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The Journal of Toxicological Sciences 2024Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages... (Comparative Study)
Comparative Study
Methylmercury is an environmental polluting organometallic compound that exhibits neurotoxicity, as observed in Minamata disease patients. Methylmercury damages peripheral nerves in Minamata patients, causing more damage to sensory nerves than motor nerves. Peripheral nerves are composed of three cell types: dorsal root ganglion (DRG) cells, anterior horn cells (AHCs), and Schwann cells. In this study, we compared cultured these three cell types derived from the rat for susceptibility to methylmercury cytotoxicity, intracellular accumulation of mercury, expression of L-type amino acid transporter 1 (LAT1), which transports methylmercury into cells, and expression of multidrug resistance-associated protein 2 (MRP2), which transports methylmercury-glutathione conjugates into the extracellular space. Of the cells examined, we found that DRG cells were the most susceptible to methylmercury with markedly higher intracellular accumulation of mercury. The constitutive level of LAT1 was higher and that of MRP2 lower in DRG cells compared with those in AHC and Schwann cells. Additionally, decreased cell viability caused by methylmercury was significantly reduced by either the LAT1 inhibitor, JPH203, or siRNA-mediated knockdown of LAT1. On the other hand, an MRP2 inhibitor, MK571, significantly intensified the decrease in the cell viability caused by methylmercury. Our results provide a cellular basis for sensory neve predominant injury in the peripheral nerves of Minamata disease patients.
Topics: Animals; Ganglia, Spinal; Methylmercury Compounds; Schwann Cells; Cell Survival; Cells, Cultured; Large Neutral Amino Acid-Transporter 1; Multidrug Resistance-Associated Proteins; Peripheral Nerves; Male; Rats; Multidrug Resistance-Associated Protein 2; ATP-Binding Cassette Transporters
PubMed: 38692911
DOI: 10.2131/jts.49.241 -
Frontiers in Medicine 2024Neuro bone tissue engineering is a multidisciplinary field that combines both principles of neurobiology and bone tissue engineering to develop innovative strategies for... (Review)
Review
Neuro bone tissue engineering is a multidisciplinary field that combines both principles of neurobiology and bone tissue engineering to develop innovative strategies for repairing and regenerating injured bone tissues. Despite the fact that regeneration and development are considered two distinct biological processes, yet regeneration can be considered the reactivation of development in later life stages to restore missing tissues. It is noteworthy that the regeneration capabilities are distinct and vary from one organism to another (teleost fishes, hydra, humans), or even in the same organism can vary dependent on the injured tissue itself (Human central nervous system vs. peripheral nervous system). The skeletal tissue is highly innervated, peripheral nervous system plays a role in conveying the signals and connecting the central nervous system with the peripheral organs, moreover it has been shown that they play an important role in tissue regeneration. Their regeneration role is conveyed by the different cells' resident in it and in its endoneurium (fibroblasts, microphages, vasculature associated cells, and Schwann cells) these cells secrete various growth factors (NGF, BDNF, GDNF, NT-3, and bFGF) that contribute to the regenerative phenotype. The peripheral nervous system and central nervous system synchronize together in regulating bone homeostasis and regeneration through neurogenic factors and neural circuits. Receptors of important central nervous system peptides such as Serotonin, Leptin, Semaphorins, and BDNF are expressed in bone tissue playing a role in bone homeostasis, metabolism and regeneration. This review will highlight the crosstalk between peripheral nerves and bone in the developmental stages as well as in regeneration and different neuro-bone tissue engineering strategies for repairing severe bone injuries.
PubMed: 38690172
DOI: 10.3389/fmed.2024.1386683 -
Frontiers in Neurology 2024Peripheral nerve injury disease is a prevalent traumatic condition in current medical practice. Despite the present treatment approaches, encompassing surgical sutures,... (Review)
Review
Peripheral nerve injury disease is a prevalent traumatic condition in current medical practice. Despite the present treatment approaches, encompassing surgical sutures, autologous nerve or allograft nerve transplantation, tissue engineering techniques, and others, an effective clinical treatment method still needs to be discovered. Exploring novel treatment methods to improve peripheral nerve regeneration requires more effort in investigating the cellular and molecular mechanisms involved. Many factors are associated with the regeneration of injured peripheral nerves, including the cross-sectional area of the injured nerve, the length of the nerve gap defect, and various cellular and molecular factors such as Schwann cells, inflammation factors, kinases, and growth factors. As crucial mediators of cellular communication, kinases exert regulatory control over numerous signaling cascades, thereby participating in various vital biological processes, including peripheral nerve regeneration after nerve injury. In this review, we examined diverse kinase classifications, distinct nerve injury types, and the intricate mechanisms involved in peripheral nerve regeneration. Then we stressed the significance of kinases in regulating autophagy, inflammatory response, apoptosis, cell cycle, oxidative processes, and other aspects in establishing conductive microenvironments for nerve tissue regeneration. Finally, we briefly discussed the functional roles of kinases in different types of cells involved in peripheral nerve regeneration.
PubMed: 38689881
DOI: 10.3389/fneur.2024.1340845 -
Journal of Surgical Case Reports Apr 2024Gastric schwannomas (GS) are rare mesenchymal tumors from Schwann cells in the gastrointestinal (GI) tract, representing 2-6% of such tumors. We report a 52-year-old...
Gastric schwannomas (GS) are rare mesenchymal tumors from Schwann cells in the gastrointestinal (GI) tract, representing 2-6% of such tumors. We report a 52-year-old woman who experienced abdominal pain, hematemesis, and melena, initially suspected of having a GI stromal tumor through ultrasound and computed tomography abdomen. Despite no active bleeding found during an upper endoscopy, she underwent a successful open subtotal gastrectomy, with histopathology confirming GS. The diagnosis of GS, which may mimic other GI conditions, relies heavily on imaging and histopathological analysis due to its nonspecific symptomatology, including the potential for both upper and lower GI bleeding. This case underscores the diagnostic challenges of GS and highlights surgical resection as the preferred treatment, generally leading to a favorable prognosis.
PubMed: 38681480
DOI: 10.1093/jscr/rjae267 -
Journal of Multidisciplinary Healthcare 2024Neurofibromatosis Type I (NF1) is a complex genetic condition that affects multiple organ systems and presents a unique set of challenges for clinicians in its... (Review)
Review
Neurofibromatosis Type I (NF1) is a complex genetic condition that affects multiple organ systems and presents a unique set of challenges for clinicians in its management. NF1 is a tumor predisposition syndrome that primarily affect the peripheral and central nervous systems via the impact of haploinsufficiency upon neural crest lineage cells including Schwann cells, melanocytes, fibroblasts, etc. NF1 can further lead to pathology of the skin, bones, visual system, and cardiovascular system, all of which can drastically reduce a patient's quality of life (QOL). This review provides a comprehensive examination of the many specialties required for the care of patients with Neurofibromatosis Type 1 (NF1). We delve into the pathogenesis and clinical presentation of NF1, highlighting its diverse manifestations and the challenges they pose in management. The review underscores the importance of a multidisciplinary approach to NF1, emphasizing how such an approach can significantly improve patient outcomes and overall QOL. Central to this approach is the role of the NF expert, who guides a multidisciplinary team (MDT) comprising healthcare professionals from many areas of expertise. The MDT collaboratively addresses the multifaceted needs of NF1 patients, ensuring comprehensive and personalized care. This review highlights the need for further investigation to optimize the workflow for NF1 patients in an MDT setting, and to improve implementation and efficacy.
PubMed: 38680880
DOI: 10.2147/JMDH.S362791 -
Cancer Science Apr 2024Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly...
Doublecortin (DCX)-positive neural progenitor-like cells are purported components of the cancer microenvironment. The number of DCX-positive cells in tissues reportedly correlates with cancer progression; however, little is known about the mechanism by which these cells affect cancer progression. Here we demonstrated that DCX-positive cells, which are found in all major histological subtypes of lung cancer, are cancer-associated Schwann cells (CAS) and contribute to the chemoresistance of lung cancer cells by establishing an adrenergic microenvironment. Mechanistically, the activation of the Hippo transducer YAP/TAZ was involved in the acquisition of new traits of CAS and DCX positivity. We further revealed that CAS express catecholamine-synthesizing enzymes and synthesize adrenaline, which potentiates the chemoresistance of lung cancer cells through the activation of YAP/TAZ. Our findings shed light on CAS, which drive the formation of an adrenergic microenvironment by the reciprocal regulation of YAP/TAZ in lung cancer tissues.
PubMed: 38676373
DOI: 10.1111/cas.16164 -
Genes Mar 2024Microribonucleic acids (miRNAs) comprising miR-23a/b clusters, specifically miR-23a and miR-27a, are recognized for their divergent roles in myelination within the...
Microribonucleic acids (miRNAs) comprising miR-23a/b clusters, specifically miR-23a and miR-27a, are recognized for their divergent roles in myelination within the central nervous system. However, cluster-specific miRNA functions remain controversial as miRNAs within the same cluster have been suggested to function complementarily. This study aims to clarify the role of miR-23a/b clusters in myelination using mice with a miR-23a/b cluster deletion (KO mice), specifically in myelin expressing proteolipid protein (PLP). Inducible conditional KO mice were generated by crossing miR-23a/b cluster mice with mice; the offspring were injected with tamoxifen at 10 days or 10 weeks of age to induce a myelin-specific miR-23a/b cluster deletion. Evaluation was performed at 10 weeks or 12 months of age and compared with control mice that were not treated with tamoxifen. KO mice exhibit impaired motor function and hypoplastic myelin sheaths in the brain and spinal cord at 10 weeks and 12 months of age. Simultaneously, significant decreases in myelin basic protein (MBP) and PLP expression occur in KO mice. The percentages of oligodendrocyte precursors and mature oligodendrocytes are consistent between the KO and control mice. However, the proportion of oligodendrocytes expressing MBP is significantly lower in KO mice. Moreover, changes in protein expression occur in KO mice, with increased leucine zipper-like transcriptional regulator 1 expression, decreased R-RAS expression, and decreased phosphorylation of extracellular signal-regulated kinases. These findings highlight the significant influence of miR-23a/b clusters on myelination during postnatal growth and aging.
Topics: Animals; MicroRNAs; Mice; Myelin Sheath; Aging; Central Nervous System; Mice, Knockout; Myelin Proteolipid Protein; Spinal Cord; Myelin Basic Protein; Oligodendroglia; Brain
PubMed: 38674338
DOI: 10.3390/genes15040402 -
Medicina (Kaunas, Lithuania) Mar 2024: Our report contributes a unique case of a non-neural GCT occurring in an unusual location, with its development during pregnancy adding to its rarity. : Granular cell...
: Our report contributes a unique case of a non-neural GCT occurring in an unusual location, with its development during pregnancy adding to its rarity. : Granular cell tumors (GCTs), also known as Abrikossoff's tumors, are rare neoplasms of Schwann cell origin with predominantly benign behavior. We present a case of a 29-year-old female with a non-neural variant of a GCT discovered incidentally during a cesarean section, situated on the posterior surface of the rectus abdominis muscle. : Histologically, the tumor exhibited features consistent with a benign non-neural GCT, confirmed through an immunohistochemical analysis. Despite the atypical presentation and challenging surgical removal due to prior scarring, the patient experienced no postoperative complications and showed no signs of recurrence during follow-up. : This case highlights the importance of considering GCTs in differential diagnoses, particularly in unusual anatomical locations, and underscores the favorable prognosis associated with timely surgical intervention.
Topics: Humans; Female; Rectus Abdominis; Adult; Granular Cell Tumor; Pregnancy; Muscle Neoplasms; Cesarean Section; Granulosa Cell Tumor
PubMed: 38674222
DOI: 10.3390/medicina60040576 -
International Journal of Molecular... Apr 2024Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to a potential reduction in life expectancy by up to 14.5... (Review)
Review
Schizophrenia is a significant worldwide health concern, affecting over 20 million individuals and contributing to a potential reduction in life expectancy by up to 14.5 years. Despite its profound impact, the precise pathological mechanisms underlying schizophrenia continue to remain enigmatic, with previous research yielding diverse and occasionally conflicting findings. Nonetheless, one consistently observed phenomenon in brain imaging studies of schizophrenia patients is the disruption of white matter, the bundles of myelinated axons that provide connectivity and rapid signalling between brain regions. Myelin is produced by specialised glial cells known as oligodendrocytes, which have been shown to be disrupted in post-mortem analyses of schizophrenia patients. Oligodendrocytes are generated throughout life by a major population of oligodendrocyte progenitor cells (OPC), which are essential for white matter health and plasticity. Notably, a decline in a specific subpopulation of OPC has been identified as a principal factor in oligodendrocyte disruption and white matter loss in the aging brain, suggesting this may also be a factor in schizophrenia. In this review, we analysed genomic databases to pinpoint intersections between aging and schizophrenia and identify shared mechanisms of white matter disruption and cognitive dysfunction.
Topics: Humans; Schizophrenia; Oligodendroglia; Aging; Animals; Genomics; White Matter; Myelin Sheath; Brain
PubMed: 38674040
DOI: 10.3390/ijms25084452 -
Biomolecules Apr 2024Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The () mouse exhibits motoneuron degeneration,...
Amyotrophic lateral sclerosis (ALS) is a fatal motoneuron degenerative disease that is associated with demyelination. The () mouse exhibits motoneuron degeneration, gliosis and myelin deterioration in the cervical spinal cord. Since male s display low testosterone (T) levels in the nervous system, we investigated if T modified myelin-relative parameters in s in the absence or presence of the aromatase inhibitor, anastrozole (A). We studied myelin by using luxol-fast-blue (LFB) staining, semithin sections, electron microscopy and myelin protein expression, density of IBA1 microglia and mRNA expression of inflammatory factors, and the glutamatergic parameters glutamine synthetase (GS) and the transporter GLT1. Controls and + T showed higher LFB, MBP and PLP staining, lower g-ratios and compact myelin than s and + T + A, and groups showing the rupture of myelin lamellae. s showed increased IBA1 cells and mRNA for CD11b and inflammatory factors (IL-18, TLR4, TNFαR and PYR) vs. controls or + T. IBA1 cells, and CD11b were not reduced in + T + A, but inflammatory factors' mRNA remained low. A reduction of GS cells and GLT-1 immunoreactivity was observed in s and + T + A vs. controls and + T. Clinically, + T but not + T + A showed enhanced muscle mass, grip strength and reduced paw abnormalities. Therefore, T effects involve myelin protection, a finding of potential clinical translation.
Topics: Animals; Mice; Myelin Sheath; Amyotrophic Lateral Sclerosis; Male; Disease Models, Animal; Testosterone; Spinal Cord; Excitatory Amino Acid Transporter 2; Microglia
PubMed: 38672445
DOI: 10.3390/biom14040428