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Discover Nano May 2024Curcumin is a polyphenol extracted from Curcuma longa's roots. Low doses of curcumin are related to anti-inflammatory, antioxidant, and neuroprotective effects, while...
Curcumin is a polyphenol extracted from Curcuma longa's roots. Low doses of curcumin are related to anti-inflammatory, antioxidant, and neuroprotective effects, while high doses are used for their lethality. This diversity of behaviors allows us to understand curcumin as a compound with hormetic action. Due to its strongly hydrophobic character, curcumin is often solubilized in organic compounds. In this way, we have recently reported the undesirable and occasionally irreversible effects of alcohol and DMSO on the viability of primary Schwann cell cultures. In this scenario, the use of nanoparticles as delivery systems has become a successful alternative strategy for these compounds. In the present work, we describe the structure of Polydopamine (PDA) nanoparticles, loaded with a low dose of curcumin (Curc-PDA) without the use of additional organic solvents. We analyzed the curcumin released, and we found two different forms of curcumin. Small increased cell viability and proliferation were observed in endoneurial fibroblast and Schwann cell primary cultures when Curc-PDA was steadily supplied for 5 days. The increased bioavailability of this natural compound and the impact on cells in culture not only confirm the properties of curcumin at very low doses but also provide a glimpse of a possible therapeutic alternative for PNS conditions in which SCs are involved.
PubMed: 38714630
DOI: 10.1186/s11671-024-04023-7 -
Ecotoxicology and Environmental Safety Jun 2024Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet...
Micro(nano)plastic, as a new type of environmental pollutant, have become a potential threat to the life and health of various stages of biology. However, it is not yet clear whether they will affect brain development in the fetal stage. Therefore, this study aims to explore the potential effects of nanoplastics on the development of fetal rat brains. To assess the allocation of NPs (25 nm and 50 nm) in various regions of the fetal brain, pregnant rats were exposed to concentrations (50, 10, 2.5, and 0.5 mg/kg) of PS-NPs. Our results provided evidence of the transplacental transfer of PS-NPs to the fetal brain, with a prominent presence observed in several cerebral regions, notably the cerebellum, hippocampus, striatum, and prefrontal cortex. This distribution bias might be linked to the developmental sequence of each brain region. Additionally, we explored the influence of prenatal exposure on the myelin development of the cerebellum, given its the highest PS-NP accumulation in offspring. Compared with control rats, PS-NPs exposure caused a significant reduction in myelin basic protein (MBP) and myelin oligodendrocyte glycoprotein (MOG) expression, a decrease in myelin thickness, an increase in cell apoptosis, and a decline in the oligodendrocyte population. These effects gave rise to motor deficits. In conclusion, our results identified the specific distribution of NPs in the fetal brain following prenatal exposure and revealed that prenatal exposure to PS-NPs can suppress myelin formation in the cerebellum of the fetus.
Topics: Animals; Female; Pregnancy; Brain; Myelin Sheath; Rats; Polystyrenes; Environmental Pollutants; Myelin Basic Protein; Maternal Exposure; Nanoparticles; Apoptosis; Microplastics; Rats, Sprague-Dawley; Maternal-Fetal Exchange; Fetus
PubMed: 38714083
DOI: 10.1016/j.ecoenv.2024.116393 -
Revista Brasileira de Psiquiatria (Sao... 2024Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood...
OBJECTIVES
Evidence from diffusion tensor imaging (DTI) and postmortem studies has demonstrated white-matter (WM) deficits in bipolar disorder (BD). Changes in peripheral blood biomarkers have also been observed; however, studies evaluating the potential relationship between brain alterations and the periphery are scarce. The objective of this systematic review is to investigate the relationship between blood-based biomarkers and WM in BD.
METHODS
PubMed, Embase, and PsycINFO were used to conduct literature searches. Cross-sectional or longitudinal studies reporting original data which investigated both a blood-based biomarker and WM (by neuroimaging) in BD were included.
RESULTS
Of 3,750 studies retrieved, 23 were included. Several classes of biomarkers were found to have a significant relationship with WM in BD. These included cytokines and growth factors (interleukin-8 [IL-8], tumor necrosis factor alpha [TNF-a], and insulin-like growth factor binding protein 3 [IGFBP-3]), innate immune system (natural killer cells [NK]), metabolic markers (lipid hydroperoxidase, cholesterol, triglycerides), the kynurenine (Kyn) pathway (5-hydroxyindoleacetic acid, kynurenic acid [Kyna]), and various gene polymorphisms (serotonin-transporter-linked promoter region).
CONCLUSION
This systematic review revealed that blood-based biomarkers are associated with markers of WM deficits observed in BD. Longitudinal studies investigating the potential clinical utility of these specific biomarkers are encouraged.
Topics: Bipolar Disorder; Humans; Biomarkers; White Matter; Myelin Sheath; Cytokines
PubMed: 38712923
DOI: 10.47626/1516-4446-2023-3267 -
BioRxiv : the Preprint Server For... Apr 2024Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we...
Neurofibromatosis Type 2 (NF-2) is a dominantly inherited genetic disorder that results from mutations in the tumor suppressor gene, neurofibromin 2 (NF2) gene. Here, we report the generation of a conditional zebrafish model of neurofibromatosis established by an inducible genetic knockout of , the zebrafish homolog of human NF2. Analysis of and expression reveals ubiquitous expression of in the early embryo, with overlapping expression in the neural crest and its derivatives and in the cranial mesenchyme. In contrast, displays lower expression levels. Induction of knockout at early stages increases the proliferation of larval Schwann cells and meningeal fibroblasts. Subsequently, in adult zebrafish, knockout triggers the development of a spectrum of tumors, including vestibular schwannomas, spinal schwannomas, meningiomas, and retinal hamartomas, mirroring the tumor manifestations observed in patients with NF-2. Collectively, these findings highlight the generation of a novel zebrafish model that mimics the complexities of the human NF-2 disorder. Consequently, this model holds significant potential for facilitating therapeutic screening and elucidating key driver genes implicated in NF-2 onset.
PubMed: 38712289
DOI: 10.1101/2024.04.23.590787 -
Cureus Apr 2024Mucosal Schwann cell hamartomas (MSCHs) are non-common noncancerous growths derived from Schwann cells in the peripheral nervous system, often found unexpectedly during...
Mucosal Schwann cell hamartomas (MSCHs) are non-common noncancerous growths derived from Schwann cells in the peripheral nervous system, often found unexpectedly during routine colonoscopy examinations. These growths primarily occur in the colon, although they can also appear in the esophagus and are not linked to familial cancer syndromes. Diagnosis relies on specific histological characteristics and staining patterns. It is essential to distinguish MSCHs accurately since their appearance can closely resemble that of malignant tumors. Characteristically, these hamartomas test positive for S-100 protein but do not exhibit markers typical of other gastrointestinal growths, such as gastrointestinal stromal tumors (negative for KIT), leiomyomas (negative for smooth muscle actin), neurofibromas (negative for CD34), and perineuromas (negative for epithelial membrane antigen or claudin-1). This report discusses the case of a 48-year-old woman who was diagnosed with MSCH during a screening colonoscopy.
PubMed: 38707060
DOI: 10.7759/cureus.57674 -
Hearing Research Jun 2024Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most... (Review)
Review
Hearing loss is a common side effect of many tumor treatments. However, hearing loss can also occur as a direct result of certain tumors of the nervous system, the most common of which are the vestibular schwannomas (VS). These tumors arise from Schwann cells of the vestibulocochlear nerve and their main cause is the loss of function of NF2, with 95 % of cases being sporadic and 5 % being part of the rare neurofibromatosis type 2 (NF2)-related Schwannomatosis. Genetic variations in NF2 do not fully explain the clinical heterogeneity of VS, and interactions between Schwann cells and their microenvironment appear to be critical for tumor development. Preclinical in vitro and in vivo models of VS are needed to develop prognostic biomarkers and targeted therapies. In addition to VS, other tumors can affect hearing. Meningiomas and other masses in the cerebellopontine angle can compress the vestibulocochlear nerve due to their anatomic proximity. Gliomas can disrupt several neurological functions, including hearing; in fact, glioblastoma multiforme, the most aggressive subtype, may exhibit early symptoms of auditory alterations. Besides, treatments for high-grade tumors, including chemotherapy or radiotherapy, as well as incomplete resections, can induce long-term auditory dysfunction. Because hearing loss can have an irreversible and dramatic impact on quality of life, it should be considered in the clinical management plan of patients with tumors, and monitored throughout the course of the disease.
Topics: Humans; Neuroma, Acoustic; Hearing Loss; Animals; Hearing; Neurilemmoma; Vestibulocochlear Nerve; Risk Factors; Neurofibromatosis 2; Meningioma
PubMed: 38703433
DOI: 10.1016/j.heares.2024.109012 -
Biomedicine & Pharmacotherapy =... Jun 2024The current pharmacological approaches to multiple sclerosis (MS) target its inflammatory and autoimmune components, but effective treatments to foster remyelination and...
The current pharmacological approaches to multiple sclerosis (MS) target its inflammatory and autoimmune components, but effective treatments to foster remyelination and axonal repair are still lacking. We therefore selected two targets known to be involved in MS pathogenesis: N-acylethanolamine-hydrolyzing acid amidase (NAAA) and glycogen synthase kinase-3β (GSK-3β). We tested whether inhibiting these targets exerted a therapeutic effect against experimental autoimmune encephalomyelitis (EAE), an animal model of MS. The combined inhibition of NAAA and GSK-3β by two selected small-molecule compounds, ARN16186 (an NAAA inhibitor) and AF3581 (a GSK-3β inhibitor), effectively mitigated disease progression, rescuing the animals from paralysis and preventing a worsening of the pathology. The complementary activity of the two inhibitors reduced the infiltration of immune cells into the spinal cord and led to the formation of thin myelin sheaths around the axons post-demyelination. Specifically, the inhibition of NAAA and GSK-3β modulated the over-activation of NF-kB and STAT3 transcription factors in the EAE-affected mice and induced the nuclear translocation of β-catenin, reducing the inflammatory insult and promoting the remyelination process. Overall, this work demonstrates that the dual-targeting of key aspects responsible for MS progression could be an innovative pharmacological approach to tackle the pathology.
Topics: Animals; Glycogen Synthase Kinase 3 beta; Encephalomyelitis, Autoimmune, Experimental; Multiple Sclerosis; Mice; Mice, Inbred C57BL; Amidohydrolases; Female; Spinal Cord; NF-kappa B; Enzyme Inhibitors; Myelin Sheath
PubMed: 38701570
DOI: 10.1016/j.biopha.2024.116677 -
Journal of Nanobiotechnology May 2024Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived...
BACKGROUND
Bone marrow mesenchymal stem cells (BMSCs) can differentiate into Schwann cells (SCs) during peripheral nerve injury; in our previous research, we showed that SC-derived exosomes (SC-exos) played a direct induction role while fibroblast-derived exosomes (Fb-exos) had no obvious induction role. The induction role of neural stem cell (NSC)-derived exosomes (NSC-exos) has also been widely confirmed. However, no studies have compared the induction effects of these three types of cells at the same time. Therefore, by investigating the effect of these three cell-derived exosomes upon the induction of BMSCs to differentiate into SCs, this study explored the role of different exosomes in promoting the differentiation of stem cells into SCs cells, and conducted a comparison between the two groups by RNA sequencing to further narrow the range of target genes and related gene pathways in order to study their related mechanisms.
MATERIALS AND METHODS
We extracted exosomes from SCs, fibroblasts (Fb) and neural stem cells (NSC) and then investigated the ability of these exosomes to induce differentiation into BMSCs under different culture conditions. The expression levels of key proteins and gene markers were detected in induced cells by fluorescence immunoassays, western blotting and polymerase chain reaction (PCR); then, we statistically compared the relative induction effects under different conditions. Finally, we analyzed the three types of exosomes by RNA-seq to predict target genes and related gene pathways.
RESULTS
BMSCs were cultured by three media: conventional (no induction), pre-induction or pre-induction + original induction medium (ODM) with exosomes of the same cell origin under different culture conditions. When adding the three different types of exosomes separately, the overall induction of BMSCs to differentiate into SCs was significantly increased (P < 0.05). The induction ability was ranked as follows: pre-induction + ODM + exosome group > pre-induction + exosome group > non-induction + exosome group. Using exosomes from different cell sources under the same culture conditions, we observed the following trends under the three culture conditions: RSC96-exos group ≥ NSC-exos group > Fb-exos group. The overall ability to induce BMSCs into SCs was significantly greater in the RSC96-exos group and the NSC-exos group. Although there was no significant difference in induction efficiency when comparing these two groups, the overall induction ability of the RSC96-exos group was slightly higher than that of the NSC-exos group. By combining the differentiation induction results with the RNA-seq data, the three types of exosomes were divided into three comparative groups: RSC vs. NSC, RSC vs. Fb and NSC vs. Fb. We identified 203 differentially expressed mRNA target genes in these three groups. Two differentially expressed genes were upregulated simultaneously, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). We did not identify any co-upregulated target genes for the miRNAs, but did identify one target gene of the lncRNAs, namely ENSRNOG00000065005. Analysis identified 90 GO terms related to nerves and axons in the mRNAs; in addition, KEGG enrichment and GASA analysis identified 13 common differential expression pathways in the three groups.
CONCLUSIONS
Our analysis found that pre-induction + ODM + RSC96/NSC-exos culture conditions were most conducive with regards to induction and differentiation. RSC96-exos and NSC-exos exhibited significantly greater differentiation efficiency of BMSCs into SCs. Although there was no statistical difference, the data indicated a trend for RSC96-exos to be advantageous We identified 203 differentially expressed mRNAs between the three groups and two differentially expressed target mRNAs were upregulated, namely riboflavin kinase (RFK, ENSRNOG00000022273) and ribosomal RNA processing 36 (Rrp36, ENSRNOG00000017836). 90 GO terms were related to nerves and axons. Finally, we identified 13 common differentially expressed pathways across our three types of exosomes. It is hoped that the efficiency of BMSCs induction differentiation into SCs can be improved, bringing hope to patients and more options for clinical treatment.
Topics: Exosomes; Schwann Cells; Mesenchymal Stem Cells; Cell Differentiation; Animals; Rats; Cells, Cultured; Fibroblasts; Neural Stem Cells; Rats, Sprague-Dawley; Bone Marrow Cells
PubMed: 38698449
DOI: 10.1186/s12951-024-02450-3 -
Regenerative Therapy Dec 2024Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches...
Brachial plexus injury (BPI) with motor neurons (MNs) damage still remain poor recovery in preclinical research and clinical therapy, while cell-based therapy approaches emerged as novel strategies. Previous work of rat skin precursor-derived Schwann cells (SKP-SCs) provided substantial foundation for repairing peripheral nerve injury (PNI). Given that, our present work focused on exploring the repair efficacy and possible mechanisms of SKP-SCs implantation on rat BPI combined with neurorrhaphy post-neurotomy. Results indicated the significant locomotive and sensory function recovery, with improved morphological remodeling of regenerated nerves and angiogenesis, as well as amelioration of target muscles atrophy and motor endplate degeneration. Besides, MNs could restore from oxygen-glucose-deprivation (OGD) injury upon SKP-SCs-sourced secretome treatment, implying the underlying paracrine mechanisms. Moreover, rat cytokine array assay detected 67 cytokines from SKP-SC-secretome, and bioinformatic analyses of screened 32 cytokines presented multiple functional clusters covering diverse cell types, including inflammatory cells, Schwann cells, vascular endothelial cells (VECs), neurons, and SKP-SCs themselves, relating distinct biological processes to nerve regeneration. Especially, a panel of hypoxia-responsive cytokines (HRCK), can participate into multicellular biological process regulation for permissive regeneration milieu, which underscored the benefits of SKP-SCs and sourced secretome, facilitating the chorus of nerve regenerative microenvironment. Furthermore, platelet-derived growth factor-AA (PDGF-AA) and vascular endothelial growth factor-A (VEGF-A) were outstanding cytokines involved with nerve regenerative microenvironment regulating, with significantly elevated mRNA expression level in hypoxia-responsive SKP-SCs. Altogether, through recapitulating the implanted SKP-SCs and derived secretome as niche sensor and paracrine transmitters respectively, HRCK would be further excavated as molecular underpinning of the neural recuperative mechanizations for efficient cell therapy; meanwhile, the analysis paradigm in this study validated and anticipated the actions and mechanisms of SKP-SCs on traumatic BPI repair, and was beneficial to identify promising bioactive molecule cocktail and signaling targets for cell-free therapy strategy on neural repair and regeneration.
PubMed: 38694448
DOI: 10.1016/j.reth.2024.04.002 -
Frontiers in Physiology 2024Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce....
Ladder-based resistance training with the progression of training load altered the tibial nerve ultrastructure and muscle fiber area without altering the morphology of the postsynaptic compartment.
Scientific evidence regarding the effect of different ladder-based resistance training (LRT) protocols on the morphology of the neuromuscular system is scarce. Therefore, the present study aimed to compare the morphological response induced by different LRT protocols in the ultrastructure of the tibial nerve and morphology of the motor endplate and muscle fibers of the soleus and plantaris muscles of young adult Wistar rats. Rats were divided into groups: sedentary control (control, n = 9), a predetermined number of climbs and progressive submaximal intensity (fixed, n = 9), high-intensity and high-volume pyramidal system with a predetermined number of climbs (Pyramid, n = 9) and lrt with a high-intensity pyramidal system to exhaustion (failure, n = 9). myelinated fibers and myelin sheath thickness were statistically larger in pyramid, fixed, and failure. myelinated axons were statistically larger in pyramid than in control. schwann cell nuclei were statistically larger in pyramid, fixed, and failure. microtubules and neurofilaments were greater in pyramid than in control. morphological analysis of the postsynaptic component of the plantar and soleus muscles did not indicate any significant difference. for plantaris, the type i myofibers were statistically larger in the pyramid and fixed compared to control. the pyramid, fixed, and failure groups for type ii myofibers had larger csa than control. for soleus, the type i myofibers were statistically larger in the pyramid than in control. pyramid and fixed had larger csa for type ii myofibers than control and failure. the pyramid and fixed groups showed greater mass progression delta than the failure. We concluded that the LRT protocols with greater volume and progression of accumulated mass elicit more significant changes in the ultrastructure of the tibial nerve and muscle hypertrophy without endplate changes.
PubMed: 38694209
DOI: 10.3389/fphys.2024.1371839