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Journal of Clinical Laboratory Analysis Aug 2022Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes,... (Review)
Review
BACKGROUND
Non-coding RNAs (ncRNAs) are involved in neuropathic pain development. Herein, we systematically searched for neuropathic pain-related ncRNAs expression changes, including microRNAs (miRNAs), long non-coding RNAs (lncRNAs), and circular non-coding RNAs (circRNAs).
METHODS
We searched two databases, PubMed and GeenMedical, for relevant studies.
RESULTS
Peripheral nerve injury or noxious stimuli can induce extensive changes in the expression of ncRNAs. For example, higher serum miR-132-3p, -146b-5p, and -384 was observed in neuropathic pain patients. Either sciatic nerve ligation, dorsal root ganglion (DRG) transaction, or ventral root transection (VRT) could upregulate miR-21 and miR-31 while downregulating miR-668 and miR-672 in the injured DRG. lncRNAs, such as early growth response 2-antisense-RNA (Egr2-AS-RNA) and Kcna2-AS-RNA, were upregulated in Schwann cells and inflicted DRG after nerve injury, respectively. Dysregulated circRNA homeodomain-interacting protein kinase 3 (circHIPK3) in serum and the DRG, abnormally expressed lncRNAs X-inactive specific transcript (XIST), nuclear enriched abundant transcript 1 (NEAT1), small nucleolar RNA host gene 1 (SNHG1), as well as ciRS-7, zinc finger protein 609 (cirZNF609), circ_0005075, and circAnks1a in the spinal cord were suggested to participate in neuropathic pain development. Dysregulated miRNAs contribute to neuropathic pain via neuroinflammation, autophagy, abnormal ion channel expression, regulating pain-related mediators, protein kinases, structural proteins, neurotransmission excitatory-inhibitory imbalances, or exosome miRNA-mediated neuron-glia communication. In addition, lncRNAs and circRNAs are essential in neuropathic pain by acting as antisense RNA and miRNA sponges, epigenetically regulating pain-related molecules expression, or modulating miRNA processing.
CONCLUSIONS
Numerous dysregulated ncRNAs have been suggested to participate in neuropathic pain development. However, there is much work to be done before ncRNA-based analgesics can be clinically used for various reasons such as conservation among species, proper delivery, stability, and off-target effects.
Topics: Ganglia, Spinal; Humans; MicroRNAs; Neuralgia; RNA, Circular; RNA, Long Noncoding
PubMed: 35808924
DOI: 10.1002/jcla.24592 -
Journal of Neurosurgery. Spine Sep 2012Using a systematic approach, the authors evaluated the current utilization, safety, and effectiveness of cellular therapies for traumatic spinal cord injuries (SCIs) in... (Review)
Review
OBJECT
Using a systematic approach, the authors evaluated the current utilization, safety, and effectiveness of cellular therapies for traumatic spinal cord injuries (SCIs) in humans.
METHODS
A systematic search and critical review of the literature published through mid-January 2012 was performed. Articles included in the search were restricted to the English language, studies with at least 10 patients, and those analyzing cellular therapies for traumatic SCI. Citations were evaluated for relevance using a priori criteria, and those that met the inclusion criteria were critically reviewed. Each article was then designated a level of evidence that was developed by the Oxford Centre for Evidence-Based Medicine.
RESULTS
The initial literature search identified 651 relevant articles, which decreased to 350 after excluding case reports and reviews. Evaluation of articles at the title/abstract level, and later at the full-text level, limited the final article set to 12 papers. The following cellular therapies employed in humans with SCI are reviewed: bone marrow mesenchymal and hematopoietic stem cells (8 studies), olfactory ensheathing cells (2 studies), Schwann cells (1 study), and fetal neurogenic tissue (1 study). Overall the quality of the literature was very low, with 3 Grade III levels of evidence and 9 Grade IV studies.
CONCLUSIONS
Several different cellular-mediated strategies for adult SCI have been reported to be relatively safe with varying degrees of neurological recovery. However, the literature is of low quality and there is a need for improved preclinical studies and prospective, controlled clinical trials.
Topics: Evidence-Based Medicine; Humans; Schwann Cells; Spinal Cord Injuries; Stem Cell Transplantation; Treatment Outcome
PubMed: 22985383
DOI: 10.3171/2012.5.AOSPINE12115 -
Neuroscience Mar 2019Extensive oligodendrocyte death after acute traumatic spinal cord injuries (TSCI) leads to axon demyelination and subsequently may leave axons vulnerable to...
Extensive oligodendrocyte death after acute traumatic spinal cord injuries (TSCI) leads to axon demyelination and subsequently may leave axons vulnerable to degeneration. Despite the present evidence showing spontaneous remyelination after TSCI the cellular origin of new myelin and the time course of the axon ensheathment/remyelination remained controversial issue. In this systematic review the trend of oligodendrocyte death after injury as well as the extent and the cellular origin of oligodendrogliogenesis were comprehensively evaluated. The study design was based on Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA)-guided systematic review. PubMed and EMBASE were searched with no temporal or linguistic restrictions. Also, hand-search was performed in the bibliographies of relevant articles. Non-interventional animal studies discussing different types of myelinating cells including oligodendrocytes, Schwann cells and oligodendrocyte progenitor cells (OPCs) were evaluated. The extent of oligodendrocyte death, oligodendrocyte differentiation and remyelination were the pathophysiological outcome measures. We found 12,359 studies, 34 of which met the inclusion criteria. The cumulative evidence shows extensive oligodendrocytes cell death during the first week post-injury (pi). OPCs and peripheral invading Schwann cells are the dominant cells contributing in myelin formation. The maximum OPC proliferation was observed at around 2 weeks pi and oligodendrogliogenesis continues at later stages until the number of oligodendrocytes return to normal tissue by one month pi. Taken together, the evidence in animals reveals the potential role for endogenous myelinating cells in the axon ensheathment/remyelination after TSCI and this can be the target of pharmacotherapy to induce oligodendrocyte differentiation and myelin formation post-injury.
Topics: Animals; Axons; Cell Death; Cell Differentiation; Disease Models, Animal; Oligodendrocyte Precursor Cells; Oligodendroglia; Remyelination; Spinal Cord Injuries
PubMed: 30685542
DOI: 10.1016/j.neuroscience.2019.01.019 -
Multiple Sclerosis (Houndmills,... Jan 2022Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in...
BACKGROUND
Immune-mediated demyelination and consequent degeneration of oligodendrocytes and axons are hallmark features of multiple sclerosis (MS). Remyelination declines in progressive MS, causing permanent axonal loss and irreversible disabilities. Strategies aimed at enhancing remyelination are critical to attenuate disease progression.
OBJECTIVE
We systematically reviewed recent advances in neuroprotective and regenerative therapies for MS, covering preclinical and clinical studies.
METHODS
We searched three biomedical databases using defined keywords. Two authors independently reviewed articles for inclusion based on pre-specified criteria. The data were extracted from each study and assessed for risk of bias.
RESULTS
Our search identified 7351 studies from 2014 to 2020, of which 221 met the defined criteria. These studies reported 262 interventions, wherein 92% were evaluated in animal models. These interventions comprised protein, RNA, lipid and cellular biologics, small molecules, inorganic compounds, and dietary and physiological interventions. Small molecules were the most highly represented strategy, followed by antibody therapies and stem cell transplantation.
CONCLUSION
While significant strides have been made to develop regenerative treatments for MS, the current evidence illustrates a skewed representation of the types of strategies that advance to clinical trials. Further examination is thus required to address current barriers to implementing experimental treatments in clinical settings.
Topics: Animals; Axons; Multiple Sclerosis; Myelin Sheath; Nerve Regeneration; Oligodendroglia; Remyelination
PubMed: 33870797
DOI: 10.1177/13524585211008760 -
Analytical Biochemistry May 2022The goal of regenerative medicine is to replace or restore missing, dysfunctional, or damaged cells, tissues and organs of a person to reproduce their normal function....
PURPOSE
The goal of regenerative medicine is to replace or restore missing, dysfunctional, or damaged cells, tissues and organs of a person to reproduce their normal function. The main approaches are cell therapy, tissue engineering, and gene therapy. Postnatal neural crest-derived multipotent stem cells (NC-MSC) are a promising cell type for use in regenerative medicine. This is due to the specific features of their embryonic origin and the role of the neural crest in phylogeny and ontogeny of vertebrates.
METHODS
The study used research in vitro culture (monolayer cell culture, 3D culture based on hydrogels, organotypic culture of hippocampal slices, spherogenesis, directed differentiation); flow cytometry; cytochemical, immune-cytochemical and histomorphometric analysis; molecular genetic (RNA (ribonucleic acid) isolation, PCR (polymerase chain reaction) with reverse transcription, real-time PCR, nucleic acid electrophoresis); microscopy (transmitted light, phase contrast, fluorescent, confocal laser scanning); microsurgical; statistical analysis.
RESULTS
In this systematic review, the results showed that recently the neural crest-derived cells have been isolated from a wide range of tissues and organs of mammals at the postnatal stage of development. These cells, at least in vitro, demonstrate the ability to self-repair and multilinear differentiation into neurons, Schwann cells, melanocytes, adipocytes, osteoblasts, chondrocytes, and other types of cells, that is, according to their functional characteristics, they are multipotent stem cells.
CONCLUSION
According to the obtained results, tissue sources of postnatal neural crest-derived multipotent stem cells differ considerably in the degree of invasiveness of biopsy sampling, as well as the possibility of obtaining a homogeneous population of NC-MSCs, which is important for further clinical use.
Topics: Animals; Cell Differentiation; Cells, Cultured; Humans; Mammals; Multipotent Stem Cells; Neural Crest; Regenerative Medicine; Stem Cells
PubMed: 35202604
DOI: 10.1016/j.ab.2022.114608 -
Pediatric Dermatology Mar 2020Neurothekeoma is a rare, benign, cutaneous neoplasm consisting of Schwann cells and perineural cells in myxoid stroma. Cellular neurothekeoma (CNT) was previously...
BACKGROUND/OBJECTIVES
Neurothekeoma is a rare, benign, cutaneous neoplasm consisting of Schwann cells and perineural cells in myxoid stroma. Cellular neurothekeoma (CNT) was previously thought to represent a morphologic variant of neurothekeoma, but recent studies have shown that CNTs are unrelated to neurothekeomas and are more likely of histiocytic lineage.
METHODS
Herein, we describe seven cases of CNT in pediatric patients. A comprehensive search of PubMed was performed, and 71 cases of cellular neurothekeoma in pediatric patients were reviewed.
RESULTS
The clinical differential diagnosis for these lesions included Spitz nevi, keloid, juvenile xanthogranuloma, cutaneous lymphoid hyperplasia, and lymphomatoid papulosis. All cases were treated by excision or excisional biopsy. Histopathologically, all demonstrated multilobular, primarily intradermal neoplasms composed of plump spindled or epithelioid mononuclear cells with abundant eosinophilic pale-staining cytoplasm. Immunophenotypic findings included CD68 and NKI/C3 positivity, and negative staining with cytokeratin, S-100, Melan-A, and SOX-10.
CONCLUSION
Cellular neurothekeoma is distinguished from conventional neurothekeoma by increased cellularity, a lack of myxoid stroma, and a lack of neural expression with immunohistochemical stains. These uncommon neoplasms should be included in the differential diagnosis of dermal nodules in children. Accurate diagnosis of these lesions is essential, as they can be mistaken for malignancy leading to unnecessary treatment.
Topics: Adolescent; Child; Child, Preschool; Cohort Studies; Female; Humans; Infant; Male; Neurothekeoma; Skin Neoplasms
PubMed: 31930561
DOI: 10.1111/pde.14043 -
Head & Neck Dec 2013Oral nerve sheath myxoma (NSM) is an uncommon benign neoplasm with Schwann-cell origin, which is frequently mistaken for neurothekeoma. We report a case of NSM on the... (Review)
Review
BACKGROUND
Oral nerve sheath myxoma (NSM) is an uncommon benign neoplasm with Schwann-cell origin, which is frequently mistaken for neurothekeoma. We report a case of NSM on the buccal mucosa in a 42-year-old woman. This case is compared with previously reported cases and a systematic review is performed.
METHODS AND RESULTS
We conducted a case report and systematic review of oral cases considered true NSMs. A literature search was performed using PubMed, Lilacs, Scielo, Cochrane, SciVerse Scopus, Web of Science, and Embase electronic database. Twenty-five cases of oral NSM were included in the systematic review.
CONCLUSION
Oral NSM is rare and may represent a diagnostic challenge for pathologists. To confirm the diagnosis of NSM, the evaluation of S-100 protein expression or other neural marker is essential. The use of the terms NSM and neurothekeoma as synonymous or as variants of the same tumor should be avoided, because they are clearly distinct lesions.
Topics: Adult; Female; Glial Fibrillary Acidic Protein; Humans; Immunohistochemistry; Mouth Mucosa; Mouth Neoplasms; Neurothekeoma; Phosphopyruvate Hydratase; S100 Proteins; Terminology as Topic
PubMed: 23616426
DOI: 10.1002/hed.23361 -
World Neurosurgery Jun 2024Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma... (Review)
Review
BACKGROUND
Schwannomas are benign peripheral nerve sheath tumors arising from myelinating Schwann cells. Although macrocystic changes are regularly encountered in schwannoma variants such as vestibular nerve tumors, they are exceedingly rare among spinal neoplasms.
METHODS
Case report and systematic review of 4 databases (Ovid Medline, PubMed, Science Direct, and SCOPUS) from inception to present. All peer-reviewed publications reporting intradural cystic thoracic schwannoma were included.
RESULTS
We identified 8 publications documenting 9 cases of cystic thoracic schwannoma. Four were female, 5 male; median age was 41 years (range, 27-80). Presentations ranged from incidental to pain, sensory changes, lower extremity paresis, or bowel/bladder dysfunction. Characteristic radiographic findings included T1 hypointensity, T2 hyperintensity, and cord effacement or compression. The present case followed a similar pattern: a 52-year-old male presented with worsening bilateral lower extremity weakness, low back pain, and gait dysfunction, worsening over 3 days. Examination also revealed decreased left lower extremity sensation. Imaging identified a well-delineated intradural, extramedullary macrocystic extending over T7-T10. The patient underwent a laminectomy resulting in complete tumor resection and restoration of intact neurologic function. Final pathology confirmed benign cystic schwannoma.
CONCLUSIONS
Macrocystic thoracic schwannomas are exceedingly rare and lack a comprehensive scheme for clinical classification of their natural history and pathogenesis. We report the 10th case of such a schwannoma, and the first associated systematic review. Although macrocystic thoracic schwannomas are not frequently encountered, accurate diagnosis and appropriate neurosurgical treatment is critical in these vulnerable patients, given the opportunity for excellent functional outcomes following neurosurgical treatment.
Topics: Humans; Neurilemmoma; Male; Middle Aged; Thoracic Vertebrae; Female; Spinal Cord Neoplasms; Adult; Aged
PubMed: 38522790
DOI: 10.1016/j.wneu.2024.03.091 -
NeuroImage Feb 2021Currently, multiple sclerosis is treated with anti-inflammatory therapies, but these treatments lack efficacy in progressive disease. New treatment strategies aim to...
OBJECTIVES
Currently, multiple sclerosis is treated with anti-inflammatory therapies, but these treatments lack efficacy in progressive disease. New treatment strategies aim to repair myelin damage and efficacy evaluation of such new therapies would benefit from validated myelin imaging techniques. Several MRI methods for quantification of myelin density are available now. This systematic review aims to analyse the performance of these MRI methods.
METHODS
Studies comparing myelin quantification by MRI with histology, the current gold standard, or assessing reproducibility were retrieved from PubMed/MEDLINE and Embase (until December 2019). Included studies assessed both myelin histology and MRI quantitatively. Correlation or variance measurements were extracted from the studies. Non-parametric tests were used to analyse differences in study methodologies.
RESULTS
The search yielded 1348 unique articles. Twenty-two animal studies and 13 human studies correlated myelin MRI with histology. Eighteen clinical studies analysed the reproducibility. Overall bias risk was low or unclear. All MRI methods performed comparably, with a mean correlation between MRI and histology of R=0.54 (SD=0.30) for animal studies, and R=0.54 (SD=0.18) for human studies. Reproducibility for the MRI methods was good (ICC=0.75-0.93, R=0.90-0.98, COV=1.3-27%), except for MTR (ICC=0.05-0.51).
CONCLUSIONS
Overall, MRI-based myelin imaging methods show a fairly good correlation with histology and a good reproducibility. However, the amount of validation data is too limited and the variability in performance between studies is too large to select the optimal MRI method for myelin quantification yet.
Topics: Animals; Brain; Humans; Magnetic Resonance Imaging; Multiple Sclerosis; Myelin Sheath; Reproducibility of Results; Spinal Cord
PubMed: 33189927
DOI: 10.1016/j.neuroimage.2020.117561 -
Journal of Neurochemistry Mar 2021The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization...
The liver-derived, circulating transport protein transthyretin (TTR) is the cause of systemic hereditary (ATTRv) and wild-type (ATTRwt) amyloidosis. TTR stabilization and knockdown are approved therapies to mitigate the otherwise lethal disease course. To date, the variety in phenotypic penetrance is not fully understood. This systematic review summarizes the current literature on TTR pathophysiology with its therapeutic implications. Tetramer dissociation is the rate-limiting step of amyloidogenesis. Besides destabilizing TTR mutations, other genetic (RBP4, APCS, AR, ATX2, C1q, C3) and external (extracellular matrix, Schwann cell interaction) factors influence the type of onset and organ tropism. The approved small molecule tafamidis stabilizes the tetramer and significantly decelerates the clinical course. By sequence-specific mRNA knockdown, the approved small interfering RNA (siRNA) patisiran and antisense oligonucleotide (ASO) inotersen both significantly reduce plasma TTR levels and improve neuropathy and quality of life compared to placebo. With enhanced hepatic targeting capabilities, GalNac-conjugated siRNA and ASOs have recently entered phase III clinical trials. Bivalent TTR stabilizers occupy both binding groves in vitro, but have not been tested in trials so far. Tolcapone is another stabilizer with the potential to cross the blood-brain barrier, but its half-life is short and liver failure a potential side effect. Amyloid-directed antibodies and substances like doxycycline aim at reducing the amyloid load, however, none of the yet developed antibodies has successfully passed clinical trials. ATTR-amyloidosis has become a model disease for pathophysiology-based treatment. Further understanding of disease mechanisms will help to overcome the remaining limitations, including application burden, side effects, and blood-brain barrier permeability.
Topics: Amyloid; Amyloidosis, Familial; Animals; Gene Knockdown Techniques; Humans; Prealbumin
PubMed: 33155274
DOI: 10.1111/jnc.15233