scholarly journals Endothelial pulsatile shear stress is a backstop for COVID-19

2020 ◽  
Vol 4 (4) ◽  
pp. 391-399
Author(s):  
Marvin A. Sackner ◽  
Jose A. Adams
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Physical Inactivity ◽  
Muscular Activity ◽  
The Body ◽  
Diverse Populations ◽  
Extensive Investigation ◽  
Pulsatile Shear Stress

There has not been any means to inhibit replication of the SARS-CoV-2 virus responsible for the rapid, deadly spread of the COVID-19 pandemic and an effective, safe, tested across diverse populations vaccine still requires extensive investigation. This review deals with the repurpose of a wellness technology initially fabricated for combating physical inactivity by increasing muscular activity. Its action increases pulsatile shear stress (PSS) to the endothelium such that the bioavailability of nitric oxide (NO) and other mediators are increased throughout the body. In vitro evidence indicates that NO inhibits SARS-CoV-2 virus replication but there are no publications of NO delivery to the virus in vivo. It will be shown that increased PSS has potential in vivo to exert anti-viral properties of NO as well as to benefit endothelial manifestations of COVID-19 thereby serving as a safe and effective backstop.

Regulation of capillary hydraulic conductivity in response to an acute change in shear

2005 ◽  
Vol 289 (5) ◽  
pp. H2126-H2135 ◽  
Author(s):  
Min-ho Kim ◽  
Norman R. Harris ◽  
John M. Tarbell
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Hydraulic Conductivity ◽  
Flow Shear ◽  
Fluid Filtration ◽  
Acute Change ◽  
Acute Changes ◽  
Mesenteric Microvessels

The effects of mechanical perturbations (shear stress, pressure) on microvascular permeability primarily have been examined in micropipette-cannulated vessels or in endothelial monolayers in vitro. The objective of this study is to determine whether acute changes in blood flow shear stress might influence measurements of hydraulic conductivity ( Lp) in autoperfused microvessels in vivo. Rat mesenteric microvessels were observed via intravital microscopy. Occlusion of a third-order arteriole with a micropipette was used to divert and increase flow through a nonoccluded capillary or fourth-order arteriolar branch. Transvascular fluid filtration rate in the branching vessel was measured with a Landis technique. Flow (shear)-induced increases in Lp disappeared within 20–30 s of the removal of the shear and could be eliminated with nitric oxide synthase inhibition. The shear-induced increase in Lp was greater in capillaries compared with terminal arterioles. An acute change in shear may regulate Lp by a nitric oxide-dependent mechanism that displays heterogeneity within a microvascular network.

Evidence of nitric oxide, a flow-dependent factor, being a trigger of liver regeneration in rats

1998 ◽  
Vol 76 (12) ◽  
pp. 1072-1079 ◽  
Author(s):  
H Helen Wang ◽  
W Wayne Lautt
Keyword(s):  
Nitric Oxide ◽  
Shear Stress ◽  
Liver Regeneration ◽  
Partial Hepatectomy ◽  
Cultured Cells ◽  
Portal Blood Flow ◽  
Liver Weight ◽  
Proliferative Effect

The hypothesis tested was that the hemodynamic consequence of partial hepatectomy (PHX) triggers the cascade of events that leads to liver regeneration. After PHX, all the portal flow must go through the remaining vascular bed, thus producing increased shear stress and release of nitric oxide (NO), which then initiates the next stages of the regeneration process. As an index of triggering of the regeneration cascade, we used an in vitro bioassay detecting the appearance of proliferating factors (PFs; various growth factors, cytokines, and hormones) in plasma 4 h after two-thirds PHX in rats. PF levels, assessed using proliferation of cultured hepatocytes, were elevated in two-thirds PHX rats, fully blocked by the NO synthase inhibitor NG-nitro-L-arginine methyl ester (L-NAME), and restored by L-arginine. L-NAME inhibited liver weight restoration at 48 h but resulted in high mortality. L-NAME lacked toxic effects in non-PHX rats. NO was directly antiproliferative on cultured cells, suggesting that the proliferative effect of NO in vivo was secondary to the activation of other proliferative stimuli. The data support the hypothesis that vascular shear stress induced release of NO following PHX serves as a primary trigger to initiate the regeneration process.Key words: shear stress, portal blood flow, hyperplasia, hepatic partial hepatectomy.

Substance P decreases fluid absorption in the renal proximal tubule

1997 ◽  
Vol 272 (5) ◽  
pp. R1396-R1401 ◽  
Author(s):  
R. D. Fildes ◽  
J. L. Atkins
Keyword(s):  
Nitric Oxide ◽  
Substance P ◽  
Proximal Tubule ◽  
Nerve Fibers ◽  
The Body ◽  
Afferent Nerve ◽  
Fluid Absorption ◽  
Organ Systems

Substance P is a neuropeptide found principally in the central nervous system and peripheral afferent nerve fibers. It is widely distributed in the body, and its local release is thought to have important effects in the normal physiology and pathophysiology of several organ systems. Substance P releases histamine from mast cells and nitric oxide from endothelial cells. Systemic infusion of substance P causes a brisk natriuresis. Previously, proximal tubule transport in the kidney was measured in vivo during the infusion of substance P. Transport was inhibited. This could have been a direct action of substance P or secondary to the release of histamine or nitric oxide. Therefore, we have now studied the effect of substance P on isolated proximal tubules perfused in vitro. We found that 10(-10) M substance P caused a 50% reduction in the rate of fluid absorption in rabbit proximal straight tubule. This effect was reversible on removal of substance P from the bath. Inhibition of nitric oxide production with NG-monomethyl-L-arginine (10(-4) M) did not influence the action of substance P at 10(-10) M. The sensitivity of the proximal tubule to low concentrations of substance P, together with the recent findings of substance P-containing afferent fibers within the cortex of the kidney, suggest a role for substance P in the control of proximal tubule reabsorption, particularly in pathophysiological conditions associated with increased afferent nerve activity, such as ureteric occlusion.

scholarly journals Cytonemes Versus Neutrophil Extracellular Traps in the Fight of Neutrophils with Microbes

2020 ◽  
Vol 21 (2) ◽  
pp. 586 ◽  
Author(s):  
Svetlana I. Galkina ◽  
Natalia V. Fedorova ◽  
Ekaterina A. Golenkina ◽  
Vladimir I. Stadnichuk ◽  
Galina F. Sud’ina
Keyword(s):  
Nitric Oxide ◽  
Membrane Vesicles ◽  
Neutrophil Extracellular Traps ◽  
The Body ◽  
Peptidylarginine Deiminase ◽  
Chromatin Decondensation ◽  
Extracellular Traps ◽  
Dna Strands

Neutrophils can phagocytose microorganisms and destroy them intracellularly using special bactericides located in intracellular granules. Recent evidence suggests that neutrophils can catch and kill pathogens extracellularly using the same bactericidal agents. For this, live neutrophils create a cytoneme network, and dead neutrophils provide chromatin and proteins to form neutrophil extracellular traps (NETs). Cytonemes are filamentous tubulovesicular secretory protrusions of living neutrophils with intact nuclei. Granular bactericides are localized in membrane vesicles and tubules of which cytonemes are composed. NETs are strands of decondensed DNA associated with histones released by died neutrophils. In NETs, bactericidal neutrophilic agents are adsorbed onto DNA strands and are not covered with a membrane. Cytonemes and NETs occupy different places in protecting the body against infections. Cytonemes can develop within a few minutes at the site of infection through the action of nitric oxide or actin-depolymerizing alkaloids of invading microbes. The formation of NET in vitro occurs due to chromatin decondensation resulting from prolonged activation of neutrophils with PMA (phorbol 12-myristate 13-acetate) or other stimuli, or in vivo due to citrullination of histones with peptidylarginine deiminase 4. In addition to antibacterial activity, cytonemes are involved in cell adhesion and communications. NETs play a role in autoimmunity and thrombosis.

scholarly journals Human in vitro model of material-driven vascular regeneration reveals how cyclic stretch and shear stress differentially modulate inflammation and tissue formation

2019 ◽  
Author(s):  
Eline E. van Haaften ◽  
Tamar B. Wissing ◽  
Nicholas A. Kurniawan ◽  
Anthal I.P.M. Smits ◽  
Carlijn V.C. Bouten
Keyword(s):  
Shear Stress ◽  
Tissue Growth ◽  
The Body ◽  
Cyclic Stretch ◽  
Tissue Formation ◽  
Vascular Regeneration ◽  
Underlying Mechanisms ◽  
Living Tissues

1AbstractResorbable synthetic scaffolds designed to regenerate living tissues and organs inside the body emerge as a clinically attractive technology to replace diseased blood vessels. However, mismatches between scaffold design and in vivo hemodynamic loading (i.e., cyclic stretch and shear stress) can result in aberrant inflammation and adverse tissue remodeling, leading to premature graft failure. Yet, the underlying mechanisms remain elusive. Here, a human in vitro model is presented that mimics the transient local inflammatory and biomechanical environments that drive scaffold-guided tissue regeneration. The model is based on the co-culture of human (myo)fibroblasts and macrophages in a bioreactor platform that decouples cyclic stretch and shear stress. Using a resorbable supramolecular elastomer as the scaffold material, it is revealed that cyclic stretch initially reduces pro-inflammatory cytokine secretion and, especially when combined with shear stress, stimulates IL-10 secretion. Moreover, cyclic stretch stimulates downstream (myo)fibroblast proliferation and neotissue formation. In turn, shear stress attenuates cyclic-stretch-induced tissue growth by enhancing MMP-1/TIMP-1-mediated collagen remodeling, and synergistically alters (myo)fibroblast phenotype when combined with cyclic stretch. The findings suggest that shear stress acts as a stabilizing factor in cyclic stretch-induced tissue formation and highlight the distinct roles of hemodynamic loads in the design of resorbable vascular grafts.

The Role of Polyphenols in the Modulation of Plasma Non-Enzymatic Antioxidant Capacity (NEAC)

2012 ◽  
Vol 82 (3) ◽  
pp. 228-232 ◽  
Author(s):  
Mauro Serafini ◽  
Giuseppa Morabito
Keyword(s):  
Antioxidant Capacity ◽  
Dietary Intervention ◽  
Ex Vivo ◽  
The Body ◽  
Dietary Polyphenols ◽  
Enzymatic Antioxidant ◽  
Endogenous Antioxidant

Dietary polyphenols have been shown to scavenge free radicals, modulating cellular redox transcription factors in different in vitro and ex vivo models. Dietary intervention studies have shown that consumption of plant foods modulates plasma Non-Enzymatic Antioxidant Capacity (NEAC), a biomarker of the endogenous antioxidant network, in human subjects. However, the identification of the molecules responsible for this effect are yet to be obtained and evidences of an antioxidant in vivo action of polyphenols are conflicting. There is a clear discrepancy between polyphenols (PP) concentration in body fluids and the extent of increase of plasma NEAC. The low degree of absorption and the extensive metabolism of PP within the body have raised questions about their contribution to the endogenous antioxidant network. This work will discuss the role of polyphenols from galenic preparation, food extracts, and selected dietary sources as modulators of plasma NEAC in humans.

Репрограммированые in vitro на М3 фенотип макрофаги останавливают рост солидной карциномы in vivo

2018 ◽  
pp. 41-46
Author(s):  
А.А. Раецкая ◽  
С.В. Калиш ◽  
С.В. Лямина ◽  
Е.В. Малышева ◽  
О.П. Буданова ◽  
...  
Keyword(s):  
Solid Tumor ◽  
Antitumor Effect ◽  
Tumor Development ◽  
Significant Inhibition ◽  
The Body ◽  
Ehrlich Carcinoma ◽  
Solid Carcinoma ◽  
Ec Cells

Цель исследования. Доказательство гипотезы, что репрограммированные in vitro на М3 фенотип макрофаги при введении в организм будут существенно ограничивать развитие солидной карциномы in vivo . Методика. Рост солидной опухоли инициировали у мышей in vivo путем подкожной инъекции клеток карциномы Эрлиха (КЭ). Инъекцию макрофагов с нативным М0 фенотипом и с репрограммированным M3 фенотипом проводили в область формирования солидной КЭ. Репрограммирование проводили с помощью низких доз сыворотки, блокаторов факторов транскрипции STAT3/6 и SMAD3 и липополисахарида. Использовали две схемы введения макрофагов: раннее и позднее. При раннем введении макрофаги вводили на 1-е, 5-е, 10-е и 15-е сут. после инъекции клеток КЭ путем обкалывания макрофагами с четырех сторон область развития опухоли. При позднем введении, макрофаги вводили на 10-е, 15-е, 20-е и 25-е сут. Через 15 и 30 сут. после введения клеток КЭ солидную опухоль иссекали и измеряли ее объем. Эффект введения макрофагов оценивали качественно по визуальной и пальпаторной характеристикам солидной опухоли и количественно по изменению ее объема по сравнению с группой без введения макрофагов (контроль). Результаты. Установлено, что M3 макрофаги при раннем введении от начала развития опухоли оказывают выраженный антиопухолевый эффект in vivo , который был существенно более выражен, чем при позднем введении макрофагов. Заключение. Установлено, что введение репрограммированных макрофагов M3 ограничивает развитие солидной карциномы в экспериментах in vivo . Противоопухолевый эффект более выражен при раннем введении М3 макрофагов. Обнаруженные в работе факты делают перспективным разработку клинической версии биотехнологии ограничения роста опухоли, путем предварительного программирования антиопухолевого врожденного иммунного ответа «в пробирке». Aim. To verify a hypothesis that macrophages reprogrammed in vitro to the M3 phenotype and injected into the body substantially restrict the development of solid carcinoma in vivo . Methods. Growth of a solid tumor was initiated in mice in vivo with a subcutaneous injection of Ehrlich carcinoma (EC) cells. Macrophages with a native M0 phenotype or reprogrammed towards the M3 phenotype were injected into the region of developing solid EC. Reprogramming was performed using low doses of serum, STAT3/6 and SMAD3 transcription factor blockers, and lipopolysaccharide. Two schemes of macrophage administration were used: early and late. With the early administration, macrophages were injected on days 1, 5, 10, and 15 following the injection of EC cells at four sides of the tumor development area. With the late administration, macrophages were injected on days 10, 15, 20, and 25. At 15 and 30 days after the EC cell injection, the solid tumor was excised and its volume was measured. The effect of macrophage administration was assessed both qualitatively by visual and palpation characteristics of solid tumor and quantitatively by changes in the tumor volume compared with the group without the macrophage treatment. Results. M3 macrophages administered early after the onset of tumor development exerted a pronounced antitumor effect in vivo , which was significantly greater than the antitumor effect of the late administration of M3 macrophages. Conclusion. The observed significant inhibition of in vivo growth of solid carcinoma by M3 macrophages makes promising the development of a clinical version of the biotechnology for restriction of tumor growth by in vitro pre-programming of the antitumor, innate immune response.

Nanocurcumin: A Double-Edged Sword for Microcancers

2020 ◽  
Vol 26 (45) ◽  
pp. 5783-5792
Author(s):  
Kholood Abid Janjua ◽  
Adeeb Shehzad ◽  
Raheem Shahzad ◽  
Salman Ul Islam ◽  
Mazhar Ul Islam
Keyword(s):  
Intracellular Signaling ◽  
Dosage Forms ◽  
The Body ◽  
In Vivo Studies ◽  
Mrna Levels ◽  
Anticancer Activities ◽  
Road Map ◽  
Anticancer Effects

There is compelling evidence that drug molecules isolated from natural sources are hindered by low systemic bioavailability, poor absorption, and rapid elimination from the human body. Novel approaches are urgently needed that could enhance the retention time as well as the efficacy of natural products in the body. Among the various adopted approaches to meet this ever-increasing demand, nanoformulations show the most fascinating way of improving the bioavailability of dietary phytochemicals through modifying their pharmacokinetics and pharmacodynamics. Curcumin, a yellowish pigment isolated from dried ground rhizomes of turmeric, exhibits tremendous pharmacological effects, including anticancer activities. Several in vitro and in vivo studies have shown that curcumin mediates anticancer effects through the modulation (upregulation and/or downregulations) of several intracellular signaling pathways both at protein and mRNA levels. Scientists have introduced multiple modern techniques and novel dosage forms for enhancing the delivery, bioavailability, and efficacy of curcumin in the treatment of various malignancies. These novel dosage forms include nanoparticles, liposomes, micelles, phospholipids, and curcumin-encapsulated polymer nanoparticles. Nanocurcumin has shown improved anticancer effects compared to conventional curcumin formulations. This review discusses the underlying molecular mechanism of various nanoformulations of curcumin for the treatment of different cancers. We hope that this study will make a road map for preclinical and clinical investigations of cancer and recommend nano curcumin as a drug of choice for cancer therapy.

scholarly journals Perilla frutescens Leaf Extract and Fractions: Polyphenol Composition, Antioxidant, Enzymes (α-Glucosidase, Acetylcholinesterase, and Tyrosinase) Inhibitory, Anticancer, and Antidiabetic Activities

Foods ◽  
2021 ◽  
Vol 10 (2) ◽  
pp. 315
Author(s):  
Zhenxing Wang ◽  
Zongcai Tu ◽  
Xing Xie ◽  
Hao Cui ◽  
Kin Weng Kong ◽  
...  
Keyword(s):  
Ethyl Acetate ◽  
Animal Experiments ◽  
Ethyl Acetate Fraction ◽  
The Body ◽  
Total Phenolic ◽  
Antioxidant Power ◽  
Glycogen Accumulation ◽  
Inhibitory Ability

This study aims to evaluate the bioactive components, in vitro bioactivities, and in vivo hypoglycemic effect of P. frutescens leaf, which is a traditional medicine-food homology plant. P. frutescens methanol crude extract and its fractions (petroleum ether, chloroform, ethyl acetate, n-butanol fractions, and aqueous phase residue) were prepared by ultrasound-enzyme assisted extraction and liquid–liquid extraction. Among the samples, the ethyl acetate fraction possessed the high total phenolic (440.48 μg GAE/mg DE) and flavonoid content (455.22 μg RE/mg DE), the best antioxidant activity (the DPPH radical, ABTS radical, and superoxide anion scavenging activity, and ferric reducing antioxidant power were 1.71, 1.14, 2.40, 1.29, and 2.4 times higher than that of control Vc, respectively), the most powerful α-glucosidase inhibitory ability with the IC50 value of 190.03 μg/mL which was 2.2-folds higher than control acarbose, the strongest proliferative inhibitory ability against MCF-7 and HepG2 cell with the IC50 values of 37.92 and 13.43 μg/mL, which were considerable with control cisplatin, as well as certain inhibition abilities on acetylcholinesterase and tyrosinase. HPLC analysis showed that the luteolin, rosmarinic acid, rutin, and catechin were the dominant components of the ethyl acetate fraction. Animal experiments further demonstrated that the ethyl acetate fraction could significantly decrease the serum glucose level, food, and water intake of streptozotocin-induced diabetic SD rats, increase the body weight, modulate their serum levels of TC, TG, HDL-C, and LDL-C, improve the histopathology and glycogen accumulation in liver and intestinal tissue. Taken together, P. frutescens leaf exhibits excellent hypoglycemic activity in vitro and in vivo, and could be exploited as a source of natural antidiabetic agent.

scholarly journals Collagen-Based Electrospun Materials for Tissue Engineering: A Systematic Review

2021 ◽  
Vol 8 (3) ◽  
pp. 39
Author(s):  
Britani N. Blackstone ◽  
Summer C. Gallentine ◽  
Heather M. Powell
Keyword(s):  
Systematic Review ◽  
Tissue Engineering ◽  
Collagen Type I ◽  
The Body ◽  
Pool Data ◽  
Type I ◽  
High Concentrations ◽  
Increased Strength

Collagen is a key component of the extracellular matrix (ECM) in organs and tissues throughout the body and is used for many tissue engineering applications. Electrospinning of collagen can produce scaffolds in a wide variety of shapes, fiber diameters and porosities to match that of the native ECM. This systematic review aims to pool data from available manuscripts on electrospun collagen and tissue engineering to provide insight into the connection between source material, solvent, crosslinking method and functional outcomes. D-banding was most often observed in electrospun collagen formed using collagen type I isolated from calfskin, often isolated within the laboratory, with short solution solubilization times. All physical and chemical methods of crosslinking utilized imparted resistance to degradation and increased strength. Cytotoxicity was observed at high concentrations of crosslinking agents and when abbreviated rinsing protocols were utilized. Collagen and collagen-based scaffolds were capable of forming engineered tissues in vitro and in vivo with high similarity to the native structures.

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