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RMD Open Aug 2023The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an adult-onset systemic autoinflammatory condition that is caused by an acquired...
The VEXAS syndrome (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) is an adult-onset systemic autoinflammatory condition that is caused by an acquired deficiency of the UBA1 gene in hematopoietic progenitor cells. The clinical spectrum of the VEXAS syndrome currently comprises a broad range of phenotypes such as vasculitis, relapsing polychondritis and Sweet's syndrome. In the past, VEXAS patients have left clinicians puzzled and the true nature of this disease has not been captured until late 2020. This viewpoint describes the relevant clinical features of the VEXAS syndrome and reviews different approaches to establish the diagnosis. Finally, future directions within the field of systemic inflammatory diseases caused by somatic mutations are being discussed.
Topics: Humans; Myelodysplastic Syndromes; Phenotype
PubMed: 37532466
DOI: 10.1136/rmdopen-2023-003332 -
The Journal of Dermatology Feb 2024Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are... (Review)
Review
Autoinflammatory diseases (AIDs) characterized by recurrent episodes of localized or systemic inflammation are disorders of the innate immune system. Skin lesions are commonly found in AIDs and cutaneous vasculitis can coexist with AIDs and even present as the most striking feature. This review aims to focus on the frequent cutaneous vasculitis association in three monogenic AIDs including familial Mediterranean fever (FMF), deficiency of adenosine deaminase type 2 (DADA2), and the recently identified adult-onset VEXAS (vacuoles, E1 enzyme, X-linked, autoinflammatory, somatic) syndrome. Cutaneous vasculitis in FMF is characterized by: (1) small-vessel vasculitis similar to IgA vasculitis with palpable purpura but increased intussusception complication and less vascular IgA deposit, and (2) cutaneous arteritis-like vasculitis presenting as subcutaneous nodules most often with higher glomerular involvement. DADA2 has a wide spectrum of clinical presentations ranging from fatal systemic vasculitis with multiple strokes, especially in pediatric patients, to limited cutaneous disease in middle-aged patients. DADA2 shares similar clinical and histopathological features with polyarteritis nodosa (PAN). As a result, DADA2 is commonly initially misdiagnosed as childhood PAN. Livedo racemosa reveals the most common cutaneous manifestation of cutaneous vasculitis in patients with DADA2. VEXAS syndrome is a life-threatening disease. A diagnosis of VEXAS syndrome should be strongly considered or could be made in patients with skin lesions characterized by Sweet syndrome-like eruption, livedo racemosa, concomitant relapsing polychondritis, deep venous thrombosis, pulmonary involvement, and progressive hematologic abnormalities such as myelodysplastic syndrome with a unique finding of cytoplasmic vacuoles in myeloid and erythroid precursor cells from bone marrow aspirate smear. As skin involvement is common in AIDs and may present as the most frequent manifestation, especially in DADA2 (70% to 90%) and VEXAS syndrome (83% to 91%), dermatologists play a crucial role in contributing to the early diagnosis of these AIDs with early initiation of the appropriate therapy to avoid progressing fatal outcomes.
Topics: Adult; Humans; Child; Middle Aged; Adenosine Deaminase; Livedo Reticularis; Intercellular Signaling Peptides and Proteins; Vasculitis; Polyarteritis Nodosa; Skin Diseases; Familial Mediterranean Fever; Mutation; Agammaglobulinemia; Myelodysplastic Syndromes; Skin Diseases, Genetic; Severe Combined Immunodeficiency
PubMed: 37955334
DOI: 10.1111/1346-8138.17030 -
Nature Microbiology Jan 2024Toxoplasma gondii is a single-celled eukaryotic parasite with a considerable host range that must invade the cells of warm-blooded hosts to survive and replicate. The... (Review)
Review
Toxoplasma gondii is a single-celled eukaryotic parasite with a considerable host range that must invade the cells of warm-blooded hosts to survive and replicate. The challenges and opportunities that such a strategy represent have been met by the evolution of effectors that are delivered into host cells, counter host defences and co-opt host cell functions for their own purposes. These effectors are delivered in two waves using distinct machinery for each. In this Review, we focus on understanding the architecture of these protein-export systems and how their protein cargo is recognized and selected. We discuss the recent findings on the role that host manipulation has in latent Toxoplasma infections. We also discuss how these recent findings compare to protein export in the related Plasmodium spp. (the causative agent of malaria) and how this can inform our understanding of host manipulation in the larger Apicomplexa phylum and its evolution.
Topics: Toxoplasma; Protozoan Proteins; Vacuoles; Plasmodium; Cells, Cultured
PubMed: 38172621
DOI: 10.1038/s41564-023-01563-z -
International Journal of General... 2024This study examines the clinical and pathological characteristics, immune profile, histological occurrence, diagnosis, and differential diagnosis of vulvar hidradenoma...
AIM
This study examines the clinical and pathological characteristics, immune profile, histological occurrence, diagnosis, and differential diagnosis of vulvar hidradenoma papilliferum.
METHODS
An analysis was conducted on clinical data, histological patterns, and immunohistochemical findings from 45 cases of vulvar hidradenoma papilliferum, and relevant published articles were reviewed. Simultaneously, high-risk HPV typing was performed on these 45 cases.
RESULTS
The 45 cases of vulvar hidradenoma papilliferum displayed tumor sizes ranging from 0.3 to 2.0 cm and were observed to be pink or red in appearance. Vacuolated cytoplasm, large abnormal nuclei, distinct nucleoli, and scattered eosinophilic luminal secretions were observed in the glands. Positive staining for CK7 and progesterone receptor (PR) with focal mammaglobin and GCDFP-15 expression was found through immunohistochemistry. CK20 staining was noted as negative.
CONCLUSION
Hidradenoma papilliferum is a rare benign tumor that originates in secretory glands. The diagnosis of this condition is aided by gross and immunohistochemical results, and differentiation from other conditions is necessary.
PubMed: 38435116
DOI: 10.2147/IJGM.S449102 -
The New Phytologist Oct 2023The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes,... (Review)
Review
The endomembrane system consists of various membrane-bound organelles including the endoplasmic reticulum (ER), Golgi apparatus, trans-Golgi network (TGN), endosomes, and the lysosome/vacuole. Membrane trafficking between distinct compartments is mainly achieved by vesicular transport. As the endomembrane compartments and the machineries regulating the membrane trafficking are largely conserved across all eukaryotes, our current knowledge on organelle biogenesis and endomembrane trafficking in plants has mainly been shaped by corresponding studies in mammals and yeast. However, unique perspectives have emerged from plant cell biology research through the characterization of plant-specific regulators as well as the development and application of the state-of-the-art microscopical techniques. In this review, we summarize our current knowledge on the plant endomembrane system, with a focus on several distinct pathways: ER-to-Golgi transport, protein sorting at the TGN, endosomal sorting on multivesicular bodies, vacuolar trafficking/vacuole biogenesis, and the autophagy pathway. We also give an update on advanced imaging techniques for the plant cell biology research.
Topics: Plants; Endosomes; Vacuoles; Multivesicular Bodies; Protein Transport; Golgi Apparatus; trans-Golgi Network
PubMed: 37507353
DOI: 10.1111/nph.19134 -
The Journal of Cell Biology Dec 2023Autophagy is a lysosomal/vacuolar delivery system that degrades cytoplasmic material. During autophagy, autophagosomes deliver cellular components to the vacuole,...
Autophagy is a lysosomal/vacuolar delivery system that degrades cytoplasmic material. During autophagy, autophagosomes deliver cellular components to the vacuole, resulting in the release of a cargo-containing autophagic body (AB) into the vacuole. AB membranes must be disrupted for degradation of cargo to occur. The lipase Atg15 and vacuolar proteases Pep4 and Prb1 are known to be necessary for this disruption and cargo degradation, but the mechanistic underpinnings remain unclear. In this study, we establish a system to detect lipase activity in the vacuole and show that Atg15 is the sole vacuolar phospholipase. Pep4 and Prb1 are required for the activation of Atg15 lipase function, which occurs following delivery of Atg15 to the vacuole by the MVB pathway. In vitro experiments reveal that Atg15 is a phospholipase B of broad substrate specificity that is likely implicated in the disruption of a range of membranes. Further, we use isolated ABs to demonstrate that Atg15 alone is able to disrupt AB membranes.
Topics: Autophagosomes; Autophagy; Lipase; Vacuoles; Autophagy-Related Proteins; Cell Membrane; Phospholipases
PubMed: 37917025
DOI: 10.1083/jcb.202306120 -
FEBS Letters Jan 2024Autophagy is an intracellular catabolic process that eliminates cytoplasmic constituents selectively by tight engulfment in an isolation membrane or recycles bulk... (Review)
Review
Autophagy is an intracellular catabolic process that eliminates cytoplasmic constituents selectively by tight engulfment in an isolation membrane or recycles bulk cytoplasm by nonselective sequestration. Completion of the isolation membrane forms a double membrane vesicle, termed autophagosome, that proceeds to fusion with the lysosome, where the inner membrane and its cytoplasmic content are degraded. Autophagosome biogenesis is unique in that the newly-formed membrane, termed phagophore, is elongated by direct lipid flow from a proximal ER-associated donor membrane. Recent years mark a tremendous advancement in delineating the direct regulation of this process by different lipid species and associated protein complexes. Here we schematically summarize the current view of autophagy and autophagosome biogenesis.
Topics: Autophagy; Autophagosomes; Lysosomes; Lipids
PubMed: 37326419
DOI: 10.1002/1873-3468.14679 -
Frontiers in Cellular and Infection... 2023Obligate intracellular pathogens occupy one of two niches - free in the host cell cytoplasm or confined in a membrane-bound vacuole. Pathogens occupying membrane-bound... (Review)
Review
Obligate intracellular pathogens occupy one of two niches - free in the host cell cytoplasm or confined in a membrane-bound vacuole. Pathogens occupying membrane-bound vacuoles are sequestered from the innate immune system and have an extra layer of protection from antimicrobial drugs. However, this lifestyle presents several challenges. First, the bacteria must obtain membrane or membrane components to support vacuole expansion and provide space for the increasing bacteria numbers during the log phase of replication. Second, the vacuole microenvironment must be suitable for the unique metabolic needs of the pathogen. Third, as most obligate intracellular bacterial pathogens have undergone genomic reduction and are not capable of full metabolic independence, the bacteria must have mechanisms to obtain essential nutrients and resources from the host cell. Finally, because they are separated from the host cell by the vacuole membrane, the bacteria must possess mechanisms to manipulate the host cell, typically through a specialized secretion system which crosses the vacuole membrane. While there are common themes, each bacterial pathogen utilizes unique approach to establishing and maintaining their intracellular niches. In this review, we focus on the vacuole-bound intracellular niches of , and .
Topics: Vacuoles; Coxiella burnetii; Anaplasma phagocytophilum; Chlamydia trachomatis; Ehrlichia chaffeensis
PubMed: 37645379
DOI: 10.3389/fcimb.2023.1206037 -
Ophthalmic Plastic and Reconstructive...VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis,...
VEXAS (Vacuoles, E1 enzyme, X-linked, Autoinflammatory, Somatic) syndrome is an adult-onset autoinflammatory disorder characterized by systemic inflammation (vasculitis, arthritis, chondritis, dermatosis) and hematologic abnormalities (thrombosis, cytopenia, vacuolization of marrow precursors). The patient demonstrated some of the adult-onset inflammatory and hematologic features, in addition to recurrent eye pain, chemosis and orbital inflammation. This case describes an instance of VEXAS syndrome in a patient with uncommon orbital symptoms such as scleritis and myositis.
Topics: Adult; Humans; Inflammation; Eye Pain; Myelodysplastic Syndromes; Myositis; Mutation
PubMed: 37405738
DOI: 10.1097/IOP.0000000000002450 -
Molecular Microbiology Aug 2023Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer... (Review)
Review
Lipid droplets (LDs) are dynamic and versatile organelles present in most eukaryotic cells. LDs consist of a hydrophobic core of neutral lipids, a phospholipid monolayer coat, and a variety of associated proteins. LDs are formed at the endoplasmic reticulum and have diverse roles in lipid storage, energy metabolism, membrane trafficking, and cellular signaling. In addition to their physiological cellular functions, LDs have been implicated in the pathogenesis of several diseases, including metabolic disorders, cancer, and infections. A number of intracellular bacterial pathogens modulate and/or interact with LDs during host cell infection. Members of the genera Mycobacterium, Legionella, Coxiella, Chlamydia, and Salmonella exploit LDs as a source of intracellular nutrients and membrane components to establish their distinct intracellular replicative niches. In this review, we focus on the biogenesis, interactions, and functions of LDs, as well as on their role in lipid metabolism of intracellular bacterial pathogens.
Topics: Lipid Droplets; Diet; Lipid Metabolism
PubMed: 37429596
DOI: 10.1111/mmi.15120