Advances in experimental medicine and biology最新文献

Cognitive decline is a critical area of research due to its profound impact on neural integrity, cognitive function, and its association with neurodegenerative diseases. Early identification of cognitive impairment is essential, as it often signals underlying neurological dysfunction, which, if left unaddressed, can lead to progressive mental deterioration. Moreover, cognitive decline extends beyond individual health, influencing high-demand environments where sustained cognitive performance is crucial for safety and decision-making. Heart rate variability (HRV), derived noninvasively from photoplethysmography (PPG), offers a real-time method for detecting autonomic dysregulation linked to cognitive fatigue. Continuous PPG monitoring under conditions of sleep deprivation, combined with machine learning algorithms such as Long Short-Term Memory (LSTM) networks, enabled accurate prediction of cognitive states based on HRV patterns through their ability to capture temporal dependencies. The findings reveal significant autonomic disturbances corresponding to mental fatigue, underscoring HRV's potential as a sensitive biomarker for cognitive decline and its applicability in transfer learning frameworks.

Genome-wide association studies (GWAS) have revolutionized our understanding of genetic contributions to complex diseases by identifying single-nucleotide polymorphisms (SNPs) associated with disease predisposition. Despite the substantial progress made in identifying risk factors for conditions like cancer and cardiovascular diseases, interpreting the functional impact of identified variants remains a challenge, particularly when silent mutations are involved. Silent mutations, once considered irrelevant to disease mechanisms, have emerged as significant players influencing mRNA formation, splicing, and translation processes. This study utilized the Genetic Association Database (GAD) to analyze and identify the significance of silent mutations across a wide range of diseases, employing advanced machine learning techniques and the Apriori algorithm to extract association rules from a biomedical dataset. The Apriori algorithm was applied to identify strong correlations between diseases and chromosomes, using parameters such as support, confidence, and lift to evaluate the strength and importance of these associations. Our results demonstrated the capability of the Apriori algorithm to uncover biologically meaningful relationships, which could be instrumental in improving our understanding of genetic predispositions and guiding precision medicine efforts. These findings underscore the importance of silent mutations in disease etiology and highlight the potential of bioinformatics tools in unraveling complex genetic interactions.

Prenatal alcohol exposure (PAE), even at low doses, has been linked to long-term alterations in alcohol-related behaviors, particularly increased alcohol consumption and preference in offspring. This chapter examines how low-dose PAE affects the motivational effects of alcohol, potentially influencing the balance between its rewarding and aversive properties. While high-dose PAE has been extensively studied for its teratogenic effects, the implications of lower, more common exposures remain less understood. Preclinical studies using rodent models suggest that even moderate PAE (1-3 g/kg/day) enhances sensitivity to alcohol's appetitive properties while reducing its aversive effects, promoting future alcohol-seeking behavior. These alterations may be mediated by neurobiological changes, including increased neurogenesis of enkephalin-expressing neurons, disruptions in dopamine and opioid signaling, and modifications in stress-related neural circuits. Behavioral paradigms, such as conditioned place preference and conditioned taste aversion, confirm that PAE enhances the reinforcing effects of ethanol while mitigating its negative consequences. Operant self-administration studies also report greater motivation after PAE. These motivational alterations correlate, albeit with studies not measuring the same variables in the same individual, with increased alcohol consumption in adolescence and adulthood. This chapter further discusses the mechanisms underlying these effects. Understanding the impact of low-dose PAE on alcohol motivation can provide crucial insights into early-life risk factors for problematic drinking and inform preventive interventions.

Gestational diabetes mellitus (GDM) is a pregnancy complication that, according to the World Health Organization, is showing an increasing prevalence trend, mirroring the continuing upward trend of diabetes mellitus (DM) in the general population. The present study was based on the questions of the Depression, Anxiety, and Stress Scale DASS-21 and the World Health Organization Quality of Life Brief WHOQOL-BREF scales (translated into Greek). One hundred five pregnant women aged 21-44 participated in the study. The participants reported good mental health (low levels of stress, anxiety, and depression) with moderate levels of nervousness impacting them. Their social life was at a good level, they were satisfied with the environment they lived in, as well as their daily life; however, their physical health was at a moderate level. Also, the trimester of pregnancy appeared to play an important role in the onset of nervousness and depression in pregnant women with GDM as well as in their quality of life during pregnancy, with pregnant women in the first trimester reporting a lower quality of life than pregnant women in other trimesters. In contrast, women in the second gestational trimester reported the lowest depression rates. There was also an association between age and the prevalence of depression, with younger and older women experiencing depression at a higher frequency. Collectively, the psychological impact of GDM as well as its impact on the quality of life of pregnant women requires further investigation.

Insects need to transport lipids through the aqueous medium of the hemolymph to the organs in demand, after they are absorbed by the intestine or mobilized from the lipid-producing organs. Lipophorin is a lipoprotein present in insect hemolymph, and is responsible for this function. A single gene encodes an apolipoprotein that is cleaved to generate apolipophorin I and II. These are the essential protein constituents of lipophorin. In some physiological conditions, a third apolipoprotein of different origin may be present. In most insects, lipophorin transports mainly diacylglycerol and hydrocarbons, in addition to phospholipids. The fat body synthesizes and secretes lipophorin into the hemolymph, and several signals, such as nutritional, endocrine, or external agents, can regulate this process. However, the main characteristic of lipophorin is the fact that it acts as a reusable shuttle, distributing lipids between organs without being endocytosed or degraded in this process. Lipophorin interacts with tissues through specific receptors of the LDL receptor superfamily, although more recent results have shown that other proteins may also be involved. In this chapter, we describe the lipophorin structure in terms of proteins and lipids, in addition to reviewing what is known about lipoprotein synthesis and regulation. In addition, we reviewed the results investigating lipophorin's function in the movement of lipids between organs and the function of lipophorin receptors in this process.

Organisms living in temperate and polar environments encounter seasonal fluctuations that entail changes in temperature, resource availability, and biotic interactions. Thus, adaptations for synchronizing the life cycle with essential resources and persisting through unfavorable conditions are critical. Diapause, a programmed period of developmental arrest and metabolic depression, is widely used by insects to survive winter and synchronize the life cycle. In some cases, insects spend over half the year (or in some cases, multiple years) in a nonfeeding diapause state. Thus, diapause is energetically challenging, and insects accumulate surplus energy stores and/or suppress metabolism to make it through the winter. As the most energy-dense, and often most abundant, energy reserve in insects, lipids play a central role in diapause energetics. In this chapter, we provide an overview of lipid metabolism in the context of diapause. First, as this is the only chapter in this book that covers diapause, we present some of the general features of diapause. We then discuss the role of lipids as an essential energy store during diapause, focusing on patterns of lipid accumulation before diapause and patterns of utilization during diapause. In the next section, we outline some other roles of lipids during diapause in addition to their role as an energy store. Finally, we end the chapter by discussing the molecular regulation of lipid metabolism in diapause, which has received increased attention in recent years.

Carbohydrates and lipids integrate into a complex metabolic network that is essential to maintain homeostasis. In insects, as in most metazoans, dietary carbohydrates are taken up as monosaccharides whose excess is toxic, even at relatively low concentrations. To cope with this toxicity, monosaccharides are stored either as glycogen or neutral lipids, the latter constituting a quasi-unlimited energy store. Breakdown of these stores in response to energy demand depends on insect species and on several physiological parameters. In this chapter, we review the multiple metabolic pathways and strategies linking carbohydrates and lipids that insects utilize to respond to nutrient availability, food scarcity or physiological activities.

Calcium (Ca²⁺) homeostasis is a critical regulator of insect cellular functions, influencing neurotransmission, muscle contraction, hormone signaling, and lipid metabolism. This chapter explores the intricate relationship between Ca²⁺ signaling and lipid metabolism, emphasizing key molecular components that mediate this interaction. Store-operated calcium entry (SOCE) mechanisms, involving sarco/endoplasmic reticulum Ca²⁺-ATPase (SERCA), inositol 1,4,5-trisphosphate receptor (IP₃R), ryanodine receptor (RyR), stromal interaction molecule (STIM), and Orai1, coordinate intracellular Ca²⁺ fluxes that regulate lipid storage, mobilization, and utilization. Other Ca²⁺-binding proteins, such as calmodulin (CaM), calcineurin (CaN), regucalcin (RgN), calreticulin (CrT), and calnexin (CnX), further modulate Ca²⁺ homeostasis and impact lipid metabolism by influencing lipolysis, lipogenesis, and lipid droplet dynamics. This chapter also highlights the role of hepatocyte-like oenocytes in lipid metabolism. These cells, analogous to mammalian hepatocytes, regulate lipid processing and mobilization during fasting, forming a metabolic axis with fat body adipocytes. While Ca²⁺ signaling is well characterized in adipocytes, its role in oenocyte lipid metabolism remains largely unexplored. However, Ca²⁺-dependent regulation of lipid metabolism in mammalian hepatocytes suggests a similar involvement in insect oenocytes. A central theme is the bidirectional relationship between Ca²⁺ homeostasis and lipid metabolism. While Ca²⁺ signaling regulates lipid accumulation and hydrolysis, impaired lipid metabolism can disrupt Ca²⁺ homeostasis. For instance, Drosophila melanogaster seipin mutants with defective lipid storage exhibit reduced SERCA activity, leading to lower ER and mitochondrial Ca²⁺ levels, which impair lipogenesis. Additionally, CaN promotes lipogenesis, whereas STIM and IP₃R serve as lipolytic regulators. This metabolic feedback loop is essential for maintaining energy balance. Understanding the Ca²⁺-lipid interplay in insects provides insights into metabolic regulation, with implications for pest management and metabolic disease research. Future studies should further investigate Ca²⁺-dependent mechanisms governing oenocyte function and systemic lipid homeostasis.

Lung cancer is associated with one of the highest cancer-related mortality rates and is the second most prevalent cancer worldwide. Diagnosis and treatment of lung cancer has different challenges as in most cases, and it is often diagnosed late when metastatic spread is widely disseminated. The development of chemo- and radioresistance of lung cancer, as well as a lack of specific treatment, has resulted in a very high mortality and morbidity. Noncoding RNAs (ncRNAs) are a group of RNAs with a wide spectrum of functions required for homeostasis. These RNAs modulate the expression of proteins posttranslationally and control the cell phenotype. Studies have shown that these RNAs could act as both oncogene and oncosuppressor, and due to their great therapeutic and diagnostic potential, recent studies have also focused on their use as biomarkers for early detection of cancers. Understanding the current findings in this field would help scientists to have an overview about different ncRNAs and their role in lung cancer progression. This chapter explores the landscape of ncRNA research related to lung cancer, highlighting the potential for novel diagnostic and therapeutic strategies.

Wound healing is a dynamic and complex process that consists of four interconnected phases: hemostasis, inflammation, proliferation, and remodeling. This complex process is based on the coordinated actions of growth factors, cytokines, and other cellular interactions. However, conditions such as diabetes and chronic illnesses can disrupt this process and lead to nonhealing wounds or chronic ulcers. This chapter addresses the molecular and cellular mechanisms that control both normal and impaired wound healing, with emphasis on diabetic ulcers, burns, and surgical wounds. Growth factors play a critical role in wound modulation and the potential of therapeutic interventions to restore balanced healing. Advances in tissue engineering and regenerative medicine, including hydrogel-based therapies and synthetic polymers, have produced promising solutions for wound management. In addition, 3D bioprinting offers the possibility of producing personalized skin grafts and wound dressings that closely resemble the natural skin structure. Clinical trials are currently evaluating these innovative approaches' effectiveness and highlighting their potential to transform therapeutic outcomes in the treatment of chronic and complex wounds.