Experientia supplementum (2012)最新文献

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.

Lung diseases are common and significant causes of illness and death around the world. Inflammasomes have emerged as an important regulator of lung diseases. The important role of IL-1 beta and IL-18 in the inflammatory response of many lung diseases has been elucidated. The cleavage to turn IL-1 beta and IL-18 from their precursors into the active forms is tightly regulated by inflammasomes. In this chapter, we structurally review current evidence of inflammasome-related components in the pathogenesis of acute and chronic lung diseases, focusing on the "inflammasome-caspase-1-IL-1 beta/IL-18" axis.

The current chapter focuses on the role of inflammasome in cancer prevention and development. Emerging evidence suggested that inflammasome is closely correlated with elevated levels of IL-1β and IL-18, activation of NF-κB signaling, enhanced mitochondrial oxidative stress, and activation of autophagic process in cancer. Meanwhile, inflammasome component NOD-like receptors (NLRs) are also involved in carcinogenesis and closely correlated to chemoresponse and prognosis. Although several lines indicated the duplex role of inflammasome in cancer development, the phenomenon might be attributed to NLR difference, cell and tissue type, cancer stage, and specific experimental conditions. Designation of inflammasome targeting strategy has become a novel tool for cancer prevention or treatment.

Although viral vectors comprise the majority of gene delivery vectors, their various safety, production, and other practical concerns have left a research gap to be addressed. The non-viral vector space encompasses a growing variety of physical and chemical methods capable of gene delivery into the nuclei of target cells. Major physical methods described in this chapter are microinjection, electroporation, and ballistic injection, magnetofection, sonoporation, optical transfection, and localized hyperthermia. Major chemical methods described in this chapter are lipofection, polyfection, gold complexation, and carbon-based methods. Combination approaches to improve transfection efficiency or reduce immunological response have shown great promise in expanding the scope of non-viral gene delivery.

The interaction between intracellular bacterial pathogens with the host immune response can result in multiple outcomes that range from asymptomatic clearance to the establishment of infection. At its core, these interactions result in multiple metabolic adaptations of both the pathogen and its host cell. There is growing evidence that the host metabolic response plays a key role in the development of immune responses against the invading pathogen. However, successful intracellular pathogens have developed multiple mechanisms to circumvent the host response to thrive in the intracellular compartment. Here, we provide a brief overview on the crucial role of fundamental metabolic host responses in the generation of protective immunity to intracellular bacterial pathogens and discuss some of the mechanisms used by these pathogens to exploit the host metabolic response to their own advantage. This understanding will further our knowledge in host-pathogen interactions and may provide new insights for the development of novel therapies.