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Annals of Anatomy = Anatomischer... Jun 2024In this manuscript, the structure of the human choroid is reviewed with emphasis of the macro- and microscopic anatomy including Bruch's membrane, choriocapillaris,... (Review)
Review
In this manuscript, the structure of the human choroid is reviewed with emphasis of the macro- and microscopic anatomy including Bruch's membrane, choriocapillaris, Sattler's and Haller's layer, and the suprachoroid. We here discuss the development of the choroid, as well as the question of choroidal lymphatics, and further the neuronal control of this tissue, as well as the pathologic angiogenesis. Wherever possible, functional aspects of the various structures are included and reviewed.
Topics: Humans; Choroid; Bruch Membrane
PubMed: 38432349
DOI: 10.1016/j.aanat.2024.152239 -
Matrix Biology : Journal of the... Jun 2024Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular... (Review)
Review
Epithelial cells adhere to a specialized extracellular matrix called the basement membrane which allows them to polarize and form epithelial tissues. The extracellular matrix provides essential physical scaffolding and biochemical and biophysical cues required for tissue morphogenesis, differentiation, function, and homeostasis. Epithelial cell adhesion to the extracellular matrix (i.e., basement membrane) plays a critical role in organizing epithelial tissues, separating the epithelial cells from the stroma. Epithelial cell detachment from the basement membrane classically results in death, though detachment or invasion through the basement membrane represents a critical step in carcinogenesis. Epithelial cells bind to the extracellular matrix via specialized matrix receptors, including integrins. Integrins are transmembrane receptors that form a mechanical linkage between the extracellular matrix and the intracellular cytoskeleton and are required for anchorage-dependent cellular functions such as proliferation, migration, and invasion. The role of integrins in the development, growth, and dissemination of multiple types of carcinomas has been investigated by numerous methodologies, which has led to great complexity. To organize this vast array of information, we have utilized the "Hallmarks of Cancer" from Hanahan and Weinberg as a convenient framework to discuss the role of integrins in the pathogenesis of cancers. This review explores this biology and how its complexity has impacted the development of integrin-targeted anti-cancer therapeutics.
Topics: Humans; Integrins; Neoplasms; Extracellular Matrix; Cell Adhesion; Epithelial Cells; Animals; Basement Membrane; Signal Transduction; Cell Movement; Neoplasm Invasiveness; Cell Proliferation
PubMed: 38677444
DOI: 10.1016/j.matbio.2024.04.003 -
Nature Communications Nov 2023ADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics....
ADP-ribosylation factor 1 (Arf1) interacts with multiple cellular partners and membranes to regulate intracellular traffic, organelle structure and actin dynamics. Defining the dynamic conformational landscape of Arf1 in its active form, when bound to the membrane, is of high functional relevance and key to understanding how Arf1 can alter diverse cellular processes. Through concerted application of nuclear magnetic resonance (NMR), neutron reflectometry (NR) and molecular dynamics (MD) simulations, we show that, while Arf1 is anchored to the membrane through its N-terminal myristoylated amphipathic helix, the G domain explores a large conformational space, existing in a dynamic equilibrium between membrane-associated and membrane-distal conformations. These configurational dynamics expose different interfaces for interaction with effectors. Interaction with the Pleckstrin homology domain of ASAP1, an Arf-GTPase activating protein (ArfGAP), restricts motions of the G domain to lock it in what seems to be a conformation exposing functionally relevant regions.
Topics: ADP-Ribosylation Factor 1; ADP-Ribosylation Factors; Membranes; GTPase-Activating Proteins; Actins
PubMed: 37989735
DOI: 10.1038/s41467-023-43008-5 -
Indian Journal of Ophthalmology Aug 2023The use of human amniotic membrane transplantation is rapidly increasing for the management of various ocular surface disorders. Despite its numerous advantages,...
BACKGROUND
The use of human amniotic membrane transplantation is rapidly increasing for the management of various ocular surface disorders. Despite its numerous advantages, amniotic membrane is not widely available due to the lack of awareness among ophthalmologists regarding its preparation and preservation techniques.
PURPOSE
To provide an instructional video demonstrating the technique of harvesting, preparation, preservation of human amniotic membrane, and its uses in the management of ocular surface diseases.
SYNOPSIS
The amniotic membrane is the innermost layer of the human placenta. Properties of the amniotic membrane, like the presence of various growth factors, anti-inflammatory and anti-angiogenic factors, and its low immunogenicity, contribute to its ability to promote epithelial growth and differentiation with the reduction in fibrosis during healing. To harvest amniotic membrane, informed consent is obtained from a patient undergoing an elective caesarian section, and the donor is screened to exclude the risk of infections. Under sterile precautions, the amniotic membrane is separated from the chorion and washed free of blood clots. With the epithelial surface up, the amniotic membrane is spread uniformly without folds or tears on individually sterilized 0.22 μm nitrocellulose filter papers of the required sizes. The prepared filter paper with the adherent amniotic membrane is placed in freshly prepared Dulbecco's Modified Eagle's Medium and stored at -80°C. The amniotic membrane can be used for surgical procedures like symblepharon release, pterygium or dermoid excision, perforated ulcers, nonhealing epithelial defects, etc.
HIGHLIGHTS
Instructional videos demonstrating the preparation and preservation of amniotic membrane are very sparse. This video clearly explains how any ophthalmologist can learn to prepare and preserve the human amniotic membrane and gives a glimpse of its properties, advantages, and scope of use.
VIDEO LINK
https://youtu.be/8HfSjXUKoiY.
Topics: Pregnancy; Female; Humans; Amnion; Eye Diseases; Conjunctiva; Plastic Surgery Procedures; Pterygium
PubMed: 37530302
DOI: 10.4103/IJO.IJO_674_23 -
Internal and Emergency Medicine Aug 2023This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases... (Review)
Review
This is a literature review describes Crohn's disease (CD) concomitant with breast cancer and summarizes possible common pathogenic mechanisms shared by the two diseases involving the IL-17 and NF-κB signaling pathways. Inflammatory cytokines including TNF-α and Th17 cells in CD patients can induce activation of the ERK1/2, NF-κB and Bcl-2 pathways. Hub genes are involved in the generation of cancer stem cells (CSCs) and are related to inflammatory mediators, including CXCL8, IL1-β and PTGS2, which promote inflammation and breast cancer growth, metastasis, and development. CD activity is highly associated with altered intestinal microbiota processes, including secretion of complex glucose polysaccharides by Ruminococcus gnavus colonies; furthermore, γ-proteobacteria and Clostridium are associated with CD recurrence and active CD, while Ruminococcaceae, Faecococcus and Vibrio desulfuris are associated with CD remission. Intestinal microbiota disorder promotes breast cancer occurrence and development. Bacteroides fragilis can produce toxins that induce breast epithelial hyperplasia and breast cancer growth and metastasis. Gut microbiota regulation can also improve chemotherapy and immunotherapy efficacy in breast cancer treatment. Intestinal inflammation can affects the brain through the brain-gut axis, which activates the hypothalamic‒pituitary‒adrenal (HPA) axis to induce anxiety and depression in patients; these effects can inhibit the antitumor immune responses of the immune system and promote breast cancer occurrence in patients with CD. There are few studies on the treatment of patients with CD concomitant with breast cancer, but published studies show three main strategies: new biological agents combined with breast cancer treatment methods, intestinal fecal bacteria transplantation, and dietary treatment.
Topics: Humans; Female; Crohn Disease; NF-kappa B; Breast Neoplasms; Intestinal Mucosa; Neoplasm Recurrence, Local; Inflammation
PubMed: 37138170
DOI: 10.1007/s11739-023-03281-0 -
Nature Communications Dec 2023Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt...
Compared to intramuscular vaccines, nasally administered vaccines have the advantage of inducing local mucosal immune responses that may block infection and interrupt transmission of respiratory pathogens. Live attenuated influenza vaccine (LAIV) is effective in preventing influenza in children, but a correlate of protection for LAIV remains unclear. Studying young adult volunteers, we observe that LAIV induces distinct, compartmentalized, antibody responses in the mucosa and blood. Seeking immunologic correlates of these distinct antibody responses we find associations with mucosal IL-33 release in the first 8 hours post-inoculation and divergent CD8 and circulating T follicular helper (cTfh) T cell responses 7 days post-inoculation. Mucosal antibodies are induced separately from blood antibodies, are associated with distinct immune responses early post-inoculation, and may provide a correlate of protection for mucosal vaccination. This study was registered as NCT04110366 and reports primary (mucosal antibody) and secondary (blood antibody, and nasal viral load and cytokine) endpoint data.
Topics: Child; Young Adult; Humans; Influenza Vaccines; Antibody Formation; Antibodies, Viral; Influenza, Human; Mucous Membrane; Vaccines, Attenuated; Immunity, Mucosal
PubMed: 38052824
DOI: 10.1038/s41467-023-43842-7 -
Proceedings of the National Academy of... Aug 2023Optogenetic tools respond to light through one of a small number of behaviors including allosteric changes, dimerization, clustering, or membrane translocation. Here, we...
Optogenetic tools respond to light through one of a small number of behaviors including allosteric changes, dimerization, clustering, or membrane translocation. Here, we describe a new class of optogenetic actuator that simultaneously clusters and translocates to the plasma membrane in response to blue light. We demonstrate that dual translocation and clustering of the BcLOV4 photoreceptor can be harnessed for novel single-component optogenetic tools, including for control of the entire family of epidermal growth factor receptor (ErbB1-4) tyrosine kinases. We further find that clustering and membrane translocation are mechanistically linked. Stronger clustering increased the magnitude of translocation and downstream signaling, increased sensitivity to light by ~threefold-to-fourfold, and decreased the expression levels needed for strong signal activation. Thus light-induced clustering of BcLOV4 provides a strategy to generate a new class of optogenetic tools and to enhance existing ones.
Topics: Optogenetics; Signal Transduction; Membranes; Cell Membrane; Dimerization; Light
PubMed: 37527339
DOI: 10.1073/pnas.2221615120 -
Nature Communications Sep 2023The outer membrane insertase of Gram-negative bacteria, BAM, is a key target for urgently needed novel antibiotics. Functional reconstitutions of BAM have so far been...
The outer membrane insertase of Gram-negative bacteria, BAM, is a key target for urgently needed novel antibiotics. Functional reconstitutions of BAM have so far been limited to synthetic membranes and with low throughput capacity for inhibitor screening. Here, we describe a BAM functional assay in native membrane environment capable of high-throughput screening. This is achieved by employing outer membrane vesicles (OMVs) to present BAM directly in native membranes. Refolding of the model substrate OmpT by BAM was possible from the chaperones SurA and Skp, with the required SurA concentration three times higher than Skp. In the OMVs, the antibiotic darobactin had a tenfold higher potency than in synthetic membranes, highlighting the need for native conditions in antibiotics development. The assay is successfully miniaturized for 1536-well plates and upscaled using large scale fermentation, resulting in high-throughput capacities to screen large commercial compound libraries. Our OMV-based assay thus lays the basis for discovery, hit validation and lead expansion of antibiotics targeting BAM.
Topics: High-Throughput Screening Assays; Membranes; Anti-Bacterial Agents; Biological Assay; Fermentation
PubMed: 37704632
DOI: 10.1038/s41467-023-41445-w -
Terminal differentiation of villus tip enterocytes is governed by distinct Tgfβ superfamily members.EMBO Reports Sep 2023The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated...
The protective and absorptive functions of the intestinal epithelium rely on differentiated enterocytes in the villi. The differentiation of enterocytes is orchestrated by sub-epithelial mesenchymal cells producing distinct ligands along the villus axis, in particular Bmps and Tgfβ. Here, we show that individual Bmp ligands and Tgfβ drive distinct enterocytic programs specific to villus zonation. Bmp4 is expressed from the centre to the upper part of the villus and activates preferentially genes connected to lipid uptake and metabolism. In contrast, Bmp2 is produced by villus tip mesenchymal cells and it influences the adhesive properties of villus tip epithelial cells and the expression of immunomodulators. Additionally, Tgfβ induces epithelial gene expression programs similar to those triggered by Bmp2. Bmp2-driven villus tip program is activated by a canonical Bmp receptor type I/Smad-dependent mechanism. Finally, we establish an organoid cultivation system that enriches villus tip enterocytes and thereby better mimics the cellular composition of the intestinal epithelium. Our data suggest that not only a Bmp gradient but also the activity of individual Bmp drives specific enterocytic programs.
Topics: Enterocytes; Ligands; Intestinal Mucosa; Transforming Growth Factor beta; Bone Morphogenetic Proteins; Cell Differentiation
PubMed: 37493498
DOI: 10.15252/embr.202256454 -
Autoimmunity Reviews Oct 2023Laminin-332 is an important component of the basement membrane. Recently, autoantibodies to Laminin-332 have been described in several autoimmune diseases. Many of these... (Review)
Review
IMPORTANCE
Laminin-332 is an important component of the basement membrane. Recently, autoantibodies to Laminin-332 have been described in several autoimmune diseases. Many of these autoimmune diseases have a high incidence of malignancy. The importance of Laminin-332 autoantibodies and its relationship to malignancy is highlighted by using Laminin-332 Pemphigoid (LM-332Pg) as a prototype.
OBJECTIVE
To identify several autoimmune diseases that have autoantibodies to Laminin-332 present, and to determine the prevalence of malignancy in them. Using Laminin-332 Pemphigoid (LM-332Pg) as a prototype, to compare clinical profiles of LM-332Pg patients with and without cancer. By identifying the temporal detection of cancer, can the influence of autoantibodies to Laminin-332 on prognosis be determined.
EVIDENCE REVIEW
A literature search was conducted to identify autoimmune and inflammatory diseases in which autoantibodies to Laminin-332 were present. Subsequently, the rate of malignancy in these autoimmune diseases was determined. A search for publications on LM-332Pg patients to determine cancer rates and clinical outcomes to examine if a relationship can be proposed, was performed.
FINDINGS
Autoantibodies to Laminin-332 were detected in recent studies of systemic lupus erythematosus (SLE), psoriasis, bronchiolitis obliterans (BO), graft-vs-host disease (GVH), bullous pemphigoid (BP), lichen planus (LP), epidermolysis bullosa acquisita (EBA), and membranous glomerulonephropathy (MGN). A high incidence of cancer rate was reported in these autoimmune diseases including primary Sjögren's syndrome (pSS), systemic sclerosis (SS), dermatomyositis (DM), multiple sclerosis (MS), immune thrombocytopenia purpura (ITP), and rheumatoid arthritis (RA). Data analysis demonstrated that LM-332Pg patients had a higher risk of developing ovarian, uterine, lung, gastric cancers and leukemia. The incidence for breast cancer was lower, when compared with global cancer rates. Patients diagnosed with cancer after the presence of LM-332Pg had higher rates of mortality and lower rates of remission, compared to those diagnosed with cancer prior to the discovery/diagnosis of LM-332Pg. When studied, levels of Laminin-332 autoantibodies correlated with the presence or absence of malignancy.
CONCLUSIONS AND RELEVANCE
Preliminary analysis suggests that autoantibodies to Laminin-332 are present in multiple autoimmune diseases, which also have a high incidence of malignancy. Detailed analysis of available data highlights that patients who developed LM-332Pg after cancer was diagnosed, had a more favorable prognosis, compared to patients who developed cancer when LM-332Pg was previously present. Preliminary data would suggest that autoantibodies to Laminin-332 could serve as an important biomarker in certain patients, for correlation with possible incidence of malignancy.
Topics: Humans; Pemphigoid, Bullous; Laminin; Pemphigoid, Benign Mucous Membrane; Autoimmune Diseases; Autoantibodies; Paraneoplastic Syndromes; Neoplasms; Mucous Membrane
PubMed: 37673192
DOI: 10.1016/j.autrev.2023.103444