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Fluoroquinolones (FQs), a class of broad-spectrum antibiotics widely used to treat human and animal diseases globally, have limited adsorption and are often excreted unchanged or as metabolites. These compounds enter the soil environment through feces, urban wastewater, or discharge of biological solids. The fluorine atoms in FQs impart high electronegativity, chemical stability, and resistance to microbial degradation, allowing them to potentially enter food chains. The persistence of FQs in soils raises questions about their impacts on plant growth, an aspect not yet conclusively determined. We reviewed whether, like other organic compounds, FQs are actively absorbed by plants, resulting in bioaccumulation and posing threats to human health. The influx of FQs has led to antibiotic resistance in soil microbes by exerting selective pressure and contributing to multidrug-resistant bacteria. Therefore, the environmental risks of FQs warrant further attention. This work provides a comprehensive review of the fate and behavior of FQs at the plant-environment interface, their migration and transport from the environment into plants, and associated toxicity. Current limitations in research are discussed and prospects for future investigations outlined. Thus, understanding antibiotic behavior in plants and translocation within tissues is not only crucial for ecosystem health (plant health), but also assessing potential human health risks. In addition, it can offer insights into the fate of emerging soil pollutants in plant-soil systems.
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Polycyclic aromatic hydrocarbons (PAHs) are a type of organic pollution that can accumulate in crops and hazard human health. This study used phenanthrene (PHE) as a model PAH and employed hydroponic experiments to illustrate the role of indole-3-acetic acid (IAA) in the regulation of PHE accumulation in wheat roots. At optimal concentrations, wheat roots treated with PHE + IAA showed a 46.9% increase in PHE concentration, whereas treatment with PHE + P-chlorophenoxyisobutyric acid resulted in a 38.77% reduction. Transcriptome analysis identified TaSAUR80-5A as the crucial gene for IAA-enhancing PHE uptake. IAA increases plasma membrane H+-ATPase activity, promoting active transport of PHE via the PHE/H+ cotransport mechanism. These results provide not only the theoretical basis necessary to better understand the function of IAA in PAHs uptake and transport by staple crops, but also a strategy for controlling PAHs accumulation in staple crops and enhancing phytoremediation of PAH-contaminated environments.
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Polycyclic aromatic hydrocarbons (PAHs) are a group of extremely carcinogenic organic pollutants. Our previous findings have demonstrated that plant roots actively take up PAHs through co-transport with H+ ions. Auxin serves as a pivotal regulator of plant growth and development. However, it remains unclear whether the hormone can enhance the uptake of PAHs by plant roots. Hence, the wheat root exposed to PAHs with/without auxins was set to investigate how the auxin promotes the PAHs uptake by roots. In our study, auxin could significantly enhance the uptake of PAHs after 4 h of exposure. After the addition of auxin, the root tissue cytoplasmic pH value was decreased and the H+ influx was observed, indicating that the extracellular space was alkalinized in a short time. The increased H+ influx rate enhanced the uptake of PAHs. In addition, the H+-ATPase activity was also increased, suggesting that auxin activated two distinct and antagonistic H+ flux pathways, and the H+ influx pathway was dominant. Our findings offer important information for exploring the mechanism underlying auxin regulation of PAHs uptake and the phytoremediation of PAH-contaminated soil and water.
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Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Hidrocarburos Policíclicos Aromáticos/análisis , Fenantrenos/metabolismo , Triticum/metabolismo , Concentración de Iones de Hidrógeno , Ácidos Indolacéticos , Contaminantes del Suelo/metabolismo , Raíces de Plantas/metabolismoRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) are a category of organic pollutants known for their high carcinogenicity. Our previous research has illustrated that plant roots actively absorb PAHs through a co-transport mechanism with H+ ions. Because auxin can increase the H+-ATPase activity, the wheat roots were exposed to PAHs with/without auxins to study whether auxins facilitate the uptake of PAHs by plant roots and to gain insights into the underlying mechanisms of this process. In our study, indole acetic acid (100 µM) and α-naphthaleneacetic acid (10 µM) significantly increased the PAHs concentrations in apoplast and symplast, and the treating time and concentrations were positively correlated with PAHs accumulations. The time-dependent kinetics for 36 h followed the Elovich equation, and the concentration-dependent kinetics of apoplastic and symplastic uptake for 4 h could be described with the Freundlich and Michaelis-Menten equations, respectively. The proportion of PAHs accumulated in apoplast could be enhanced by auxins in most treatments. Our findings offer novel insights into the mechanisms of PAH uptake by plant roots under auxin exposure. Additionally, this research aids in refining strategies for ensuring crop safety and improving phytoremediation of PAH-contaminated soil and water.
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Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Contaminantes del Suelo , Plantones/química , Triticum , Raíces de Plantas/química , Contaminantes del Suelo/análisis , Ácidos IndolacéticosRESUMEN
The study focuses on the uptake, accumulation, and translocation of polycyclic aromatic hydrocarbons (PAHs) in cereals, specifically exploring the role of peroxidase (UniProt accession: A0A3B5XXD0, abbreviation: PX1) and unidentified protein (UniProt accession: A0A3B6LUC6, abbreviation: UP1) in phenanthrene solubilization within wheat xylem sap. This research aims to clarify the interactions between these proteins and phenanthrene. Employing both in vitro and in vivo analyses, we evaluated the solubilization capabilities of recombinant transport proteins for phenanthrene and examined the relationship between protein expression and phenanthrene concentration. UP1 displayed greater transport efficiency, while PX1 excelled at lower concentrations. Elevated PX1 levels contributed to phenanthrene degradation, marginally diminishing its transport. Spectral analyses and molecular dynamics simulations validated the formation of stable protein-phenanthrene complexes. The study offers crucial insights into PAH-related health risks in crops by elucidating the mechanisms of PAH accumulation facilitated by transport proteins.
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Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Proteínas Portadoras/metabolismo , Triticum/metabolismo , Raíces de Plantas/metabolismo , Fenantrenos/análisis , Fenantrenos/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismoRESUMEN
Nanoplastics are an emerging environmental pollutant, having a potential risk to the terrestrial ecosystem. In the natural environment, almost all the micro-or nano-plastics will be aged by many factors and their characterizations of the surface will be modified. However, the toxicity and mechanism of the modified polystyrene nanoparticles (PS-NPs) to plant cells are not clear. In the study, the amino- and carboxyl-modified PS-NPs with different sizes (20 and 200 nm) were selected as the typical representatives to investigate their effects on protoplast cell viability, reactive oxygen species (ROS) production in the cell and the leakage of cell-inclusion and apoptosis. The results indicated that the 20 nm amino-modified PS-NPs (PS-20A) could significantly damage the structure of the cell, especially the cell membrane, chloroplast and mitochondrion. After being modified by amino group, smaller size nanoplastics had the potential to cause more severe damage. In addition, compared with carboxyl-modified PS-NPs, the amino-modified PS-NPs induced more ROS production and caused higher membrane permeability/lactate dehydrogenase (LDH) leakage. Apoptosis assay indicated that the proportion of viable cells in the PS-20A treatment decreased significantly, and the proportion of necrotic cells increased by four times. This study provides new insights into the toxicity and damage mechanism of PS-NPs to terrestrial vascular plants at the cellular level, and guides people to pay attention to the quality and safety of agricultural products caused by nanoplastics.
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Nanopartículas , Contaminantes Químicos del Agua , Humanos , Anciano , Poliestirenos/toxicidad , Poliestirenos/química , Triticum , Microplásticos/toxicidad , Ecosistema , Especies Reactivas de Oxígeno , Protoplastos , Contaminantes Químicos del Agua/toxicidad , Nanopartículas/toxicidad , Nanopartículas/químicaRESUMEN
Background: Inferior clinical outcomes have been reported in patients with degenerative lumbar spondylolisthesis (DLS) accompanied by lumbar degenerative scoliosis, but little attention has been paid to its radiologic assessment or preoperative planning. The aim of this study was to analyze the effect of transforaminal lumbar interbody fusion on patients with DLS and lumbar degenerative scoliosis and explore the surgical aspects benefiting the restoration of lumbar degenerative scoliosis. Methods: All patients with DLS and lumbar degenerative scoliosis undergoing single-level unilateral transforaminal lumbar interbody fusion surgery between July 1, 2015, and April 30, 2021, were screened in this retrospective cohort study. Clinical outcomes including visual analog scale (VAS), Oswestry disability index (ODI), and radiographic parameters of sagittal and coronal alignment, cage spatial locations, and angle of pedicle screw (parallel, cranial, and caudad angle) were assessed. Coronal asymmetry was demonstrated by the intervertebral height difference between the medial and lateral margins of indexed intersegmental space. The correlations between Δintervertebral height difference (postoperative intervertebral height difference-preoperative intervertebral height difference) and radiographic parameters and clinical outcomes were analyzed by univariable, multivariable, mediation, and correlation analyses. Significance was set at a bilateral P<0.05. Results: A total of 57 included patients were followed up for a minimum of 1 year. Reduction of VAS, ODI, and improvement of radiographic parameters were found after surgery. The cranial angle of the lower pedicle screw positively correlated with Δintervertebral height difference restoration (b=0.54; standard error=0.11; P<0.001). Conclusions: Transforaminal lumbar interbody fusion surgery appears to be an effective approach to improving the radiographic and clinical outcomes of patients with DLS and lumbar degenerative scoliosis. The cranial direction of the lower pedicle screws in single-level unilateral transforaminal lumbar interbody fusion surgery may be associated with a better postoperative restoration of lumbar degenerative scoliosis.
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Microplastics (MPs) are the widespread emerging pollutants in the terrestrial systems, and photo-oxidation is an effective process for aging MPs on land. Here, four common commercial MPs were exposed to ultraviolet (UV) light to simulate the photo-aging of MPs on soil, and the changes in surface properties and eluates of photoaging MPs were studied. Results revealed that polyvinyl chloride (PVC) and polystyrene (PS) exhibited more pronounced physicochemical changes than polypropylene (PP) and polyethylene (PE) during photoaging on the simulated topsoil, due to the dechlorination of PVC and the debenzene ring of PS. Oxygenated groups accumulated in aged MPs were strongly correlated with dissolved organic matters (DOMs) leaching. Through analysis of the eluate, we found that photoaging altered the molecular weight and aromaticity of DOMs. PS-DOMs showed the greatest increase in humic-like substances after aging, whereas PVC-DOMs exhibited the highest amount of additive leaching. The chemical properties of additives explained their differences in photodegradation responses, which also accounted for the greater importance of chemical structure of MPs to their structural stability. These findings demonstrate that the extensive presence of cracks in aged MPs facilitates DOMs formation and the complexity of DOMs composition poses a potential threat to soil and groundwater safety.
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We postulate that myelin injury contributes to cholesterol release from myelin and cholesterol dysmetabolism which contributes to Abeta dysmetabolism, and combined with genetic and AD risk factors, leads to increased Abeta and amyloid plaques. Increased Abeta damages myelin to form a vicious injury cycle. Thus, white matter injury, cholesterol dysmetabolism and Abeta dysmetabolism interact to produce or worsen AD neuropathology. The amyloid cascade is the leading hypothesis for the cause of Alzheimer's disease (AD). The failure of clinical trials based on this hypothesis has raised other possibilities. Even with a possible new success (Lecanemab), it is not clear whether this is a cause or a result of the disease. With the discovery in 1993 that the apolipoprotein E type 4 allele (APOE4) was the major risk factor for sporadic, late-onset AD (LOAD), there has been increasing interest in cholesterol in AD since APOE is a major cholesterol transporter. Recent studies show that cholesterol metabolism is intricately involved with Abeta (Aß)/amyloid transport and metabolism, with cholesterol down-regulating the Aß LRP1 transporter and upregulating the Aß RAGE receptor, both of which would increase brain Aß. Moreover, manipulating cholesterol transport and metabolism in rodent AD models can ameliorate pathology and cognitive deficits, or worsen them depending upon the manipulation. Though white matter (WM) injury has been noted in AD brain since Alzheimer's initial observations, recent studies have shown abnormal white matter in every AD brain. Moreover, there is age-related WM injury in normal individuals that occurs earlier and is worse with the APOE4 genotype. Moreover, WM injury precedes formation of plaques and tangles in human Familial Alzheimer's disease (FAD) and precedes plaque formation in rodent AD models. Restoring WM in rodent AD models improves cognition without affecting AD pathology. Thus, we postulate that the amyloid cascade, cholesterol dysmetabolism and white matter injury interact to produce and/or worsen AD pathology. We further postulate that the primary initiating event could be related to any of the three, with age a major factor for WM injury, diet and APOE4 and other genes a factor for cholesterol dysmetabolism, and FAD and other genes for Abeta dysmetabolism.
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BACKGROUND: After ischemic stroke (IS), peripheral leukocytes infiltrate the damaged region and modulate the response to injury. Peripheral blood cells display distinctive gene expression signatures post-IS and these transcriptional programs reflect changes in immune responses to IS. Dissecting the temporal dynamics of gene expression after IS improves our understanding of immune and clotting responses at the molecular and cellular level that are involved in acute brain injury and may assist with time-targeted, cell-specific therapy. METHODS: The transcriptomic profiles from peripheral monocytes, neutrophils, and whole blood from 38 ischemic stroke patients and 18 controls were analyzed with RNA-seq as a function of time and etiology after stroke. Differential expression analyses were performed at 0-24 h, 24-48 h, and >48 h following stroke. RESULTS: Unique patterns of temporal gene expression and pathways were distinguished for monocytes, neutrophils, and whole blood with enrichment of interleukin signaling pathways for different time points and stroke etiologies. Compared to control subjects, gene expression was generally upregulated in neutrophils and generally downregulated in monocytes over all times for cardioembolic, large vessel, and small vessel strokes. Self-organizing maps identified gene clusters with similar trajectories of gene expression over time for different stroke causes and sample types. Weighted Gene Co-expression Network Analyses identified modules of co-expressed genes that significantly varied with time after stroke and included hub genes of immunoglobulin genes in whole blood. CONCLUSIONS: Altogether, the identified genes and pathways are critical for understanding how the immune and clotting systems change over time after stroke. This study identifies potential time- and cell-specific biomarkers and treatment targets.
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Accidente Cerebrovascular Isquémico , Accidente Cerebrovascular , Humanos , Monocitos/metabolismo , Transcriptoma , Neutrófilos/metabolismo , Accidente Cerebrovascular Isquémico/genética , Perfilación de la Expresión Génica , Redes Reguladoras de GenesRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) are a class of highly carcinogenic organic pollutants. Our previous results revealed that the active uptake of PAHs by plant roots is performed through H+/PAHs co-transport. However, the proteins and mechanisms of co-transport of PAHs remain unknown. We hypothesized that ABC transporters are involved in PAHs co-transport via the roots. We found a total of 47 ABC transporters with alkalinity and hydrophobicity which were up-regulated or newly expressed in the wheat roots after phenanthrene exposure. And the concentration of ABC transporters rose. There was a positive relationship between the concentration of phenanthrene and ABC transporter expression in the wheat roots. Additionally, the trend observed in the ABC transporters expression was also found in the gene expression. With energies below -6 kcal mol-1, a stable docking conformation formed between ABC transporters and PAHs. π-π stacking and van der Waals force bound PAHs to ABCB or ABCG. The binding strength of ABCB subfamily proteins with homodimers is stronger than that of ABCG subfamily proteins with single molecules. ABC transporters may transport PAHs by forming a dimer-shaped pocket, translocating it into cells, then opening it within the cells, to release the bound PAHs. These results contributed to our understanding of how ABC transporters aid plant root uptake of PAHs.
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Hidrocarburos Policíclicos Aromáticos , Triticum , Triticum/metabolismo , Hidrocarburos Policíclicos Aromáticos/metabolismo , Transportadoras de Casetes de Unión a ATP/metabolismo , Raíces de Plantas/metabolismo , Membrana Celular/metabolismoRESUMEN
The wide existence of microplastics (MPs) in the terrestrial systems is proved by -many studies, and their presence could potentially change the soil chem-physical properties and processes. Various types of microplastics may have different behaviors, inducing distinct effects on the soil ecosystems. However, the knowledge of microplastic impacts on rhizosphere soil bacterial community structure is limited. In our study, three types of microplastics, i.e., polyethylene (PE), polyvinylchloride (PVC) and polystyrene (PS), with the same particle size (200 µm) and concentration (2%) were used to investigate their influences on the rhizosphere soil bacterial communities. Results revealed that the alpha diversities (richness, evenness and diversity) of microbiota in the rhizosphere soil were variously decreased by the microplastics, especially the PE MPs. The relative abundance of some various phyla and genera related to pollution degradation was miscellaneously increased, indicating that the MPs with different characterizations may have miscellaneous biodegradation pathways. Moreover, the PICRUSt2 analysis demonstrated that PS decreased most functional category levels and led to a decrease of bacterial genus number, however, PE and PVC improved metabolic pathways and xenobiotics biodegradation and metabolism. Our findings offer important knowledge of how the microplastics with different characterizations influence rhizosphere soil bacterial communities and their related function.
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Microbiota , Contaminantes del Suelo , Bacterias/genética , Microplásticos/toxicidad , Plásticos , Polietileno , Poliestirenos/análisis , Cloruro de Polivinilo , Rizosfera , Suelo/química , Microbiología del Suelo , Contaminantes del Suelo/análisis , TriticumRESUMEN
Polycyclic aromatic hydrocarbons (PAHs) have the potential to cause cancer, teratogenicity, and mutagenesis in humans. Long-term plant safe production relies on how PAHs are transported and coordinated across organs. However, the acropetal transfer mechanism of PAHs in staple crop stems, particularly in xylem, a critical path, is unknown. Herein, we first confirmed the presence of specific interaction between the proteins and phenanthrene by employing the magnetic phenanthrene-bound bead immunoassay and label free liquid chromatograph mass spectrometer (LC-MS/MS), suggesting that peroxidase (uniprot accession: A0A3B5XXD0) and unidentified proteins (uniprot accession: A0A3B6LUC6) may function as the carriers to load and acropetally translocate phenanthrene (a model PAH) in wheat xylem. This specified binding of protein-phenanthrene may form through hydrophobic interactions in the conservative binding region, as revealed by protein structural investigations and molecular docking. To further investigate the role of these proteins in phenanthrene solubilization, phenanthrene exposure was conducted: a substantial quantity of peroxidase was produced; an unusually high expression of uncharacterized proteins was observed, indicating their positive effects in the acropetal transfer of phenanthrene in wheat xylem. These data confirmed that the two proteins are crucial in the solubilization of phenanthrene in wheat xylem sap. Our findings provide fresh light on the molecular mechanism of PAH loading in plant xylem and techniques for ensuring the security of staple crops and improving the efficacy of phytoremediation in a PAH-contaminated environment.
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Fenantrenos , Hidrocarburos Policíclicos Aromáticos , Cromatografía Liquida , Humanos , Simulación del Acoplamiento Molecular , Peroxidasas/metabolismo , Fenantrenos/metabolismo , Raíces de Plantas/metabolismo , Hidrocarburos Policíclicos Aromáticos/análisis , Espectrometría de Masas en Tándem , Triticum/metabolismo , XilemaRESUMEN
Nanoscale plastic particles are widely found in the terrestrial environment and being increasingly studied in recent years. However, the knowledge of their translocation and accumulation mechanism controlled by nanoplastic characterizations in plant tissues is limited, especially in plant cells. Here, 20 mg L-1 polystyrene nanoparticles (PS NPs) with different sizes and amino/carboxy groups were employed to investigate the internalization process in wheat roots and cells. From the results, we found that the uptake of small-size PS NPs in the root tissues was increased compared to that of large-size ones, but no PS NPs were observed in the vascular cylinder. Similar results were observed in their cellular uptake process. Besides, the cell wall could block the entry of large-size PS NPs while the cell membrane could not. The -NH2 group on the PS NPs surface could benefit their tissular/cellular translocation compared to the -COOH group. The internalization of PS NPs was controlled by both particle size and surface functional group, and the size should be the primary factor. Our findings offer important information for understanding the PS NPs behaviors in plant tissues, especially at the cellular level, and assessing their potential risk to food safety, quality, and agricultural sustainability.
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Nanopartículas , Poliestirenos , Tamaño de la Partícula , TriticumRESUMEN
Cerebral white matter hyperintensities are an important contributor to ageing brain pathology. Progression in white matter hyperintensity volume is associated with cognitive decline and gait impairment. Understanding the factors associated with white matter hyperintensity progression provides insight into pathogenesis and may identify novel treatment targets to improve cognitive health. We postulated that the immune system interaction with cerebral vessels and tissue may be associated with disease progression, and thus evaluated the relationship of blood leucocyte gene expression to progression of cerebral white matter hyperintensities. A brain MRI was obtained at baseline in 166 patients assessed for a cognitive complaint, and then repeated at regular intervals over a median of 5.9 years (interquartile range 3.5-8.2 years). White matter hyperintensity volumes were measured by semi-automated segmentation and percentage change in white matter hyperintensity per year calculated. A venous blood sample obtained at baseline was used to measure whole-genome expression by RNA sequencing. The relationship between change in white matter hyperintensity volumes over time and baseline leucocyte gene expression was analysed. The mean age was 77.8 (SD 7.5) years and 60.2% of participants were female. The median white matter hyperintensity volume was 13.4â ml (SD 17.4â ml). The mean change in white matter hyperintensity volume was 12% per year. Patients were divided in quartiles by percentage change in white matter hyperintensity volume, which was: -3.5% per year in quartile 1, 7.4% per year in quartile 2, 11.7% in quartile 3 and 33.6% per year in quartile 4. There were 148 genes associated with changing white matter hyperintensity volumes over time (P < 0.05 r > |0.2|). Genes and pathways identified have roles in endothelial dysfunction, extracellular matrix remodelling, altered remyelination, inflammation and response to ischaemia. ADAM8, CFD, EPHB4, FPR2, Wnt-B-catenin, focal adhesion kinase and SIGLEC1 were among the identified genes. The progression of white matter hyperintensity volumes over time is associated with genes involved in endothelial dysfunction, extracellular matrix remodelling, altered remyelination, inflammation and response to ischaemia. Further studies are needed to evaluate the role of peripheral inflammation in relation to rate of white matter hyperintensity progression and the contribution to cognitive decline.
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Disfunción Cognitiva , Leucoaraiosis , Sustancia Blanca , Proteínas ADAM , Anciano , Anciano de 80 o más Años , Disfunción Cognitiva/patología , Progresión de la Enfermedad , Femenino , Expresión Génica , Humanos , Inflamación/patología , Leucocitos , Imagen por Resonancia Magnética , Masculino , Proteínas de la Membrana , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Microplastics wildly occur in soil and they can become the carriers of persistent contaminants. However, the influence of microplastics on polycyclic aromatic hydrocarbons vertical translocation in the soil system after rainfall is limitedly understood. Here, experiments were conducted to study the influence of polyethylene (PE), polystyrene (PS) and polyvinyl chloride (PVC) microplastics on the leaching behavior and bioavailability of phenanthrene (Phe). The adsorption capacity of phenanthrene on the microplastics followed the order of PS > PE > PVC. The Phe concentrations in the top soil layer after 15 days of leaching with water were 30.25, 28.32 and 27.25 mg kg-1 for the treatments of Phe-PS, Phe-PE and Phe-PVC respectively, which is consistent with the adsorption capacities of microplastics. The concentrations of Phe were correlated with the microplastic adsorption capacities at soil depths of 5-45 cm. Under long-term leaching, Phe could reach the deeper soil layer. Phe concentrations significantly decreased in the leachate over time. Phe concentrations in wheat had a positive correlation with that in leachate/leached top soil layer. Our findings are beneficial to accurately evaluate the ecological risk of the combined contamination of PAHs and microplastics, and improve the understanding of the environmental behaviors of different microplastics.
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Fenantrenos , Contaminantes del Suelo , Adsorción , Disponibilidad Biológica , Microplásticos , Fenantrenos/análisis , Plásticos , Suelo , TriticumRESUMEN
The peripheral immune system response to Intracerebral Hemorrhage (ICH) may differ with ICH in different brain locations. Thus, we investigated peripheral blood mRNA expression of Deep ICH, Lobar ICH, and vascular risk factor-matched control subjects (n = 59). Deep ICH subjects usually had hypertension. Some Lobar ICH subjects had cerebral amyloid angiopathy (CAA). Genes and gene networks in Deep ICH and Lobar ICH were compared to controls. We found 774 differentially expressed genes (DEGs) and 2 co-expressed gene modules associated with Deep ICH, and 441 DEGs and 5 modules associated with Lobar ICH. Pathway enrichment showed some common immune/inflammatory responses between locations including Autophagy, T Cell Receptor, Inflammasome, and Neuroinflammation Signaling. Th2, Interferon, GP6, and BEX2 Signaling were unique to Deep ICH. Necroptosis Signaling, Protein Ubiquitination, Amyloid Processing, and various RNA Processing terms were unique to Lobar ICH. Finding amyloid processing pathways in blood of Lobar ICH patients suggests peripheral immune cells may participate in processes leading to perivascular/vascular amyloid in CAA vessels and/or are involved in its removal. This study identifies distinct peripheral blood transcriptome architectures in Deep and Lobar ICH, emphasizes the need for considering location in ICH studies/clinical trials, and presents potential location-specific treatment targets.
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Corpora amylacea (CA) increase in number and size with aging. Their origins and functions remain unknown. Previously, we found that Alzheimer's disease (AD) brains have more CA in the periventricular white matter (PVWM) compared to aging controls. In addition, CA is associated with neurodegeneration as indicated by colocalization of degraded myelin basic protein (dMBP) with periodic acid-Schiff (PAS), a CA marker. We also found that bacterial lipopolysaccharide is present in aging brains, with more LPS in AD compared with controls. Periodic acid-Schiff staining is used to identify CA by virtue of their high polysaccharide content. Despite the growing knowledge of CA as a contributor to AD pathology, the molecules that contribute to the polysaccharides in CA are not known. Notably, lipopolysaccharides (LPS) are important cell-surface polysaccharides found in all Gram-negative bacteria. However, it is unknown whether PAS could detect LPS, whether the LPS found in aging brains contribute to the polysaccharide found in CA, and whether LPS associate with myelin injury. In this study, we found that aging brains had a myelin deficit zone (MDZ) adjacent to the ventricles in PVWM. The MDZ contained vesicles, most of which were CA. LPS and dMBP levels were higher in AD than in control brains. LPS was colocalized with dMBP in the vesicles/CA, linking white matter injury with a bacterial pro-inflammatory molecule. The vesicles also contained oxidized fibers, C-reactive protein, NG2, and GALC, markers of oligodendrocyte precursor cells (OPCs) and oligodendrocyte cells (OLs), respectively. The vesicles/CA were surrounded by dense astrocyte processes in control and AD brains. LPS was co-localized with CA by double staining of PAS with LPS in aging brains. The relationship of LPS with PAS staining was confirmed by PAS staining of purified LPS on nitrocellulose membranes. These findings reveal that LPS is one of the polysaccharides found in CA which can be stained with PAS. In addition, vesicles/CA are associated with oxidized and damaged myelin. The LPS in these vesicles/CA may have contributed to this oxidative myelin damage and may have contributed to oxidative stress to OPCs and OLs which could impair the ability to repair damaged myelin in AD and control brains.
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The function of poly(ADP-ribosyl) polymerase 1 (PARP1) in myelination and remyelination of the central nervous system (CNS) remains enigmatic. Here, we report that PARP1 is an intrinsic driver for oligodendroglial development and myelination. Genetic PARP1 depletion impairs the differentiation of oligodendrocyte progenitor cells (OPCs) into oligodendrocytes and impedes CNS myelination. Mechanistically, PARP1-mediated PARylation activity is not only necessary but also sufficient for OPC differentiation. At the molecular level, we identify the RNA-binding protein Myef2 as a PARylated target, which controls OPC differentiation through the PARylation-modulated derepression of myelin protein expression. Furthermore, PARP1's enzymatic activity is necessary for oligodendrocyte and myelin regeneration after demyelination. Together, our findings suggest that PARP1-mediated PARylation activity may be a potential therapeutic target for promoting OPC differentiation and remyelination in neurological disorders characterized by arrested OPC differentiation and remyelination failure such as multiple sclerosis.
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Diferenciación Celular , Sistema Nervioso Central/metabolismo , Vaina de Mielina/metabolismo , Poli(ADP-Ribosa) Polimerasa-1/metabolismo , Poli ADP Ribosilación/fisiología , Animales , Supervivencia Celular/efectos de los fármacos , Sistema Nervioso Central/crecimiento & desarrollo , Cuprizona/farmacología , Femenino , Masculino , Ratones , Ratones Endogámicos C57BL , Ratones Noqueados , Esclerosis Múltiple/inducido químicamente , Esclerosis Múltiple/metabolismo , Esclerosis Múltiple/patología , Vaina de Mielina/genética , Proteínas del Tejido Nervioso/genética , Proteínas del Tejido Nervioso/metabolismo , Células Precursoras de Oligodendrocitos/citología , Células Precursoras de Oligodendrocitos/metabolismo , Factor de Transcripción 2 de los Oligodendrocitos/deficiencia , Factor de Transcripción 2 de los Oligodendrocitos/genética , Factor de Transcripción 2 de los Oligodendrocitos/metabolismo , Oligodendroglía/citología , Oligodendroglía/metabolismo , Oligodendroglía/fisiología , Poli(ADP-Ribosa) Polimerasa-1/deficiencia , Poli(ADP-Ribosa) Polimerasa-1/genética , ARN/metabolismo , Remielinización/efectos de los fármacos , Proteínas Represoras/genética , Proteínas Represoras/metabolismoRESUMEN
BACKGROUND: Compared to other risk factors, adjacent facet joint degeneration (AFD) is the main contributor to adjacent segment disease (ASD). The interbody cage may be a potential indirect risk of AFD. This study investigated the correlations among the lumbar sagittal balance parameters, the inter-body cage's intraoperative positioning variables, and adjacent facet joint degeneration following the transforaminal lumbar interbody fusion (TLIF) technique. METHODS: Patients who accepted single-level TLIF for symptomatic lumbar degenerative disease and were followed up for at least six months were enrolled in this study. According to the inclusive and exclusive criteria, 93 patients were included (44 males and 49 females). X-ray and computed tomography (CT) images were obtained before and six months after surgery. The vertebral contour and the center of the marker mass in the cage were calculated using a geometric algorithm. Orthopedic surgeons measured the disc height, lordosis angle, and facet joint degeneration. Patient-reported outcomes, including the Oswestry Disability Index (ODI) and the visual analog scale (VAS), were used to assess the clinical outcomes. The Student's t-test, Wilcoxon rank-sum test, and Chi-square test were used for the statistical analyses. RESULTS: The average age was 53.7 years old (range, 27-84 years). The average functional disability outcome assessed by the ODI was 61.2, and the average back and leg pain assessed by the VAS was 6.2 and 6.9, respectively. The patients were categorized into a normal group and an abnormal (AFD) group according to whether the facet joint degeneration was aggravated. The abnormal group had a higher back pain VAS score (P=0.031) and lower sagittal vertical position (P=0.027). The other parameters were similar at baseline (P>0.05). The cage's sagittal vertical position decreased significantly with AFD aggravation (OR, 0.737; 95% CI, 0.561-0.969). CONCLUSIONS: In patients with AFD aggravation, the preoperative VAS and postoperative ODI scores were significantly higher. The cage position parameters were related to AFD. A lower cage center was associated with a greater incidence of AFD.