Advances in experimental medicine and biology最新文献

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.

Nuclear transport is the basis for the biological reaction of eukaryotic cells, as it is essential to coordinate nuclear and cytoplasmic events separated by nuclear envelope. Although we currently understand the basic molecular mechanisms of nuclear transport in detail, many unexplored areas remain. For example, it is believed that the regulations and biological functions of the nuclear transport receptors (NTRs) highlights the significance of the transport pathways in physiological contexts. However, physiological significance of multiple parallel transport pathways consisting of more than 20 NTRs is still poorly understood, because our knowledge of each pathway, regarding their substrate information or how they are differently regulated, is still limited. In this report, we describe studies showing how nuclear transport systems in general are affected by temperature rises, namely, thermal stress or heat stress. We will then focus on Importin α family members and unique transport factor Hikeshi, because these two NTRs are affected in heat stress. Our present review will provide an additional view to point out the importance of diversity of the nuclear transport pathways in eukaryotic cells.

Traditionally, immunoglobulin (Ig) expression has been attributed solely to B cells/plasma cells with well-documented and accepted regulatory mechanisms governing Ig expression in B cells. Ig transcription is tightly controlled by a series of transcription factors. However, increasing evidence has recently demonstrated that Ig is not only produced by B cell lineages but also by various types of non-B cells (non-B-Ig). Under physiological conditions, non-B-Ig not only exhibits antibody activity but also regulates cellular biological activities (such as promoting cell proliferation, adhesion, and cytoskeleton protein activity). In pathological conditions, non-B-Ig is implicated in the development of various diseases including tumour, kidney disease, and other immune-related disorders. The mechanisms underline Ig gene rearrangement and transcriptional regulation of Ig genes in non-B cells are not fully understood. However, existing evidence suggests that these mechanisms in non-B cells differ from those in B cells. For instance, non-B-Ig gene rearrangement occurs in an RAG-independent manner; and Oct-1 and Oct-4, rather than Oct-2, are required for the transcriptional regulation of non-B derived Igs. In this chapter, we will describe and compare the mechanisms of gene rearrangement and expression regulation between B-Ig and non-B-Ig.

Transient receptor potential ankyrin 1 (TRPA1) is a polymodal cation channel that plays a pivotal role in pain generation after exposure to irritant chemicals and is involved in the sensation of a wide variety of pathological pain. TRPA1 was first reported to be sensitive to noxious cold, but its intrinsic cold sensitivity still remains under debate. To address this issue, we focused on cold hypersensitivity induced by oxaliplatin, a platinum-based chemotherapeutic drug, as a peculiar adverse symptom of acute peripheral neuropathy. We and other groups have shown that oxaliplatin enhances TRPA1 sensitivity to its chemical agonists and reactive oxygen species (ROS). Our in vitro and animal model studies revealed that oxaliplatin, or its metabolite oxalate, inhibits hydroxylation of a proline residue within the N-terminus of human TRPA1 (hTRPA1) via inhibition of prolyl hydroxylase domain-containing protein (PHD), which induces TRPA1 sensitization to ROS. Although hTRPA1 is insensitive to cold, PHD inhibition endows hTRPA1 with cold sensitivity through sensing the small amount of ROS produced after exposure to cold. Hence, we propose that PHD inhibition can unveil the cold sensitivity of hTRPA1 by converting ROS signaling into cold sensitivity. Furthermore, in this review, we summarize the role of TRPA1 in painful cold hypersensitivity during peripheral vascular impairment.

Electroconvulsive therapy is one of the useful treatment methods for symptom improvement and remission in patients with treatment-resistant depression. Considering the various clinical characteristics of patients experiencing depression, key indicators are extracted from structural brain magnetic resonance imaging, functional brain magnetic resonance imaging, and electroencephalography (EEG) data taken before treatment, and applied as explanatory variables in machine learning and network analysis. Studies that attempt to make reliable predictions about the degree of response to electroconvulsive treatment and the possibility of remission in patients with treatment-resistant depression are continuously being published. In addition, studies are being conducted to identify the correlation with clinical improvement by taking structural-functional brain magnetic resonance imaging after electroconvulsive therapy in depressed patients. By reviewing and integrating the results of the latest studies on the above matters, we aim to present the usefulness of electroconvulsive therapy for improving the personalized prognosis of patients with treatment-resistant depression.

Depressive disorders are an enormous societal burden given their high prevalence and impact on all facets of being human (e.g., relationships, emotions, motivation). There is a variety of evidence-based psychological treatments, with cognitive behavioral therapy (CBT) being the gold standard for major depression. Research has shown that mindfulness-based interventions (MBIs) such as mindfulness-based cognitive therapy (MBCT) are an effective relapse prevention and treatment for depression and that MBIs can be integrated in individual therapy. Furthermore, various delivery modes (e.g., digital-delivered therapy) and settings are offered to best meet different needs and improve accessibility: Evidence suggests that therapist-guided digital CBT, blended therapy, and, to some degree, digitalized MBIs may be an efficacious supplement to traditional face-to-face therapy. This chapter provides an overview of the principles and evidence base for CBT and MBCT as well as different delivery modes for depressive disorders in adults. Finally, chances and challenges of integration are discussed as implications for practice, as well as recommendations and ideas for future research.