Experientia supplementum (2012)最新文献

The gastrointestinal (GI) tract is the residence of trillions of microorganisms that include bacteria, archaea, fungi and viruses. The collective genomes of whole microbial communities (microbiota) integrate the gut microbiome. Up to 100 genera and 1000 distinct bacterial species were identified in digestive tube niches. Gut microbiomes exert permanent pivotal functions by promoting food digestion, xenobiotic metabolism and regulation of innate and adaptive immunological processes. Proteins, peptides and metabolites released locally and at distant sites trigger many cell signalling and pathways. This intense crosstalk maintains the host-microbial homeostasis. Diet, age, diet, stress and diseases cause increases or decreases in relative abundance and diversity bacterial specie of GI and other body sites. Studies in animal models and humans have shown that a persistent imbalance of gut's microbial community, named dysbiosis, relates to inflammatory bowel diseases (IBD), irritable bowel syndrome (IBS), diabetes, obesity, cancer, cardiovascular and central nervous system disorders. Notably specific bacterial communities are promising clinical target to treat inflammatory and infectious diseases. In this context, intestinal microbiota transplantation (IMT) is one optional treatment for IBD, in particular to patients with recurrent Clostridium difficile-induced pseudo-membrane colitis. Here we discuss on recent discoveries linking whole gut microbiome dysbiosis to metabolic and inflammatory diseases and potential prophylactic and therapeutic applications of faecal and phage therapy, probiotic and prebiotic diets.

The inflammasomes are innate immune system sensors that control the activation of caspase-1 and induce inflammation in response to infectious microbes and molecules originating from host proteins, leading to the release of pro-inflammatory cytokines, Il1b and IL18, and a particular inflammatory type of cell death termed pyroptosis. It is broadly considered that chronic inflammation may be a common link in age-related diseases, aging being the greatest risk factor for the development of chronic diseases. In this sense, we discuss the role of inflammasomes in non-infectious inflammation and their interest in aging and age-related diseases.

Unresolved inflammation is harmful to any tissues in the organism. Bone in particular is vulnerable to inflammatory assaults because its integrity depends on the activity of osteoclasts, which arise from myeloid precursors. Osteoclasts are responsible for bone resorption in normal and disease conditions. Increased osteolysis is a common feature of inflammatory disorders and a risk factor for bone fractures. Thus, bone is impacted negatively not only by local and systemic inflammatory mediators, but also directly, by alterations affecting myelopoiesis and lineage allocations. Such perturbations are characteristics of dysregulated inflammasomes, which are key regulators of innate immunity. In this review, we discuss the role of inflammasomes in bone diseases caused by sterile or non-sterile inflammation.

The dawn of nanoparticle-encapsulated genes is a revolutionary move in gene therapy. It promises to specifically and safely transport genetic cargo through biological systems within a non-viral "Trojan horse" system.

A robust biomarker screening and validation is crucial for overcoming the current limits in the clinical management of infectious diseases. In this chapter, a general workflow for metabolomics is summarized. Subsequently, an overview of the major contributions of this omics science to the field of biomarkers of infectious diseases is discussed. Different approaches using a variety of analytical platforms can be distinguished to unveil the key metabolites for the diagnosis, prognosis, response to treatment and susceptibility for infectious diseases. To allow the implementation of such biomarkers into the clinics, the performance of large-scale studies employing solid validation criteria becomes essential. Focusing on the etiological agents and after an extensive review of the field, we present a comprehensive revision of the main metabolic biomarkers of viral, bacterial, fungal, and parasitic diseases. Finally, we discussed several articles which show the strongest validation criteria. Following these research avenues, precious clinical resources will be revealed, allowing for reduced misdiagnosis, more efficient therapies, and affordable costs, ultimately leading to a better patient management.

Viruses are intracellular parasites that rely on host machinery to replicate and achieve a successful infection. Viruses have evolved to retain a broad range of strategies to manipulate host cell metabolism and metabolic resources, channeling them toward the production of virion components leading to viral production. Although several viruses share similar strategies for manipulating host cell metabolism, these processes depend on several factors, namely, the viral life cycle and the metabolic and energetic status of the infected cell. Based on this knowledge, the development of new therapeutic approaches that circumvent viral spread through the target of altered metabolic pathways is an opportunity to tackle the infection. However, finding effective broad-spectrum strategies that aim at restoring to homeostasis the metabolic alterations induced upon virus infection is still a Holy Grail quest for antiviral therapies. Here, we review the strategies by which viruses manipulate host metabolism for their own benefit, with a particular emphasis on carbohydrate, glutamine, and lipid metabolism.

A complex network that embraces parasite-host intrinsic factors and the microenvironment regulated the interaction between a parasite and its host. Nutritional pressures exerted by both elements of this duet thus dictate this host-parasite niche. To survive and proliferate inside a host and a harsh nutritional environment, the parasites modulate different nutrient sensing pathways to subvert host metabolic pathways. Such mechanism is able to change the flux of distinct nutrients/metabolites diverting them to be used by the parasites. Apart from this nutritional strategy, the scavenging of nutrients, particularly host fatty acids, constitutes a critical mechanism to fulfil parasite nutritional requirements, ultimately defining the host metabolic landscape. The host metabolic alterations that result from host-parasite metabolic coupling can certainly be considered important targets to improve diagnosis and also for the development of future therapies. Metabolism is in fact considered a key element within this complex interaction, its modulation being crucial to dictate the final infection outcome.

Metabolism is highly coordinated component of the cellular activity that involves sequential chemical transformations, within a so-called metabolic network. Through these coordinated actions, living organisms acquire energy and biosynthetic precursors to maintain cellular homeostasis and function. Metabolism relies on the breaking down of macromolecules to produce energy [catabolism] and/or intermediary metabolites that are then used to construct essential building blocks for macromolecule production [anabolism]. Overall, these metabolic processes are controlled by cellular energy status: when the energy released from catabolic processes exceeds the cellular demands the storage of metabolites in the form of lipids and glycogen takes place. These phenomena have been vastly associated with the genesis of metabolic disorders, such as obesity. In recent years, we have assisted to a rediscovery of metabolism through the identification of metabolic intermediaries that act as key players on differentiation, proliferation, and function of immune cells. This recent acknowledgement of the impact of metabolism in the overall immune response originated the ground-breaking field of immunometabolism. Here, we will provide a holistic view of metabolism highlighting the biochemical principles underlying its regulation.

Gene therapy is the delivery of nucleic acid for the expression of a therapeutic product in order to treat diseases on a genetic level. This is especially well suited for diseases that involve missing, defective, or overexpressing genes.

The immune system, like all other systems, responds to perturbations of the baseline, homeostatic functioning of immune cells. These perturbations come in the form of infection, tumors, autoantigens, and can occur after mismatched transplantation. During response, immune cells alter their metabolic activities. However, the subsets of the same cell type differ to distinctively associate specific immune function to a particular metabolic profile. The response is mounted as a joint function of metabolic receptor and immune receptor signaling that target various metabolic pathways: glycolysis the pentose phosphate pathway; oxidative phosphorylation; beta-oxidation of fatty acids and transamination. The products from these cycles are integrated in the tricarboxylic acid cycle. However, many more pathways lead to many secondary metabolites that are not directly related to energy derivation or maintaining structure of the cells. These secondary metabolites can again work in an autocrine manner to re-tune the immune cells to optimize their restorative effector functions.