Antimicrobial modification of PLA scaffolds with ascorbic and fumaric acids via plasma treatment

An optimal medical scaffold should be biocompatible and biodegradable and should have adequate mechanical properties and scaffold architecture porosity, a precise three-dimensional shape, and a reasonable manufacturing method. Polylactic acid (PLA) is a natural biodegradable thermoplastic aliphatic polyester that can be fabricated into nanofiber structures through many techniques, and electrospinning is one of the most widely used methods. Medical fiber mat scaffolds have been associated with inflammation and infection and, in some cases, have resulted in tissue degradation. Therefore, surface modification with antimicrobial agents represents a suitable solution if the mechanical properties of the fiber mats are not affected. In this study, the surfaces of electrospun PLA fiber mats were modified with naturally occurring L-ascorbic acid (ASA) or fumaric acid (FA) via a plasma treatment method. It was found that 30 s of radio-frequency (RF) plasma treatment was effective enough for the wettability enhancement and hydroperoxide formation needed for subsequent grafting reactions with antimicrobial agents upon their decomposition. This modification led to changes in the surface properties of the PLA fiber mats, which were analyzed by various spectroscopic and microscopic techniques. FTIR-ATR confirmed the chemical composition changes after the modification process and the surface morphology/topography changes were proven by SEM and AFM. Moreover, nanomechanical changes of prepared PLA fiber mats were investigated by AFM using amplitude modulation-frequency modulation (AM-FM) technique. A significant enhancement in antimicrobial activity of such modified PLA fiber mats against gram-positive Staphylococcus aureus and gram-negative Escherichia coli are demonstrated herein. © 2020 The AuthorsQatar National Research Fund (a member of The Qatar Foundation) [22-076-1-011]; Qatar University Collaborative Grant [QUCG-CAM-20/21-3]; Czech Science FoundationGrant Agency of the Czech Republic [19-16861S

Dexamethasone and transdehydroandrosterone significantly reduce pulmonary epithelial cell injuries associated with mechanical ventilation.

Many patients who suffer from pulmonary diseases cannot inflate their lungs normally, as they need mechanical ventilation (MV) to assist them. The stress associated with MV can damage the delicate epithelium in small airways and alveoli, which can cause complications resulting in ventilation-induced lung injuries (VILIs) in many cases, especially in patients with acute respiratory distress syndrome (ARDS). Therefore, efforts were directed to develop safe modes for MV. In our work, we propose a different approach to decrease injuries of epithelial cells (EpCs) upon MV. We alter EpCs' cytoskeletal structure to increase their survival rate during airway reopening conditions associated with MV. We tested two anti-inflammatory drugs dexamethasone (DEX) and transdehydroandrosterone (DHEA) to alter the cytoskeleton. Cultured rat L2 alveolar EpCs were exposed to airway reopening conditions using a parallel-plate perfusion chamber. Cells were exposed to a single bubble propagation to simulate stresses associated with mechanical ventilation in both control and study groups. Cellular injury and cytoskeleton reorganization were assessed via fluorescence microscopy, whereas cell topography was studied via atomic force microscopy (AFM). Our results indicate that culturing cells in media, DEX solution, or DHEA solution did not lead to cell death (static cultures). Bubble flows caused significant cell injury. Preexposure to DEX or DHEA decreased cell death significantly. The AFM verified alteration of cell mechanics due to actin fiber depolymerization. These results suggest potential beneficial effects of DEX and DHEA for ARDS treatment for patients with COVID-19. They are also critical for VILIs and applicable to future clinical studies. Preexposure of cultured cells to either dexamethasone or transdehydroandrosterone significantly decreases cellular injuries associated with mechanical ventilation due to their ability to alter the cell mechanics. This is an alternative protective method against VILIs instead of common methods that rely on modification of mechanical ventilator modes.This study was made possible by an Undergraduate Research Experience Program Award [UREP21-050-3-010] from the Qatar National Research Fund (a member of The Qatar Foundation). The publication of this article was funded by the Qatar National Library

Soluble ACE2 and Angiotensin II levels Modulated in Hypertensive COVID-19 Patients treated with different Antihypertension Drugs

Hypertension is a major risk factor and common comorbidity among severe Coronavirus Disease 2019 (COVID-19) patients. Prominent antihypertensive drugs, such as angiotensin-converting-enzyme inhibitors (ACEi) and angiotensin receptor blockers (ARB) can modulate the expression of angiotensin-converting enzyme 2 (ACE2) and may influence COVID-19 prognosis. Other classes of antihypertensive drugs, such as beta-blockers (BB) and calcium channel blockers (CCB) are associated with reduced mortality. Still, their effect on the circulating levels of ACE2 and angiotensin II, as well as the severity of COVID-19, are less characterized. Two hundred hypertensive COVID-19 patients on four different classes of antihypertensive medication (ACEi, ARB, BB, and CCB), with different COVID-19 severities (mild, moderate, and severe) were recruited, and clinical data were assessed. Sera-circulating ACE2 and angiotensin II levels were measured using standard ELISA kits. Linear regression models were used to assess the effect of antihypertensive medications on circulating levels of ACE2 and angiotensin II in relation to disease severity and other clinical indices. Included patients were on ACEi (n=57), ARB (n=68), BB (n=15), or CCB (n=30), with mild (n=76), moderate (n=76), or severe (n=52) COVID-19. ACE2 levels were higher in patients with severe COVID-19 than those with mild (p=0.04) and moderate (p=0.007) disease. ACE2 levels correlated positively with the length of hospital stay (r=0.3, p=0.003), while angiotensin II levels decreased with disease severity (p=0.04). Higher ACE2 levels were associated with elevated CRP and D-dimer, while higher angiotensin II levels were associated with lower levels of CRP, D-dimer, and troponin. Among the four treated groups, patients on ARB exhibited elevation in ACE2 levels with increased disease severity (p=0.01), whereas patients on ACEi showed lower angiotensin II levels with increased disease severity. Patients on BB showed the lowest disease severity compared to other treated groups. Our data show increased COVID-19 severity with elevated levels of circulating ACE2 and lower levels of angiotensin II and suggest a protective effect of BB treatment against disease severity in hypertensive patients, independently of ACE2 and angiotensin II levels

Surface Modification of Poly(lactic acid) Film via Cold Plasma Assisted Grafting of Fumaric and Ascorbic Acid

Plant-based materials have found their application in the packaging with a yearly growing production rate. These naturally biodegradable polymers are obtained from renewable and sustainable natural resources with reduced environmental impact and affordable cost. These materials have found their utilization in fully-renewable plant-based packaging products, such as Tetra Pak®-like containers, by replacing commonly-used polyethylene as the polymer component. Poly(lactic acid) (PLA) is one of the representative plant-based polymers because of its eco-friendliness and excellent chemical and mechanical properties. In this work, a PLA surface was modified by various food additives, namely ascorbic acid (ASA) and fumaric acid (FA), using plasma-initiated grafting reactions in order to improve the surface and adhesion properties of PLA. Various analytical and microscopic techniques were employed to prove the grafting process. Moreover, the improved adhesion of the modified PLA foil to aluminum (Al) foil in a laminate configuration was proven by peel resistance measurements. The peel resistance of modified PLA increased by 74% and 184% for samples modified by ASA and FA, respectively, compared with untreated PLA

Soluble ACE2 and angiotensin II levels are modulated in hypertensive COVID-19 patients treated with different antihypertension drugs.

This study examines the effect of antihypertensive drugs on ACE2 and Angiotensin II levels in hypertensive COVID-19 patients. Hypertension is a common comorbidity among severe COVID-19 patients. ACE2 expression can be modulated by antihypertensive drugs such as ACEis and ARBs, which may affect COVID-19's prognosis. BB and CCB reduce mortality, according to some evidence. Their effect on circulating levels of ACE2 and angiotensin II, as well as the severity of COVID-19, is less well studied. The clinical data were collected from 200 patients in four different antihypertensive medication classes (ACEi, ARB, BB, and CCB). Angiotensin II and ACE2 levels were determined using standard ELISA kits. ACE2, angiotensin II, and other clinical indices were evaluated by linear regression models. Patients on ACEi ( = 57), ARB ( = 68), BB ( = 15), or CCB ( = 30) in this study had mild ( = 76), moderate ( = 76), or severe ( = 52) COVID-19. ACE2 levels were higher in COVID-19 patients with severe disease ( = 0.04) than mild ( = 0.07) and moderate ( = 0.007). The length of hospital stay is correlated with ACE2 levels ( = 0.3,  = 0.003). Angiotensin II levels decreased with severity ( = 0.04). Higher ACE2 levels are associated with higher CRP and D-dimer levels. Elevated Angiotensin II was associated with low levels of CRP, D-dimer, and troponin. ACE2 levels increase with disease severity in patients taking an ARB ( = 0.01), patients taking ACEi, the degree of disease severity was associated with a decrease in angiotensin II. BB patients had the lowest disease severity. We found different levels of soluble ACE2, and angiotensin II are observed among COVID-19 patients taking different antihypertensive medications and exhibiting varying levels of disease severity. COVID-19 severity increases with elevated ACE2 levels and lower angiotensin II levels indicating that BB treatment reduces severity regardless of levels of ACE2 and angiotensin II.Open Access funding is provided by the Qatar National Library. This report was made possible by an RRC award [RRC-2-076] from the Qatar National Research Fund (a member of The Qatar Foundation). The statements made herein are solely the responsibility of the authors. We would like to acknowledge Qatar BioBank for helping with the logistics of the collected samples, Prof. Nahla Afifi, Dr. Marwa A. El Deeb, and Ms. Sidra Abdulshakoor. The publication of this paper is covered by Qatar National Library