Search Results (72)

Background: There is growing interest in the potential role of manganese (Mn) in the development of Alzheimer’s Disease and related dementias (ADRD). Methods: In this nested pilot study of a ferroalloy worker cohort, we investigated the impact of chronic occupational Mn exposure on cognitive function through β-amyloid (Aβ) deposition and multi-omics profiling. We evaluated six male Mn-exposed workers (median age 63, exposure duration 31 years) and five historical controls (median age: 60 years), all of whom had undergone brain PET scans. Exposed individuals showed significantly higher Aβ deposition in exposed individuals (p < 0.05). The average annual cumulative respirable Mn was 329.23 ± 516.39 µg/m³ (geometric mean 118.59), and plasma Mn levels were significantly elevated in the exposed group (0.704 ± 0.2 ng/mL) compared to controls (0.397 ± 0.18 in controls). Results: LC-MS/MS-based pathway analyses revealed disruptions in olfactory signaling, mitochondrial fatty acid β-oxidation, biogenic amine synthesis, transmembrane transport, and choline metabolism. Simoa analysis showed notable alterations in ADRD-related plasma biomarkers. Protein microarray revealed significant differences (p < 0.05) in antibodies targeting neuronal and autoimmune proteins, including Aβ (25–35), GFAP, serotonin, NOVA1, and Siglec-1/CD169. Conclusion: These findings suggest Mn exposure is associated with neurodegenerative biomarker alterations and disrupted biological pathways relevant to cognitive decline. Full article

Nose-to-brain drug delivery is an innovative approach that leverages the unique anatomical pathways connecting the nasal cavity to the brain, including the olfactory and trigeminal nerve routes. This method bypasses the blood–brain barrier, enabling direct and efficient transport of therapeutic agents to the central nervous system. It offers significant advantages, such as rapid drug action, reduced systemic side effects, and improved patient compliance through non-invasive administration. This entry summarizes factors affecting the nose-to-brain delivery of drugs and the recent development of nanoparticle-based nose-to-brain delivery. Full article

The Junggar Bactrian camel, a primitive indigenous breed in China, exhibits low reproductive efficiency under natural grazing conditions. This is partly attributed to the development of the epididymis and the quality of semen, both of which directly affect reproductive performance. The epididymis is a key male reproductive organ responsible for sperm storage and transport. However, the gene expression profile of camel epididymal tissue remains poorly understood. In this study, we conducted whole-transcriptome sequencing of epididymal tissues from Junggar Bactrian camels before and after sexual maturity. A total of 683 differentially expressed mRNAs (DEmRNAs) were identified, including TPM2, ITGA5, FASN, and ACP5, of which 415 were upregulated and 268 were downregulated. Additionally, 260 differentially expressed long non-coding RNAs (DELncRNAs), including LOC123611838, LOC105083505, and LOC123614702, were identified, with 113 upregulated and 147 downregulated. An additional 11 differentially expressed microRNAs (DEmiRNAs), including eca-miR-206 and eca-miR-216a, were also detected. Gene Ontology (GO) annotation and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analyses revealed that key differentially expressed genes (DEGs), including TPM2, ITGA5, DDIT4, FASN, and ACP5, were mainly involved in pathways such as Cell Adhesion Molecules, Phospholipase D signaling, Cytokine–Cytokine Receptor Interaction, and Olfactory Transduction. This study presents a comprehensive whole-transcriptome analysis of the epididymis in Junggar Bactrian camels before and after sexual maturity, identifying key genes and regulatory pathways associated with epididymal development and reproductive function. These findings provide a theoretical foundation and valuable data for future research on reproductive performance and epididymal biology in Bactrian camels. Full article

As population aging becomes an increasingly critical global issue, the incidence of central nervous system (CNS) diseases, including Alzheimer’s disease (AD), Parkinson’s disease (PD), and stroke, has risen sharply. However, the blood–brain barrier (BBB) presents a significant obstacle to the effective treatment of these CNS disorders, limiting the ability of therapeutic agents to reach the brain. In this context, intranasal drug delivery, which bypasses the BBB, has attracted considerable attention in recent years. By utilizing pathways such as the olfactory and trigeminal nerves, intranasal drug delivery facilitates the rapid transport of drugs to the brain, thereby enhancing both the bioavailability and targeting efficiency of the drugs. This review provides an overview of the molecular mechanisms underlying intranasal drug delivery, its advancements in the treatment of CNS diseases, strategies to improve delivery efficiency, and a discussion of the challenges and potential future directions in this field. The aim of this paper is to offer valuable insights and guidance for researchers and clinicians working in the area of CNS disease treatment. Full article

Nasal nanodrug delivery has gained prominence as a non-invasive method for administering therapeutic agents to the brain. However, the limited nasal cavity volume and the low drug loading capacity of nanoparticles contribute to a reduced accumulation of the drug within the brain tissue. Therefore, the aim of the present study was to investigate the role of the drug delivery combination “transnasal route + nanoparticle drug delivery system + chemical osmosis technology” in promoting drug accumulation in the brain. We constructed an in vitro olfactory sheath cell model based on the direct nose–brain pathway and a vascular endothelial cell model based on the indirect pathway, and investigated the transport behaviors and mechanisms of Poly(lactic-co-glycolicacid)-Nanoparticles (PLGA-NPs) in combination with two terpene aroma constituents (menthol and curcumol). Menthol and curcumol significantly improved the intracellular accumulation of PLGA-NPs, which may be related to changes in the endocytosis pathway and intercellular tight junction proteins. Meanwhile, the results of laser scanning confocal microscopy and atomic force microscopy showed that menthol and curcumol disrupted different tight junction proteins of vascular endothelial cells, and the biomechanical properties (e.g., rigidity and roughness) of the olfactory sheath cells and vascular endothelial cell cytomembranes were also greatly changed. The delivery system of “transnasal route + nanoparticle drug delivery system + chemical osmosis technology” has great potential for intranasal delivery of drugs for the treatment of brain diseases. Full article

An abnormal accumulation of misfolded proteins is a common feature shared by most neurodegenerative disorders. Olfactory dysfunction (OD) is common in the elderly population and is present in 90% of patients with Alzheimer’s or Parkinson’s disease, usually preceding the cognitive and motor symptoms onset by several years. Early Aβ, tau, and α-synuclein protein aggregates deposit in brain structures involved in odor processing (olfactory bulb and tract, piriform cortex, amygdala, entorhinal cortex, and hippocampus) and seem to underly OD. The glymphatic system is a glial-associated fluid transport system that facilitates the movement of brain fluids and removes brain waste during specific sleep stages. Notably, the glymphatic system became less functional in aging and it is impaired in several conditions, including neurodegenerative diseases. As the nasal pathway has been recently described as the main outflow exit of cerebrospinal fluid and solutes, we hypothesized that OD may indeed be a clinical marker of early glymphatic dysfunction through abnormal accumulation of pathological proteins in olfactory structures. This effect may be more pronounced in peri- and postmenopausal women due to the well-documented impact of estrogen loss on the locus coeruleus, which may disrupt multiple mechanisms involved in glymphatic clearance. If this hypothesis is confirmed, olfactory dysfunction might be considered as a clinical proxy of glymphatic failure in neurodegenerative diseases. Full article

During their lives, insects must cope with a plethora of chemicals, of which a few will have an impact at the behavioral level. To detect these chemicals, insects use several protein families located in their main olfactory organs, the antennae. Inside the antennae, odorant-binding proteins (OBPs), as the most studied protein family, bind volatile chemicals to transport them. Pheromone-binding proteins (PBPs) and general-odorant-binding proteins (GOPBs) are two subclasses of OBPs and have evolved in moths with a putative olfactory role. Predictions for OBP–chemical interactions have remained limited, and functional data collected over the years unused. In this study, chemical, protein and functional data were curated, and related datasets were created with descriptors. Regression algorithms were implemented and their performance evaluated. Our results indicate that XGBoostRegressor exhibits the best performance (R² of 0.76, RMSE of 0.28 and MAE of 0.20), followed by GradientBoostingRegressor and LightGBMRegressor. To the best of our knowledge, this is the first study showing a correlation among chemical, protein and functional data, particularly in the context of the PBP/GOBP family of proteins in moths. Full article

V-ATPases are ubiquitous and evolutionarily conserved rotatory proton pumps, which are crucial for maintaining various biological functions. Previous investigations have shown that a V-ATPase is present in the support cells of moth trichoid sensilla and influences their olfactory sensory neuron performance. Generally, V-ATPases are thought to regulate the pH value within the sensillum lymph, and aid K⁺ homeostasis within the sensillum. This, in turn, could influence various mechanisms involved within the support cells, like maintaining the receptor membrane potential (receptor current), nutrient and ion transport, odorant solubility, and various signaling mechanisms. In this study, we identify V-ATPase expression and localization in the Drosophila melanogaster antenna using bioinformatics and immunohistochemistry. Elucidating an olfactory V-ATPase function will improve our current understanding of how support cells contribute to Drosophila’s sense of smell. Full article

Stingless bees (Hymenoptera; Apidae; Meliponini), with a biodiversity of 605 species, harvest and transport corbicula pollen to the nest, like Apis mellifera, but process and store the pollen in cerumen pots instead of beeswax combs. Therefore, the meliponine pollen processed in the nest was named pot-pollen instead of bee bread. Pot-pollen has nutraceutical properties for bees and humans; it is a natural medicinal food supplement with applications in health, food science, and technology, and pharmaceutical developments are promising. Demonstrated synergism between Tetragonisca angustula pot-pollen ethanolic extracts, and antibiotics against extensively drug-resistant (XDR) bacteria revealed potential to combat antimicrobial resistance (AMR). Reviewed pot-pollen VOC richness was compared between Australian Austroplebeia australis (27), Tetragonula carbonaria (31), and Tetragonula hogkingsi (28), as well as the Venezuelan Tetragonisca angustula (95). Bioactivity and olfactory attributes of the most abundant VOCs were revisited. Bibliometric analyses with the Scopus database were planned for two unrelated topics in the literature for potential scientific advances. The top ten most prolific authors, institutions, countries, funding sponsors, and sources engaged to disseminate original research and reviews on pot-pollen (2014–2023) and direct injection food flavor (1976–2023) were ranked. Selected metrics and plots were visualized using the Bibliometrix-R package. A scholarly approach gained scientific insight into the interaction between an ancient fermented medicinal pot-pollen and a powerful bioanalytical technique for fermented products, which should attract interest from research teams for joint projects on direct injection in pot-pollen flavor, and proposals on stingless bee nest materials. Novel anti-antimicrobial-resistant agents and synergism with conventional antibiotics can fill the gap in the emerging potential to overcome antimicrobial resistance. Full article

To better cope with stress in emergencies, emergency personnel undergo virtual reality (VR) stress training. Such training typically includes visual, auditory and sometimes tactile impressions, whereas olfactory stimuli are mostly neglected. This concept paper therefore examines whether odors might be beneficial for further enhancing the experience of presence and immersion into a simulated environment. The aim is to demonstrate the benefits of VR civilian stress training for emergency personnel and to investigate the role of odors as stressors by manipulating the degree of perceived psychophysiological stress via olfactory impressions. Moreover, the current paper presents the development and validation of a convenient and portable fragrance dosing system that allows personalized odor presentation in VR. The presented system can transport reproducible small quantities of an air-fragrance mixture close to the human nose using piezoelectric stainless steel micropumps. The results of the fluidic system validation indicate that the micropump is suitable for releasing odors close to the nose with constant amounts of odor presentation. Furthermore, the theoretical background and the planned experimental design of VR stress training, including odor presentation via olfactory VR technology, are elucidated. Full article

Equine herpesvirus type 1 (EHV-1) causes rhinopneumonitis, abortion, and neurological outbreaks (equine herpesvirus myeloencephalopathy, EHM) in horses. EHV-1 also causes lethal encephalitis in small laboratory animals such as mice and hamsters experimentally. EHV-1 ORF76 is a homolog of HSV-1 US9, which is a herpesvirus kinase. Starting with an EHV-1 bacterial artificial chromosome clone of neuropathogenic strain Ab4p (pAb4p BAC), we constructed an ORF76 deletion mutant (Ab4p∆ORF76) by replacing ORF76 with the rpsLneo gene. Deletion of ORF76 had no influence on replication, cell-to-cell spread in cultured cells, or replication in primary neuronal cells. In Western blots of EHV-1-infected cell lysates, an EHV-1 US9-specific polyclonal antibody detected multiple bands ranging from 35 to 42 kDa. In a CBA/N1 mouse infection model following intranasal inoculation, the parent and Ab4p∆ORF76 revertant caused the same histopathology in the brain and olfactory bulbs. The parent, Ab4p∆ORF76, and revertant mutant replicated similarly in the olfactory mucosa, although Ab4p∆ORF76 was not transported to the olfactory bulbs and was unable to infect the CNS. These results indicated that ORF76 (US9) plays an essential role in the anterograde spread of EHV-1. Full article

Numerous insects are attracted to low levels of ammonia, utilizing it as a cue to locate food sources. The Ammonium Transporter (Amt), a highly conserved, atypical olfactory receptor, has been shown to mediate the detection of ammonia in insects. While the attraction of Tephritidae to ammonia is well established, knowledge about the Amt in this family is limited. The species Bactrocera dorsalis (Hendel 1912), Bactrocera cucurbitae (Coquillett 1899), Bactrocera correcta Bezzi 1916 and Bactrocera tau (Walker 1849), which are common agricultural pests within Tephritidae, exhibit numerous ecological similarities, offering a solid foundation for studying Amt characteristics in this family. In this study, we elucidated the sequences, evolutionary relationships, and expression patterns of Amt in these four species. The results indicated that these Amts share the same open reading frame, containing 1770 bp that encode a protein of 589 amino acid residues. These Amt proteins exhibit the typical structural characteristics of Amts, including an 11-transmembrane domain with an extracellular N-terminus and an intracellular C-terminus. They also have the ability to form trimers in the membrane. Additionally, they contain three conserved amino acid residues essential for ammonia transport: A189, H195, and H352. Phylogenetic and expression pattern analyses showed that they are highly conserved in Diptera and are significantly expressed in antennae. This study is the first report characterizing the Amt gene in four Tephritidae species. These findings provide a foundation for further exploration into the roles of these genes in their particular biological contexts. Full article

Direct nose-to-brain drug delivery, a promising approach for treating neurological disorders, faces challenges due to anatomical variations between adults and children. This study aims to investigate the spatial particle deposition of micron-sized particles in the nasal cavity among adult and pediatric subjects. This study focuses on the olfactory region considering the effect of intrasubject parameters and particle properties. Two child and two adult nose models were developed based on computed tomography (CT) images, in which the olfactory region of the four nasal cavity models comprises 7% to 10% of the total nasal cavity area. Computational Fluid Dynamics (CFD) coupled with a discrete phase model (DPM) was implemented to simulate the particle transport and deposition. To study the deposition of micrometer-sized drugs in the human nasal cavity during a seated posture, particles with diameters ranging from 1 to 100 μm were considered under a flow rate of 15 LPM. The nasal cavity area of adults is approximately 1.2 to 2 times larger than that of children. The results show that the regional deposition fraction of the olfactory region in all subjects was meager for 1–100 µm particles, with the highest deposition fraction of 5.7%. The deposition fraction of the whole nasal cavity increased with the increasing particle size. Crucially, we identified a correlation between regional deposition distribution and nasal cavity geometry, offering valuable insights for optimizing intranasal drug delivery. Full article

Alzheimer’s disease (AD) is a neurodegenerative olfactory disorder affecting millions of people worldwide. Alterations in the hexosamine- or glucose-related pathways have been described through AD progression. Specifically, an alteration in glucosamine 6 phosphate isomerase 2 (GNPDA2) protein levels has been observed in olfactory areas of AD subjects. However, the biological role of GNPDA2 in neurodegeneration remains unknown. Using mass spectrometry, multiple GNPDA2 interactors were identified in human nasal epithelial cells (NECs) mainly involved in intraciliary transport. Moreover, GNPDA2 overexpression induced an increment in NEC proliferation rates, accompanied by transcriptomic alterations in Type II interferon signaling or cellular stress responses. In contrast, the presence of beta-amyloid or mutated Tau-P301L in GNPDA2-overexpressing NECs induced a slowdown in the proliferative capacity in parallel with a disruption in protein processing. The proteomic characterization of Tau-P301L transgenic zebrafish embryos demonstrated that GNPDA2 overexpression interfered with collagen biosynthesis and RNA/protein processing, without inducing additional changes in axonal outgrowth defects or neuronal cell death. In humans, a significant increase in serum GNPDA2 levels was observed across multiple neurological proteinopathies (AD, Lewy body dementia, progressive supranuclear palsy, mixed dementia and amyotrophic lateral sclerosis) (n = 215). These data shed new light on GNPDA2-dependent mechanisms associated with the neurodegenerative process beyond the hexosamine route. Full article

Pheromone-binding proteins (PBPs) play important roles in binding and transporting sex pheromones. However, the PBP genes identified in coleopteran insects and their information sensing mechanism are largely unknown. Cyrtotrachelus buqueti (Coleoptera: Curculionidae) is a major insect pest of bamboo plantations. In this study, a novel PBP gene, CbuqPBP2, from C. buqueti was functionally characterized. CbuqPBP2 was more abundantly expressed in the antennae of both sexes than other body parts, and its expression level was significantly male-biased. Fluorescence competitive binding assays showed that CbuqPBP2 exhibited the strongest binding affinity to dibutyl phthalate (K_i = 6.32 μM), followed by styrene (K_i = 11.37 μM), among twelve C. buqueti volatiles. CbuqPBP2, on the other hand, showed high binding affinity to linalool (K_i = 10.55), the main volatile of host plant Neosinocalamus affinis. Furthermore, molecular docking also demonstrated the strong binding ability of CbuqPBP2 to dibutyl phthalate, styrene, and linalool, with binding energy values of −5.7, −6.6, and −6.0 kcal/mol, respectively, and hydrophobic interactions were the prevailing forces. The knockdown of CbuqPBP2 expression via RNA interference significantly reduced the electroantennography (EAG) responses of male adults to dibutyl phthalate and styrene. In conclusion, these results will be conducive to understanding the olfactory mechanisms of C. buqueti and promoting the development of novel strategies for controlling this insect pest. Full article