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Theranostics 2021Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs,... (Review)
Review
Exosomes are cell-derived nanovesicles that are involved in the intercellular transportation of materials. Therapeutics, such as small molecules or nucleic acid drugs, can be incorporated into exosomes and then delivered to specific types of cells or tissues to realize targeted drug delivery. Targeted delivery increases the local concentration of therapeutics and minimizes side effects. Here, we present a detailed review of exosomes engineering through genetic and chemical methods for targeted drug delivery. Although still in its infancy, exosome-mediated drug delivery boasts low toxicity, low immunogenicity, and high engineerability, and holds promise for cell-free therapies for a wide range of diseases.
Topics: Animals; Drug Delivery Systems; Exosomes; Humans; Membrane Proteins; Membranes; Protein Engineering
PubMed: 33537081
DOI: 10.7150/thno.52570 -
Medicina (Kaunas, Lithuania) Oct 2021The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous... (Review)
Review
The pemphigoid family of dermatoses is characterized by autoimmune subepidermal blistering. The classic paradigm for pemphigoid, and the most common member, is bullous pemphigoid. Its variable clinical presentation, with or without frank bullae, is linked by significant pruritus afflicting the elderly. Mucous membrane pemphigoid is an umbrella term for a group of subepidermal blistering dermatoses that favor the mucosal membranes and can scar. Epidermolysis bullosa acquisita is a chronic blistering disorder characterized by skin fragility, sensitivity to trauma, and its treatment-refractory nature. Clinicians that encounter these pemphigoid disorders may benefit from an overview of their clinical presentation, diagnostic work-up, and therapeutic management, with an emphasis on the most frequently encountered pemphigoid disease, bullous pemphigoid.
Topics: Aged; Humans; Mucous Membrane; Pemphigoid, Bullous; Skin Diseases, Vesiculobullous
PubMed: 34684098
DOI: 10.3390/medicina57101061 -
Developmental Cell Oct 2020In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous... (Review)
Review
In eukaryotic cells, various membrane-bound organelles compartmentalize diverse cellular activities in a spatially and temporally controlled manner. Numerous membraneless organelles assembled via liquid-liquid phase separation (LLPS), known as condensates, also facilitate compartmentalization of cellular functions. Emerging evidence shows that these two organelle types interact in many biological processes. Membranes modulate the biogenesis and dynamics of phase-separated condensates by serving as assembly platforms or by forming direct contacts. Phase separation of membrane-associated proteins participates in various trafficking events, such as clustering of vesicles for temporally controlled fusion and storage, and transport of membraneless condensates on membrane-bound organelles. Phase separation also acts in cargo trafficking pathways by sorting and docking cargos for translocon-mediated transport across membranes, by shuttling cargos through the nuclear pore complex, and by triggering the formation of surrounding autophagosomes for delivery to lysosomes. The coordinated actions of membrane-bound and membraneless organelles ensure spatiotemporal control of various cellular functions.
Topics: Autophagosomes; Biology; Biophysical Phenomena; Cell Physiological Phenomena; Humans; Membranes; Organelles
PubMed: 32726575
DOI: 10.1016/j.devcel.2020.06.033 -
Kidney International Jan 2020Membranous nephropathy is characterized by deposition of immune complexes along the glomerular basement membrane. PLA2R and THSD7A are target antigens in 70% and 1-5% of... (Observational Study)
Observational Study
Membranous nephropathy is characterized by deposition of immune complexes along the glomerular basement membrane. PLA2R and THSD7A are target antigens in 70% and 1-5% of primary membranous nephropathy cases, respectively. In the remaining cases, the target antigen is unknown. Here, laser microdissection of glomeruli followed by mass spectrometry was used to identify novel antigen(s) in PLA2R-negative membranous nephropathy. An initial pilot mass spectrometry study in 35 cases of PLA2R-negative membranous nephropathy showed high spectral counts for neural tissue encoding protein with EGF-like repeats, NELL-1, in six cases. Mass spectrometry failed to detect NELL-1 in 23 PLA2R-associated membranous nephropathy and 88 controls. NELL-1 was localized by immunohistochemistry, which showed bright granular glomerular basement membrane staining for NELL-1 in all six cases. Next, an additional 23 NELL-1 positive cases of membranous nephropathy were identified by immunohistochemistry in a discovery cohort of 91 PLA2R-negative membranous nephropathy cases, 14 were confirmed by mass spectrometry. Thus, 29 of 126 PLA2R-negative cases were positive for NELL-1. PLA2R-associated membranous nephropathy and controls stained negative for NELL-1. We then identified five NELL-1 positive cases of membranous nephropathy out of 84 PLA2R and THSD7A-negative cases in two validation cohorts from France and Belgium. By confocal microscopy, both IgG and NELL-1 co-localized to the glomerular basement membrane. Western blot analysis showed reactivity to NELL-1 in five available sera, but no reactivity in control sera. Clinical and biopsy findings of NELL-1 positive membranous nephropathy showed features of primary membranous nephropathy. Thus, a subset of membranous nephropathy is associated with accumulation and co-localization of NELL-1 and IgG along the glomerular basement membrane, and with anti-NELL-1 antibodies in the serum. Hence, NELL-1 defines a distinct type of primary membranous nephropathy.
Topics: Aged; Autoantibodies; Autoantigens; Biopsy; Calcium-Binding Proteins; Case-Control Studies; Cohort Studies; Female; Glomerular Basement Membrane; Glomerulonephritis, Membranous; Humans; Laser Capture Microdissection; Male; Mass Spectrometry; Microscopy, Confocal; Microscopy, Electron; Microscopy, Fluorescence; Middle Aged; Pilot Projects; Receptors, Phospholipase A2; Thrombospondins
PubMed: 31901340
DOI: 10.1016/j.kint.2019.09.014 -
Developmental Biology Jun 2021During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important... (Review)
Review
During development, a single cell is transformed into a highly complex organism through progressive cell division, specification and rearrangement. An important prerequisite for the emergence of patterns within the developing organism is to establish asymmetries at various scales, ranging from individual cells to the entire embryo, eventually giving rise to the different body structures. This becomes especially apparent during gastrulation, when the earliest major lineage restriction events lead to the formation of the different germ layers. Traditionally, the unfolding of the developmental program from symmetry breaking to germ layer formation has been studied by dissecting the contributions of different signaling pathways and cellular rearrangements in the in vivo context of intact embryos. Recent efforts, using the intrinsic capacity of embryonic stem cells to self-assemble and generate embryo-like structures de novo, have opened new avenues for understanding the many ways by which an embryo can be built and the influence of extrinsic factors therein. Here, we discuss and compare divergent and conserved strategies leading to germ layer formation in embryos as compared to in vitro systems, their upstream molecular cascades and the role of extrinsic factors in this process.
Topics: Animals; Embryonic Stem Cells; Extraembryonic Membranes; Gastrulation; Germ Layers; Humans; Signal Transduction
PubMed: 33352181
DOI: 10.1016/j.ydbio.2020.12.014 -
International Journal of Implant... Jul 2021This systematic review aimed to propose a treatment protocol for repairing intraoperative perforation of the Schneiderian membrane during maxillary sinus floor... (Meta-Analysis)
Meta-Analysis Review
Management of Schneiderian membrane perforations during maxillary sinus floor augmentation with lateral approach in relation to subsequent implant survival rates: a systematic review and meta-analysis.
BACKGROUND
This systematic review aimed to propose a treatment protocol for repairing intraoperative perforation of the Schneiderian membrane during maxillary sinus floor augmentation (MSFA) procedures with lateral window technique. In turn, to assess subsequent implant survival rates placed below repaired membranes compared with intact membranes and therefore determine whether membrane perforation constitutes a risk factor for implant survival.
MATERIAL AND METHODS
This review was conducted according to PRISMA guidelines. Two independent reviewers conducted an electronic search for articles published between 2008 and April 30, 2020, in four databases: (1) The National Library of Medicine (MEDLINE/PubMed) via Ovid; (2) Web of Science (WOS); (3) SCOPUS; and (4) Cochrane Central Register of Controlled Trials (CENTRAL); also, a complementary handsearch was carried out. The Newcastle-Ottawa Quality Assessment Scale was used to assess the quality of evidence in the studies reviewed.
RESULTS
Seven articles fulfilled the inclusion criteria and were analyzed. A total of 1598 sinus lift surgeries were included, allowing the placement of 3604 implants. A total of 1115 implants were placed under previously perforated and repaired membranes, obtaining a survival rate of 97.68%, while 2495 implants were placed below sinus membranes that were not damaged during surgery, obtaining a survival rate of 98.88%. The rate of Schneiderian membrane perforation shown in the systematic review was 30.6%. In the articles reviewed, the most widely used technique for repairing perforated membranes was collagen membrane repair.
CONCLUSIONS
Schneiderian membrane perforation during MFSA procedures with lateral approach is not a risk factor for dental implant survival (p=0.229; RR 0.977; 95% CI 0.941-1.015). The knowledge of the exact size of the membrane perforation is essential for deciding on the right treatment plan.
Topics: Maxillary Sinus; Nasal Mucosa; Prostheses and Implants; Sinus Floor Augmentation; Survival Rate; United States
PubMed: 34250560
DOI: 10.1186/s40729-021-00346-7 -
Biochimica Et Biophysica Acta.... Mar 2023Proteins can organize into dynamic, functionally important assemblies on fluid membrane surfaces. Phase separation has emerged as an important mechanism for forming such... (Review)
Review
Proteins can organize into dynamic, functionally important assemblies on fluid membrane surfaces. Phase separation has emerged as an important mechanism for forming such protein assemblies on the membrane during cell signaling, endocytosis, and cytoskeleton regulation. Protein-protein phase separation thus adds novel fluid mosaics to the classical Singer and Nicolson model. Protein condensates formed in this process can modulate membrane morphologies. This is evident from recent reports of protein condensate-driven membrane reshaping in processes such as endocytosis, autophagosome formation, and protein storage vacuole morphogenesis in plants. Lateral phase separation (on the membrane surface) of peripheral curvature coupling proteins can modulate such membrane morphological transitions. Additionally, three-dimensional protein phase separation can result in droplets that through adhesion can affect membrane shape changes. How do these condensate-driven curvature generation mechanisms contrast with the classically recognized scaffolding and amphipathic helix insertion activities of specific membrane remodeling proteins? A salient feature of these condensate-driven membrane activities is that they depend upon both macroscopic features (such as interfacial energies of the condensate, membrane, and cytosol) as well as microscopic, molecular-level interactions (such as protein-lipid binding). This review highlights the current understanding of the mechanisms underlying curvature generation by protein condensates in various biological pathways.
Topics: Membrane Proteins; Membranes
PubMed: 36642341
DOI: 10.1016/j.bbamem.2023.184121 -
Current Opinion in Microbiology Aug 2023The formation of lateral microdomains is emerging as a central organizing principle in bacterial membranes. These microdomains are targets of antibiotic development and... (Review)
Review
The formation of lateral microdomains is emerging as a central organizing principle in bacterial membranes. These microdomains are targets of antibiotic development and have the potential to enhance natural product synthesis, but the rules governing their assembly are unclear. Previous studies have suggested that microdomain formation is promoted by lipid phase separation, particularly by cardiolipin (CL) and isoprenoid lipids, and there is strong evidence that CL biosynthesis is required for recruitment of membrane proteins to cell poles and division sites. New work demonstrates that additional bacterial lipids may mediate membrane protein localization and function, opening the field for mechanistic evaluation of lipid-driven membrane organization in vivo.
Topics: Membrane Proteins; Membranes; Bacteria; Cardiolipins; Biophysics; Cell Membrane
PubMed: 37058914
DOI: 10.1016/j.mib.2023.102315 -
International Journal of Molecular... Jul 2022Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane... (Review)
Review
Eukaryotic cells contain membranes with various curvatures, from the near-plane plasma membrane to the highly curved membranes of organelles, vesicles, and membrane protrusions. These curvatures are generated and sustained by curvature-inducing proteins, peptides, and lipids, and describing these mechanisms is an important scientific challenge. In addition to that, some molecules can sense membrane curvature and thereby be trafficked to specific locations. The description of curvature sensing is another fundamental challenge. Curved lipid membranes and their interplay with membrane-associated proteins can be investigated with molecular dynamics (MD) simulations. Various methods for simulating curved membranes with MD are discussed here, including tools for setting up simulation of vesicles and methods for sustaining membrane curvature. The latter are divided into methods that exploit scaffolding virtual beads, methods that use curvature-inducing molecules, and methods applying virtual forces. The variety of simulation tools allow researcher to closely match the conditions of experimental studies of membrane curvatures.
Topics: Cell Membrane; Lipid Bilayers; Membranes; Molecular Dynamics Simulation; Proteins
PubMed: 35897670
DOI: 10.3390/ijms23158098 -
Developmental Cell Aug 2023Membranes are essential for life. They act as semi-permeable boundaries that define cells and organelles. In addition, their surfaces actively participate in biochemical... (Review)
Review
Membranes are essential for life. They act as semi-permeable boundaries that define cells and organelles. In addition, their surfaces actively participate in biochemical reaction networks, where they confine proteins, align reaction partners, and directly control enzymatic activities. Membrane-localized reactions shape cellular membranes, define the identity of organelles, compartmentalize biochemical processes, and can even be the source of signaling gradients that originate at the plasma membrane and reach into the cytoplasm and nucleus. The membrane surface is, therefore, an essential platform upon which myriad cellular processes are scaffolded. In this review, we summarize our current understanding of the biophysics and biochemistry of membrane-localized reactions with particular focus on insights derived from reconstituted and cellular systems. We discuss how the interplay of cellular factors results in their self-organization, condensation, assembly, and activity, and the emergent properties derived from them.
Topics: Cell Membrane; Membranes; Signal Transduction; Cell Nucleus
PubMed: 37419118
DOI: 10.1016/j.devcel.2023.06.001