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Viruses Mar 2024The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene... (Review)
Review
The post-transcriptional regulatory element (PRE) is present in all HBV mRNAs and plays a major role in their stability, nuclear export, and enhancement of viral gene expression. Understanding PRE's structure, function, and mode of action is essential to leverage its potential as a therapeutic target. A wide range of PRE-based reagents and tools have been developed and assessed in preclinical and clinical settings for therapeutic and biotechnology applications. This manuscript aims to provide a systematic review of the characteristics and mechanism of action of PRE, as well as elucidating its current applications in basic and clinical research. Finally, we discuss the promising opportunities that PRE may provide to antiviral development, viral biology, and potentially beyond.
Topics: Animals; Humans; Antiviral Agents; Gene Expression Regulation, Viral; Hepatitis B; Hepatitis B virus; RNA Processing, Post-Transcriptional; RNA, Messenger; RNA, Viral
PubMed: 38675871
DOI: 10.3390/v16040528 -
Frontiers in Cardiovascular Medicine 2024Neural crest cells (NCCs) are multipotent and are attributed to the combination of complex multimodal gene regulatory mechanisms. Cardiac neural crest (CNC) cells,...
INTRODUCTION
Neural crest cells (NCCs) are multipotent and are attributed to the combination of complex multimodal gene regulatory mechanisms. Cardiac neural crest (CNC) cells, originating from the dorsal neural tube, are pivotal architects of the cardio-neuro-vascular domain, which orchestrates the embryogenesis of critical cardiac and vascular structures. Remarkably, while the scientific community compiled a comprehensive inventory of neural crest derivatives by the early 1980s, our understanding of the CNC's role in various cardiovascular disease processes still needs to be explored. This review delves into the differentiation of NCC, specifically the CNC cells, and explores the diverse facets of non-syndromic cardiovascular neurocristopathies.
METHODS
A systematic review was conducted as per the PRISMA Statement. Three prominent databases, PubMed, Scopus, and Embase, were searched, which yielded 1,840 studies. We excluded 1,796 studies, and the final selection of 44 studies formed the basis of this comprehensive review.
RESULTS
Neurocristopathies are a group of genetic disorders that affect the development of cells derived from the NC. Cardiovascular neurocristopathy, i.e., cardiopathy and vasculopathy, associated with the NCC could occur in the form of (1) cardiac septation disorders, mainly the aortico-pulmonary septum; (2) great vessels and vascular disorders; (3) myocardial dysfunction; and (4) a combination of all three phenotypes. This could result from abnormalities in NCC migration, differentiation, or proliferation leading to structural abnormalities and are attributed to genetic, familial, sporadic or acquired causes.
DISCUSSION
Phenotypic characteristics of cardiovascular neurocristopathies, such as bicuspid aortic valve and thoracic aortic aneurysm, share a common embryonic origin and are surprisingly prevalent in the general population, necessitating further research to identify the underlying pathogenic and genetic factors responsible for these cardiac anomalies. Such discoveries are essential for enhancing diagnostic screening and refining therapeutic interventions, ultimately improving the lives of individuals affected by these conditions.
PubMed: 38660479
DOI: 10.3389/fcvm.2024.1333265 -
Frontiers in Neurology 2024Artificial intelligence (AI) technology has made breakthroughs in spinal cord neural injury and restoration in recent years. It has a positive impact on clinical...
BACKGROUND
Artificial intelligence (AI) technology has made breakthroughs in spinal cord neural injury and restoration in recent years. It has a positive impact on clinical treatment. This study explores AI research's progress and hotspots in spinal cord neural injury and restoration. It also analyzes research shortcomings related to this area and proposes potential solutions.
METHODS
We used CiteSpace 6.1.R6 and VOSviewer 1.6.19 to research WOS articles on AI research in spinal cord neural injury and restoration.
RESULTS
A total of 1,502 articles were screened, in which the United States dominated; Kadone, Hideki (13 articles, University of Tsukuba, JAPAN) was the author with the highest number of publications; ARCH PHYS MED REHAB (IF = 4.3) was the most cited journal, and topics included molecular biology, immunology, neurology, sports, among other related areas.
CONCLUSION
We pinpointed three research hotspots for AI research in spinal cord neural injury and restoration: (1) intelligent robots and limb exoskeletons to assist rehabilitation training; (2) brain-computer interfaces; and (3) neuromodulation and noninvasive electrical stimulation. In addition, many new hotspots were discussed: (1) starting with image segmentation models based on convolutional neural networks; (2) the use of AI to fabricate polymeric biomaterials to provide the microenvironment required for neural stem cell-derived neural network tissues; (3) AI survival prediction tools, and transcription factor regulatory networks in the field of genetics were discussed. Although AI research in spinal cord neural injury and restoration has many benefits, the technology has several limitations (data and ethical issues). The data-gathering problem should be addressed in future research, which requires a significant sample of quality clinical data to build valid AI models. At the same time, research on genomics and other mechanisms in this field is fragile. In the future, machine learning techniques, such as AI survival prediction tools and transcription factor regulatory networks, can be utilized for studies related to the up-regulation of regeneration-related genes and the production of structural proteins for axonal growth.
PubMed: 38628700
DOI: 10.3389/fneur.2024.1361235 -
Dementia & Neuropsychologia 2024The immediate early gene exhibits activation markers in the nervous system consisting of ARC, EGR-1, and c-Fos and is related to synaptic plasticity, especially in the... (Review)
Review
UNLABELLED
The immediate early gene exhibits activation markers in the nervous system consisting of ARC, EGR-1, and c-Fos and is related to synaptic plasticity, especially in the hippocampus. Immediate early gene expression is affected by physical exercise, which induces direct ARC, EGR-1, and c-Fos expression.
OBJECTIVE
To assess the impact of exercise, we conducted a literature study to determine the expression levels of immediate early genes (ARC, c-Fos, and EGR-1).
METHODS
The databases accessed for online literature included PubMed-Medline, Scopus, and ScienceDirect. The original English articles were selected using the following keywords in the title: (Exercise OR physical activity) AND (c-Fos) AND (Hippocampus), (Exercise OR physical activity) AND (ARC) AND (Hippocampus), (Exercise OR physical activity) AND (EGR-1 OR zif268) AND (Hippocampus).
RESULTS
Physical exercise can affect the expression of EGR-1, c-Fos, and ARC in the hippocampus, an important part of the brain involved in learning and memory. High-intensity physical exercise can increase c-Fos expression, indicating neural activation. Furthermore, the expression of the ARC gene also increases due to physical exercise. ARC is a gene that plays a role in synaptic plasticity and regulation of learning and memory, changes in synaptic structure and increased synaptic connections, while EGR-1 also plays a role in synaptic plasticity, a genetic change that affects learning and memory. Overall, exercise or regular physical exercise can increase the expression of ARC, c-Fos, and EGR-1 in the hippocampus. This reflects the changes in neuroplasticity and synaptic plasticity that occur in response to physical activity. These changes can improve cognitive function, learning, and memory.
CONCLUSION
c-Fos, EGR-1, and ARC expression increases in hippocampal neurons after exercise, enhancing synaptic plasticity and neurogenesis associated with learning and memory.
PubMed: 38628561
DOI: 10.1590/1980-5764-DN-2023-0015 -
Neurosurgical Review Apr 2024Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after... (Review)
Review
Recent studies suggest that differential DNA methylation could play a role in the mechanism of cerebral vasospasm (CVS) and delayed cerebral ischemia (DCI) after aneurysmal subarachnoid hemorrhage (aSAH). Considering the significance of this matter and a lack of effective prophylaxis against DCI, we aim to summarize the current state of knowledge regarding their associations with DNA methylation and identify the gaps for a future trial. PubMed MEDLINE, Scopus, and Web of Science were searched by two authors in three waves for relevant DNA methylation association studies in DCI after aSAH. PRISMA checklist was followed for a systematic structure. STROBE statement was used to assess the quality and risk of bias within studies. This research was funded by the National Science Centre, Poland (grant number 2021/41/N/NZ2/00844). Of 70 records, 7 peer-reviewed articles met the eligibility criteria. Five studies used a candidate gene approach, three were epigenome-wide association studies (EWAS), one utilized bioinformatics of the previous EWAS, with two studies using more than one approach. Methylation status of four cytosine-guanine dinucleotides (CpGs) related to four distinct genes (ITPR3, HAMP, INSR, CDHR5) have been found significantly or suggestively associated with DCI after aSAH. Analysis of epigenetic clocks yielded significant association of lower age acceleration with radiological CVS but not with DCI. Hub genes for hypermethylation (VHL, KIF3A, KIFAP3, RACGAP1, OPRM1) and hypomethylation (ALB, IL5) in DCI have been indicated through bioinformatics analysis. As none of the CpGs overlapped across the studies, meta-analysis was not applicable. The identified methylation sites might potentially serve as a biomarker for early diagnosis of DCI after aSAH in future. However, a lack of overlapping results prompts the need for large-scale multicenter studies. Challenges and prospects are discussed.
Topics: Humans; Subarachnoid Hemorrhage; DNA Methylation; Cerebral Infarction; Brain Ischemia; Biomarkers; Vasospasm, Intracranial; Cadherin Related Proteins
PubMed: 38594575
DOI: 10.1007/s10143-024-02381-5 -
Translational Psychiatry Mar 2024There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and...
There is widespread overlap across major psychiatric disorders, and this is the case at different levels of observations, from genetic variants to brain structures and function and to symptoms. However, it remains unknown to what extent these commonalities at different levels of observation map onto each other. Here, we systematically review and compare the degree of similarity between psychiatric disorders at all available levels of observation. We searched PubMed and EMBASE between January 1, 2009 and September 8, 2022. We included original studies comparing at least four of the following five diagnostic groups: Schizophrenia, Bipolar Disorder, Major Depressive Disorder, Autism Spectrum Disorder, and Attention Deficit Hyperactivity Disorder, with measures of similarities between all disorder pairs. Data extraction and synthesis were performed by two independent researchers, following the PRISMA guidelines. As main outcome measure, we assessed the Pearson correlation measuring the degree of similarity across disorders pairs between studies and biological levels of observation. We identified 2975 studies, of which 28 were eligible for analysis, featuring similarity measures based on single-nucleotide polymorphisms, gene-based analyses, gene expression, structural and functional connectivity neuroimaging measures. The majority of correlations (88.6%) across disorders between studies, within and between levels of observation, were positive. To identify a consensus ranking of similarities between disorders, we performed a principal component analysis. Its first dimension explained 51.4% (95% CI: 43.2, 65.4) of the variance in disorder similarities across studies and levels of observation. Based on levels of genetic correlation, we estimated the probability of another psychiatric diagnosis in first-degree relatives and showed that they were systematically lower than those observed in population studies. Our findings highlight that genetic and brain factors may underlie a large proportion, but not all of the diagnostic overlaps observed in the clinic.
Topics: Humans; Depressive Disorder, Major; Autism Spectrum Disorder; Mental Disorders; Bipolar Disorder; Schizophrenia; Attention Deficit Disorder with Hyperactivity
PubMed: 38555309
DOI: 10.1038/s41398-024-02866-3 -
Journal of Cancer Research and Clinical... Mar 2024The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain. (Meta-Analysis)
Meta-Analysis
Analyzing the associations between tertiary lymphoid structures and postoperative prognosis, along with immunotherapy response in gastric cancer: findings from pooled cohort studies.
BACKGROUND
The clinical significance of tertiary lymphoid structure (TLS) in gastric cancer (GC) was uncertain.
METHODS
A systematic search was performed in public databases for eligible studies as of April 2, 2023. Meta-analyses were performed to interrogate the associations between TLS levels and prognosis and immunotherapy response of GC. Bioinformatic analyses based on the nine-gene signature of TLS were further conducted to capture the biological underpinnings.
RESULTS
Eleven studies containing 4224 GC cases were enrolled in the meta-analysis. TLS levels positively correlated with smaller tumor size, earlier T stage and N stage. Moreover, higher TLS levels were detected in diffuse and mix subtypes of GC (P < 0.001). Higher TLS levels strongly predicted favorable postoperative overall survival of GC, with HR of 0.36 (95%CI 0.26-0.50, P < 0.001) and 0.55 (95%CI 0.45-0.68, P < 0.001) of univariate and multivariate Cox analysis, respectively. Higher TLS levels were also in favor of the treatment response of anti-PD-1 inhibitors as later-line therapy of GC. TLS levels positively correlated with immune effector cells infiltration, diversity and richness of T cell receptor and B cell receptor repertoire, immune checkpoint genes expression, and immune-related genes mutation of GC in the TCGA-STAD cohort, representing higher immunogenicity and immunoactivity. Moreover, moderate accuracy of TLS levels in predicting benefit from anti-PD-1 inhibitors in the PRJEB25780 cohort was also validated (AUC 0.758, 95%CI 0.583-0.933), higher than the microsatellite instability-score and Epstein-Barr virus status.
CONCLUSIONS
TLS levels demonstrated potential in predicting the postoperative prognosis and immunotherapy response of GC.
Topics: Humans; Cohort Studies; Epstein-Barr Virus Infections; Herpesvirus 4, Human; Immune Checkpoint Inhibitors; Immunotherapy; Prognosis; Stomach Neoplasms; Tertiary Lymphoid Structures; Tumor Microenvironment
PubMed: 38519621
DOI: 10.1007/s00432-024-05672-y -
Frontiers in Pharmacology 2024To highlight the knowledge structure and evolutionary trends in research on autophagy in lung cancer. Research publications on autophagy in lung cancer were retrieved...
To highlight the knowledge structure and evolutionary trends in research on autophagy in lung cancer. Research publications on autophagy in lung cancer were retrieved from the Web of Science Core Collection database. VOSviewer and CiteSpace data analysis software were used for the bibliometric and visualization analysis of countries, institutions, authors, journals, and keywords related to this field. From 2013 to 2022, research on autophagy in lung cancer developed rapidly, showing rising trends in annual publications and citations. China (1,986 papers; 48,913 citations), Shandong University (77 publications; 1,460 citations), and Wei Zhang (20 publications; 342 citations) were the most productive and influential country, institution, and author, respectively. The journal with the most publications and citations on autophagy in lung cancer was the International Journal of Molecular Sciences (93 publications; 3,948 citations). An analysis of keyword co-occurrence showed that related research topics were divided into five clusters: 1) Mechanisms influencing autophagy in lung cancer and the role of autophagy in lung cancer; 2) Effect of autophagy on the biological behavior of lung cancer; 3) Regulatory mechanisms of 2 cell death processes: autophagy and apoptosis in lung cancer cells; 4) Role of autophagy in lung cancer treatment and drug resistance; and 5) Role of autophagy-related genes in the occurrence and development of lung cancer. Cell proliferation, migration, epithelial-mesenchymal transition, and tumor microenvironment were the latest high-frequency keywords that represented promising future research directions. This is the first comprehensive study describing the knowledge structure and emerging frontiers of research on autophagy in lung cancer from 2013 to 2022 by means of a bibliometric analysis. The study points to promising future research directions focusing on in-depth autophagy mechanisms, clinical applications, and potential therapeutic strategies, providing a valuable reference for researchers in the field. : [https://systematicreview.gov/], identifier [registration number].
PubMed: 38476332
DOI: 10.3389/fphar.2024.1352422 -
International Journal of Molecular... Feb 2024Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular... (Review)
Review
Arrhythmogenic right ventricular cardiomyopathy (ARVC) is a genetic disorder characterized by the progressive fibro-fatty replacement of the right ventricular myocardium, leading to myocardial atrophy. Although the structural changes usually affect the right ventricle, the pathology may also manifest with either isolated left ventricular myocardium or biventricular involvement. As ARVC shows an autosomal dominant pattern of inheritance with variable penetrance, the clinical presentation of the disease is highly heterogeneous, with different degrees of severity and patterns of myocardial involvement even in patients of the same familiar group with the same gene mutation: the pathology spectrum ranges from the absence of symptoms to sudden cardiac death (SCD) sustained by ventricular arrhythmias, which may, in some cases, be the first manifestation of an otherwise silent pathology. An evidence-based systematic review of the literature was conducted to evaluate the state of the art of the diagnostic techniques for the correct post-mortem identification of ARVC. The research was performed using the electronic databases PubMed and Scopus. A methodological approach to reach a correct post-mortem diagnosis of ARVC was described, analyzing the main post-mortem peculiar macroscopic, microscopic and radiological alterations. In addition, the importance of performing post-mortem genetic tests has been underlined, which may lead to the correct identification and characterization of the disease, especially in those ARVC forms where anatomopathological investigation does not show evident morphostructural damage. Furthermore, the usefulness of genetic testing is not exclusively limited to the correct diagnosis of the pathology, but is essential for promoting targeted screening programs to the deceased's family members. Nowadays, the post-mortem diagnosis of ARVC performed by forensic pathologist remains very challenging: therefore, the identification of a clear methodological approach may lead to both a reduction in under-diagnoses and to the improvement of knowledge on the disease.
Topics: Humans; Arrhythmogenic Right Ventricular Dysplasia; Autopsy; Myocardium; Databases, Factual; Death, Sudden, Cardiac
PubMed: 38473714
DOI: 10.3390/ijms25052467 -
Parasites & Vectors Mar 2024The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon... (Review)
Review
BACKGROUND
The study of parasites provides insight into intricate ecological relationships in ecosystem dynamics, food web structures, and evolution on multiple scales. Hepatozoon Eucoccidiorida: Hepatozoidae) is a genus of protozoan hemoparasites with heteroxenous life cycles that switch infections between vertebrates and blood-feeding invertebrates. The most comprehensive review of the genus was published 26 years ago, and currently there are no harmonized data on the epizootiology, diagnostics, genotyping methods, evolutionary relationships, and genetic diversity of Hepatozoon in the Americas.
METHODS
Here, we provide a comprehensive review based on the PRISMA method regarding Hepatozoon in wild mammals within the American continent, in order to generate a framework for future research.
RESULTS
11 out of the 35 countries of the Americas (31.4%) had data on Hepatozoon, with Carnivora and Rodentia orders having the most characterizations. Bats, ungulates, and shrews were the least affected groups. While Hepatozoon americanum, H. americanum-like, H. canis, H. didelphydis, H. felis, H. milleri, H. griseisciuri, and H. procyonis correspond to the identified species, a plethora of genospecies is pending for a formal description combining morphology and genetics. Most of the vectors of Hepatozoon in the Americas are unknown, but some flea, mite, and tick species have been confirmed. The detection of Hepatozoon has relied mostly on conventional polymerase chain reaction (PCR), and the implementation of specific real time PCR for the genus needs to be employed to improve its diagnosis in wild animals in the future. From a genetic perspective, the V4 region of the 18S rRNA gene has been widely sequenced for the identification of Hepatozoon in wild animals. However, mitochondrial and apicoplast markers should also be targeted to truly determine different species in the genus. A phylogenetic analysis of herein retrieved 18S ribosomal DNA (rDNA) sequences showed two main clades of Hepatozoon: Clade I associated with small mammals, birds, and herpetozoa, and Clade II associated with Carnivora. The topology of the tree is also reflected in the haplotype network.
CONCLUSIONS
Finally, our review emphasizes Hepatozoon as a potential disease agent in threatened wild mammals and the role of wild canids as spreaders of Hepatozoon infections in the Americas.
Topics: Animals; Cats; Ecosystem; Phylogeny; Chiroptera; Eucoccidiida; Shrews; Animals, Wild; Canidae
PubMed: 38444020
DOI: 10.1186/s13071-024-06154-3