Advances in experimental medicine and biology最新文献

Pheromones are utilized to a great extent in insects. Many of these pheromones are biosynthesized through a pathway involving fatty acids. This chapter will provide examples where the biosynthetic pathways of fatty acid-derived pheromones have been studied in detail. These include pheromones from Lepidoptera, Coleoptera, and Hymenoptera. Many species of Lepidoptera utilize fatty acids as precursors to pheromones with a functional group that include aldehydes, alcohols, and acetate esters. In addition, the biosynthesis of hydrocarbons will be briefly examined because many insects utilize hydrocarbons or modified hydrocarbons as pheromones.

To ensure optimum health and performance, lipid metabolism needs to be temporally aligned to other body processes and to daily changes in the environment. Central and peripheral circadian clocks and environmental signals such as light provide internal and external time cues to the body. Importantly, each of the key organs involved in insect lipid metabolism contains a molecular clockwork which ticks with a varying degree of autonomy from the central clock in the brain. In this chapter, we review our current knowledge about peripheral clocks in the insect fat body, gut and oenocytes, and light- and circadian-driven diel patterns in lipid metabolites and lipid-related transcripts. In addition, we highlight selected neuroendocrine signaling pathways that are or may be involved in the temporal coordination and control of lipid metabolism.

Modern insects have inhabited the earth for hundreds of millions of years, and part of their successful adaptation lies in their many reproductive strategies. Insect reproduction is linked to a high metabolic rate that provides viable eggs in a relatively short time. In this context, an accurate interplay between the endocrine system and the nutrients synthetized and metabolized is essential to produce healthy offspring. Lipids guarantee the metabolic energy needed for egg formation and represent the main energy source consumed during embryogenesis. Lipids availability is tightly regulated by a complex network of endocrine signals primarily controlled by the central nervous system (CNS) and associated endocrine glands, the corpora allata (CA) and corpora cardiaca (CC). This endocrine axis provides hormones and neuropeptides that significatively affect tissues closely involved in successful reproduction: the fat body, which is the metabolic center supplying the lipid resources and energy demanded in egg formation, and the ovaries, where the developing oocytes recruit lipids that will be used for optimal embryogenesis. The post-genomic era and the availability of modern experimental approaches have advanced our understanding of many processes involved in lipid homeostasis; therefore, it is crucial to integrate the findings of recent years into the knowledge already acquired in the last decades. The present chapter is devoted to reviewing major recent contributions made in elucidating the impact of the CNS/CA/CC-fat body-ovary axis on lipid metabolism in the context of insect reproduction, highlighting areas of fruitful research.

Lipids are a diverse group of compounds that play several important roles in insect physiology. Among biological lipids, the fundamental category comprises fatty acyl structures, with significant members being fatty acids (FAs). They play several crucial functions in insect physiology; they are used as the source of energy for flight and play key roles in the insect immune system. The FAs present in the insect cuticle are known to demonstrate antibacterial and antifungal activity and are considered as potential insecticides. The most abundant family of lipids are the glycerolipids, with numerous cellular functions including storage of energy, structural compartmentation of cells and organelles, and important signaling activities required for regulation of physiological processes (i.e., growth, development, reproduction, diapause, and overwintering). The phospholipids are also highly diversified key components of all cell membranes; they can modify cellular components in response to rapid cold-hardening (RCH), enhancing membrane fluidity and improving survival at low temperatures. The sphingolipids are important structural and signaling bioactive compounds, mostly detected in membranes.Insects are sterol-auxotrophs: they do not have genes, which code enzymes converting farnesyl pyrophosphate to squalene. Similarly, to mammals, the production of steroids in insects is regulated by cytochrome P450 enzymes that convert sterols (mostly cholesterol) to hormonally active steroids. The major molting hormone in insects is 20-hydroxyecdysone, and cholesterol is the required precursor; however, several exemptions from this rule have been noted. This manuscript also reviews the roles of prenol lipids, isoprenoids, lipid vitamins, polyketides, and waxes in the vital processes of insects.

Recent advancements in personalized treatments, such as anthracycline chemotherapy, coupled with timely diagnoses, have contributed to a decrease in cancer-specific mortality rates and an improvement in cancer prognosis. Anthracyclines, a potent class of antibiotics, are extensively used as anticancer medications to treat a broad spectrum of tumors. Despite these advancements, a considerable number of cancer survivors face increased risks of treatment complications, particularly the cardiotoxic effects of chemotherapeutic drugs like anthracyclines. These effects can range from subclinical manifestations to severe consequences such as irreversible heart failure and death, highlighting the need for effective management of chemotherapy side effects for improved cancer care outcomes. Given the lack of specific treatments, early detection of subclinical cardiac events post-anthracycline therapy and the implementation of preventive strategies are vital. An interdisciplinary approach involving cardiovascular teams is crucial for the prevention and efficient management of anthracycline-induced cardiotoxicity. Various factors, such as age, gender, duration of treatment, and comorbidities, should be considered significant risk factors for developing chemotherapy-related cardiotoxicity. Tools such as electrocardiography, echocardiography, nuclear imaging, magnetic resonance imaging, histopathologic evaluations, and serum biomarkers should be appropriately used for the early detection of anthracycline-related cardiotoxicity. Furthermore, understanding the underlying biological mechanisms is key to developing preventive measures and personalized treatment strategies to mitigate anthracycline-induced cardiotoxicity. Exploring specific cardiotoxic mechanisms and identifying genetic variations can offer fresh perspectives on innovative, personalized treatments. This chapter aims to discuss cardiomyopathy following anthracycline therapy, with a focus on molecular mechanisms, preventive strategies, and emerging treatments.

Transcriptional control of lipid metabolism uses a framework that parallels the control of lipid metabolism at the protein or enzyme level, via feedback and feed-forward mechanisms. Increasing the substrates for an enzyme often increases enzyme gene expression, for example. A paucity of product can likewise potentiate transcription or stability of the mRNA encoding the enzyme or enzymes needed to produce it. In addition, changes in second messengers or cellular energy charge can act as on/off switches for transcriptional regulators to control transcript (and protein) abundance. Insects use a wide range of DNA-binding transcription factors (TFs) that sense changes in the cell and its environment to produce the appropriate change in transcription at gene promoters. These TFs work together with histones, spliceosomes, and additional RNA processing factors to ultimately regulate lipid metabolism. In this chapter, we will first focus on the important TFs that control lipid metabolism in insects. Next, we will describe non-TF regulators of insect lipid metabolism such as enzymes that modify acetylation and methylation status, transcriptional coactivators, splicing factors, and microRNAs. To conclude, we consider future goals for studying the mechanisms underlying the control of lipid metabolism in insects.

Lipids are essential in insects and play pleiotropic roles in energy storage, serving as a fuel for energy-driven processes such as reproduction, growth, development, locomotion, flight, starvation response, and diapause induction, maintenance, and termination. Lipids also play fundamental roles in signal transduction, hormone synthesis, forming components of the cell membrane, and thus are essential for maintenance of normal life functions. In insects, the neuroendocrine system serves as a master regulator of most life activities, including growth and development. It is thus important to pay particular attention to the regulation of lipid metabolism through the endocrine system, especially when considering the involvement of peptide hormones in the processes of lipogenesis and lipolysis. In insects, there are several lipogenic and lipolytic hormones that are involved in lipid metabolism such as insulin-like peptides (ILPs), adipokinetic hormone (AKH), 20-hydroxyecdysone (20-HE), juvenile hormone (JH), and serotonin. Other neuropeptides such as diapause hormone-pheromone biosynthesis activating neuropeptide (DH-PBAN), CCHamide-2, short neuropeptide F, and the cytokines Unpaired 1 and 2 may play a role in inducing lipogenesis. On the other hand, neuropeptides such as neuropeptide F, allatostatin-A, corazonin, leukokinin, tachykinins, limostatins, and insulin-like growth factor (ILP6) stimulate lipolysis. This chapter briefly discusses the current knowledge of the endocrine regulation of lipid metabolism in insects that could be utilized to reveal differences between insects and mammalian lipid metabolism which may help understand human diseases associated with dysregulation of lipid metabolism. Physiological similarities of insects to mammals make them valuable model systems for studying human diseases characterized by disrupted lipid metabolism, including conditions like diabetes, obesity, arteriosclerosis, and various metabolic syndromes.

Beyond their role as protein-building units, amino acids are modulators of multiple behaviours in different microorganisms. In the root-colonizing beneficial bacterium Pseudomonas putida (recently proposed to be reclassified as alloputida) KT2440, current evidence suggests that arginine functions both as a metabolic indicator and as an environmental signal molecule, modulating processes such as chemotactic responses, siderophore-mediated iron uptake or the levels of the intracellular second messenger cyclic diguanylate (c-di-GMP). Using microcalorimetry and extracellular flux analysis, in this work we have studied the metabolic adaptation of P. putida KT2440 to the presence of L-arginine in the growth medium, and the influence of mutations related to arginine metabolism. Arginine causes rapid changes in the respiratory activity of P. putida, particularly magnified in a mutant lacking the transcriptional regulator ArgR. The metabolic activity of mutants affected in arginine transport and metabolism is also altered during biofilm formation in the presence of the amino acid. The results obtained here further support the role of arginine as a metabolic signal in P. putida and the relevance of ArgR in the adaptation to the amino acid. They also serve as proof of concept on the use of calorimetric and extracellular flux techniques to analyse metabolic responses in bacteria and the impact of different mutant backgrounds on such responses.

Introduction: Invasive fungal infections (IFI) are a group of life-threatening diseases associated with significant morbidity, mortality and high healthcare costs. Some modern management programs known as AFS (antifungal stewardship programs) have now been developed. The purpose of this systematic review is to evaluate the different declinations of antifungal stewardship programs (AFPs).

Methods: Articles were systematically reviewed using the PRISMA checklist 2020. EMBASE and MEDLINE/PubMED were searched using the term "antifungal stewardship" (2012-2022 data) on 2 January 2023. Eligible studies were those that described an AFS and included an intervention, performance evaluation and outcome measures.

Results: A total of 22/796 studies were included. Approximately two-thirds (16) were published between 2018 and 2022. 16 (72.7%) stated a minimal complete AFS team. 12 (54.5%) adopted a non-compulsory AFS approach, 6(27.3%) had an Educational AFS and 4(18.2%) a compulsory AFS. Cost analyses of 12 studies showed a decrease for 7 (31.8%) compared to an increase for 5 (22.7%). In terms of outcomes, 18 studies showed a lower (10;45.5%) or the same (8;36.4%) pre-post intervention mortality rate.

Conclusion: AFS programs seem to be related to lower costs and better outcomes and should thus be implemented in tandem with antimicrobial stewardship programs.