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Inflammation and Regeneration Dec 2022Axons play an essential role in the connection of the nervous system with the rest of the body. Axon lesions often lead to permanent impairment of motor and cognitive... (Review)
Review
BACKGROUND
Axons play an essential role in the connection of the nervous system with the rest of the body. Axon lesions often lead to permanent impairment of motor and cognitive functions and the interaction with the outside world. Studies focusing on axon regeneration have become a research field with considerable interest. The purpose of this study is to obtain an overall perspective of the research field of axonal regeneration and to assist the researchers and the funding agencies to better know the areas of greatest research opportunities.
METHODS
We conducted a bibliometric analysis and Latent Dirichlet Allocation (LDA) analysis of the global literature on axon regeneration based on the Web of Science (WoS) over the recent 22 years, to address the research hotspots, publication trends, and understudied areas.
RESULTS
A total of 21,018 articles were included, which in the recent two decades has increased by 125%. Among the top 12 hotspots, the annual productions rapidly increased in some topics, including axonal regeneration signaling pathway, axon guidance cues, neural circuits and functional recovery, nerve conduits, and cells transplant. Comparatively, the number of studies on axon regeneration inhibitors decreased. As for the topics focusing on nerve graft and transplantation, the annual number of papers tended to be relatively stable. Nevertheless, the underlying mechanisms of axon regrowth have not been completely uncovered. A lack of notable research on the epigenetic programs and noncoding RNAs regulation was observed. The significance of cell-type-specific data has been highlighted but with limited research working on that. Functional recovery from neuropathies also needs further studies.
CONCLUSION
The last two decades witnessed tremendous progress in the field of axon regeneration. There are still a lot of challenges to be tackled in translating these technologies into clinical practice.
PubMed: 36476643
DOI: 10.1186/s41232-022-00244-4 -
Journal of Neurogenetics Mar 2018Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel...
Non-syndromic intellectual disability (NS-ID) is a genetically heterogeneous disorder, with more than 200 candidate genes to date. Despite the increasing number of novel mutations detected, a relatively low number of recurrently mutated genes have been identified, highlighting the complex genetic architecture of the disorder. A systematic search of PubMed and Medline identified 245 genes harbouring non-synonymous variants, insertions or deletions, which were identified as candidate NS-ID genes from case reports or from linkage or pedigree analyses. From this list, 33 genes are common to syndromic intellectual disability (S-ID) and 58 genes are common to certain neurological and neuropsychiatric disorders that often include intellectual disability as a clinical feature. We examined the evolutionary constraint and brain expression of these gene sets, and we performed gene network and protein-protein interaction analyses using GeneGO MetaCore and DAPPLE, respectively. The 245 NS-ID candidate genes were over-represented in axon guidance, synaptogenesis, cell adhesion and neurotransmission pathways, all of which are key neurodevelopmental processes for the establishment of mature neuronal circuitry in the brain. These 245 genes exhibit significantly elevated expression in human brain and are evolutionarily constrained, consistent with expectations for a brain disorder such as NS-ID that is associated with reduced fecundity. In addition, we report enrichment of dopaminergic and glutamatergic pathways for those candidate NS-ID genes that are common to S-ID and/or neurological and neuropsychiatric disorders that exhibit intellectual disability. Collectively, this study provides an overview and analysis of gene networks associated with NS-ID and suggests modulation of neurotransmission, particularly dopaminergic and glutamatergic systems as key contributors to synaptic dysfunction in NS-ID.
Topics: Gene Regulatory Networks; Humans; Intellectual Disability
PubMed: 29199528
DOI: 10.1080/01677063.2017.1404058 -
International Immunopharmacology May 2024Hallmark features of the tumor microenvironment include immune cells, stromal cells, blood vessels, and extracellular matrix (ECM), providing a conducive environment for... (Review)
Review
Hallmark features of the tumor microenvironment include immune cells, stromal cells, blood vessels, and extracellular matrix (ECM), providing a conducive environment for the growth and survival of tumors. Recent advances in the understanding of cancer biology have highlighted the functional role of semaphorins (SEMAs). SEMAs are a large and diverse family of widely expressed secreted and membrane-binding proteins, which were initially implicated in axon guidance and neural development. However, it is now clear that they are widely expressed beyond the nervous system and participate in regulating immune responses and cancer progression. In fact, accumulating evidence disclosed that different SEMAs can either stimulate or restrict tumor progression, some of which act as important regulators of tumor angiogenesis. Conversely, limited information is known about the functional relevance of SEMA signals in TME. In this setting, we systematically elaborate the role SEMAs and their major receptors played in characterized components of TME. Furthermore, we provide a convergent view of current SEMAs pharmacological progress in clinical treatment and also put forward their potential application value and clinical prospects in the future.
Topics: Animals; Humans; Neoplasms; Neovascularization, Pathologic; Semaphorins; Signal Transduction; Tumor Microenvironment
PubMed: 38603857
DOI: 10.1016/j.intimp.2024.112035 -
Molecular Neurobiology Dec 2019Late-onset Alzheimer's disease (LOAD) is a high-occurrence neurological disorder but the difficulty in identifying precise and early biomarkers has complicated the...
Late-onset Alzheimer's disease (LOAD) is a high-occurrence neurological disorder but the difficulty in identifying precise and early biomarkers has complicated the understanding of the disease and the development of new treatments. In this sense, important knowledge is emerging regarding novel molecular and biological candidates with diagnostic potential, including microRNAs (miRNAs), which have a key role in gene repression. The aim of this systematic review was to define the role of miRNAs' expression as biomarkers for LOAD both in brain tissues, which could help understand the biology of the disease, and circulating tissues, which could serve as non-invasive markers of the pathology. A systematic search was performed in Web of Science and PubMed using the keywords ((Alzheimer or Alzheimer's) and (microRNA or microRNAs or miRNA or miRNAs or miR)) until August 2018 to retrieve all articles that presented independent original data evaluating the impact of miRNA expression on the development of LOAD in human population. A total of 90 studies investigating the role of miRNAs' expression in the development of LOAD were identified. While other widely studied miRNAs such as hsa-miR-146a presented contradictory results among studies, deregulation in brain tissue of seven miRNAs, hsa-miR-16-5p, hsa-miR-34a-5p, hsa-miR-107, hsa-miR-125-5p, hsa-miR-132-3p, hsa-miR-181-3p, and hsa-miR-212-3p, was consistently identified in LOAD patients. Their role in the disease could be mediated through the regulation of key pathways, such as axon guidance, longevity, insulin, and MAPK signaling pathway. However, regarding their role as non-invasive biomarkers of LOAD in fluids, although the limited results available are promising, further studies are required.
Topics: Alzheimer Disease; Biomarkers; Brain; Circulating MicroRNA; Gene Expression Regulation; Humans; MicroRNAs
PubMed: 31240600
DOI: 10.1007/s12035-019-01676-9 -
International Journal of Molecular... Apr 2019Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the...
Despite numerous studies on major depressive disorder (MDD) susceptibility, the precise underlying molecular mechanism has not been elucidated which restricts the development of etiology-based disease-modifying drug. Major depressive disorder treatment is still symptomatic and is the leading cause of (~30%) failure of the current antidepressant therapy. Here we comprehended the probable genes and pathways commonly associated with antidepressant response and MDD. A systematic review was conducted, and candidate genes/pathways associated with antidepressant response and MDD were identified using an integrative genetics approach. Initially, single nucleotide polymorphisms (SNPs)/genes found to be significantly associated with antidepressant response were systematically reviewed and retrieved from the candidate studies and genome-wide association studies (GWAS). Also, significant variations concerning MDD susceptibility were extracted from GWAS only. We found 245 (Set A) and 800 (Set B) significantly associated genes with antidepressant response and MDD, respectively. Further, gene set enrichment analysis revealed the top five co-occurring molecular pathways ( ≤ 0.05) among the two sets of genes: Cushing syndrome, Axon guidance, cAMP signaling pathway, Insulin secretion, and Glutamatergic synapse, wherein all show a very close relation to synaptic plasticity. Integrative analyses of candidate gene and genome-wide association studies would enable us to investigate the putative targets for the development of disease etiology-based antidepressant that might be more promising than current ones.
Topics: Antidepressive Agents; Cyclic AMP; Depressive Disorder, Major; Genome-Wide Association Study; Genomics; Humans; Pharmacogenomic Variants; Polymorphism, Single Nucleotide; Selective Serotonin Reuptake Inhibitors; Signal Transduction; Workflow
PubMed: 31018568
DOI: 10.3390/ijms20081993 -
Frontiers in Endocrinology 2024Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations...
BACKGROUND
Pituitary stalk interruption syndrome (PSIS) is a complex clinical syndrome characterized by varied pituitary hormone deficiencies, leading to severe manifestations across multiple systems. These include lifelong infertility, short stature, mental retardation, and potentially life-threatening pituitary crises if not promptly diagnosed and treated. Despite extensive research, the precise pathogenesis of PSIS remains unclear. Currently, there are two proposed theories regarding the pathogenic mechanisms: the genetic defect theory and the perinatal injury theory.
METHODS
We systematically searched English databases (PubMed, Web of Science, Embase) and Chinese databases (CNKI, WanFang Med Online, Sinomed) up to February 24, 2023, to summarize studies on gene sequencing in PSIS patients. Enrichment analyses of reported mutated genes were subsequently performed using the Metascape platform.
RESULTS
Our study included 37 articles. KEGG enrichment analysis revealed mutated genes were enriched in the Notch signaling pathway, Wnt signaling pathway, and Hedgehog signaling pathway. GO enrichment analysis demonstrated mutated genes were enriched in biological processes such as embryonic development, brain development, axon development and guidance, and development of other organs.
CONCLUSION
Based on our summary and analyses, we propose a new hypothesis: disruptions in normal embryonic development, partially stemming from the genetic background and/or specific gene mutations in individuals, may increase the likelihood of abnormal fetal deliveries, where different degrees of traction during delivery may lead to different levels of pituitary stalk interruption and posterior lobe ectopia. The clinical diversity observed in PSIS patients may result from a combination of genetic background, specific mutations, and variable degrees of traction during delivery.
Topics: Humans; Hedgehog Proteins; Pituitary Diseases; Pituitary Gland; Hypopituitarism; Mutation; Syndrome
PubMed: 38464967
DOI: 10.3389/fendo.2024.1338781