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Clinical Microbiology Reviews Apr 2017Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response... (Review)
Review
Respiratory syncytial virus (RSV) is an important etiological agent of respiratory infections, particularly in children. Much information regarding the immune response to RSV comes from animal models and studies. Here, we provide a comprehensive description of the human immune response to RSV infection, based on a systematic literature review of research on infected humans. There is an initial strong neutrophil response to RSV infection in humans, which is positively correlated with disease severity and mediated by interleukin-8 (IL-8). Dendritic cells migrate to the lungs as the primary antigen-presenting cell. An initial systemic T-cell lymphopenia is followed by a pulmonary CD8 T-cell response, mediating viral clearance. Humoral immunity to reinfection is incomplete, but RSV IgG and IgA are protective. B-cell-stimulating factors derived from airway epithelium play a major role in protective antibody generation. Gamma interferon (IFN-γ) has a strongly protective role, and a Th2-biased response may be deleterious. Other cytokines (particularly IL-17A), chemokines (particularly CCL-5 and CCL-3), and local innate immune factors (including cathelicidins and IFN-λ) contribute to pathogenesis. In summary, neutrophilic inflammation is incriminated as a harmful response, whereas CD8 T cells and IFN-γ have protective roles. These may represent important therapeutic targets to modulate the immunopathogenesis of RSV infection.
Topics: Cytokines; Humans; Respiratory Syncytial Virus Infections; Respiratory Syncytial Viruses; T-Lymphocytes
PubMed: 28179378
DOI: 10.1128/CMR.00090-16 -
Frontiers in Psychiatry 2021Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce...
Clinical studies suggest the therapeutic potential of psychedelics, including ayahuasca, DMT, psilocybin, and LSD, in stress-related disorders. These substances induce cognitive, antidepressant, anxiolytic, and antiaddictive effects suggested to arise from biological changes similar to conventional antidepressants or the rapid-acting substance ketamine. The proposed route is by inducing brain neuroplasticity. This review attempts to summarize the evidence that psychedelics induce neuroplasticity by focusing on psychedelics' cellular and molecular neuroplasticity effects after single and repeated administration. When behavioral parameters are encountered in the selected studies, the biological pathways will be linked to the behavioral effects. Additionally, knowledge gaps in the underlying biology of clinical outcomes of psychedelics are highlighted. The literature searched yielded 344 results. Title and abstract screening reduced the sample to 35; eight were included from other sources, and full-text screening resulted in the final selection of 16 preclinical and four clinical studies. Studies ( = 20) show that a single administration of a psychedelic produces rapid changes in plasticity mechanisms on a molecular, neuronal, synaptic, and dendritic level. The expression of plasticity-related genes and proteins, including Brain-Derived Neurotrophic Factor (BDNF), is changed after a single administration of psychedelics, resulting in changed neuroplasticity. The latter included more dendritic complexity, which outlasted the acute effects of the psychedelic. Repeated administration of a psychedelic directly stimulated neurogenesis and increased BDNF mRNA levels up to a month after treatment. Findings from the current review demonstrate that psychedelics induce molecular and cellular adaptations related to neuroplasticity and suggest those run parallel to the clinical effects of psychedelics, potentially underlying them. Future (pre)clinical research might focus on deciphering the specific cellular mechanism activated by different psychedelics and related to long-term clinical and biological effects to increase our understanding of the therapeutic potential of these compounds.
PubMed: 34566723
DOI: 10.3389/fpsyt.2021.724606 -
Behavioral and Brain Functions : BBF May 2022Genetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior. In this systematic review... (Review)
Review
Genetic variants of DCX, COMT and FMR1 have been linked to neurodevelopmental disorders related to intellectual disability and social behavior. In this systematic review we examine the roles of the DCX, COMT and FMR1 genes in the context of hippocampal neurogenesis with respect to these disorders with the aim of identifying important hubs and signaling pathways that may bridge these conditions. Taken together our findings indicate that factors connecting DCX, COMT, and FMR1 in intellectual disability and social behavior may converge at Wnt signaling, neuron migration, and axon and dendrite morphogenesis. Data derived from genomic research has identified a multitude of genes that are linked to brain disorders and developmental differences. Information about where and how these genes function and cooperate is lagging behind. The approach used here may help to shed light on the biological underpinnings in which key genes interface and may prove useful for the testing of specific hypotheses.
Topics: Catechol O-Methyltransferase; Cognitive Dysfunction; Fragile X Mental Retardation Protein; Hippocampus; Humans; Intellectual Disability; Neurogenesis; Social Behavior
PubMed: 35590332
DOI: 10.1186/s12993-022-00191-7 -
Behavioural Brain Research Oct 2023SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe,... (Review)
Review
SARS-CoV-2 infection produces a wide range of symptoms. Some of the structural changes caused by the virus in the nervous system are found in the medial temporal lobe, and several neuropsychological sequelae of COVID-19 are related to the function of the hippocampus. The main objective of the systematic review is to update and further analyze the existing evidence of hippocampal and related cortices' structural and functional alterations due to SARS-CoV-2 infection. Both clinical and preclinical studies that used different methodologies to explore the effects of this disease at different stages and grades of severity were considered, besides exploring related cognitive and emotional symptomatology. A total of 24 studies were identified by searching in SCOPUS, Web Of Science (WOS), PubMed, and PsycInfo databases up to October 3rd, 2022. Thirteen studies were performed in clinical human samples, 9 included preclinical animal models, 3 were performed post-mortem, and 1 included both post-mortem and preclinical samples. Alterations in the hippocampus were detected in the acute stage and after several months of infection. Clinical studies revealed alterations in hippocampal connectivity and metabolism. Memory alterations correlated with altered metabolic profiles or changes in grey matter volumes. Hippocampal human postmortem and animal studies observed alterations in neurogenesis, dendrites, and immune response, besides high apoptosis and neuroinflammation. Preclinical studies reported the viral load in the hippocampus. Olfactory dysfunction was associated with alterations in brain functionality. Several clinical studies revealed cognitive complaints, neuropsychological alterations, and depressive and anxious symptomatology.
Topics: Animals; Humans; COVID-19; SARS-CoV-2; Hippocampus; Temporal Lobe
PubMed: 37703951
DOI: 10.1016/j.bbr.2023.114662 -
Cureus Mar 2023Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens... (Review)
Review
Human immunodeficiency virus (HIV) is a viral infection which progressively leads to acquired immunodeficiency syndrome (AIDS) in the absence of treatment. This happens through the destruction of crucial cells in the immune system, such as the helper T cells, dendritic cells, and macrophages. Since the first case was isolated in the 20th century, the disease has spread rapidly among humans, with significant renal, cardiovascular, respiratory, and neurological complications. It is predominantly sexually transmitted but non-sexual transmission. A relationship between HIV and renal diseases has been suggested for a long time, but only a few systematic studies have centered on this association. This systematic review aims to analyze the possible association between HIV and renal diseases as well as the range and pathogenesis of these renal diseases. HIV remains a critical infectious disease globally, inciting substantial morbidity and mortality. Studies have shown that people living with HIV (PLWH) are at increased risk of acute and chronic kidney disease. This review is based on Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. PubMed, Google Scholar, and Cochrane databases were searched exhaustively using the inclusion criteria of free full-text English papers that have exclusively studied humans in the last 20 years. Sixteen articles were selected including a systematic review, observational studies, and comprehensive narrative reviews on the role of HIV in the etiology of renal diseases, and were systemically reviewed and analyzed to elicit the wide range of possible renal complications resulting from HIV infection.
PubMed: 37123789
DOI: 10.7759/cureus.36755 -
Biomolecules Nov 2023Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular... (Review)
Review
Mitochondria are ancient endosymbiotic double membrane organelles that support a wide range of eukaryotic cell functions through energy, metabolism, and cellular control. There are over 1000 known proteins that either reside within the mitochondria or are transiently associated with it. These mitochondrial proteins represent a functional subcellular protein network (mtProteome) that is encoded by mitochondrial and nuclear genomes and significantly varies between cell types and conditions. In neurons, the high metabolic demand and differential energy requirements at the synapses are met by specific modifications to the mtProteome, resulting in alterations in the expression and functional properties of the proteins involved in energy production and quality control, including fission and fusion. The composition of mtProteomes also impacts the localization of mitochondria in axons and dendrites with a growing number of neurodegenerative diseases associated with changes in mitochondrial proteins. This review summarizes the findings on the composition and properties of mtProteomes important for mitochondrial energy production, calcium and lipid signaling, and quality control in neural cells. We highlight strategies in mass spectrometry (MS) proteomic analysis of mtProteomes from cultured cells and tissue. The research into mtProteome composition and function provides opportunities in biomarker discovery and drug development for the treatment of metabolic and neurodegenerative disease.
Topics: Humans; Proteome; Neurodegenerative Diseases; Proteomics; Mitochondria; Neurons; Mitochondrial Proteins
PubMed: 38002320
DOI: 10.3390/biom13111638 -
Infection and Drug Resistance 2022Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main... (Review)
Review
Antigen-presenting cells recognize respiratory syncytial virus antigens, and produce cytokines and chemokines that act on immune cells. Dendritic cells play the main role in inflammatory cytokine responses. Similarly, alveolar macrophages produce IFN-β, IFN-α, TNF-α, IL-6, CXCL10, and CCL3, while alternatively activated macrophages differentiate at the late phase, and require IL-13 or IL-4 cytokines. Furthermore, activated NKT cells secrete IL-13 and IL-4 that cause lung epithelial, endothelial and fibroblasts to secrete eotaxin that enhances the recruitment of eosinophil to the lung. CD8 and CD4T cells infection by the virus decreases the IFN-γ and IL-2 production. Despite this, both are involved in terminating virus replication. CD8T cells produce a larger amount of IFN-γ than CD4T cells, and CD8T cells activated under type 2 conditions produce IL-4, down regulating CD8 expression, granzyme and IFN-γ production. Antiviral inhibitors inhibit biological functions of viral proteins. Some of them directly target the virus replication machinery and are effective at later stages of infection; while others inhibit F protein dependent fusion and syncytium formation. TMC353121 reduces inflammatory cytokines, TNF-α, IL-6, and IL-1β and chemokines, KC, IP-10, MCP and MIP1-α. EDP-938 inhibits viral nucleoprotein (N), while GRP-156784 blocks the activity of respiratory syncytial virus ribonucleic acid (RNA) polymerase. PC786 inhibits non-structural protein 1 (NS-1) gene, RANTES transcripts, virus-induced CCL5, IL-6, and mucin increase. In general, it is an immune reaction that is blamed for the disease severity and pathogenesis in respiratory syncytial virus infection. Anti-viral inhibitors not only inhibit viral entry and replication, but also may reduce inflammatory cytokines and chemokines. Many respiratory syncytial virus inhibitors are proposed; however, only palivizumab and ribavirin are approved for prophylaxis and treatment, respectively. Hence, this review is focused on immunity cell responses to respiratory syncytial virus and the role of antiviral inhibitors.
PubMed: 36540102
DOI: 10.2147/IDR.S387479 -
Human Vaccines & Immunotherapeutics Dec 2024Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the... (Meta-Analysis)
Meta-Analysis
Cell-based therapeutic cancer vaccines use autologous patient-derived tumor cells, allogeneic cancer cell lines or autologous antigen presenting cells to mimic the natural immune process and stimulate an adaptive immune response against tumor antigens. The primary objective of this study is to perform a systematic literature review with an embedded meta-analysis of all published Phase 2 and 3 clinical trials of cell-based cancer vaccines in human subjects. The secondary objective of this study is to review trials demonstrating biological activity of cell-based cancer vaccines that could uncover additional hypotheses, which could be used in the design of future studies. We performed the systematic review and meta-analysis according to the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. The final review included 36 studies - 16 single-arm studies, and 20 controlled trials. Our systematic review of the existing literature revealed largely negative trials and our meta-analysis did not show evidence of clinical benefit from cell-based cancer-vaccines. However, as we looked beyond the stringent inclusion criteria of our systematic review, we identified significant examples of biological activity of cell-based cancer vaccines that are worth highlighting. In conclusion, the existing literature on cell-based cancer vaccines is highly variable in terms of cancer type, vaccine therapies and the clinical setting with no overall statistically significant clinical benefit, but there are individual successes that represent the promise of this approach. As cell-based vaccine technology continues to evolve, future studies can perhaps fulfill the potential that this exciting field of anti-cancer therapy holds.
Topics: Humans; Cancer Vaccines; Neoplasms; Antigens, Neoplasm; Adaptive Immunity
PubMed: 38544385
DOI: 10.1080/21645515.2024.2323256 -
Molecular Psychiatry Oct 2023Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents,...
Adolescence represents a critical period for brain and behavioural health and characterised by the onset of mood, psychotic and anxiety disorders. In rodents, neurogenesis is very active during adolescence, when is particularly vulnerable to stress. Whether stress-related neurogenesis changes influence adolescence onset of psychiatric symptoms remains largely unknown. A systematic review was conducted on studies investigating changes in hippocampal neurogenesis and neuroplasticity, hippocampal-dependent cognitive functions, and behaviour, occurring after adolescence stress exposure in mice both acutely (at post-natal days 21-65) and in adulthood. A total of 37 studies were identified in the literature. Seven studies showed reduced hippocampal cell proliferation, and out of those two reported increased depressive-like behaviours, in adolescent rodents exposed to stress. Three studies reported a reduction in the number of new-born neurons, which however were not associated with changes in cognition or behaviour. Sixteen studies showed acutely reduced hippocampal neuroplasticity, including pre- and post-synaptic plasticity markers, dendritic spine length and density, and long-term potentiation after stress exposure. Cognitive impairments and depressive-like behaviours were reported by 11 of the 16 studies. Among studies who looked at adolescence stress exposure effects into adulthood, seven showed that the negative effects of stress observed during adolescence on either cell proliferation or hippocampal neuroplasticity, cognitive deficits and depressive-like behaviour, had variable impact in adulthood. Treating adolescent mice with antidepressants, glutamate receptor inhibitors, glucocorticoid antagonists, or healthy diet enriched in omega-3 fatty acids and vitamin A, prevented or reversed those detrimental changes. Future research should investigate the translational value of these preclinical findings. Developing novel tools for measuring hippocampal neurogenesis in live humans, would allow assessing neurogenic changes following stress exposure, investigating relationships with psychiatric symptom onset, and identifying effects of therapeutic interventions.
Topics: Animals; Mice; Brain; Cognition; Hippocampus; Neurogenesis; Rodentia; Stress, Psychological
PubMed: 37612364
DOI: 10.1038/s41380-023-02229-2 -
Frontiers in Immunology 2023Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of... (Meta-Analysis)
Meta-Analysis
BACKGROUND
Malignant glioma is the most common intracranial malignant tumor with the highest mortality. In the era of immunotherapy, it is important to determine what type of immunotherapy provides the best chance of survival.
METHOD
Here, the efficacy and safety of immunotherapy in high-grade glioma (HGG) were evaluated by systematic review and meta-analysis. The differences between various types of immunotherapy were explored. Retrieved hits were screened for inclusion in 2,317 articles. We extracted the overall survival (OS) and progression-free survival (PFS) hazard ratios (HRs) as two key outcomes for examining the efficacy of immunotherapy. We also analyzed data on the reported corresponding adverse events to assess the safety of immunotherapy. This study was registered with PROSPERO (CRD42019112356).
RESULTS
We included a total of 1,271 patients, of which 524 received a combination of immunotherapy and standard of care (SOC), while 747 received SOC alone. We found that immunotherapy extended the OS (HR = 0.74; 95% confidence interval [CI], 0.56-0.99; = -2.00, = 0.0458 < 0.05) and PFS (HR = 0.67; 95% CI, 0.45-0.99; = -1.99, = 0.0466 < 0.05), although certain adverse events occurred (proportion = 0.0773, 95% CI, 0.0589-0.1014). Our data have demonstrated the efficacy of the dendritic cell (DC) vaccine in prolonging the OS (HR = 0.38; 95% CI, 0.21-0.68; Z = -3.23; = 0.0012 < 0.05) of glioma patients. Oncolytic viral therapy (VT) only extended patient survival in a subgroup analysis (HR = 0.60; 95% CI, 0.45-0.80; = -3.53; = 0.0004 < 0.05). By contrast, immunopotentiation (IP) did not prolong OS (HR = 0.69; 95% CI, 0.50-0.96; = -2.23; = 0.0256).
CONCLUSION
Thus, DC vaccination significantly prolonged the OS of HGG patients, however, the efficacy of VT and IP should be explored in further studies. All the therapeutic schemes evaluated were associated with certain side effects.
SYSTEMATIC REVIEW REGISTRATION
https://www.crd.york.ac.uk/PROSPERO/display_record.php?RecordID=112356.
Topics: Humans; Standard of Care; Glioma; Brain Neoplasms; Progression-Free Survival; Immunotherapy
PubMed: 37483593
DOI: 10.3389/fimmu.2023.966696