3g of BBG (STEMI-BBG, n=19) or without supplementation (STEMI-C, n=18).
Nanoparticle tracking analysis (NTA) detected pEXOs size and levels. Senescent human umbilical vein endothelial cells (HUVECs) induced by H2O2 (100 μmol/l for 24 h) were detected by assessing senescence-
associated β-galactosidase activity. HUVECs were treated with pEXOs (107particles/ml) for 24h without and with H2O2. Dihydroethidium staining detected oxygen free radicals (ROS) in HUVECs. Results: pEXOs levels were significantly increased at T1 in STEMI-BBG group, but not in STEMI-C patients. The NTA revealed that large pEXOs contribute to this increase, but not the other exosomal subpopulations. T0 and T1 pEXOs isolated from all patients induced premature endothelial senescence in the absence of ROS increase. Otherwise, T1 pEXOs isolated from STEMI-BBG patients significantly prevented worsening of
endothelial senescence induced by exogenous H2O2 via reducing oxidative stress (p<0.05), but not T1 pEXOs from STEMI-C.
Conclusion: Our findings indicate that pEXOs obtained from reperfused non-diabetic STEMI patients spread pro-senescent signals into HUVECs. However, the presence of pEXOs isolated from reperfused STEMI patients fed BBG-enriched pasta did not exacerbate the endothelial senescence induced by H2O2. We can hypothesize that these effects could be related to different transcriptional landscape related to microenvironment
How do pectin methylesterases and their inhibitors affect the spreading of tobamovirus?
Full text linkAfter replication in the cytoplasm, viruses spread from the infected cell into the neighboring cells through plasmodesmata, membranous channels embedded by the cell wall. As obligate parasites, viruses have acquired the ability to utilize host factors that unwillingly cooperate for the viral infection process. For example, the viral movement proteins (MP) interacts with the host pectin methylesterase (PME) and both proteins cooperate to sustain the viral spread. However, how and where PMEs interact with MPs and how the PME/MP complexes favor the viral translocation is not well understood. Recently, we demonstrated that the overexpression of PME inhibitors (PMEIs) in tobacco and Arabidopsis plants limits the movement of Tobacco mosaic virus and Turnip vein clearing virus and reduces plant susceptibility to these viruses. Here we discuss how overexpression of PMEI may reduce tobamovirus spreading
Prestroke barley beta-D-glucan supplementation protects heart and brain from consequences of ischemic stroke regardless of caloric restriction
No full textBackground: Chronic psychosocial stress (PS) and diet-induced obesity cause HBAd, yet its impact on post-stroke outcome is uncertain. 3% barley beta-D-glucan (BBG) supplementation in a high-fat diet (HFD) prevented HBAd in obese PS-exposed mice. We hypothesize that prestroke BBG dietary supplementation may protect heart and brain from stroke's severe consequences regardless of calorie restriction.
Methods: MCAO was performed on adult male C57BL/6J mice with (n=8) and without (n=8) HBAd. Long-term PS exposure caused HBAd in HFD-induced obese mice. HBAd mice were administered an HFD diet with (HFD-beta, n=4) or without (HFD, n=4) 3% BBG before a stroke. Both groups got a month-long normocaloric diet without BBG after stroke. Baseline and 30-day post-stroke motor brain and heart function were assessed. Grid walking, cylinder tests, and
echocardiography measured motor brain and heart function
Results: HBAd mice exhibited severe stroke-induced brain injury compared to mice without HBAd. Motor recovery was significantly improved in HFD-beta mice within 30 days after MCAO, whereas
heart rate was significantly reduced by 30% in both groups without changes of left ventricular systolic and diastolic function. However, heart rate was positively correlated with brain motor recovery only in treated mice. After stroke, HFD-beta had significantly lower end-diastolic interventricular septum thickness than HFD mice.
Conclusions: Pre-stroke HFD BBG supplementation reduced brain ischemia damage and cardiac remodeling in mice with lowered heart rate. Our data suggest BBG supplementation of HFD is sufficient to preserve brain and cardiac function after a stroke in high-risk patients regardless subsequent caloric restriction
Organ Neuroprosthetics: Connecting Transplanted and Artificial Organs with the Nervous System
Full text linkImplantable neural interfaces with the central and peripheral nervous systems are currently used to restore sensory, motor, and cognitive functions in disabled people with very promising results. They have also been used to modulate autonomic activities to treat diseases such as diabetes or hypertension. Here, this study proposes to extend the use of these technologies to (re-)establish the connection between new (transplanted or artificial) organs and the nervous system in order to increase the long-term efficacy and the effective biointegration of these solutions. In this perspective paper, some clinically relevant applications of this approach are briefly described. Then, the choices that neural engineers must implement about the type, implantation location, and closed-loop control algorithms to successfully realize this approach are highlighted. It is believed that these new "organ neuroprostheses" are going to become more and more valuable and very effective solutions in the years to come
Overexpression of Pectin methylesterase inhibitors in Arabidopsis affects defence against pathogens
No full textPectins are a family of complex galacturonic acid rich polysaccharides present in the primary cell wall and intercellular spaces of higher plants. Pectins are synthesized in the Golgi and released in muro as highly methylesterified forms and soon thereafter de-esterified by pectin methylesterase (PME). PMEs produced by plants take part in important physiological processes and also have a role in resistance to fungi and bacteria as well as in the systemic spread of tobacco mosaic virus. In addition to the transcriptional control, PME activity is post-translationally regulated by specific proteinaceous inhibitors (PMEIs). PMEIs are encoded in Arabidopsis by a small gene family of two members named AtPMEI-1 and AtPMEI-2. PMEIs typically inhibit PMEs of plant origin and do not affect the activity of microbial enzymes. To understand the role of AtPMEI-1 and AtPMEI-2 in resistance to pathogens we have stably over-expressed AtPMEI-1 and AtPMEI-2 in Arabidopsis plants. The overexpression of the inhibitors resulted in a decreased PME activity and in a significant increase in the degree of pectin methylesterification. Transformed plants were more resistant to the necrotrophic fungus Botrytis cinerea. The analysis of the resistance of the transformed plants to bacterial and viral pathogens is in progress
Control of autocrine and paracrine myocardial signals: an emerging therapeutic strategy in heart failure
No full textA growing body of evidence supports the hypothesis that autocrine and paracrine mechanisms, mediated by factors released by the resident cardiac cells, could play an essential role in the reparative process of the failing heart. Such signals may influence the function of cardiac stem cells via several mechanisms, among which the most extensively studied are cardiomyocyte survival and angiogenesis. Moreover, besides promoting cytoprotection and angiogenesis, paracrine factors released by resident cardiac cells may alter cardiac metabolism and extracellular matrix turnover, resulting in more favorable post-injury remodeling. It is reasonable to believe that critical intracellular signals are activated and modulated in a temporal and spatial manner exerting different effects, overall depending on the microenvironment changes present in the failing myocardium. The recent demonstration that chemically, mechanically or genetically activated cardiac cells may release peptides to protect tissue against ischemic injury provides a potential route to achieve the delivery of specific proteins produced by these cells for innovative pharmacological regenerative therapy of the heart. It is important to keep in mind that therapies currently used to treat heart failure (HF) and leading to improvement of cardiac function fail to induce tissue repair/regeneration. As a matter of facts, if specific autocrine/paracrine cell-derived factors that improve cardiac function will be identified, pharmacological-based therapy might be more easily translated into clinical benefits than cell-based therapy. This review will focus on the recent development of potential pharmacologic targets to promote and drive at molecular level the cardiac repair/regeneration in HF
Host pectin methylesterase plays a role in the susceptibility to necrotrophic pathogens
No full textThe host cell wall is a primary target during growth of
necrotrophic pathogens. During the first stages of infection,
pectin, one of the main components of the plant cell wall, is degraded
by pectinolytic enzymes produced by the majority of fungal
and bacterial pathogens. Some evidence indicates that variation
of the pectin structure and composition may cause an altered
disease response upon infection with pathogens. Pectin is synthesized
and secreted into the cell wall in a highly methylesterified
form and, soon thereafter, deesterified in muro by pectin
methylesterases (PMEs). The action of PME makes pectin susceptible
to degradation by enzymes such as endo-polygalacturonases
(PGs) and pectate lyases (PELs). Endogenous PME activity
is controlled through the interaction with the pectin
methylesterase inhibitor (PMEI). PMEI over-expression and
PME knockout have been used to stably increase pectin
methylesterification in Arabidopsis plants. We have shown that
the increase of pectin methylesterification and the lack of a specific
PME activity correlate to a decreased susceptibility of Arabidopsis
to the necrotrophic pathogens Pectobacterium carotovorum
and Botrytis cinerea. The reduced symptoms of transformed
plants have been related to the inability of the pathogens to take
advantage of host PMEs and to their impaired ability to grow on
methylesterified pectins
Importance of functional food compounds in cardioprotection through action on the epigenome.
No full textFood constituents can either promote cardiovascular health or serve in its demise. In view of the lack of more effective pharmacological interventions in cardiovascular disease (CVDs), attention has focused on the potential protective effects of diet. Food components and their metabolites are emerging as major regulators of the human epigenome, which is being linked to CVDs. In this review, we summarize data from studies that suggest an important role for bioactive food compounds in cardioprotection and the potential for harnessing the epigenome as a nutrient sensor target in CVDs. While clinical data strongly support a role for effective diet intervention in CVDs protection, studies linking changes to human epigenome are now warranted for mechanistic insight and development of personalized care
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