Project description:Yellow fever (YF) was one of the most dangerous infectious diseases of the 18th and 19th centuries, resulting in mass casualties in Africa and the Americas. The etiologic agent is yellow fever virus (YFV), and its live-attenuated form, YFV-17D, remains one of the most potent vaccines ever developed. During the first half of the 20th century, vaccination combined with mosquito control eradicated YFV transmission in urban areas. However, the recent 2016-2018 outbreaks in areas with historically low or no YFV activity have raised serious concerns for an estimated 400-500 million unvaccinated people who now live in at-risk areas. Once a forgotten disease, we highlight here that YF still represents a very real threat to human health and economies. As many gaps remain in our understanding of how YFV interacts with the human host and causes disease, there is an urgent need to address these knowledge gaps and propel YFV research forward.
Project description:Mesenchymal stem cells (MSCs) are self-renewable, multipotent stem cells that regulate the phenotype and function of all immune cells that participate in anti-tumor immunity. MSCs modulate the antigen-presenting properties of dendritic cells, affect chemokine and cytokine production in macrophages and CD4+ T helper cells, alter the cytotoxicity of CD8+ T lymphocytes and natural killer cells and regulate the generation and expansion of myeloid-derived suppressor cells and T regulatory cells. As plastic cells, MSCs adopt their phenotype and function according to the cytokine profile of neighboring tumor-infiltrated immune cells. Depending on the tumor microenvironment to which they are exposed, MSCs may obtain pro- and anti-tumorigenic phenotypes and may enhance or suppress tumor growth. Due to their tumor-homing properties, MSCs and their exosomes may be used as vehicles for delivering anti-tumorigenic agents in tumor cells, attenuating their viability and invasive characteristics. Since many factors affect the phenotype and function of MSCs in the tumor microenvironment, a better understanding of signaling pathways that regulate the cross-talk between MSCs, immune cells and tumor cells will pave the way for the clinical use of MSCs in cancer immunotherapy. In this review article, we summarize current knowledge on the molecular and cellular mechanisms that are responsible for the MSC-dependent modulation of the anti-tumor immune response and we discuss different insights regarding therapeutic potential of MSCs in the therapy of malignant diseases.
Project description:Parkinson's disease (PD) is a neurodegenerative disease affecting 7-10 million people worldwide. Currently, there is no treatment available to prevent or delay PD progression, partially due to the limited understanding of the pathological events which lead to the death of dopaminergic neurons in the substantia nigra in the brain, which is known to be the cause of PD symptoms. The current available treatments aim at compensating dopamine (DA) deficiency in the brain using its precursor levodopa, dopaminergic agonists and some indirect dopaminergic agents. The immune system is emerging as a critical player in PD. Therefore, immune-based approaches have recently been proposed to be used as potential antiparkinsonian agents. It has been well-known that dopaminergic pathways play a significant role in regulating immune responses in the brain. Although dopaminergic agents are the primary antiparkinsonian treatments, their immune regulatory effect has yet to be fully understood. The present review summarises the current available evidence of the immune regulatory effects of DA and its mimics and discusses dopaminergic agents as antiparkinsonian drugs. Based on the current understanding of their involvement in the regulation of neuroinflammation in PD, we propose that targeting immune pathways involved in PD pathology could offer a better treatment outcome for PD patients.
Project description:This data series contains spotted oligo microarray data from 10 different experiments using Agilent Rat v2 microarrays. This data is being made public in support of Fillon S et al. Journal of Immunology, (2006). Proinflammatory bacterial components are at least partially responsible for causing the clinical features of sepsis, a syndrome that causes >100,000 deaths each year in the US (1). In the case of Gram positive infection, a key bacterial element recognized by the innate immune system is the cell wall, a complex network of peptidoglycan covalently linked to teichoic acids, proteins and lipoproteins. The current model of innate immune recognition of Gram positive bacteria suggests bacterial cell wall interacts with host recognition proteins, such as toll-like receptors (TLR) and Nod proteins. We describe an additional recognition system mediated by the platelet activating factor receptor (PAFr) and directed to the pathogen associated molecular pattern (PAMP) phosphorylcholine that results in uptake of bacterial components into host cells. Intravascular choline-containing cell walls bound to endothelial cells and caused rapid lethality in wild type, Tlr2-/- and Nod2-/- mice, but not in Pafr-/- mice. Cell wall exited the vasculature into the heart and brain, accumulating within endothelial cells, cardiomyocytes and neurons in a PAFr-dependent way. Physiological consequences of the cell wall/PAFr interaction were cell specific, being noninflammatory in endothelial cells and neurons, but causing rapid loss of cardiomyocyte contractility that contributed to death. Thus, PAFr shepherds phosphorylcholine-containing bacterial components such as cell wall into host cells from where the response ranges from quiescence to severe pathophysiology. Keywords: Competitive hybridizations The ten experiments in this series comprise of four distinct experiments, two of which were performed as biological triplicates and two as biological duplicates. The table below describes the overall design in detail: File Name Experiment 16011868017643v41_GEO_format.txt RBCEC Replicate 1 16011868017644v41_GEO_format.txt RBCEC Replicate 2 251186821865v41_GEO_format.txt Neuron Replicate 1 16011868021377v41_GEO_format.txt Neuron Replicate 2 251186821690v41_GEO_format.txt CW/Lyt44 Replicate 1 251186821691v41_GEO_format.txt CW/Lyt44 Replicate 2 251186821692v41_GEO_format.txt CW/Lyt44 Replicate 1 251186821693v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 1 251186821694v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 2 251186829677v41_GEO_format.txt CW+TNF/Lyt44+TNF Replicate 3
Project description:Cancer immunotherapies have changed the landscape of cancer management and improved the standard treatment protocols used in multiple tumors. This has led to significant improvements in progression-free survival and overall survival rates. In this review article, we provide an insight into the major immunotherapeutic methods that are currently under investigation for colorectal cancer (CRC) and their clinical implementations. We emphasize therapies that are based on monoclonal antibodies (mAbs) and adoptive cell therapy, their mechanisms of action, their advantages, and their potential in combination therapy. We also highlight the clinical trials that have demonstrated both the therapeutic efficacy and the toxicities associated with each method. In addition, we summarize emerging targets that are now being evaluated as potential interventions for CRC. Finally, we discuss current challenges and future direction for the cancer immunotherapy field.
Project description:Background and aimQingfei Jiedu Granules (QFJD) are a new Traditional Chinese Medicine (TCM) which has been clinically used against coronavirus pneumonia in China. In this study, the therapeutic effect and the underlying mechanisms of QFJD against influenza were investigated.Experimental procedurePneumonia mice were induced by influenza A virus. Survival rate, weight loss, lung index and lung pathology were measured to evaluate the therapeutic effect of QFJD. The expression of inflammatory factors and lymphocytes was used to assess anti-inflammatory and immunomodulatory effect of QFJD. Gut microbiome analysis was performed to decipher the potential effect of QFJD on intestinal microbiota. Metabolomics approach was conducted to explore the overall metabolic regulation of QFJD.Result and conclusionQFJD shows a significant therapeutic effect on the treatment of influenza and the expression of many pro-inflammatory cytokines were obviously inhibited. QFJD also markedly modulates the level of T and B lymphocytes. The high-dose QFJD has shown similar therapeutic efficiency compared to positive drugs. QFJD profoundly enriched Verrucomicrobia and maintained the balance between Bacteroides and Firmicutes. QFJD associated with 12 signaling pathways in metabolomics study, 9 of which were the same as the model group and were closely related to citrate cycle and amino acid metabolism.To sum up, QFJD is a novel and promising drug against influenza. It can regulate inflammation, immunity, metabolism, and gut microbiota to fight influenza. Verrucomicrobia shows great potential to improve influenza infection and may be an important target.
Project description:Purpose of reviewTuberculous meningitis is the most devastating manifestation of infection with Mycobacterium tuberculosis and represents a medical emergency. Approximately one half of tuberculous meningitis patients die or suffer severe neurologic disability. The goal of this review will be to review the pathogenic, clinical, and radiologic features of tuberculous meningitis and to highlight recent advancements in translational and clinical science.Recent findingsPharmacologic therapy includes combination anti-tuberculosis drug regimens and adjunctive corticosteroids. It is becoming clear that a successful treatment outcome depends on an immune response that is neither too weak nor overly robust, and genetic determinants of this immune response may identify which patients will benefit from adjunctive corticosteroids. Recent clinical trials of intensified anti-tuberculosis treatment regimens conducted in Indonesia and Vietnam, motivated by the pharmacologic challenges of treating M. tuberculosis infections of the central nervous system, have yielded conflicting results regarding the survival benefit of intensified treatment regimens. More consistent findings have been observed regarding the relationship between initial anti-tuberculosis drug resistance and mortality among tuberculous meningitis patients. Prompt initiation of anti-tuberculosis treatment for all suspected cases remains a key aspect of management. Priorities for research include the improvement of diagnostic testing strategies and the optimization of host-directed and anti-tuberculosis therapies.
Project description:The presence of arterial media calcification, a highly complex and multifactorial disease, puts patients at high risk for developing serious cardiovascular consequences and mortality. Despite the numerous insights into the mechanisms underlying this pathological mineralization process, there is still a lack of effective treatment therapies interfering with the calcification process in the vessel wall. Current anti-calcifying therapeutics may induce detrimental side effects at the level of the bone, as arterial media calcification is regulated in a molecular and cellular similar way as physiological bone mineralization. This especially is a complication in patients with chronic kidney disease and diabetes, who are the prime targets of this pathology, as they already suffer from a disturbed mineral and bone metabolism. This review outlines recent treatment strategies tackling arterial calcification, underlining their potential to influence the bone mineralization process, including targeting vascular cell transdifferentiation, calcification inhibitors and stimulators, vascular smooth muscle cell (VSMC) death and oxidative stress: are they a friend or foe? Furthermore, this review highlights nutritional additives and a targeted, local approach as alternative strategies to combat arterial media calcification. Paving a way for the development of effective and more precise therapeutic approaches without inducing osseous side effects is crucial for this highly prevalent and mortal disease.
Project description:BackgroundTo contain and curb the spread of COVID-19, the governments of countries around the world have used different strategies (lockdown, mandatory vaccination, immunity passports, voluntary social distancing, etc).ObjectiveThis study aims to examine the reactions produced by the public announcement of a binding political decision presented by the president of the French Republic, Emmanuel Macron, on July 12, 2021, which imposed vaccination on caregivers and an immunity passport on all French people to access restaurants, cinemas, bars, and so forth.MethodsTo measure these announcement reactions, 901,908 unique tweets posted on Twitter (Twitter Inc) between July 12 and August 11, 2021, were extracted. A neural network was constructed to examine the arguments of the tweets and to identify the types of arguments used by Twitter users.ResultsThis study shows that in the debate about mandatory vaccination and immunity passports, mostly "con" arguments (399,803/847,725, 47%; χ26=952.8; P<.001) and "scientific" arguments (317,156/803,583, 39%; χ26=5006.8; P<.001) were used.ConclusionsThis study shows that during July and August 2021, social events permeating the public sphere and discussions about mandatory vaccination and immunity passports collided on Twitter. Moreover, a political decision based on scientific arguments led citizens to challenge it using pseudoscientific arguments contesting the effectiveness of vaccination and the validity of these political decisions.