Medical Ethics Consultations in the Opinion of Shine Medical doctors

New therapeutic strategies are needed for the growing unmet clinical needs in liver disease and fibrosis. Platelet activation and PDGF activity are recognized as important therapeutic targets; however, no therapeutic approach has yet addressed these two upstream drivers of liver fibrosis. We therefore designed a matrix-targeting glycan therapeutic, SBR-294, to inhibit collagen-mediated platelet activation while also inhibiting PDGF activity. Herein we describe the synthesis and characterization of SBR-294 and demonstrate its potential therapeutic benefits in vitro and in vivo. In vitro SBR-294 was found to bind collagen (EC50 = 23 nM), thereby inhibiting platelet-collagen engagement (IC50 = 60 nM). Additionally, SBR-294 was found to bind all PDGF homodimeric isoforms and to inhibit PDGF-BB mediated hepatic stellate cell activation and proliferation. Translating these mechanisms in vivo, SBR-294 reduced fibrosis by up to 54% in the CCl4 mouse model (p = 0.0004), as measured by Sirius red histological analysis. Additional fibrosis measurements were also supportive of the therapeutic benefit in this model. These results support the therapeutic benefit of platelet and PDGF antagonism and warrant further investigation of SBR-294 as a potential treatment for liver fibrosis.Hierarchical collagen fibers are the primary source of strength in musculoskeletal tendons, ligaments, and menisci. It has remained a challenge to develop these large fibers in engineered replacements or in vivo after injury. The objective of this study was to investigate the ability of restrained cell-seeded high density collagen gels to drive hierarchical fiber formation for multiple musculoskeletal tissues. We found boundary conditions applied to high density collagen gels were capable of driving tenocytes, ligament fibroblasts, and meniscal fibrochondrocytes to develop native-sized hierarchical collagen fibers 20-40 μm in diameter. The fibers organize similar to bovine juvenile collagen with native fibril banding patterns and hierarchical fiber bundles 50-350 μm in diameter by 6 weeks. Mirroring fiber organization, tensile properties of restrained samples improved significantly with time, reaching ~1 MPa. Additionally, tendon, ligament, and meniscal cells produced significantly different sized fibers, different degrees of crimp, and different GAG concentrations, which corresponded with respective juvenile tissue. Selleck HSP inhibitor To our knowledge, these are some of the largest, most organized fibers produced to date in vitro. Further, cells produced tissue specific hierarchical fibers, suggesting this system is a promising tool to better understand cellular regulation of fiber formation to better stimulate it in vivo after injury.The vaccine field is pursuing diverse approaches to translate the molecular insights from analyses of effective antibodies and their targeted epitopes into immunogens capable of eliciting protective immune responses. Here we review current antibody-guided strategies including conformation-based, epitope-based, and lineage-based vaccine approaches, which are yielding promising vaccine candidates now being evaluated in clinical trials. We summarize directions being employed by the field, including the use of sequencing technologies to monitor and track developing immune responses for understanding and improving antibody-based immunity. We review opportunities and challenges to transform powerful new discoveries into safe and effective vaccines, which are encapsulated by vaccine efforts against a variety of pathogens including HIV-1, influenza A virus, malaria parasites, respiratory syncytial virus, and SARS-CoV-2. Overall, this review summarizes the extensive progress that has been made to realize antibody-guided structure-based vaccines, the considerable challenges faced, and the opportunities afforded by recently developed molecular approaches to vaccine development.
To evaluate the feasibility, safety, and effectiveness of N-butyl cyanoacrylate (NBCA) embolization for the treatment of aortic dissection.
In this single-center retrospective study conducted from February 2003 to June 2019, NBCA embolization of an aortic false lumen was attempted in 12 patients (median age, 59 y; range, 41-68 y) and thoracic endovascular aortic repair (TEVAR) was performed in 53 patients (median age, 59 y; range, 37-70 y) for aortic dissection with one or more indications of persisting pain, malperfusion, rupture or impending rupture, maximal aortic diameter ≥ 55 mm, and/or rapid aortic enlargement. The main exclusion criterion for embolization was the presence of fast blood flow in the aortic false lumen on aortography. The efficacy of NBCA embolization and TEVAR was compared by evaluating technical and clinical outcomes, repeat intervention-free survival (RFS), and overall survival (OS).
Technical success was achieved in 11 of the 12 patients treated with NBCA embolization (91.7%), and clinical success was achieved in 9 of these 11 (81.8%). No significant difference was found between embolization and TEVAR in clinical success rates (embolization, 81.8%; TEVAR, 84.9%; P= .409) or procedure-related complications (embolization, 1 patient [8.3%]; TEVAR, 4 patients [7.5%]; P= .701). In addition, embolization showed comparable 5-y RFS (embolization, 82.5% ± 9.3; TEVAR, 85.5% ± 4.8; P= .641) and 5-y OS (embolization, 100%; TEVAR, 95.4% ± 3.2; P= .744) rates to TEVAR.
NBCA embolization of the false lumen in aortic dissection seems to be a safe and effective treatment modality for the closure of false lumen in selected patients.
NBCA embolization of the false lumen in aortic dissection seems to be a safe and effective treatment modality for the closure of false lumen in selected patients.The effect of biochar additions on N leaching and retention in tea soils and its microbial mechanism are still unclear. In this study, effects of biochar additions at rates of 0, 3% and 6% on N leaching, N retention and microbial responses in two tea soils with 20- and 60-year plantation ages were investigated under application with 15N-labeled urea. The results showed that cumulative mass of leached NH4+-N, NO3--N and TN was reduced by 20.9%-91.9%, 35.1%-66.9% and 40.0%-72.8% under biochar additions, respectively. The retention of TN in soil was increased by 1.2%-5.8% under biochar amendment. Fertilizer-N in the leachate was reduced by 28.8%-62.1%, while fertilizer-N retention in the soils was enhanced by 3.2%-23.9% with biochar application. Biochar addition of 6% showed the highest mitigation of N leaching and enhancement of TN retention across the two soils. Biochar additions increased soil microbial biomass and enzyme activities and changed the bacterial community composition, indicating that biochar addition increased the microbial N requirement, stimulated soil N cycling, including nitrification and denitrification processes, and enhanced microbial N immobilization in the tea soils.