-
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 -
Joint Bone Spine Mar 2023Despite available therapies, persistently active and corticosteroid-dependent Systemic Lupus Erythematosus (SLE) represent a significant therapeutic challenge. The...
INTRODUCTION
Despite available therapies, persistently active and corticosteroid-dependent Systemic Lupus Erythematosus (SLE) represent a significant therapeutic challenge. The purpose of this systematic review was to provide an updated view of targeted therapies currently in clinical development in SLE, with a special focus on the most promising ones.
METHODS
We performed a systematic review of targeted therapies in clinical development in SLE in clinicaltrials.gov (search date: 28th of August 2022). Targeted therapies (defined as drugs specifically designed to block certain molecules, receptors, or pathways involved in the development of SLE) were extracted. For each investigational drug, we considered only the study at the most advanced stage of clinical development.
RESULTS
The systematic review yielded a total of 92 targeted therapies (58 biological DMARDs [bDMARDs] and 34 targeted synthetic [ts]DMARDs) assessed in a total of 203 clinical trials. The candidate drugs reached phase I (n=20), Ia/IIb (n=6), phase II (n=51), phase II/III (n=1), phase III (n=13) and phase IV (n=1). These trials were reported as recruiting (n=31), active but not recruiting (n=8), not yet recruiting (n=4), enrolling by invitation (n=2), completed (n=31), prematurely terminated (n=12) and withdrawn in 1 (status unknown in 3). The main investigational drugs for SLE target inflammatory cytokines, chemokines or their receptors (n=19), intracellular signaling pathways (n=18), B cells (n=14) or plasma cells (n=7),T/B cells co-stimulation molecules (n=10), complement molecules (n=5),T lymphocytes (n=2), plasmacytoid dendritic cells (n=2), as well as various other immune targets (n=15).
CONCLUSION
The pipeline of investigational drugs in SLE is highly diversified and will hopefully enable more optimal Treat-To-Target with the goal of disease modification. Companion biomarkers will be needed to better characterized SLE heterogeneity and optimize treatment selection at the individual-patient level.
Topics: Humans; Antibodies, Monoclonal; Drugs, Investigational; Lupus Erythematosus, Systemic; Antirheumatic Agents; Biological Products
PubMed: 36623799
DOI: 10.1016/j.jbspin.2023.105523 -
International Journal of Radiation... 2023Radiotherapy (RT) and immunotherapy are powerful anti-tumor treatment modalities. Experimental research has demonstrated an important interplay between the cytotoxic...
PURPOSE
Radiotherapy (RT) and immunotherapy are powerful anti-tumor treatment modalities. Experimental research has demonstrated an important interplay between the cytotoxic effects of RT and the immune system. This systematic review provides an overview of the basics of anti-tumor immunity and focuses on the mechanisms underlying the interplay between RT and immune anti-tumor response that set the molecular basis of immuno-RT.
CONCLUSIONS
An 'immunity acquired equilibrium' mimicking tumor dormancy can be achieved post-irradiation treatment, with the balance shifted toward tumor eradication or regrowth when immune cells' cytotoxic effects or cancer proliferation rate prevail, respectively. RT has both immunosuppressive and immune-enhancing properties. The latter effect is also known as radio-vaccination. Its mechanisms involve up- or down-regulation of membrane molecules, such as PD-L1, HLA-class-I, CD80/86, CD47, and Fas/CD95, that play a vital role in immune checkpoint pathways and increased cytokine expression (e.g. INFα,β,γ, IL1,2, and TNFα) by cancer or immune cells. Moreover, the interactions of radiation with the tumor microenvironment (fibroblasts, tumor-infiltrating lymphocytes, monocytes, and dendritic cells are also an important component of radio-vaccination. Thus, RT may have anti-tumor vaccine properties, whose sequels can be exploited by immunotherapy agents to treat different cancer subtypes effectively.
Topics: Humans; Neoplasms; Immunotherapy; Antineoplastic Agents; Lymphocytes, Tumor-Infiltrating; Cytokines; Tumor Microenvironment
PubMed: 36383201
DOI: 10.1080/09553002.2023.2144960 -
Journal of Biomedical Nanotechnology Mar 2016In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking... (Review)
Review
In preceding decades, different mechanisms have been proposed to "instruct" dendritic cells (DCs) to induce immune responses against tumor antigens (TAs), thus breaking immune tolerance. Immunotherapy has been, for the last two decades, an attractive and promising therapeutic approach to fight cancer. This review will approach the nature of the immune response during cancer development and its correlation with DC function, as well as cancer vaccine principles and limitations. An overview of several delivery strategies used for in vivo modulation of DCs and direct activation of T cells will be provided, highlighting their advantages, limitations, and optimization strategies. This manuscript also presents a critical and systematic review of recent clinical trials that are investigating the therapeutic effect of these approaches, discussing prognostic outcomes of combined-treatment modalities.
Topics: Animals; Dendritic Cells; Humans; Immunotherapy; Molecular Targeted Therapy; Nanoparticles; Neoplasms; Treatment Outcome
PubMed: 27280242
DOI: 10.1166/jbn.2016.2157 -
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 -
Critical Reviews in Toxicology Aug 2021Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in...
Endocrine-disrupting chemicals (EDCs) refer to a group of chemicals that cause adverse effects in human health, impairing hormone production and regulation, resulting in alteration of homeostasis, reproductive, and developmental, and immune system impairments. The immunotoxicity of EDCs involves many mechanisms altering gene expression that depend on the activation of nuclear receptors such as the aryl hydrocarbon receptor (AHR), the estrogen receptor (ER), and the peroxisome proliferator-activated receptor (PPAR), which also results in skin and intestinal disorders, microbiota alterations and inflammatory diseases. This systematic review aims to review different mechanisms of immunotoxicity and immunomodulation of T cells, focusing on T regulatory (Treg) and Th17 subsets, B cells, and dendritic cells (DCs) caused by specific EDCs such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD), bisphenols (BPs) and polyfluoroalkyl substances (PFASs). To achieve this objective, a systematic study was conducted searching various databases including PubMed and Scopus to find , , and biomonitoring studies that examine EDC-dependent mechanisms of immunotoxicity. While doing the systematic review, we found species- and cell-specific outcomes and a translational gap between and experiments. Finally, an adverse outcome pathway (AOP) framework is proposed, which explains mechanistically toxicity endpoints emerging from different EDCs having similar key events and can help to improve our understanding of EDCs mechanisms of immunotoxicity. In conclusion, this review provides insights into the mechanisms of immunotoxicity mediated by EDCs and will help to improve human health risk assessment.
Topics: Endocrine Disruptors; Humans; Immune System; Polychlorinated Dibenzodioxins; Receptors, Estrogen
PubMed: 35015608
DOI: 10.1080/10408444.2021.2009438 -
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 -
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