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Annals of Clinical and Translational... Feb 2021To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor...
OBJECTIVE
To determine whether animals with Japanese macaque encephalomyelitis (JME), a spontaneous demyelinating disease similar to multiple sclerosis (MS), harbor myelin-specific T cells in their central nervous system (CNS) and periphery.
METHODS
Mononuclear cells (MNCs) from CNS lesions, cervical lymph nodes (LNs) and peripheral blood of Japanese macaques (JMs) with JME, and cervical LN and blood MNCs from healthy controls or animals with non-JME conditions were analyzed for the presence of myelin-specific T cells and changes in interleukin 17 (IL-17) and interferon gamma (IFNγ) expression.
RESULTS
Demyelinating JME lesions contained CD4 T cells and CD8 T cells specific to myelin oligodendrocyte glycoprotein (MOG), myelin basic protein (MBP), and/or proteolipid protein (PLP). CD8 T-cell responses were absent in JME peripheral blood, and in age- and sex-matched controls. However, CD4 Th1 and Th17 responses were detected in JME peripheral blood versus controls. Cervical LN MNCs from eight of nine JME animals had CD3 T cells specific for MOG, MBP, and PLP that were not detected in controls. Mapping myelin epitopes revealed a heterogeneity in responses among JME animals. Comparison of myelin antigen sequences with those of JM rhadinovirus (JMRV), which is found in JME lesions, identified six viral open reading frames (ORFs) with similarities to myelin antigen sequences. Overlapping peptides to these JMRV ORFs did not induce IFNγ responses.
INTERPRETATIONS
JME possesses an immune-mediated component that involves both CD4 and CD8 T cells specific for myelin antigens. JME may shed new light on inflammatory demyelinating disease pathogenesis linked to gamma-herpesvirus infection.
Topics: Animals; Autoimmune Diseases; Demyelinating Diseases; Encephalomyelitis; Enzyme-Linked Immunosorbent Assay; Epitope Mapping; Epitopes; Female; Herpesviridae Infections; Interferon-gamma; Interleukin-17; Macaca fuscata; Male; Monkey Diseases; Myelin Basic Protein; Myelin Proteolipid Protein; Myelin Sheath; Myelin-Oligodendrocyte Glycoprotein; Rhadinovirus; T-Lymphocytes
PubMed: 33440071
DOI: 10.1002/acn3.51303 -
Animal Biotechnology Nov 2024NK-lysins from chicken, bovine and human are used as antiviral and antibacterial agents. Gram-negative and gram-positive microorganisms, including and , are susceptible...
NK-lysins from chicken, bovine and human are used as antiviral and antibacterial agents. Gram-negative and gram-positive microorganisms, including and , are susceptible to NK-lysin treatment. The presence of dominant TEM-1 gene was noted in all untreated and treated bacteria, while TOHO-1 gene was absent in all bacteria. Importantly, β-lactamase genes CTX-M-1, CTX-M-8, and CTX-M-9 genes were detected in untreated bacterial strains; however, none of these were found in any bacterial strains following treatment with NK-lysin peptides. NK-lysin peptides are also used to test for inhibition of infectivity, which ranged from 50 to 90% depending on NK-lysin species. Chicken, bo vine and human NK-lysin peptides are demonstrated herein to have antibacterial activity and antiviral activity against Rotavirus (strain SA-11). On the basis of the comparison between these peptides, potent antiviral activity of bovine NK-lysin against Rotavirus (strain SA-11) is particularly evident, inhibiting infection by up to 90%. However, growth was also significantly inhibited by chicken and human NK-lysin peptides, restricted by 80 and 50%, respectively. This study provided a novel treatment using NK-lysin peptides to inhibit expression of β-lactamase genes in β-lactam antibiotic-resistant bacterial infections.
Topics: Animals; Cattle; Humans; Anti-Bacterial Agents; Drug Resistance, Bacterial; Peptides; beta-Lactamases; Escherichia coli; Antiviral Agents; Proteolipids
PubMed: 38100547
DOI: 10.1080/10495398.2023.2290520 -
Journal of Visualized Experiments : JoVE Mar 2021Membrane proteins are vital for cell function and thus represent important drug targets. Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy offers a unique...
Membrane proteins are vital for cell function and thus represent important drug targets. Solid-state Nuclear Magnetic Resonance (ssNMR) spectroscopy offers a unique access to probe the structure and dynamics of such proteins in biological membranes of increasing complexity. Here, we present modern solid-state NMR spectroscopy as a tool to study structure and dynamics of proteins in natural lipid membranes and at atomic scale. Such spectroscopic studies profit from the use of high-sensitivity ssNMR methods, i.e., proton-(H)-detected ssNMR and DNP (Dynamic Nuclear Polarization) supported ssNMR. Using bacterial outer membrane beta-barrel protein BamA and the ion channel KcsA, we present methods to prepare isotope-labeled membrane proteins and to derive structural and motional information by ssNMR.
Topics: Bacterial Proteins; Cell Membrane; Inclusion Bodies; Isotope Labeling; Membrane Proteins; Nuclear Magnetic Resonance, Biomolecular; Point Mutation; Potassium Channels; Protein Refolding; Proteolipids; Protons; Staining and Labeling
PubMed: 33749679
DOI: 10.3791/62197 -
Brain Sciences May 2020Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in... (Review)
Review
Multiple sclerosis (MS) is an autoimmune disease of the central nervous system and is considered to be the leading non-traumatic cause of neurological disability in young adults. Current treatments for MS comprise long-term immunosuppressant drugs and disease-modifying therapies (DMTs) designed to alter its progress with the enhanced risk of severe side effects. The Holy Grail for the treatment of MS is to specifically suppress the disease while at the same time allow the immune system to be functionally active against infectious diseases and malignancy. This could be achieved via the development of immunotherapies designed to specifically suppress immune responses to self-antigens (e.g., myelin antigens). The present study attempts to highlight the various antigen-specific immunotherapies developed so far for the treatment of multiple sclerosis (e.g., vaccination with myelin-derived peptides/proteins, plasmid DNA encoding myelin epitopes, tolerogenic dendritic cells pulsed with encephalitogenic epitopes of myelin proteins, attenuated autologous T cells specific for myelin antigens, T cell receptor peptides, carriers loaded/conjugated with myelin immunodominant peptides, etc), focusing on the outcome of their recent preclinical and clinical evaluation, and to shed light on the mechanisms involved in the immunopathogenesis and treatment of multiple sclerosis.
PubMed: 32486045
DOI: 10.3390/brainsci10060333 -
Scientific Reports Feb 2022Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown...
Malignant melanoma is the main cause of death in patients with skin cancer. Overexpression of Proteolipid protein 2 (PLP2) increased tumor metastasis and the knockdown of PLP2 inhibited the growth and metastasis of melanoma cells. In the present work, we studied the antitumor activity of peptide Rb4 derived from protein PLP2. In vitro, Rb4 induced F-actin polymerization, prevented F-actin depolymerization and increased the ER-derived cytosolic calcium. Such effects were associated with necrosis of murine melanoma B16F10-Nex2 cells and with inhibition of the viability of human cancer cell lines. Loss of plasma membrane integrity, dilation of mitochondria, cytoplasm vacuolation and absence of chromatin condensation characterized tumor cell necrosis. Cleavage of PARP-1 and inhibition of RIP1 expression were also observed. In vivo, peptide Rb4 reduced the lung metastasis of tumor cells and delayed the subcutaneous melanoma growth in a syngeneic model. Rb4 induced the expression of two DAMPs molecules, HMGB1 and calreticulin, in B16F10-Nex2. Our results suggest that peptide Rb4 acts directly on tumor cells inducing the expression of DAMPs, which trigger the immunoprotective effect in vivo against melanoma cells. We suggest that peptide Rb4 is a promising compound to be developed as an anticancer drug.
Topics: Animals; Antineoplastic Agents; Calreticulin; Cell Death; Cell Line, Tumor; Gene Expression; HMGB1 Protein; Humans; MARVEL Domain-Containing Proteins; Melanoma; Mice; Necrosis; Nuclear Pore Complex Proteins; Peptides; Poly (ADP-Ribose) Polymerase-1; Proteolipids; RNA-Binding Proteins; Skin Neoplasms
PubMed: 35190586
DOI: 10.1038/s41598-022-06429-8 -
Respirology (Carlton, Vic.) Apr 2024Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults.
BACKGROUND AND OBJECTIVE
Variants in surfactant genes SFTPC or ABCA3 are responsible for interstitial lung disease (ILD) in children and adults, with few studies in adults.
METHODS
We conducted a multicentre retrospective study of all consecutive adult patients diagnosed with ILD associated with variants in SFTPC or ABCA3 in the French rare pulmonary diseases network, OrphaLung. Variants and chest computed tomography (CT) features were centrally reviewed.
RESULTS
We included 36 patients (median age: 34 years, 20 males), 22 in the SFTPC group and 14 in the ABCA3 group. Clinical characteristics were similar between groups. Baseline median FVC was 59% ([52-72]) and DLco was 44% ([35-50]). An unclassifiable pattern of fibrosing ILD was the most frequent on chest CT, found in 85% of patients, however with a distinct phenotype with ground-glass opacities and/or cysts. Nonspecific interstitial pneumonia and usual interstitial pneumonia were the most common histological patterns in the ABCA3 group and in the SFTPC group, respectively. Annually, FVC and DL declined by 1.87% and 2.43% in the SFTPC group, respectively, and by 0.72% and 0.95% in the ABCA3 group, respectively (FVC, p = 0.014 and DL , p = 0.004 for comparison between groups). Median time to death or lung transplantation was 10 years in the SFTPC group and was not reached at the end of follow-up in the ABCA3 group.
CONCLUSION
SFTPC and ABCA3-associated ILD present with a distinct phenotype and prognosis. A radiologic pattern of fibrosing ILD with ground-glass opacities and/or cysts is frequently found in these rare conditions.
Topics: Male; Adult; Child; Humans; Retrospective Studies; Lung Diseases, Interstitial; Lung; Idiopathic Pulmonary Fibrosis; Cysts; Pulmonary Surfactant-Associated Protein C; ATP-Binding Cassette Transporters
PubMed: 38345107
DOI: 10.1111/resp.14667 -
BMC Biology Feb 2024Membranes are protein and lipid structures that surround cells and other biological compartments. We present a conceptual model wherein all membranes are organized into...
Membranes are protein and lipid structures that surround cells and other biological compartments. We present a conceptual model wherein all membranes are organized into structural and functional zones. The assembly of zones such as receptor clusters, protein-coated pits, lamellipodia, cell junctions, and membrane fusion sites is explained to occur through a protein-lipid code. This challenges the theory that lipids sort proteins after forming stable membrane subregions independently of proteins.
Topics: Proteolipids; Membranes; Carrier Proteins; Cell Membrane
PubMed: 38414038
DOI: 10.1186/s12915-024-01849-6 -
The Journal of Pediatrics Dec 2020
Topics: Biological Products; Double-Blind Method; Humans; Infant, Newborn; Peptide Fragments; Phosphatidylcholines; Phospholipids; Pulmonary Surfactant-Associated Protein B; Pulmonary Surfactant-Associated Protein C; Respiratory Distress Syndrome, Newborn; Surface-Active Agents
PubMed: 32798565
DOI: 10.1016/j.jpeds.2020.08.029 -
Cell Stress Dec 2022(Macro)autophagy is a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and...
(Macro)autophagy is a major lysosome-dependent degradation mechanism which engulfs, removes and recycles unwanted cytoplasmic material, including damaged organelles and toxic protein aggregates. Although a few studies implicate autophagy in CNS demyelinating pathologies, its role, particularly in mature oligodendrocytes and CNS myelin, remains poorly studied. Here, using both pharmacological and genetic inhibition of the autophagic machinery, we provide evidence that autophagy is an essential mechanism for oligodendrocyte maturation . Our study reveals that two core myelin proteins, namely proteolipid protein (PLP) and myelin basic protein (MBP) are incorporated into autophagosomes in oligodendrocytes, resulting in their degradation. Furthermore, we ablated , a core gene of the autophagic machinery, specifically in myelinating glial cells by tamoxifen administration ( ) and showed that myelin maintenance is perturbed, leading to PLP accumulation. Significant morphological defects in myelin membrane such as decompaction accompanied with increased axonal degeneration are observed. As a result, the mice exhibit behavioral deficits. In summary, our data highlight that the maintenance of adult myelin homeostasis in the CNS requires the involvement of a fully functional autophagic machinery.
PubMed: 36478958
DOI: 10.15698/cst2022.12.274 -
The Rise of Extracellular Vesicles as New Age Biomarkers in Cancer Diagnosis: Promises and Pitfalls.Technology in Cancer Research &... 2023Cell-to-cell interactions in the intricate microenvironment of tissue have a significant impact on the progression of cancer at every stage. Both cancer cells and... (Review)
Review
Cell-to-cell interactions in the intricate microenvironment of tissue have a significant impact on the progression of cancer at every stage. Both cancer cells and stromal cells are responsible for the secretion of soluble chemical compounds as well as membrane-encased components, which both influence and govern the cell-to-cell interactions within the micro-environment of tumor cells. These membrane structures are identified as extracellular vesicles (EVs), which include exosomes and microvesicles. These nanosized vesicles are made up of bilayered proteolipids and have dimensions ranging from 50 to 1000 nm. It has been speculated that extracellular vesicles that originate from cancer cells perform a variety of functions in the development and progression of cancer which may involve the transport of regulatory materials, such as oncogenic proteins between nearby cells and to distant biological locations. In addition, their level in the serum of cancer patients is noticeably higher than those of healthy controls. The release of extracellular vesicles into the extracellular space is a continual process in both healthy and diseased cells. These extracellular vesicles hold molecular signatures that are defining features of health as well as disease. And hence, the EVs present in biological fluids provide unparalleled and noninvasive access to the necessary molecular details about the health status of the cells. Recent discoveries about these complex extracellular organelles have accelerated the discovery of cancer-specific biological markers as well as the development of unique diagnostic tools based on extracellular vesicles. In this mini-review, we aim to highlight the hopes and hypes associated with the applications of extracellular vesicles as biomarkers for cancer diagnosis.
Topics: Humans; Extracellular Vesicles; Neoplasms; Biomarkers; Exosomes; Cell-Derived Microparticles; Tumor Microenvironment
PubMed: 36604966
DOI: 10.1177/15330338221149266