Search Results (595)

Legumes are vital sources of protein, dietary fibre and nutrients, making them crucial for global food security and sustainable agriculture. However, their widespread acceptance and consumption are often limited by undesirable sensory characteristics, such as “a beany flavour”, bitterness or variable textures. Addressing these challenges requires a comprehensive understanding of the complex molecular mechanisms governing appearance, aroma, taste, flavour, texture and palatability in legumes, aiming to enhance their sensory appeal. This review highlights the transformative power of multi-omics approaches in dissecting these intricate biological pathways and facilitating the targeted enhancement of legume sensory qualities. By integrating data from genomics, transcriptomics, proteomics and metabolomics, the genetic and biochemical networks that directly dictate sensory perception can be comprehensively unveiled. The insights gained from these integrated multi-omics studies are proving instrumental in developing strategies for sensory enhancement. They enable the identification of key biomarkers for desirable traits, facilitating more efficient marker-assisted selection (MAS) and genomic selection (GS) in breeding programs. Furthermore, a molecular understanding of sensory pathways opens avenues for precise gene editing (e.g., using CRISPR-Cas9) to modify specific genes, reduce off-flavour compounds or optimise texture. Beyond genetic improvements, multi-omics data also inform the optimisation of post-harvest handling and processing methods (e.g., germination and fermentation) to enhance desirable sensory profiles and mitigate undesirable ones. This holistic approach, spanning from the genetic blueprint to the final sensory experience, will accelerate the development of new legume cultivars and products with enhanced palatability, thereby fostering increased consumption and ultimately contributing to healthier diets and more resilient food systems worldwide. Full article

Cyclic nucleotide signaling pathways play essential roles in the physiology of the nematode Caenorhabditis elegans, influencing processes such as reproduction, environmental sensing, and cellular homeostasis. The intracellular levels of cAMP and cGMP are tightly regulated by their synthesis by adenylyl and guanylyl cyclases and their degradation catalyzed by 3′,5′-cyclic nucleotide phosphodiesterases (PDEs). Mammals possess eleven PDE families (PDE1 through PDE11), whereas nematode genomes contain six PDE genes orthologous to six of the mammalian PDE families. Despite their evolutionary conservation, the signaling pathways, regulatory mechanisms, and enzymatic properties of nematode PDEs remain incompletely understood. This review synthesizes current knowledge on the regulation of cyclic nucleotide levels in C. elegans, highlighting how dysregulation of nematode PDEs affects a wide range of physiological and behavioral processes, including sensory transduction, development, and locomotion. Full article

Migraine is a neurovascular paroxysmal disorder characterized by neurogenic inflammation and has a remarkable impact on the quality of life. The Food and Drug Administration (FDA) approved onabotulinumtoxin A in 2010 for the prophylactic treatment of chronic migraine. Today, in its 4th decade, it is approved in 100 countries for 15 main indications. Its mechanism of action, based on the inhibition of neurotransmitter release from primary sensory neurons, is very complex: it affords antinociception, but it also has an analgesic effect on neuropathic pain conditions and reduces the need for rescue medications. Genetic variants have been investigated for their potential role in the pathogenesis and clinical expression of migraine and of the response to treatments. These studies primarily involved genes associated with vascular regulation and cardiovascular pathology, including those encoding angiotensin-converting enzyme (ACE) and methylenetetrahydrofolate reductase (MTHFR). However, epigenetics and, particularly, genetic and epigenetic modifications are still poorly studied in terms of understanding the mechanisms implicated in susceptibility to migraine, aura, chronification and response to symptomatic and preventive treatments. In particular, the aim of the present study is to gather evidence on the genetic variants and epigenetic modifications affecting the pathway of the calcitonin gene-related peptide (CGRP), the target of onabotulinumtoxin A and of all the novel monoclonal antibodies. Full article

Endometriosis is the extrauterine engraftment of endometrium-like tissue, causing chronic pain. Complex sensory–vascular–immune interactions, including growth factors, cytokines, and neuropeptides, are implicated in its pathophysiology, but the mechanisms remain unknown. Here, epidermal growth factor (EGF), vascular endothelial growth factor, interleukins (IL-1β, IL-6, IL-8), macrophage migration inhibitory factor (MIF), calcitonin gene-related peptide, and somatostatin were measured in the serum of endometriosis patients with different disease severities, menstruation cycle- and pharmacotherapy-related hormonal status compared with controls. Mediator levels in deep-infiltrating rectosigmoid nodules were also compared with those in non-endometriotic colon tissues. Pain was assessed by the visual analogue scale. Serum EGF was significantly lower in mild endometriosis and in the secretory phase. MIF and IL-6 were higher in stage I–IV endometriosis, with MIF also higher in the secretory phase and in patients not receiving oral contraceptives. Somatostatin was lower in mild endometriosis than that in healthy individuals and the severe endometriosis group. No tissue-level differences were found. A strong positive correlation between serum EGF and somatostatin levels and dysmenorrhea and dysuria was detected in mild cases. It is concluded that certain serum alterations may be related to severity- and hormone status-dependent endometriosis mechanisms, but their diagnostic/prognostic value seems to be limited due to variability and lack of specificity. Full article

Spinal cord injury (SCI) is a severe neurological condition that typically results in irreversible loss of motor and sensory function. Emerging evidence indicates that neuroplasticity, the ability of the nervous system to reorganize by forming new neural connections, plays a pivotal role in structural and functional recovery post-injury. This insight lays the groundwork for the development of rehabilitation and therapeutic strategies designed to leverage neuroplasticity. In this review, we offer an exhaustive overview of the neuroplastic alterations and mechanisms that occur following an SCI. We examine the role of neuroplasticity in functional recovery and outline therapeutic approaches designed to augment neuroplasticity post-SCI. The process of neuroplasticity post-SCI involves several physiological processes, such as neurogenesis, synaptic remodeling, dendritic spine formation, and axonal sprouting. Together, these processes contribute to the reestablishment of neural circuits and functional restoration. Enhancing neuroplasticity is a promising strategy for improving functional outcomes post-SCI; however, its effectiveness is influenced by numerous factors, including age, injury severity, time since the injury, and the specific therapeutic interventions employed. A variety of strategies have been suggested to promote neuroplasticity and expedite recovery, including pharmacological treatments, biomaterial-based therapies, gene editing, stem cell transplantation, and rehabilitative training. The combination of personalized rehabilitation programs with innovative therapeutic techniques holds considerable potential for maximizing the benefits of neuroplasticity and enhancing clinical outcomes in SCI management. Full article

Multiple chemical sensitivity (MCS) is a disease of unknown etiology with multiple symptoms. Triggered by exposure to environmental chemicals, it results in multiorgan effects. Studies on MCS use different approaches, ranging from searches for environmental triggers to susceptibility genes. Genetic research deals with genes for chemical detoxification, oxidative stress, inflammation, and neurodegeneration, as well as immune function and mast cell activation, with uneven results. The sensory hyperexcitability symptom has not been studied yet but has recently been linked to a member of the SLC gene superfamily. To explore its role in MCS disease, a complete-exome analysis was performed in a small number of subjects. Low-frequency genetic variants were analyzed for each individual, and their homozygous or heterozygous presence was determined in four groups of genes related either to the SLC superfamily members or to previous studies in MCS. We found homozygous rare variants in affected individuals only for the SLC gene superfamily, where each patient had at least one. Variants in heterozygosis and certain SNPs also point to SLC genes related to neurotransmitter synthesis, release, and clearance, as well as to the level of cellular excitability, as potentially underlying the differences. Full article

Crowding stress is an inevitable stressor in intensive farming, yet its underlying mechanisms are still obscure, severely hindering the aquaculture industry’s healthy development. As the primary sensory and regulatory organ for stressors, the brain plays a crucial role in stress responses. In this study, the effect of crowding stress on the telencephalon (Tel) and hypothalamus (Hy) has been explored using RNA sequencing. After four weeks of crowding stress, neuroinflammation-related genes were significantly induced in both the Tel and Hy. Additionally, cell fate-related processes were markedly altered. Neurogenesis-related pathways, including the Wnt and Hedgehog signaling pathways, were significantly enriched in both regions. The apoptosis-related genes (caspase3, p53) were predominantly downregulated in the Tel (log₂Fold Change: −1.27 and −0.71, respectively), while ferroptosis-related genes (ho1, ncoa4) were specifically activated in the Hy (log₂Fold Change: 1.15 and 0.73, respectively). The synaptic plasticity-related genes (prkcg, cacna1d) were significantly downregulated in both the Tel (log₂Fold Change: −1.78 and −0.88) and Hy (log₂Fold Change: −1.99 and −1.52). Furthermore, neurotransmitter synthesis (γ-aminobutyric acid (GABA) and serotonin (5-HT)) was disrupted in the Tel, whereas growth-related hormone gene expression was markedly altered in the Hy. These findings provide novel insights into the neurobiological mechanisms of chronic crowding stress in fish, laying a foundation for developing brain-targeted strategies to enhance welfare and mitigate stress in intensive largemouth bass farming. Full article

Chronic pain is a multifactorial and complex condition that significantly affects individuals’ quality of life. The underlying mechanisms of chronic pain involve complex alterations in neural circuits, gene expression, and cellular signaling pathways. Recently, ncRNAs, such as miRNAs, lncRNAs, circRNAs, and siRNAs, have been identified as crucial regulators in the pathophysiology of chronic pain. These ncRNAs modulate gene expression at both the transcriptional and post-transcriptional levels, affecting pain-related pathways like inflammation, neuronal plasticity, and sensory processing. miRNAs have been shown to control genes involved in pain perception and nociceptive signaling, while lncRNAs interact with chromatin remodeling factors and transcription factors to modify pain-related gene expression. CircRNAs act as sponges for miRNAs, thereby influencing pain mechanisms. siRNAs, recognized for their gene-silencing capabilities, also participate in regulating the expression of pain-related genes. This review examines the diverse roles of ncRNAs in chronic pain, emphasizing their potential as biomarkers for pain assessment and as targets for novel therapeutic strategies. A profound understanding of the ncRNA-mediated regulatory networks involved in chronic pain could result in more effective and personalized pain management solutions. Full article

The influence of different Saccharomyces cerevisiae (Sc) strains and hop varieties on the physical, chemical and sensory properties of beer was investigated. ISE77, an oenological Sc strain screened for the IRC7 gene and β-lyase activity, and a commercial yeast, as a control, were experimented with two hops (dry hopping), Mosaic^® (M) and Hallertau Mittelfrüh (HM). Both hop variety and yeast strain exerted a considerable influence on the organoleptic profile of the beer. Samples with M hops exhibited elevated levels of specific volatile compounds (e.g., limonene and linalool). ISE77 generated higher levels of esters, irrespective of the hop variety employed, imparting fruity and floral characteristics. Moreover, the beers fermented with ISE77 showed herbal and spicy notes. Regardless of the hop variety, samples brewed with the control yeast showed higher honey and caramel note levels. Beers fermented with ISE77 and HM exhibited remarkable similarities to those produced with ISE77 and M, particularly for some odour attributes (citrus, exotic fruits, and aromatic herbs). These attributes were more intense than in beers fermented with the control yeast and HM. This study demonstrated the potential of oenological Sc strains to achieve innovative brewing outcomes when combined with selected hops. Full article

Rotator cuff tears are a leading cause of shoulder pain and dysfunction, yet the molecular mechanisms that link tendon injury to inflammation and nociceptive signaling remain poorly understood. Netrin-1, a classical axon guidance cue signaling through dependence receptors UNC5B and Neogenin-1, has been implicated in both neuronal plasticity and inflammatory processes, but its role in tendon pathology has not been explored. A rat supraspinatus tear model was employed to assess, in vivo, the expression of genes encoding netrin-1 (Ntn1) and its receptors (Unc5b and Neo1) at 0, 7, 14, 28, and 56 days post-injury (n = 10 per time point). Primary rat tenocytes isolated from rotator cuff tissue were treated in vitro with recombinant netrin-1, and transcriptional changes in genes encoding TNF-α (Tnfa), IL-6 (Il6), MMP-1 (Mmp1), and MMP-3 (Mmp3) were quantified by qRT-PCR. Separately, human iPSC-derived sensory neurons were exposed to netrin-1, and dose- and time-dependent effects on neurite outgrowth were measured at 4 and 14 days in culture. In injured tendons, Ntn1 mRNA increased significantly at day 14 (p = 0.010) and 28 (p = 0.042), Unc5b at day 7 (p = 0.002) and 14 (p < 0.001), and Neo1 at day 14 (p < 0.001) versus intact controls. Tenocyte exposure to 500 ng/mL netrin-1 induced transient upregulation of Tnfa (3 h, p = 0.023; 6 h, p = 0.009) and Il6 (3 h–24 h, all p < 0.013), as well as Mmp3 (3–24 h, p < 0.043) and Mmp1 (6 h–24 h, p < 0.024); no induction was observed at 50 ng/mL. In sensory neurons, 50 ng/mL of netrin-1 enhanced neurite extension at day 4 (p = 0.006) but not at 500 ng/mL or at day 14 for either dose. Netrin-1 and its receptors are upregulated in a rat rotator cuff tear model, and netrin-1 elicits distinct pro-inflammatory and matrix-remodeling responses in tenocytes while promoting early neurite growth in sensory neurons. These findings suggest netrin-1 as a key modulator of tendon inflammation, matrix turnover, and peripheral nerve plasticity following injury. Full article

Background and Objectives: We have previously reported that omega-3 polyunsaturated fatty acids (PUFAs) derived from fish oil (FO) is an effective treatment for type 1 and type 2 diabetes neural and vascular complications. As omega-3 PUFAs become more widely used as a nutritional and disease modifying supplement an important question to be addressed is what is the preferred source of omega-3 PUFAs? Methods: Using a type 2 diabetic rat model and early and late intervention protocols we examined the effect of dietary treatment with omega-3 PUFAs derived from menhaden (fish) oil (MO), krill oil (KO), algal oils consisting primarily of eicosapentaenoic acid (EPA), docosahexaenoic acid (DHA) or combination of EPA + DHA, or pharmaceutical-derived ethyl esters of EPA, DHA or combination of EPA + DHA. Nerve related endpoints included motor and sensory nerve conduction velocity, heat sensitivity of the hind paw, intraepidermal nerve density, cornea nerve fiber length, and cornea sensitivity. Vascular reactivity to acetylcholine and calcitonin gene-related peptide by epineurial arterioles that provide blood to the sciatic nerve was also examined. Results: The dose of each omega-3 PUFA supplement increased the content of EPA, docosapentaenoic acid (DPA), and/or DHA in red blood cell membranes, serum and liver. Diabetes caused a significant decrease of 30–50% of neural function and fiber occupancy of the skin and cornea and vascular reactivity. Treatment with MO, KO or the combination of EPA + DHA provided through algal oil or ethyl esters provided significant improvement of each neural endpoint and vascular function. Algal oil or ethyl ester of EPA alone was the least effective with algal oil or ethyl ester of DHA alone providing benefit that approached combination therapies for some endpoints. Conclusions: We confirm that omega-3 PUFAs are an effective treatment for DPN and sources other than fish oil are similarly effective. Full article

The gut-brain axis (GBA) represents an operant acting in a two-direction communication system between the gastrointestinal tract and the central nervous system, mediated by the enteric nervous system (ENS), vagus nerve, immune pathways, and endocrine signaling. In recent years, evidence has highlighted the pivotal role of the gut microbiota in modulating this axis, forming the microbiota-gut-brain axis (MGBA). Our review synthesizes current knowledge on the anatomical and functional substrates of gut-brain communication, focusing on interoceptive signaling, the roles of intrinsic primary afferent neurons (IPANs) and enteroendocrine cells (EECs) and the influence of microbial metabolites, including short-chain fatty acids (SCFAs), bile acids, and indoles. These agents modulate neurotransmission, epithelial barrier function, and neuroimmune interactions. The vagus nerve serves as a primary pathway for afferent sensory signaling from the gut influenced indirectly by the ENS and microbiota. Dysbiosis has been associated with altered gut-brain signaling and implicated in the pathophysiology of disorders ranging from irritable bowel syndrome to mood disorders and neurodegeneration. Microbial modulation of host gene expression via epigenetic mechanisms, including microRNAs, adds another layer of complexity. The gut has a crucial role as an active sensory and signaling organ capable of influencing higher-order brain functions. Understanding the MGBA has significant implications for new therapeutic interventions targeting the microbiome to manage neurogastroenterological and even neuropsychiatric conditions. Full article

Metal ion measurements using inductively coupled plasma optical emission spectroscopy revealed twofold-higher zinc content in rat brain compared to spinal cord. One hypothesis to explain this difference is the high prevalence of synapses that corelease glutamate and zinc in the brain, marked by the vesicular Zinc Transporter-3 (ZnT3). In contrast, spinal cord tissue showed significantly higher calcium content, reflecting calcifications in the arachnoid. The above observations were made in 60-day-old adult male and female rats fed ad libitum or a restricted diet. In this study, we asked if the calcium and zinc content of the brain and spinal cord was species-specific or evolutionarily conserved, and whether the distinct concentration of zinc in the brain and spinal cord resulted from a different expression pattern of ZnT3, the primary transporter in synaptic vesicles. To address these questions, we examined 8-week-old wild-type male and female mice raised under conventional laboratory conditions and used a knock-in mouse that expresses a human influenza hemagglutinin epitope tag at the C terminus of the endogenous ZnT3 gene to assess the transporter’s abundance in spinal cord sections. Our results show conserved inverse differences in zinc and calcium content in mouse brain and spinal cord, but detectable ZnT3 signal in spinal cord. Whereas vesicular zinc modulates glutamatergic and GABAergic signaling and sensory processing, the functional significance of calcium aggregates in the arachnoid remains unknown. Full article

Olfaction has been extensively studied in the yellow fever mosquito, Aedes aegypti. This species uses its sense of smell to find blood hosts and other resources, contributing to its impact as a vector for human pathogens. Two major families of protein-coding genes, the odorant receptors (Ors) and the ionotropic receptors (Irs), provide the mosquito with sensitivities to distinct classes of volatile compounds in the antennae. Individual tuning receptors in both families require co-receptors for functionality: Orco for all Ors, and Ir8a for many Irs, especially ones that are involved in carboxylic acid detection. In Drosophila melanogaster, disruptions of Orco or Ir8a impair receptor function, tuning receptor expression, and membrane localization, leading to general anosmia. We reasoned that Orco and Ir8a might also be important for coordinated chemosensory receptor expression in the antennal sensory neurons of Ae. aegypti. To test this, we performed RNAseq and differential expression analysis in wildtype versus Orco^−/− and Ir8a^−/− mutant adult female antennae. Our analyses revealed Or and Ir tuning receptors are broadly under-expressed in Orco^−/− mutants, while a subset of tuning Irs are under-expressed in Ir8a mutants. Other chemosensory and non-chemosensory genes are also dysregulated in these mutants. Furthermore, we identify differentially expressed transcription factors including homologs of the Drosophila melanogaster Mip120 gene. These data suggest a previously unknown pleiotropic role for the Orco and Ir8a co-receptors in the coordination of expression of chemosensory receptors within the antennae of Ae. aegypti by participating in a feedback loop involving amos and members of the MMB/dREAM complex. Full article

Fruit astringency, which primarily results from the interaction between polyphenolic compounds such as tannins and salivary proteins, is a critical sensory attribute that limits the commercial value and consumer acceptance of many fruits. A thorough understanding of the mechanisms underlying astringency formation and the development of efficient and safe de-astringency technologies are crucial for the fruit industry. This review systematically elucidates the molecular basis of fruit astringency, focusing on the biosynthesis pathways, accumulation dynamics, and transcriptional regulatory networks of key phenolic substances, such as tannins, as well as their modulation by environmental factors. It also evaluates the efficacy and current applications of existing de-astringency methods and discusses the potential impacts of different treatments on fruit quality attributes. This study thoroughly analyzes the major challenges faced by current technologies, including balancing de-astringency efficiency with quality preservation, ensuring environmental friendliness and food safety, reducing costs, and promoting wider application. Finally, future research directions are discussed, emphasizing the importance of precise genetic improvement using tools such as gene editing, developing green and efficient processes, achieving intelligent process control, and focusing on synergistic quality regulation and the exploration of functional value. This review aims to provide an integrated knowledge framework for developing innovative, efficient, safe, and sustainable fruit de-astringency solutions, offering a scientific reference to advance technological upgrades in the fruit industry. Full article