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Journal of Translational Medicine Dec 2023Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development...
BACKGROUND
Magnetic resonance fingerprinting (MRF) enables fast myelin quantification via the myelin water fraction (MWF), offering a noninvasive method to assess brain development and disease. However, MRF-derived MWF lacks histological evaluation and remains unexamined in relation to leukodystrophy. This study aimed to access MRF-derived MWF through histology in mice and establish links between myelin, development, and leukodystrophy in mice and children, demonstrating its potential applicability in animal and human studies.
METHODS
3D MRF was performed on normal C57BL/6 mice with different ages, megalencephalic leukoencephalopathy with subcortical cyst 1 wild type (MLC1 WT, control) mice, and MLC 1 knock-out (MLC1 KO, leukodystrophy) mice using a 3 T MRI. MWF values were analyzed from 3D MRF data, and histological myelin quantification was carried out using immunohistochemistry to anti-proteolipid protein (PLP) in the corpus callosum and cortex. The associations between 'MWF and PLP' and 'MWF and age' were evaluated in C57BL/6 mice. MWF values were compared between MLC1 WT and MLC1 KO mice. MWF of normal developing children were retrospectively collected and the association between MWF and age was assessed.
RESULTS
In 35 C57BL/6 mice (age range; 3 weeks-48 weeks), MWF showed positive relations with PLP immunoreactivity in the corpus callosum (β = 0.0006, P = 0.04) and cortex (β = 0.0005, P = 0.006). In 12-week-old C57BL/6 mice MWF showed positive relations with PLP immunoreactivity (β = 0.0009, P = 0.003, R = 0.54). MWF in the corpus callosum (β = 0.0022, P < 0.001) and cortex (β = 0.0010, P < 0.001) showed positive relations with age. Seven MLC1 WT and 9 MLC1 KO mice showed different MWF values in the corpus callous (P < 0.001) and cortex (P < 0.001). A total of 81 children (median age, 126 months; range, 0-199 months) were evaluated and their MWF values according to age showed the best fit for the third-order regression model (adjusted R range, 0.44-0.94, P < 0.001).
CONCLUSION
MWF demonstrated associations with histologic myelin quantity, age, and the presence of leukodystrophy, underscoring the potential of 3D MRF-derived MWF as a rapid and noninvasive quantitative indicator of brain myelin content in both mice and humans.
Topics: Child; Humans; Mice; Animals; Myelin Sheath; Water; Retrospective Studies; Mice, Inbred C57BL; Magnetic Resonance Imaging; Brain; Neurodegenerative Diseases
PubMed: 38102606
DOI: 10.1186/s12967-023-04788-y -
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 -
Molecular Biology Reports Dec 2023The Proteolipid Protein 2 (PLP2), a protein in the Endoplasmic Reticulum (ER) membrane, has been reported to be highly expressed in various tumors. Previous studies have...
BACKGROUND
The Proteolipid Protein 2 (PLP2), a protein in the Endoplasmic Reticulum (ER) membrane, has been reported to be highly expressed in various tumors. Previous studies have demonstrated that the reduced PLP2 can induce apoptosis and autophagy through ER stress-related pathways, leading to a decreased proliferation and aggressiveness. However, there is no research literature on the role of PLP2 in Acute Myeloid Leukemia (AML).
METHODS
PLP2 expression, clinical data, genetic mutations, and karyotype changes from GEO, TCGA, and timer2.0 databases were analyzed through the R packages. The possible functions and pathways of cells were explored through GO, KEGG, and GSEA enrichment analysis using the clusterProfiler R package. Immuno-infiltration analysis was conducted using the Cibersort algorithm and the Xcell R package. RT-PCR and western blot techniques were employed to identify the PLP2 expression, examine the knockdown effects in THP-1 cells, and assess the expression of genes associated with endoplasmic reticulum stress and apoptosis. Flow cytometry was utilized to determine the apoptosis and survival rates of different groups.
RESULTS
PLP2 expression was observed in different subsets of AML and other cancers. Enrichment analyses revealed that PLP2 was involved in various tumor-related biological processes, primarily apoptosis and lysosomal functions. Additionally, PLP2 expression showed a strong association with immune cell infiltration, particularly monocytes. In vitro, the knockdown of PLP2 enhanced endoplasmic reticulum stress-related apoptosis and increased drug sensitivity in THP-1 cells.
CONCLUSIONS
PLP2 could be a novel therapeutic target in AML, in addition, PLP2 is a potential endoplasmic reticulum stress regulatory gene in AML.
Topics: Humans; Apoptosis; Endoplasmic Reticulum; Endoplasmic Reticulum Stress; Leukemia, Myeloid, Acute; Proteolipids
PubMed: 38085372
DOI: 10.1007/s11033-023-08994-1 -
International Journal of Molecular... Nov 2023Chlorogenic acid (CGA), a polyphenol found mainly in coffee and tea, exerts antioxidant, anti-inflammatory and anti-apoptotic effects at the gastrointestinal level....
Chlorogenic acid (CGA), a polyphenol found mainly in coffee and tea, exerts antioxidant, anti-inflammatory and anti-apoptotic effects at the gastrointestinal level. However, although CGA is known to cross the blood-brain barrier (BBB), its effects on the CNS are still unknown. Oligodendrocytes (OLs), the myelin-forming cells in the CNS, are the main target in demyelinating neuroinflammatory diseases such as multiple sclerosis (MS). We evaluated the antioxidant, anti-inflammatory and anti-apoptotic roles of CGA in M03-13, an immortalized human OL cell line. We found that CGA reduces intracellular superoxide ions, mitochondrial reactive oxygen species (ROS) and NADPH oxidases (NOXs) /dual oxidase 2 (DUOX2) protein levels. The stimulation of M03-13 cells with TNFα activates the nuclear factor kappa-light-chain-enhancer of activated B cell (NF-kB) pathway, leading to an increase in superoxide ion, NOXs/DUOX2 and phosphorylated extracellular regulated protein kinase (pERK) levels. In addition, tumor necrosis factor alpha (TNF-α) stimulation induces caspase 8 activation and the cleavage of poly-ADP-ribose polymerase (PARP). All these TNFα-induced effects are reversed by CGA. Furthermore, CGA induces a blockade of proliferation, driving cells to differentiation, resulting in increased mRNA levels of myelin basic protein (MBP) and proteolipid protein (PLP), which are major markers of mature OLs. Overall, these data suggest that dietary supplementation with this polyphenol could play an important beneficial role in autoimmune neuroinflammatory diseases such as MS.
Topics: Humans; Antioxidants; Chlorogenic Acid; Tumor Necrosis Factor-alpha; Superoxides; Neuroinflammatory Diseases; Dual Oxidases; Anti-Inflammatory Agents; Polyphenols; Oligodendroglia
PubMed: 38069054
DOI: 10.3390/ijms242316731 -
Vernix caseosa reveals mechanistic clues linking maternal obesity to atopic dermatitis pathogenesis.The Journal of Allergy and Clinical... Mar 2024Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix...
BACKGROUND
Maternal overweight and obesity have been associated with an increased risk of atopic dermatitis (AD) in the offspring, but the underlying mechanisms are unclear. Vernix caseosa (VC) is a proteolipid material covering the fetus produced during skin development. However, whether maternal prepregnancy weight excess influences fetal skin development is unknown. Characterizing the VC of newborns from mothers with prepregnancy overweight and obesity might reveal AD-prone alterations during fetal skin development.
OBJECTIVE
We sought to explore AD biomarkers and staphylococcal loads in VC from the offspring of mothers who were overweight/obese (O/O) before pregnancy versus in those from offspring of normal weight mothers.
METHODS
The VC of newborns of 14 O/O and 12 normal weight mothers were collected immediately after birth. Biomarkers were determined by ELISA and staphylococcal species by quantitative PCR.
RESULTS
The VC from the O/O group showed decreased expression of skin barrier proteins (filaggrin and loricrin) and increased levels of proinflammatory biomarkers (IgA, thymic stromal lymphopoietin [TSLP], S100A8, IL-25, and IL-33). No differences in concentrations of antimicrobial peptides and enzymes were detected. The VC from the O/O group had a lower Staphylococcus epidermidis and Staphylococcus hominis commensal bacterial load, whereas Staphylococcus aureus bacterial load was not significantly different between the 2 groups. Maternal body mass index was negatively correlated with VC filaggrin expression and S epidermidis load and was positively associated with TSLP concentration. One-year follow-up established that the offspring of O/O mothers had a higher incidence of AD that was specifically linked with decreased VC filaggrin expression and lower S epidermidis load.
CONCLUSIONS
VC from neonates of mothers with prepregnancy overweight and obesity exhibit skin barrier molecular alterations and staphylococcal dysbiosis that suggest early mechanistic clues to this population's increased risk of AD.
Topics: Humans; Infant, Newborn; Female; Pregnancy; Dermatitis, Atopic; Filaggrin Proteins; Obesity, Maternal; Vernix Caseosa; Overweight; Skin; Cytokines; Thymic Stromal Lymphopoietin; Obesity; Biomarkers
PubMed: 38048884
DOI: 10.1016/j.jaci.2023.09.042 -
The Journal of Experimental Biology Jan 2024In order to complete their energetically demanding journeys, migratory birds undergo a suite of physiological changes to prepare for long-duration endurance flight,...
In order to complete their energetically demanding journeys, migratory birds undergo a suite of physiological changes to prepare for long-duration endurance flight, including hyperphagia, fat deposition, reliance on fat as a fuel source, and flight muscle hypertrophy. In mammalian muscle, SLN is a small regulatory protein which binds to sarco/endoplasmic reticulum Ca2+-ATPase (SERCA) and uncouples Ca2+ transport from ATP hydrolysis, increasing energy consumption, heat production, and cytosolic Ca2+ transients that signal for mitochondrial biogenesis, fatigue resistance and a shift to fatty acid oxidation. Using a photoperiod manipulation of captive gray catbirds (Dumetella carolinensis), we investigated whether SLN may play a role in coordinating the development of the migratory phenotype. In response to long-day photostimulation, catbirds demonstrated migratory restlessness and significant body fat stores, alongside higher SLN transcription while SERCA2 remained constant. SLN transcription was strongly correlated with h-FABP and PGC1α transcription, as well as fat mass. However, SLN was not significantly correlated with HOAD or CD36 transcripts or measurements of SERCA activity, SR membrane Ca2+ leak, Ca2+ uptake rates, pumping efficiency or mitochondrial biogenesis. Therefore, SLN may be involved in the process of storing fat and shifting to fat as a fuel, but the mechanism of its involvement remains unclear.
Topics: Animals; Calcium; Sarcoplasmic Reticulum Calcium-Transporting ATPases; Muscle Proteins; Proteolipids; Endoplasmic Reticulum; Songbirds; Mammals
PubMed: 38044822
DOI: 10.1242/jeb.246897 -
Pediatric Pulmonology Feb 2024
Topics: Infant; Humans; Pulmonary Surfactant-Associated Protein C; Mutation
PubMed: 38038158
DOI: 10.1002/ppul.26722 -
Medicina (Kaunas, Lithuania) Nov 2023Diverticulosis is frequently accompanied by altered bowel habits. The biogenic amines within colonic mucosa control bowel motility, and in particular, alterations in...
Diverticulosis is frequently accompanied by altered bowel habits. The biogenic amines within colonic mucosa control bowel motility, and in particular, alterations in serotonin signaling may play a role in colon diverticulosis. The aim of the study was to assess the concentration of biogenic amines and serotonin receptor expression in the colonic mucosa in patients with diverticulosis and healthy controls. This prospective, comparative study included 59 individuals: 35 with sigmoid diverticulosis and 24 healthy controls. The study was held at the Department of Gastroenterology and Internal Medicine, Medical University of Warsaw, Poland. Mucosal samples were taken from the right and left colon during a colonoscopy in all patients. Concentrations of norepinephrine, 3-methoxy-4-hydroxyphenylglycol, dopamine, homovanillic acid, serotonin, and 5hydroxyindoleacetic acid were measured with high-performance liquid chromatography. Expressions of human 5-hydroxytryptamine receptor 3A, 5-hydroxytryptamine receptor 4, 5-hydroxytryptamine receptor 7, solute carrier family 6 member 4 (SERT) for serotonin, as well as the neuroglia activation markers glial fibrillary acidic protein, S100 calcium-binding protein B, and proteolipid protein 1, were assessed with polymerase chain reaction. The median age and sex distribution were comparable in both study groups (median 69 y vs. 52 y; < 0.455 and males/females in cases 11/17 vs. 18/19 in controls; < 0.309). In diverticulosis patients, there was a higher concentration of serotonin in the left affected colon compared to the right healthy part of the colon (median 8239 pg/mg vs. 6326 pg/mL; < 0.01). The expression was lower in the affected left segment compared to the right colon (median 0.88 vs. 1.36; < 0.01). There was a higher colonic mucosa concentration of serotonin (median 8239 pg/mg vs. 6000 pg/mL; < 0.02) and 5hydroxyindoleacetic acid/serotonin ratio (median 0.27 vs. 0.47; < 0.01) in diverticulosis patients compared to controls in the left side of the colon. The concentration of serotonin in the mucosa of the colon segment affected by diverticula is higher than in the healthy segment in the same individuals and higher than in healthy controls. These results underline serotonin signaling in colon diverticulosis pathophysiology.
Topics: Humans; Male; Female; Serotonin; Prospective Studies; Hydroxyindoleacetic Acid; Colon; Receptors, Serotonin; Diverticulum
PubMed: 38003994
DOI: 10.3390/medicina59111945 -
Plant & Cell Physiology Jun 2024Monogalactosyldiacylglycerol (MGDG) is the main lipid constituent of thylakoids and a structural component of photosystems and photosynthesis-related proteo-lipid...
Inter-Organellar Effects of Defective ER-Localized Linolenic Acid Formation on Thylakoid Lipid Composition, Non-Photochemical Quenching of Chlorophyll Fluorescence and Xanthophyll Cycle Activity in the Arabidopsis fad3 Mutant.
Monogalactosyldiacylglycerol (MGDG) is the main lipid constituent of thylakoids and a structural component of photosystems and photosynthesis-related proteo-lipid complexes in green tissues. Previously reported changes in MGDG abundance upon stress treatments are hypothesized to reflect mobilization of MGDG-based polyunsaturated lipid intermediates to maintain extraplastidial membrane integrity. While exchange of lipid intermediates between compartmental membranes is well documented, physiological consequences of mobilizing an essential thylakoid lipid, such as MGDG, for an alternative purpose are not well understood. Arabidopsis seedlings exposed to mild (50 mM) salt treatment displayed significantly increased abundance of both MGDG and the extraplastidial lipid, phosphatidylcholine (PC). Interestingly, similar increases in MGDG and PC were observed in Arabidopsis fad3 mutant seedlings defective in endoplasmic reticulum (ER)-localized linolenic acid formation, in which compensatory plastid-to-ER-directed mobilization of linolenic acid-containing intermediates takes place. The postulated (salt) or evident (fad3) plastid-ER exchange of intermediates concurred with altered thylakoid function according to parameters of photosynthetic performance. While salt treatment of wild-type seedlings inhibited photosynthetic parameters in a dose-dependent manner, interestingly, untreated fad3 mutants did not show overall reduced photosynthetic quantum yield. By contrast, we observed a reduction specifically of non-photochemical quenching (NPQ) under high light, representing only part of observed salt effects. The decreased NPQ in the fad3 mutant was accompanied by reduced activity of the xanthophyll cycle, leading to a reduced concentration of the NPQ-effective pigment zeaxanthin. The findings suggest that altered ER-located fatty acid unsaturation and ensuing inter-organellar compensation impacts on the function of specific thylakoid enzymes, rather than globally affecting thylakoid function.
Topics: Arabidopsis; Thylakoids; Endoplasmic Reticulum; alpha-Linolenic Acid; Arabidopsis Proteins; Galactolipids; Chlorophyll; Xanthophylls; Mutation; Fatty Acid Desaturases; Fluorescence; Seedlings; Photosynthesis
PubMed: 37991227
DOI: 10.1093/pcp/pcad141 -
Protein Science : a Publication of the... Jan 2024Pulmonary surfactant (PS) is a lipid-protein complex that forms films reducing surface tension at the alveolar air-liquid interface. Surfactant protein C (SP-C) plays a...
Pulmonary surfactant (PS) is a lipid-protein complex that forms films reducing surface tension at the alveolar air-liquid interface. Surfactant protein C (SP-C) plays a key role in rearranging the lipids at the PS surface layers during breathing. The N-terminal segment of SP-C, a lipopeptide of 35 amino acids, contains two palmitoylated cysteines, which affect the stability and structure of the molecule. The C-terminal region comprises a transmembrane α-helix that contains a ALLMG motif, supposedly analogous to a well-studied dimerization motif in glycophorin A. Previous studies have demonstrated the potential interaction between SP-C molecules using approaches such as Bimolecular Complementation assays or computational simulations. In this work, the oligomerization state of SP-C in membrane systems has been studied using fluorescence spectroscopy techniques. We have performed self-quenching and FRET assays to analyze dimerization of native palmitoylated SP-C and a non-palmitoylated recombinant version of SP-C (rSP-C) using fluorescently labeled versions of either protein reconstituted in different lipid systems mimicking pulmonary surfactant environments. Our results reveal that doubly palmitoylated native SP-C remains primarily monomeric. In contrast, non-palmitoylated recombinant SP-C exhibits dimerization, potentiated at high concentrations, especially in membranes with lipid phase separation. Therefore, palmitoylation could play a crucial role in stabilizing the monomeric α-helical conformation of SP-C. Depalmitoylation, high protein densities as a consequence of membrane compartmentalization, and other factors may all lead to the formation of protein dimers and higher-order oligomers, which could have functional implications under certain pathological conditions and contribute to membrane transformations associated with surfactant metabolism and alveolar homeostasis.
Topics: Pulmonary Surfactant-Associated Protein C; Pulmonary Surfactants; Fluorescence Resonance Energy Transfer; Lipids; Surface-Active Agents
PubMed: 37984447
DOI: 10.1002/pro.4835