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The Versatile Roles of Exosomes in Neurodegenerative Disorders: From Pathological Mechanism and Diagnostic Biomarkers to Therapeutic Application.

Neurodegenerative diseases are characterized by cognitive or motor impairments resulting from the progressive degeneration of neurons or myelin sheaths. Currently, the majority of these disorders remain incurable, leading to significant detriments in patients' quality of life and imposing substantial economic burdens. Exosomes are a type of extracellular vesicles secreted by cells into the extracellular space, typically range from 30 to 150 nanometers in diameter. These vesicles have been identified in a variety of cell types and can participate in various physiological and pathological proces…

Comprehensive account of exosome isolation from rat substantia nigra for mass spectrometry-based proteomics study.

Exosomes, small extracellular vesicles originating from endocytic processes, have garnered increasing attention due to their roles in both physiological functions and pathological conditions. Initially identified in the 1980 s, exosomes are formed within multivesicular bodies (MVBs) through the invagination of the endosomal membrane, leading to the creation of intraluminal vesicles (ILVs). These ILVs can either be degraded by lysosomes or released into the extracellular space as exosomes, facilitating intercellular communication. In the nervous system, exosomes are implicated in various functi…

HMGB1 contributes to pancreatic fibrosis by regulating TLR4-mediated autophagy and the NLRP3 inflammasome pathway in chronic pancreatitis.

The characteristic pathological change in chronic pancreatitis (CP) is pancreatic fibrosis. In the early stages of CP development, injured a … ranslocates from the nucleus of acinar cells to the cytoplasm and is subsequently released into the extracellular space, thereby promoting the progression of pancreatic fibrosis in CP. PSC was isolated and exposed to varying concentrations of HMGB1 in vitro. Resatorvid and si-TLR4 were applied to verify that the functions of HMGB1 were realized by combining with TLR4 …

Dynamic Changes in Function and Proteomic Composition of Extracellular Vesicles from Hepatic Stellate Cells during Cellular Activation.

: During chronic liver injury, hepatic stellate cells (HSC) undergo activation and are the principal cellular source of collagenous scar. In … dominated, while EVs from P1 mHSC contained 337 proteins and these were principally associated with extracellular spaces or matrix, proteasome, collagens, vesicular transport, metabolic enzymes, ribosomes and chaperones. EVs from the activated LX-2 human HSC (hHSC) line also promoted fibrogenic gene expression in D4 mHSC in vitro and contained 524 proteins, many of w …

Betaherpesvirus Virion Assembly and Egress.

Virions are the vehicle for cell-to-cell and host-to-host transmission of viruses. Virions need to be assembled reliably and efficiently, be released from infected cells, survive in the extracellular environment during transmission, recognize and then trigger entry of appropriate target cells, and disassemble in an orderly manner during initiation of a new infection. The betaherpesvirus subfamily includes four human herpesviruses (human cytomegalovirus and human herpesviruses 6A, 6B, and 7), as well as viruses that are the basis of important animal models of infection and immunity. Similar to

High membrane permeability for melatonin.

The pineal gland, an endocrine organ in the brain, synthesizes and secretes the circulating night hormone melatonin throughout the night. Th … diffusion. Circumstances are suggested when 5-HT and possibly catecholamines may also appear in the extracellular space passively by membrane diffusion.

Interleukin-33 biology with potential insights into human diseases.

Interleukin (IL)-33 is a member of the IL-1 family of cytokines. IL-33 is a nuclear protein that is also released into the extracellular space, and thus acts as a dual-function molecule, as does IL-1α. Extracellular IL-33 binds to the cell-surface receptor ST2, leading to the activation of intracellular signaling pathways similar to those used by IL-1. Unlike conventional cytokines, IL-33 might be secreted via unconventional pathways, and can be released upon cell injury as an alarmin. IL-33 is expressed in cells that are in contact with the environment, and acts as an early inducer of inflamm…

Silencing of TMS1/ASC promotes resistance to anoikis in breast epithelial cells.

Ductal carcinoma in situ (DCIS) is characterized by ductal epithelial cells that have filled the luminal space of the breast duct and survive despite loss of extracellular matrix contact. In normal epithelial cells, the loss of such contact triggers a form of apoptosis known as detachment-induced apoptosis or "anoikis." TMS1/ASC is a bipartite adaptor molecule that participates in inflammatory and apoptotic signaling pathways. Epigenetic silencing of TMS1 has been observed in a significant proportion of human breast and other cancers, but the mechanism by which TMS1 silencing contributes to ca

Vitamin A deficiency injures liver parenchyma and alters the expression of hepatic extracellular matrix.

Vitamin A is an essential lipid-soluble nutrient that is crucial for morphogenesis and adult tissue maintenance. The retinoid homeostasis in the liver depends on a regular supply of vitamin A from an adequate dietary intake to preserve the normal organ structure and functions. This study focuses on the effect of vitamin A deficiency on the morphology and extracellular proteins expression of the liver in adult Wistar rats. Animals were fed with a normal (control group) or deficient vitamin A diet for 3 months. At the end of the experimental period, histological examination of the livers under l

Механизм смерти клеток во время вирусной инфекции Западного Нила зависит от начальной инфекционной дозы.

Механизм вызванной вирусом смерти клеток Западного Нила (ВН) определяется первоначальной инфекционной дозой. В клетках Веро, инфицированных вирусом ВН на м.о. 10 или более, морфологические изменения, характерные для некроза, наблюдались еще на 8 часов после заражения (p.i.). Патологические изменения включали обширную опухоль клеток и потерю целостности плазменной мембраны, о чем свидетельствуют оптическая и электронная микроскопия. Высокая активность внеклеточного лактата дегидрогеназы (LDH) была отмечена наряду с утечкой белка высокой подвижности группы 1 (HMGB1) в внеклеточное пространство.

Совпадение в аннотации оригинала
The mechanism of West Nile (WN) virus-induced cell death is determined by the initial infectious dose. In Vero cells infected with WN virus … ) activity was observed together with leakage of the high mobility group 1 (HMGB1) protein into the extracellular space. When cells undergo necrosis, they release the HMGB1 protein, a pro-inflammatory mediator cytokine. At high infectious doses, loss of cell plasma membrane integrity was due to the profuse budding of WN progeny virus particles during maturation. When …

Ultrastructural characterization of the accessory lobes of Lachi in the lumbosacral spinal cord of the pigeon with special reference to intrinsic mechanoreceptors.

The lumbosacral spinal cord of birds is unique among vertebrates in that segmentally organized accessory lobes protrude from the ventrolateral spinal cord into the vertebral canal. Recently, it has been suggested that these lobes may be part of an extralabyrinthine sense organ of equilibrium. For a better understanding of such a function, a complete analysis of the structural basis was performed by means of electron microscopy. The lobes consist of multipolar neurons, myelinated and unmyelinated axons, glia-derived glycogen cells, glial cells, and capillaries. The dorsal part of the lobe is co

Pulmonary alveolar proteinosis. A report of two cases with diagnostic features in bronchoalveolar lavage specimens.

BACKGROUND: Pulmonary alveolar proteinosis (PAP) is a rare condition that has been associated with myriad diseases and disorders. Alveolar spaces are progressively filled with a phospholipoproteinaceous material, presumably related to a derangement of surfactant production and/or catabolism. The cytologic features of PAP in bronchoalveolar lavage (BAL) sediments are unique, and recognition of these characteristics can help guide clinical intervention. CASES: A 47-year-old male with a history of progressive dyspnea and recent pneumonia presented with a five-lobe alveolar infiltrate and subsequ

Neuronal origin of cerebral amyloidogenic proteins: their role in Alzheimer's disease and unconventional virus diseases of the nervous system.

The protein component of Alzheimer's disease amyloid (neurofibrillary tangles, amyloid plaque cores and congophilic angiopathy) is an aggreg … the degree of N-terminal heterogeneity, the A4 monomer aggregates first in neurons and later in the extracellular space. Using antisera raised against synthetic peptides, we can demonstrate that the N-terminus contains an epitope for neurofibrillary tangles, and the inner region of the molecule contains an epitope for the extracellular amyloid fibrils. There is a non …

Modeling glioma-induced impairments on the glymphatic system.

Altered glymphatic function is observed for many neurological diseases. Glioma, one of the most common brain cancers, is known to have alter … local changes of porosity (i.e. the volume fraction of certain compartments such as perivascular or extracellular spaces), result in a disruption of the transport of solutes in the brain. Our results indicate that an effect similar to the enhanced permeability and retention is obtained using biologically relevant changes of parameter values of our model. Our mathemat …

The journey of maternal platelets through the utero-placental circulation: routes, interactions, and physiological implications.

Maternal platelets fulfil an exceptional and multifaceted plethora of roles during pregnancy, extending far beyond their traditional function in hemostasis. Increasing evidence suggests that platelets participate in placental development, immune modulation, and vascular adaptation at the maternal-fetal interface. This review traces the journey of maternal platelets from a possible adaptation of megakaryopoiesis in the maternal bone marrow to their first encounter with trophoblast cells during early placentation, continuing their way into the intervillous space and eventually leaving the utero-

Modulation of solute diffusivity in brain tissue as a novel mechanism of transcranial direct current stimulation (tDCS).

The breadth of brain disorders and functions reported responsive to transcranial direct current stimulation (tDCS) suggests a generalizable mechanism of action. Prior efforts characterized its cellular targets including neuron, glia and endothelial cells. We propose tDCS also modulates the substance transport in brain tissue. High resolution multiphoton microscopy imaged the spread across rat brain tissue of fluorescently-labeled solutes injected through the carotid artery after tDCS. The effective solute diffusion coefficient of brain tissue (Deff) was determined from the spatio-temporal solu

[The morphology of the connective tissue matrix and lymphatic bed of the external genitalia in primary massive localized lymphedema].

OBJECTIVE: To identify the structural organization of connective tissue and vascular bed of the external genitalia in primary massive localized lymphedema. To analyze a clinical case of the development of massive localized lymphedema of the external genitalia concurrent with primary lymphedema of the lower limb in a patient with a normal body mass index. MATERIAL AND METHODS: The samples obtained by resection during volume reduction surgery were used to study the morphological features of the lymphatic bed and extracellular matrix of the scrotal skin and testicular dartos versus the samples w

Neuroimaging Findings in Patients with Mucopolysaccharidosis: What You Really Need to Know.

Mucopolysaccharidosis (MPS) is an inherited metabolic disease and a member of the group of lysosomal storage disorders. Its hallmark is a deficiency of lysosomal enzymes involved in the degradation of mucopolysaccharides, also known as glycosaminoglycans (GAGs). The products of GAG degradation accumulate within lysosomes and in the extracellular space, thereby interfering with the degradation of other macromolecules. This process leads to chronic degeneration of cells, which in turn affects multiple organs and systems. There are seven distinct types of MPS (I, II, III, IV, VI, VII, and IX), wh…

Distribution volumes of macromolecules in human ovarian and endometrial cancers--effects of extracellular matrix structure.

Elements of the extracellular matrix (ECM), notably collagen and glucosaminoglycans, will restrict part of the space available for soluble macromolecules simply because the molecules cannot occupy the same space. This phenomenon may influence macromolecular drug uptake. To study the influence of steric and charge effects of the ECM on the distribution volumes of macromolecules in human healthy and malignant gynecologic tissues we used as probes 15 abundant plasma proteins quantified by high-resolution mass spectrometry. The available distribution volume (VA) of albumin was increased in ovarian

Compartmentalization of the human stratum corneum by persistent tight junction-like structures.

Several tight junction (TJ) proteins were detected in the living layers of adult human epidermis, and TJ-like membrane ridges were observed … embrane interdigitations between corneocytes. Their presence could contribute to subdivision of the extracellular spaces of SC into consecutive individualized compartments. Intercellular lipids, enzymes and other (glyco)protein content could thus evolve in the keratinized epidermal layer at different paces, as preprogrammed in the underlying living cells and influenc …