Ebola Virus GP Activates Endothelial Cells via Host Cytoskeletal Signaling Factors

Ebola virus disease (EVD) is a lethal disease caused by the highly pathogenic Ebola virus (EBOV), and its major symptoms in severe cases include vascular leakage and hemorrhage. These symptoms are caused by abnormal activation and disruption of endothelial cells (ECs) whose mediators include EBOV glycoprotein (GP) without the need for viral replication. However, the detailed molecular mechanisms underlying virus–host interactions remain largely unknown. Here, we show that EBOV-like particles (VLPs) formed by GP, VP40, and NP activate ECs in a GP-dependent manner, as demonstrated by the upregulation of intercellular adhesion molecules-1 (ICAM-1) expression. VLPs-mediated ECs activation showed a different kinetic pattern from that of TNF-α-mediated activation and was associated with apoptotic ECs disruption. In contrast to TNF-α, VLPs induced ICAM-1 overexpression at late time points. Furthermore, screening of host cytoskeletal signaling inhibitors revealed that focal adhesion kinase inhibitors were found to be potent inhibitors of ICAM-1 expression mediated by both TNF-α and VLPs. Our results suggest that EBOV GP stimulates ECs to induce endothelial activation and dysfunction with the involvement of host cytoskeletal signaling factors, which represent potential therapeutic targets for EVD.

Anti-SARS-CoV-2 antibody levels and kinetics of vaccine response: potential role for unresolved inflammation following recovery from SARS-CoV-2 infection

The immune response after SARS-CoV-2 vaccine administration appears to be characterized by high inter-individual variation, even in SARS-CoV-2 positive subjects, who could have experienced different post-infection, unresolved conditions. We monitored anti-SARS-CoV-2 IgG levels and kinetics along with circulating biomarkers in a cohort of 175 healthcare workers during early immunization with COVID-19 mRNA-LNP BNT162b2 vaccine, to identify the associated factors. Subjects with a previous SARS-CoV-2 infection were characterized by higher BMI and CRP levels and lower neutrophil count with respect to naïve subjects. Baseline IgG levels resulted associated with CRP independently on BMI and inflammatory diseases. Among 137 subjects undergoing vaccination and monitored after the first and the second dose, three kinetic patterns were identified. The pattern showing a rapid growth was characterized by higher IgG levels at baseline and higher CRP and MCHC levels than negative subjects. Subjects previously exposed to SARS-CoV-2 showed higher levels of CRP, suggesting persistence of unresolved inflammation. These levels are the main determinant of IgG levels at baseline and characterized subjects belonging to the best performing, post-vaccine antibody kinetic pattern.

Preparation of magnetic methotrexate nanocarrier coated with extracted hydroxyapatite of sea urchin (Echinometra mathaei)

New polymer-coated magnetic nanocarrier using magnetic iron oxide nanoparticles coated with chitosan and nanohydroxyapatite extracted from Sea urchin that both have anti-cancer properties showed good ability to Methotrexate (MTX) delivery. Iron oxide nanoparticles and hydroxyapatite prepared by co-precipitation and hydrothermal methods respectively. To stabilize the nanoparticles and optimization of the nanoparticles with hydroxyapatite, 3-chloropropyltrioethoxysilane and chitosan were performed. The water-soluble anticancer drug Methotrexate was selected as the drug model. The drug loading percentage was % 86.66, loading efficiency was % 99.5 and the polydispersity of the nanoparticles was 0.01. The kinetic pattern of drug release is consistent with the Peppas equation and the results of the thermal analysis confirm the stability of the crystalline form of the drug. The FTIR results and FE-SEM images showed that the nanoparticles were successfully prepared and coated and their size ranged from 30 nm to 1.5μm. The VSM analysis confirms the magnetic properties of the nanoparticles and the magnetic indices for the magnetic nanocarrier and the magnetic nanocarrier carrying MTX are 23 and 19 emu/g–1, respectively. The present study demonstrates the potential of iron oxide nanoparticles for the design of new magnetic nanocarrier and for guiding Methotrexate drug therapy in cancer chemotherapy.

Therapeutic administration of etoposide coincides with reduced systemic HMGB1 levels in macrophage activation syndrome

Background Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation. Methods Standard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation. Results This therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently. Conclusion Systemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.

Joint internal moments in subjects with unilateral transtibial amputation during walking

Background: Subjects with a unilateral transtibial amputation (UTA) that have used prosthesis for over five years have a higher occurrence rate of osteoarthritis at the knee and hip joints of the intact limb. Objective: To research the joint internal moments of the hip, knee, and ankle in the sagittal and frontal planes during gait in persons with UTA. Methods: 25 individuals with UTA (50.26 years ± 13.76) and 25 subjects without amputation (46.71 years ± 13.76) participated in this study. Gait analysis was carried out using a Vicon® Motion System (Oxford Metrics, Oxford, UK) with eight 100 Hz cameras with infrared strobes, two 1000 Hz AMTI® force-plates. Results: People with UTA walk with a greater hip extensor moment in both intact and prosthetic limbs. The hip abductor moment was lower on the prosthetic limb compared to the intact limb and the control group. At the knee joint, the subjects with UTA walked with a reduced knee extensor and valgus moment on their prosthetic limb compared to the control group. At the ankle joint, the statistical analysis showed that the individuals with UTA walked with a reduced plantarflexor moment during the stance period on the intact limb compared to the people without amputation. Conclusions: Subjects with UTA walk with a different joint kinetic pattern in the sagittal and frontal planes compared to non-disabled individuals.

Therapeutic Administration of Etoposide Coincides With Reduced Systemic HMGB1 Levels in Macrophage Activation Syndrome

Background: Macrophage activation syndrome (MAS) is a potentially fatal complication of systemic inflammation. HMGB1 is a nuclear protein released extracellularly during proinflammatory lytic cell death or secreted by activated macrophages, NK cells, and additional cell types during infection or sterile injury. Extracellular HMGB1 orchestrates central events in inflammation as a prototype alarmin. TLR4 and the receptor for advanced glycation end products operate as key HMGB1 receptors to mediate inflammation. Methods: Standard ELISA and cytometric bead array-based methods were used to examine the kinetic pattern for systemic release of HMGB1, ferritin, IL-18, IFN-γ, and MCP-1 before and during treatment of four children with critical MAS. Three of the patients with severe underlying systemic rheumatic diseases were treated with biologics including tocilizumab or anakinra when MAS developed. All patients required intensive care therapy due to life-threatening illness. Add-on etoposide therapy was administered due to insufficient clinical response with standard treatment. Etoposide promotes apoptotic rather than proinflammatory lytic cell death, conceivably ameliorating subsequent systemic inflammation. Results: This therapeutic intervention brought disease control coinciding with a decline of the increased systemic HMGB1, IFN-γ, IL-18, and ferritin levels whereas MCP-1 levels evolved independently. Conclusion: Systemic HMGB1 levels in MAS have not been reported before. Our results suggest that the molecule is not merely a biomarker of inflammation, but most likely also contributes to the pathogenesis of MAS. These observations encourage further studies of HMGB1 antagonists. They also advocate therapeutic etoposide administration in severe MAS and provide a possible biological explanation for its mode of action.

INTERACTIVE KINETIC CANOPY WITH INDUSTRIAL ARCHITECTURE LEGACY PRESERVATION APPROACH

Architecture has long sought to improve both in terms of form, space and other elements. Meanwhile, the use of innovative techniques that enhance design is always one of the concerns in the field of design. Biomimetic and Nature-Friendly architecture have always inspired by natural organisms aims to emphasize harmony with the environment. From another approach, contemporary industrial architecture has a valuable place in this knowledge, and the restoration and preservation of this heritage is a serious subject. Using attractive methods like an integration of new technology and monumental heritage lead to a profound impact. To this end, designing a canopy using an interactive and kinetic pattern to value this theme can be effective on sustainable development goals in area. This canopy which is inspired by biomimetic pattern and natural potentials from the site, responses to external motivation and adapts its kinetic movements to follow human interactions. The innovative techniques are involved with choosing a precise geometrical frame and order, kinetic patterns suitable for the project and finally fabrication of an scale model from actual dimensions. By choosing a suitable site that houses building of contemporary industrial architecture such as a railway station, this paper aims at learning from nature to fulfill industrial heritage legacy retention that is in both physical and spiritual interaction with humans. Keywords: Contemporary Industrial Architecture, Sustainable Development, Smart Canopy, Industrial Heritage, Biomimetic Design

Surfactant Catalyzed Oxidation of Ethanolamines by Cerium(IV)

Effect of surfactant medium on the kinetics of oxidation of amino alcohol by cerium(IV) has been reported. Two amino alcohols namely, monoethanolamine (MEA) and triethanolamine (TEA) are chosen for kinetic study. Sizeable changes in reaction rate are noted only in presence of sodium lauryl sulphate (NaLS) as surfactant. Both the amino alcohols exhibit rate maxima at around the cmc of NaLS, beyond which the kψ-[NaLS] profile shows slow increase in rate constant with increasing NaLS concentration. Suitable model has been used to explain the kinetic pattern post CMC and from this the micelle-reactant binding constant values have been evaluated. From the temperature dependence study, the activation parameters for the oxidation reactions have been computed and these are compared against those obtained for aqueous medium. Based on all information, plausible mechanism for micellar catalysis has been presented.

A non-uniform dip slip formula to calculate the coseismic deformation: Case study of Tohoku Mw9.0 Earthquake

The distribution of slip faults along the fault plane plays a special role in the kinetic pattern of tectonic deformation. To better understand the coseismic deformation and geodynamics of the earthquake, this paper applied the pile-up theory and derived an analytical formula to describe the non-uniform slip distribution along the fault width. To validate the new formula, it was tested with the coseismic displacements at the global positioning system (GPS) stations for the Tohoku earthquake in 11 March, 2011. Then, the computed horizontal and vertical displacements calculated using NDSM were compared to back-slip model (BSM) using GPS data obtained from the Jet Propulsion Laboratory (JPL). Finally, the theoretical analysis revealed that the analytical formulas derived here can be perceived as the expansion and perfection of the uniform dislocation model. Meanwhile, our results showed that the characteristics of the spatial distribution deformation from NDSM are similar to those derived by GPS measurements. Furthermore, the near-field RMS errors indicated that the horizontal displacements estimated using NDSM is 27.5%, and 35.6% for the vertical components. Our new formulas and findings could assist better portray the crustal deformation in some region and geodynamics in specific earthquake.