Perindopril and losartan attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike protein.

Thrombotic events are highly prevalent in coronavirus disease 2019 (COVID-19), especially in patients presenting with risk factors of adverse outcomes such as obesity. Recently, the associations between the angiotensin converting enzyme 2 (ACE2) pathway and thrombosis have been reported. Angiotensin-converting enzyme inhibitors (ACEI) and angiotensin II receptor blockers (ARBs) are widely used cardiovascular pharmacologic agents that upregulate ACE2 levels. An observation of the alterations in pro-coagulation factors after exposure to ACEIs and ARBs may provide valuable insight into the thrombosis mechanism and how it may relate to ACE2. This study use adipose tissue harvested from an obese male donor was isolated and exposed to perindopril, losartan, and ACE2 recombinant as binding assay, following exposure with 10 nm of SARS-CoV-2 S1 spike protein. After 48 hours, tissue factor (TF) and plasminogen activator inhibitor-1 (PAI-1) as pro-coagulation factors as well as ACE2 levels and binding evaluated. The results shows TF level was significantly reduced in Perindopril group compared to control (4.834; p=0.005), while a non-significant reduction was observed in Losartan group (5.624; p=0.111). However, Losartan group showed a better reduction of PAI-1 levels (2.633; p≤0.001) than Perindopril group (3.484; p=0.001). These findings were consistent with the observations in ACE2 recombinant group, suggesting that both drugs lowered the bindings of ACE2 and SARS-CoV-2 spike proteins. This study indicated that both perindopril and losartan may attenuate pro-coagulation factors in human adipocytes exposed to SARS-CoV-2 spike proteins, and therefore showcased a potential role of ACE2 in the mechanism of COVID-19-related thrombosis. Further investigation in non-COVID-19 populations should commence and may be of value to expanding this potential in general cardiovascular diseases.

Post-corrosion mechanical properties of absorbable open cell iron foams with hollow struts.

In-depth analyses of post-corrosion mechanical properties and architecture of open cell iron foams with hollow struts as absorbable bone scaffolds were carried out. Variations in the architectural features of the foams after 14 days of immersion in a Hanks' solution were investigated using micro-computed tomography and scanning electron microscope images. Finite element Kelvin foam model was developed, and the numerical modeling and experimental results were compared against each other. It was observed that the iron foam samples were mostly corroded in the periphery regions. Except for quasi-elastic gradient, other mechanical properties (i.e. compressive strength, yield strength and energy absorbability) decreased monotonically with immersion time. Presence of adherent corrosion products enhanced the load-bearing capacity of the open cell iron foams at small strains. The finite element prediction for the quasi-elastic response of the 14-day corroded foam was in an agreement with the experimental results. This study highlights the importance of considering corrosion mechanism when designing absorbable scaffolds; this is indispensable to offer desirable mechanical properties in porous materials during degradation in a biological environment.

Effect of Nigella sativa Supplementation on Oxidative Stress and Antioxidant Parameters: A Meta-Analysis of Randomized Controlled Trials.

INTRODUCTION: Nigella sativa is a commonly used traditional medicine which has been shown to have antioxidant properties. However, its supplementation in patients of clinical trials showed conflicting results. Materials and Method. Relevant articles were searched through PubMed/Medline, SCOPUS, and Google Scholar databases using "Nigella sativa" or "black seed" or "black caraway" or "thymoquinone" and "oxidative stress" or "antioxidant" and "clinical trial" keywords. Randomized, placebo-controlled human interventions using Nigella sativa were included in this study. The methodological quality of studies was assessed using Jadad's quality scales. RESULTS: Five studies using 293 subjects met the inclusion criteria. The overall quality of all included trials was determined based on the low risk of bias and the high quality of reported information (Jadad score ≥ 3). Meta-analysis of 293 eligible subjects showed that treatment with Nigella sativa improved the superoxide dismutase (SOD) level (48.18; 95% CI 30.29 to 66.08; p < 0.01), but there was no significant effect on the malondialdehyde (MDA) level (-5.32; 95% CI -1.19 to 0.128; p=0.114) and total antioxidant capacity (TAC) level (0.219; 95% CI -0.136 to 0.573; p = 0.227). CONCLUSION: This meta-analysis suggests that Nigella sativa supplementation in humans may benefit as an antioxidant by increasing SOD levels but has no significant effect on the MDA level and TAC level.

In vitro degradation and cell viability assessment of Zn-3Mg alloy for biodegradable bone implants.

This article reports the in vitro degradation and cytotoxicity assessment of Zn-3Mg alloy developed for biodegradable bone implants. The alloy was prepared using casting, and its microstructure was composed of Mg2Zn11 intermetallic phase distributed within a Zn-rich matrix. The degradation assessment was done using potentiodynamic polarization and electrochemical impedance spectrometry. The cell viability and the function of normal human osteoblast cells were assessed using 3-(4,5-dimethylthiazol-2-yl)-5-(3-carboxymethoxyphenyl)-2-(4-sulfophenyl)-2H-tetrazolium and alkaline phosphatase extracellular enzyme activity assays. The results showed that the degradation rate of the alloy was slower than those of pure Zn and pure Mg due to the formation of a high polarization resistance oxide film. The alloy was cytocompatible with the normal human osteoblast cells at low concentrations (<0.5 mg/mL), and its alkaline phosphatase activity was superior to pure Mg. This assessment suggests that Zn-3Mg alloy has the potential to be developed as a material for biodegradable bone implants, but the toxicity limit must be carefully observed.

Cytotoxicity evaluation of biodegradable Zn-3Mg alloy toward normal human osteoblast cells.

The recent proposal of using Zn-based alloys for biodegradable implants was not supported with sufficient toxicity data. This work, for the first time, presents a thorough cytotoxicity evaluation of Zn-3Mg alloy for biodegradable bone implants. Normal human osteoblast cells were exposed to the alloy's extract and three main cell-material interaction parameters: cell health, functionality and inflammatory response, were evaluated. Results showed that at the concentration of 0.75mg/ml alloy extract, cell viability was reduced by ~50% through an induction of apoptosis at day 1; however, cells were able to recover at days 3 and 7. Cytoskeletal changes were observed but without any significant DNA damage. The downregulation of alkaline phosphatase protein levels did not significantly affect the mineralization process of the cells. Significant differences of cyclooxygenase-2 and prostaglandin E2 inflammatory biomarkers were noticed, but not interleukin 1-beta, indicating that the cells underwent a healing process after exposure to the alloy. Detailed analysis on the cell-material interaction is further discussed in this paper.

Partially degradable friction-welded pure iron-stainless steel 316L bone pin.

This article describes the development of a partially degradable metal bone pin, proposed to minimize the occurrence of bone refracture by avoiding the creation of holes in the bone after pin removal procedure. The pin was made by friction welding and composed of two parts: the degradable part that remains in the bone and the nondegradable part that will be removed as usual. Rods of stainless steel 316L (nondegradable) and pure iron (degradable) were friction welded at the optimum parameters: forging pressure = 33.2 kPa, friction time = 25 s, burn-off length = 15 mm, and heat input = 4.58 J/s. The optimum tensile strength and elongation was registered at 666 MPa and 13%, respectively. A spiral defect formation was identified as the cause for the ductile fracture of the weld joint. A 40-µm wide intermetallic zone was identified along the fusion line having a distinct composition of Cr, Ni, and Mo. The corrosion rate of the pin gradually decreased from the undeformed zone of pure iron to the undeformed zone of stainless steel 316L. All metallurgical zones of the pin showed no toxic effect toward normal human osteoblast cells, confirming the ppb level of released Cr and Ni detected in the cell media were tolerable.

Degradation behavior of biodegradable Fe35Mn alloy stents.

This article reports a degradation study that was done on stent prototypes made of biodegradable Fe35Mn alloy in a simulated human coronary arterial condition. The stent degradation was observed for a short-term period from 0.5 to 168 h, which simulates the early period of stenting procedure. Potentiodynamic polarization and electrochemical impedance spectroscopy were used to quantify degradation rate and surface property of the stents. Results showed that signs of degradation were visible on both crimped and expanded stents after 1 h of test, mostly located on the stent's curvatures. The degradation rate of stent was higher compared to that of the original alloy, indicating the surface altering effect of stent fabrication processing to degradation. A single oxide layer was formed and detected as a porous structure with capacitive behavior. Expanded stents exhibited lower polarization resistance compared to the nonexpanded ones, indicating the cold work effect of expansion procedure to degradation.

In vitro and in vivo degradation evaluation of novel iron-bioceramic composites for bone implant applications.

Biodegradable metals such as magnesium, iron and their alloys have been known as potential materials for temporary medical implants. However, most of the studies on biodegradable metals have been focusing on optimizing their mechanical properties and degradation behavior with no emphasis on improving their bioactivity behavior. We therefore investigated the possibility of improving iron biodegradation rate and bioactivity by incorporating various bioactive bioceramics. The iron-based bioceramic (hydroxyapatite, tricalcium phosphate and biphasic calcium phosphate) composites were prepared by mechanical mixing and sintering process. Degradation studies indicated that the addition of bioceramics lowered the corrosion potential of the composites and slightly increased their corrosion rate compared to that of pure iron. In vitro cytotoxicity results showed an increase of cellular activity when rat smooth muscle cells interacted with the degrading composites compared to pure iron. X-ray radiogram analysis showed a consistent degradation progress with that found in vivo and positive tissue response up to 70 days implantation in sheep animal model. Therefore, the iron-based bioceramic composites have the potential to be used for biodegradable bone implant applications.

Porous biodegradable metals for hard tissue scaffolds: a review.

Scaffolds have been utilized in tissue regeneration to facilitate the formation and maturation of new tissues or organs where a balance between temporary mechanical support and mass transport (degradation and cell growth) is ideally achieved. Polymers have been widely chosen as tissue scaffolding material having a good combination of biodegradability, biocompatibility, and porous structure. Metals that can degrade in physiological environment, namely, biodegradable metals, are proposed as potential materials for hard tissue scaffolding where biodegradable polymers are often considered as having poor mechanical properties. Biodegradable metal scaffolds have showed interesting mechanical property that was close to that of human bone with tailored degradation behaviour. The current promising fabrication technique for making scaffolds, such as computation-aided solid free-form method, can be easily applied to metals. With further optimization in topologically ordered porosity design exploiting material property and fabrication technique, porous biodegradable metals could be the potential materials for making hard tissue scaffolds.

Developments in metallic biodegradable stents.

Interest in metallic degradable biomaterials research has been growing in the last decade. Both scientific journals and patent databases record a high increase in publications in this area. Biomedical implants with temporary function, such as coronary stents, are the targeted applications for this novel class of biomaterials. It is expected that stents made of degradable biomaterials, named biodegradable stents, will provide a temporary opening into a narrowed arterial vessel until the vessel remodels and will progressively disappear thereafter. Biodegradable stents made of metal have recently been progressed into preclinical tests in humans after their first introduction in early 2000s. By referring to patents and journal publications, this paper reviews the developments in biodegradable stents, with emphasis on those made of metals, starting from the first design ideas to validation testing.