Advances in experimental medicine and biology最新文献

Optical coherence tomography (OCT) is a widely used imaging modality for diagnosing and monitoring macular diseases, including diabetic macular edema (DME) and choroidal neovascularization (CNV), both of which can cause severe visual impairment. Clinicians rely on various OCT biomarkers to identify these conditions. An algorithm was developed in Python to extract biomarker-associated features from OCT images and applied to a pre-labeled dataset containing normal, DME, and CNV images. Distribution analysis confirmed that the extracted features aligned with the existing literature. Using these features, LightGBM classified the OCT images, achieving 91% accuracy and 98% area under the receiver operating characteristic curve. Based on these promising results, this algorithm could contribute to the development of more advanced feature extraction methodologies for the diagnosis of macular diseases using traditional machine learning approaches. Such algorithms could potentially be integrated into automated patient screening systems.

Glioblastoma multiforme (GBM) is a highly aggressive and heterogeneous brain tumor, characterized by poor prognosis and resistance to conventional therapies. Despite advances in multimodal treatment approaches, such as surgery, radiation, and chemotherapy, the prognosis for GBM remains poor, largely due to its molecular complexity and resistance to therapies. To further understand the genetic underpinnings of GBM, this study presents a comprehensive differential gene expression analysis using RNA-sequencing data from the Gene Expression Omnibus (GEO) database. PyDESeq2, the Python implementation of DESeq2, was used to analyze transcriptional changes across glioblastoma and normal brain tissues. This study adopts a two-phase approach: (1) stratifying samples into age groups (≤65 years and ≤76 years) to examine age-related gene expression differences in both GBM and normal brain tissues, and (2) comparing global differential expression patterns between GBM and normal tissues to identify genes consistently dysregulated in GBM. In the age-stratified analysis, we identified several genes that were significantly upregulated or downregulated in younger versus middle-aged individuals, revealing age-specific transcriptional signatures. Principal Component Analysis (PCA) was applied to visualize the variance between GBM and normal brain tissue, confirming distinct transcriptional clustering between diseased and healthy states. This work contributes to the growing field of precision oncology by providing a detailed characterization of age-related and disease-specific transcriptional changes in glioblastoma. The identification of key DEGs and enriched pathways in GBM enhances our understanding of the molecular mechanisms underlying this aggressive cancer and opens new avenues for the development of age-specific, targeted therapeutic strategies.

Huntington's Disease (HD) is an inherited, progressive, deteriorating, and non-curable disease affecting physical and cognitive states. Recent advancements in cell and gene therapy have brought in new treatment options that challenge Huntington's Disease, with the ultimate goal to modify its trajectory. This article emphasizes the role of nurses in Huntington's Disease advanced treatments. Furthermore, it underlines the importance of patient-oriented care as well as the ethical considerations that may occur.

Substance use during pregnancy is highly prevalent worldwide leading to a spectrum of lifelong neurobehavioral consequences. One of the most commonly observed effects of prenatal substance use is an increased risk of emotional processing deficits and developing an affective disorder, particularly anxiety and depression, with evidence of symptoms emerging in infancy and both persisting and becoming increasingly exacerbated into adulthood. Among the various substances misused during pregnancy, alcohol, nicotine, cannabis, and opioids have been noted as the most commonly used for a variety of reasons. Despite the legal status of these substances, it is evident that prenatal exposure to alcohol, nicotine, cannabis, and opioids produces a myriad of neurobiological alterations that may underlie the development of negative affective behaviors in the offspring. This chapter discusses the existing clinical and preclinical (using animal models) literature that has identified the spectrum of negative affective behaviors and associated neurobiological alterations across the lifespan resulting from prenatal exposure to these specific substances.

Fetal alcohol spectrum disorder (FASD) encompasses a broad range of central nervous system (CNS)-related disabilities representing a mild-to-severe continuum of neurodevelopmental disorders that include mood and sensory function. The prevalence of FASD is estimated at ~5% in school-aged children who are prone to develop inappropriate responses to stressful stimuli leading to higher rates of anxiety and low touch tolerance. Low touch tolerance has been self-reported in 33.6% of FASD-affected individuals. The FASD manifestations of sensory abnormalities like pathological light-touch hypersensitivity, a hallmark of chronic pain may be a result of abnormal neurological relays the spinal cord, and from spinal cord to brain. Animal modeling of FASD that utilize prenatal alcohol exposure (PAE) demonstrate mood disorders such as anxiety-like behavior and low touch tolerance, which support these clinical observations of mood and tactile dysregulation.In an effort to contextualize central nervous system (CNS) processing of stress and resultant mood disorders that are exacerbated by PAE, this review outlines the fundamentals of the neurocircuitry of stress from the perspective of the central autonomic network (CAN), differentiating physiological vs. psychological stressors with a focus on elements of the limbic system, including the medial prefrontal cortex (mPFC), amygdala (AMG), hippocampus (HIPP), hypothalamus, cingulate cortex, and brainstem periaqueductal gray (PAG), locus coeruleus (LC), and the nucleus of the solitary tract (NTS) of the medulla. The review addresses stress-sensitized CNS circuits and the underlying immune signaling molecules that may be responsible for heightened stress responses. Adolescence will be discussed as a critical corticolimbic developmental period that is itself highly susceptible to stressors, which is further impacted by PAE leading to stress-related anxiety with lifelong consequences.Linking the heightened neuroimmune response of offspring with PAE, a discussion is included of rodent models demonstrating PAE as a risk factor for developing painful tactile neuropathies following sciatic nerve injury mediated by sensitized and over-active spinal glial cytokine actions. Included in this discussion is the role of limbic forebrain, subcortical and even brainstem circuits that process and regulate mood and stress also engage the emotional and sensory-discriminative aspects of pain processing. Lastly, the impact of PAE on sensitized neuroimmune factors that link stress to touch allodynia in the absence of nerve injury is briefly discussed. These topics aim to help the reader gauge the profound impact of PAE on the CAN, and immune signaling molecules in limbic areas and spinal cord that drive sensitized stress sequelae, which should now include exaggerated pain states as well as anxiety disorders.

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.

Insects are the most successful animal group by various ecological and evolutionary metrics, including species count, adaptation diversity, biomass, and environmental influence. This book delves into the underlying reasons behind insects' dominance on Earth. Lipids play pivotal roles in insect biology, serving as fuel for physiological processes, signaling molecules, and structural components of biomembranes and providing waterproofing against dehydration, among other functions. The study of insect flight has been instrumental in advancing our understanding of insect metabolism, with the migratory locust (Locusta migratoria) and the tobacco hornworm (Manduca sexta) serving as prominent models. Throughout the 1980s and 1990s, numerous studies shed light on the role of adipokinetic hormone (AKH), a crucial neuropeptide in lipid mobilization, to support the extraordinary energy demands of insect flight. Remarkably, AKH was the first identified peptide hormone in insects. These pioneering works linking lipids and flight laid the groundwork for subsequent research characterizing the physiological roles of other neuroendocrine factors in energy substrate mobilization across diverse insect species. However, in the omics era, one may be surprised by the limited understanding of the complex cascade of events governing lipid supply to insect flight muscles. Thus, this chapter aims to provide a concise overview of the evolutionary significance of insect flight, emphasizing key advancements that expand our classical knowledge in this field. Ultimately, we hope this chapter serves as a modest tribute to the pioneering researchers of one of the most captivating areas in insect biology, inspiring further exploration into the myriad roles of lipids in insect biology.

Insects are incapable of biosynthesising sterols de novo so they need to obtain them from their diets or, in certain cases, from symbiotic microorganisms. Sterols serve a structural role in cellular membranes and act as precursors for signalling molecules and defence compounds. Many phytophagous insects dealkylate phytosterols to yield primarily cholesterol, which is also the main sterol that carnivorous and omnivorous insects obtain in their diets. Some phytophagous species have secondarily lost the capacity to dealkylate and consequently use phytosterols for structural and functional roles. The polyhydroxylated steroid hormones of insects, the ecdysteroids, are derived from cholesterol (or phytosterols in non-dealkylating phytophagous species) and regulate many crucial aspects of insect development and reproduction by means of precisely regulated titres resulting from controlled synthesis, storage and further metabolism/excretion. Ecdysteroids differ significantly from vertebrate steroid hormones in their chemical, biochemical and biological properties. Defensive steroids (cardenolides, bufadienolides, cucurbitacins and ecdysteroids) can be accumulated from host plants or biosynthesised within the insect, depending on species, stored in significant amounts in the insect and released when it is attacked. Other allelochemical steroids serve as pheromones. Vertebrate-type steroids have also been conclusively identified from insect sources, but debate continues about their significance. Side chain dealkylation of phytosterols, ecdysteroid metabolism and ecdysteroid mode of action are targets of potential insect control strategies.

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.

The rapid advancement in molecular biology and bioinformatics has enabled the development of sophisticated software tools for protein modeling and optimization. This chapter presents the development and application of a novel software suite, "D³," designed for 3D protein modeling and optimization, utilizing advanced computational techniques. The study provides a comprehensive overview of the methodology, implementation, and results obtained from applying the software in a laboratory environment. The findings demonstrate the effectiveness of the tool in accurately predicting protein structures, paving the way for future applications in drug design and molecular biology research.