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Journal of Extracellular Vesicles Apr 2022Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles...
Nanoparticles can acquire a plasma protein corona defining their biological identity. Corona functions were previously considered for cell-derived extracellular vesicles (EVs). Here we demonstrate that nano-sized EVs from therapy-grade human placental-expanded (PLX) stromal cells are surrounded by an imageable and functional protein corona when enriched with permissive technology. Scalable EV separation from cell-secreted soluble factors via tangential flow-filtration (TFF) and subtractive tandem mass-tag (TMT) proteomics revealed significant enrichment of predominantly immunomodulatory and proangiogenic proteins. Western blot, calcein-based flow cytometry, super-resolution and electron microscopy verified EV identity. PLX-EVs partly protected corona proteins from protease digestion. EVs significantly ameliorated human skin regeneration and angiogenesis in vivo, induced differential signalling in immune cells, and dose-dependently inhibited T cell proliferation in vitro. Corona removal by size-exclusion or ultracentrifugation abrogated angiogenesis. Re-establishing an artificial corona by cloaking EVs with fluorescent albumin as a model protein or defined proangiogenic factors was depicted by super-resolution microscopy, electron microscopy and zeta-potential shift, and served as a proof-of-concept. Understanding EV corona formation will improve rational EV-inspired nano-therapy design.
Topics: Extracellular Vesicles; Female; Humans; Immunomodulation; Placenta; Pregnancy; Protein Corona; Proteomics
PubMed: 35398993
DOI: 10.1002/jev2.12207 -
Journal of Clinical Oncology : Official... Sep 2022JCO Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy. We report long-term results, including data from the continued access...
JCO Blastic plasmacytoid dendritic cell neoplasm (BPDCN) is an aggressive myeloid malignancy. We report long-term results, including data from the continued access phase, of the largest prospective BPDCN trial evaluating the CD123-targeted therapy tagraxofusp (TAG) in adults with treatment-naive and relapsed/refractory BPDCN. The primary outcome was complete response (CR) + clinical CR (CRc: CR with residual skin abnormality not indicative of active disease). Eighty-four (65 treatment-naive and 19 relapsed/refractory) of 89 patients received TAG 12 μg/kg once daily; the median follow-up was 34.0 months. For treatment-naive patients, the overall response rate was 75%; 57% achieved CR + CRc. The median time to remission was 39 (range, 14-131) days, and the median CR + CRc duration was 24.9 (95% CI, 3.8 to not reached) months. Nineteen patients (51%) with CR + CRc were bridged to stem-cell transplant, with a median CR + CRc duration of 22.2 (range, 1.5-57.4) months. Most common adverse events were increased alanine (64%) or aspartate (60%) aminotransferase and hypoalbuminemia (51%); most occurred in cycle 1 and were transient. Capillary leak syndrome occurred in 21% of patients (grade ≥ 3: 7%). In first-line patients with BPDCN, TAG monotherapy resulted in high and durable responses, allowing many to bridge to stem-cell transplant. TAG was generally well-tolerated with a predictable and manageable safety profile.
Topics: Acute Disease; Adult; Clinical Trials as Topic; Dendritic Cells; Hematologic Neoplasms; Humans; Interleukin-3 Receptor alpha Subunit; Myeloproliferative Disorders; Prospective Studies; Recombinant Fusion Proteins; Skin Neoplasms
PubMed: 35820082
DOI: 10.1200/JCO.22.00034 -
European Journal of Physical and... Apr 2021During its fourth year of existence, Cochrane Rehabilitation went on to promote evidence-informed health decision-making in rehabilitation. In 2020, the outbreak of the... (Review)
Review
During its fourth year of existence, Cochrane Rehabilitation went on to promote evidence-informed health decision-making in rehabilitation. In 2020, the outbreak of the COVID-19 pandemic has made it necessary to alter priorities. In these challenging times, Cochrane Rehabilitation has firstly changed its internal organisation and established a new relevant project in line with pandemic needs: the REH-COVER (Rehabilitation - COVID-19 evidence-based response) action. The aim was to focus on the timely collection, review and dissemination of summarised and synthesised evidence relating to COVID-19 and rehabilitation. Cochrane Rehabilitation REH-COVER action has included in 2020 five main initiatives: 1) rapid living systematic reviews on rehabilitation and COVID-19; 2) interactive living evidence map on rehabilitation and COVID-19; 3) definition of the research topics on "rehabilitation and COVID-19" in collaboration with the World Health Organization (WHO) rehabilitation programme; 4) Cochrane Library special collection on Coronavirus (COVID-19) rehabilitation; and 5) collaboration with COVID-END for the topics "rehabilitation" and "disability." Furthermore, we are still carrying on five different special projects: Be4rehab; RCTRACK; definition of rehabilitation for research purposes; ebook project; and a prioritization exercise for Cochrane Reviews production. The Review Working Area continued to identify and "tag" the rehabilitation-relevant reviews published in the Cochrane library; the Publication Working Area went on to publish Cochrane Corners, working more closely with the Cochrane Review Groups (CRGs) and Cochrane Networks, particularly with Cochrane Musculoskeletal, Oral, Skin and Sensory Network; the Education Working Area, the most damaged in 2020, tried to continue performing educational activities such as workshops in different online meetings; the Methodology Working Area organized the third and fourth Cochrane Rehabilitation Methodological (CRM) meetings respectively in Milan and Orlando; the Communication Working Area spread rehabilitation evidences through different channels and translated the contents in different languages.
Topics: COVID-19; Decision Making; Humans; Pandemics; Retrospective Studies; SARS-CoV-2
PubMed: 33971699
DOI: 10.23736/S1973-9087.21.06877-5 -
ELife Dec 2022The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue...
The human endometrium experiences repetitive cycles of tissue wounding characterised by piecemeal shedding of the surface epithelium and rapid restoration of tissue homeostasis. In this study, we used a mouse model of endometrial repair and three transgenic lines of mice to investigate whether epithelial cells that become incorporated into the newly formed luminal epithelium have their origins in one or more of the mesenchymal cell types present in the stromal compartment of the endometrium. Using scRNAseq, we identified a novel population of PDGFRb + mesenchymal stromal cells that developed a unique transcriptomic signature in response to endometrial breakdown/repair. These cells expressed genes usually considered specific to epithelial cells and in silico trajectory analysis suggested they were stromal fibroblasts in transition to becoming epithelial cells. To confirm our hypothesis we used a lineage tracing strategy to compare the fate of stromal fibroblasts (PDGFRa+) and stromal perivascular cells (NG2/CSPG4+). We demonstrated that stromal fibroblasts can undergo a mesenchyme to epithelial transformation and become incorporated into the re-epithelialised luminal surface of the repaired tissue. This study is the first to discover a novel population of wound-responsive, plastic endometrial stromal fibroblasts that contribute to the rapid restoration of an intact luminal epithelium during endometrial repair. These findings form a platform for comparisons both to endometrial pathologies which involve a fibrotic response (Asherman's syndrome, endometriosis) as well as other mucosal tissues which have a variable response to wounding.
Topics: Female; Mice; Humans; Animals; Menstruation; Endometrium; Endometriosis; Mesenchymal Stem Cells; Epithelial Cells; Sequence Analysis, RNA
PubMed: 36524724
DOI: 10.7554/eLife.77663 -
The Journal of Clinical and Aesthetic... Jan 2023We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, , or other caustic agents.
OBJECTIVE
We sought to describe skin injuries associated with unapproved topical mole and skin tag removers containing concentrated salicylic acid, , or other caustic agents.
METHODS
We identified skin injuries associated with unapproved non-device topical mole and skin tag removers reported to the US Food and Drug Administration (FDA) through October 30, 2021 or described in Amazon consumer product reviews between 2019 and 2021.
RESULTS
We identified 38 cases, including 30 from Amazon consumer product reviews and eight reported to the FDA. Twenty-eight were from 2021. The most common reason for use was for mole and/or skin tag removal. Listed ingredients included salicylic acid, , botanicals (includes homeopathic products), and calcium oxide. Seven cases involved products without ingredients listed. Adverse events included burns, pain, and ulceration, some resulting in permanent scarring and disfigurement. There were 14 facial injuries, including four adjacent to the eye. Reported treatments included antibiotics, hospital care, wound care, and dermatology advice to have a skin graft.
LIMITATIONS
Limitations include underreporting of adverse events to the FDA, limited clinical details and potential bias in consumer reviews, and poor replicability of review searches due to the dynamic nature of the Amazon website.
CONCLUSION
Unapproved, non-device topical mole and skin tag removers are associated with serious skin injuries. We found Amazon consumer reviews to be a novel and useful data source for safety surveillance of these types of skin products. When dermatologists are consulted about skin injuries, exposure to these products should be considered in the differential diagnosis.
PubMed: 36743972
DOI: No ID Found -
JID Innovations : Skin Science From... May 2023Pemphigoid diseases are a group of autoimmune disorders characterized by subepidermal blistering in the skin and mucosa. Among them, mucous membrane pemphigoid (MMP)...
Pemphigoid diseases are a group of autoimmune disorders characterized by subepidermal blistering in the skin and mucosa. Among them, mucous membrane pemphigoid (MMP) autoantibodies are characterized by targeting multiple molecules in the hemidesmosomes, including collagen XVII, laminin-332, and integrin a6/β4. Traditionally, recombinant proteins of the autoantigens have been employed to identify circulating autoantibodies by immune assays. However, developing an efficient detection system for MMP autoantibodies has been challenging because the autoantibodies have heterogeneous profiles and the antibody titers are typically low. In this study, we introduce an ELISA that takes advantage of a native autoantigen complex rather than simple recombinant proteins. We generated HaCaT keratinocytes with a DDDDK-tag knocked in at the locus by CRISPR/Cas9-mediated gene editing. Immunoprecipitation using the DDDDK-tag isolated a native complex that contained full-length and processed collagen XVII and integrin α6/β4. Then, we used the complex proteins to prepare an ELISA system and enrolled 55 MMP cases to validate its diagnostic performance. The sensitivity and specificity of the ELISA for detecting MMP autoantibodies were 70.9% and 86.7%, respectively, far superior to those of conventional assays. In autoimmune diseases such as MMP, in which autoantibodies target various molecules, isolating the antigen-protein complexes can help establish a diagnostic system.
PubMed: 36992950
DOI: 10.1016/j.xjidi.2023.100193 -
Journal of Digital Imaging Oct 2022Clinical images are vital for diagnosing and monitoring skin diseases, and their importance has increased with the growing popularity of machine learning. Lack of...
Clinical images are vital for diagnosing and monitoring skin diseases, and their importance has increased with the growing popularity of machine learning. Lack of standards has stifled innovation in dermatological imaging, unlike other image-intensive specialties such as radiology. We investigate the meta-requirements for utilizing the popular DICOM standard for metadata management of images in dermatology. We propose practical design solutions and provide open-source tools to integrate dermatologists' workflow with enterprise imaging systems. Using the tool, dermatologists can tag, search, organize and convert clinical images to the DICOM format. We believe that our less disruptive approach will improve the adoption of standards in the specialty.
Topics: Humans; Dermatology; Diagnostic Imaging; Metadata; Radiology Information Systems; Workflow
PubMed: 35488074
DOI: 10.1007/s10278-022-00636-5