Search Results (3,179)

Down syndrome (DS) is the most common survivable chromosome trisomy, with an incidence of about 1 in 600–700 births. Consequences of chromosome 21 trisomy include developmental delays, congenital cardiac abnormalities, skeletal abnormalities, and age-related dementia of the Alzheimer’s disease (AD) type. Up to 90% of individuals with DS develop dementia symptoms in their 40s or 50s. Because the biological mechanisms involved in DS-related developmental and age-related pathology are less known, animal models consisting of both lower-order and higher-order animals have been developed. We here review the most pertinent and well-studied DS animal models including models developed in C. elegans, Drosophila, zebrafish, and mice. Molecular pathways involved in DS morbidity that were discovered in animal models will also be discussed. Full article

In space environments, microgravity, high radiation, and weak magnetic fields induce behavioral alterations in animals, resulting in erratic movement patterns that complicate tracking. These challenges impede accurate behavioral analysis, especially in multi-object scenarios. To address this issue, this study proposes a deep learning-based multi-object tracking (MOT) framework specifically designed for space animals. The proposed method decouples appearance and motion features through dual-stream inputs and employs modality-specific encoders (MSEs), which are fused via a heterogeneous graph network to model cross-modal spatio-temporal relationships. Additionally, an object re-detection module is integrated to maintain identity continuity during occlusions or rapid movements. This approach is validated using public datasets of space-observed Drosophila and zebrafish, with experimental results demonstrating superior performance compared with existing tracking methods. This work highlights the potential of artificial intelligence as a valuable tool in behavioral studies, enabling reliable animal tracking and analysis under extreme space conditions and supporting future research in space life sciences. Full article

Studies aiming at evaluating specific changes in gene expression in male zebrafish brains as a consequence of the exposure to acute stressors have not been conducted so far. However, the identification of genes that specifically respond to certain stress situations would improve our understanding of stress responses in fish. For this, a stress trial with acutely stressed male zebrafish was conducted, aiming at identifying relevant differences in gene expressions in different brain parts over time. The qPCR results showed changes of gene expression of genes belonging to the immediate early genes and the stress axis, as well as genes regulating the appetite or serotonergic and dopaminergic pathways in the different brain parts across all treatment groups. Several genes, including urotensin 1, corticotropin-releasing hormone-binding protein, and succinate dehydrogenase, were identified as strongly contributing to the outcome of stress regulation, but these genes considerably differ for each brain part. Thus, the study confirmed that the gene expression patterns strongly depend on the species that is investigated, the quality of the stressor, and the time point of investigation. Furthermore, the current results evaluating only the responses of males will allow the evaluation of gender-specific responses to stress in this fish species in the future. Full article

Perfluorooctane sulfonate (PFOS) is a representative persistent organic pollutant that exerts toxic effects on aquatic organisms. As an alternative to PFOS, sodium p-perfluorous nonenoxybenzene sulfonate (OBS) has been frequently detected in aquatic environments and human tissues in recent years. However, its toxic effects on aquatic organisms and potential health risks to humans remain unclear. Zebrafish embryos are transparent and amenable to in vivo manipulation and observation. Therefore, in the present study, we investigated its developmental toxicity in zebrafish embryos, with PFOS as the positive control. We exposed zebrafish embryos to different concentrations of OBS (15, 20, and 25 mg/L) and PFOS (15 mg/L) for 2–168 h post fertilization (hpf) and then examined physiological and gene expression changes. At 24 hpf, spontaneous twitches in the 25 mg/L OBS group decreased to (5 ± 0.34)/min. By 48 hpf, the 20 mg/L OBS group’s hatching rate was (47.78 ± 2.22)%, significantly lower than the control. At 72 hpf, heart rates in both the PFOS and OBS groups were elevated, at 82 ± 0.6, 84.5 ± 0.5, 89.4 ± 0.3, and 93.7 ± 0.4, respectively. Similarly to PFOS, OBS induced developmental toxicity in zebrafish embryos. In addition, both OBS and PFOS exposure downregulated the expression level of anti-apoptotic Bcl-2 in zebrafish embryos, with a notable 0.53-fold decrease observed in the 25 mg/L OBS group. Conversely, they upregulated the expression levels of pro-apoptotic Bax, Caspase-3, and Caspase-9, with Caspase-3 expression increasing 1.14-, 1.5-, and 1.7-fold in the 15 mg/L PFOS, 20 mg/L OBS, and 25 mg/L OBS groups, respectively. These OBS- and PFOS-induced changes in gene expression increased apoptosis, suggesting that OBS can induce developmental toxicity in zebrafish embryos, and that its effect is comparable to that of PFOS. Therefore, considering its aquatic toxicity, measures aimed at limiting or remediating OBS pollution in the environment are necessary. Full article

Background/Objectives: Perturbation in terminal N-glycan processing is a feature of congenital disorders of glycosylation and neurological disorders. Since treatment options are limited, N-glycans are plausible therapeutic targets. Here, we investigated the consequences of substituting complex/hybrid with oligomannose types of N-glycans on nervous and musculature systems, employing mgat1a and mgat1b mutant zebrafish models. Methods: CRISPR Cas9 technology was employed to engineer the mgat1a zebrafish model. The N-glycan populations in Wt AB, mgat1a−/− and mgat1b−/− zebrafish were characterized via lectin blotting. Motor and sensory functions were measured by tail-coiling and touch-evoked response assays in embryos and larvae. Swimming locomotion and anxiety-like behavior were characterized in adult Wt AB, and mutant zebrafish using motility and novel tank dive assays. Results: The mgat1a−/− model had increased oligomannosylated proteins compared to Wt AB in embryos and dissected brain, spinal cord, skeletal muscle, heart, swim bladder, and skin from adults, supporting a global knockdown of GnT-I activity. Higher levels were also observed in mgat1a−/− relative to mgat1b−/−, except in the brain. Band patterns for oligomannosylated proteins were different between all three zebrafish lines. The mgat1−/− embryos and larvae had deficient motor and sensory functions which persisted into adulthood, with a higher deficiency in mgat1b−/−. Anxiety-like behavior was decreased and increased in adult mgat1a−/− and mgat1b−/−, respectively, compared to Wt AB. Conclusions: Taken together, this study revealed that aberrant terminal N-glycan processing impacts brain, spinal and muscle control, and hence will enhance our understanding of the vital role of complex/hybrid N-glycans in nervous system health. Full article

Although cyclic adenosine monophosphate (cAMP) is not a major secondary messenger in the visual transduction cascade in vertebrates, it may modulate photoreceptor functions. The effects of cAMP have been extensively studied in rods; however, its role in cones remains less understood. The aim of this study was to investigate the effects of increased levels of cAMP on the photoresponses of isolated blue- and green-sensitive cones in adult zebrafish (Danio rerio). To examine the effects of elevated cAMP on individual cone spectral types, photoreceptor currents were recorded using a suction pipette method. The adenylate cyclase activator forskolin was used to increase intracellular cAMP levels. Sensitivity and photoresponse parameters were compared before and after forskolin application. An increase in cAMP levels has similar effects on photoresponses of blue- and green-sensitive cones. Forskolin application to both types of cones resulted in a slight increase in sensitivity, with significant slowing of the phototransduction cascade shutdown processes and a marked increase in the integration time of photoresponses. These findings suggest that intracellular cAMP levels, which fluctuate in the retina during the diurnal cycle, can modulate cone function. The observed effects of cAMP are consistent with its action on one of its main putative targets, opsin kinases. Full article

Aluminium (Al) is a widespread environmental contaminant known to induce oxidative stress and genotoxic effects in aquatic organisms. While its neurotoxic properties are well documented, the molecular impact of Al on the visual system remains poorly understood. In this study, adult zebrafish (Danio rerio) were exposed to 11 mg/L Al for 10, 15, and 20 days to investigate the oxidative and genotoxic responses in ocular tissue. Activities of antioxidant enzymes superoxide dismutase (SOD) and catalase (CAT) were measured in eye supernatants to detect oxidative stress. Additionally, the activities of poly (ADP-ribose) polymerase (PARP) and poly (ADP-ribose) glycohydrolase (PARG) were assessed in tissue homogenates to evaluate oxidative DNA damage and repair processes. The results indicate that these enzymes respond to counteract the increased reactive oxygen species (ROS) induced by aluminium exposure. However, their activity may not sufficiently reduce ROS levels to fully prevent oxidative DNA damage, as evidenced by a significant rise in PARP activity during short exposure times. Over longer exposures, PARP activity returned to baseline, suggesting ocular cells may adapt to aluminium toxicity. We propose that this reduction in PARP activity is a cellular survival mechanism, as sustained activation can deplete energy reserves and trigger cell death. Finally, thin-layer chromatography confirmed that PARG facilitates the breakdown of poly (ADP-ribose) (PAR) into ADP-ribose, demonstrating the dynamic regulation of the PAR cycle, which is crucial to preventing parthanatos. Full article

Histamine can damage the antioxidant and immune systems in fish and crustaceans. Rutin, a natural substance with a diverse phenolic structure, has demonstrated antioxidant and anti-inflammatory properties. However, whether rutin can mitigate histamine-induced negative effects remains uninvestigated in fish models. This study investigated the effect of 0.1–100 μM rutin preincubation on histamine (29.5 mM)-induced cytotoxicity in zebrafish liver cells (ZFL) and its potential mechanisms. Results showed that 0.1–100 μM rutin significantly improved ZFL cell survival following histamine stimulation and protected cellular morphology. Rutin inhibited the adverse effects of histamine on ZFL by scavenging or suppressing the accumulation of reactive oxygen species (ROS), H₂O₂, and malondialdehyde (MDA), while increasing the activities of superoxide dismutase (SOD), catalase (CAT), and total antioxidant capacity (T-AOC). At the protein level, 10 μM rutin significantly promoted Nrf2 protein expression. HO-1 protein was significantly up-regulated after preincubation with 0.1–10 μM rutin, whereas IL-1β protein levels were significantly down-regulated. The mechanism may involve activation of the Nrf2 antioxidant signaling pathway and inhibition of the NF-κB inflammatory signaling pathway. In summary, within the experimental concentration range, 10 μM rutin showed the strongest inhibitory effects on histamine-induced ZFL cell death and oxidative stress. This study provides a theoretical basis and data support for evaluating rutin’s feasibility as a green aquatic feed additive. Full article

Tetramethyl bisphenol A (TMBPA), a novel alternative to Bisphenol A, is widely used as an industrial flame retardant and a raw material for tetramethyl polycarbonate plastics. With the increasing use of TMBPA, its aquatic ecological risks remain unclear. Therefore, this study investigated the developmental toxicity of TMBPA using zebrafish (Danio rerio) as a model, exposing embryos to 0.5, 5, 50, and 200 μg/L TMBPA for 120 h. The results showed that treatment with 5, 50, and 200 μg/L TMBPA decreased the hatching rate of zebrafish embryos at 48 h post-fertilization (hpf), while no significant difference was observed at 72 hpf. Meanwhile, TMBPA exposure at all concentrations showed no significant effect on the survival rate. Furthermore, a high concentration of TMBPA (200 μg/L) significantly reduced the total length and suppressed swimming ability in zebrafish larvae. In addition, gene expression analysis revealed impacts on antioxidant system (cat, gpx, mn-sod, keap1, ucp2, nrf2), hypothalamic–pituitary–thyroid (HPT) axis (ttr, ugt1ab, trβ), cardiac developmental (tbx2b, myl7, bmp4, notch1b, amhc), and the hypothalamic–pituitary–adrenal (HPA) axis (pomca and nr3c1). The results indicated that TMBPA exposure adversely disrupted embryo hatching and larval development of zebrafish, accompanied by altering the expression of functional genes in larvae. These results provide further evidence for the potential environmental hazard posed by TMBPA. Full article

Glyphosate (GLY) and microcystin-LR (MC-LR) frequently co-occur in natural water bodies. In this study, a subacute exposure test was conducted on zebrafish treated with 3.5 mg/L GLY and 35 μg/L MC-LR, individually and in combination, for 21 d to determine their effects on the gills of zebrafish and their potential mechanisms. The hematoxylin and eosin staining and scanning electron microscopy examination results showed that GLY and MC-LR exposure caused structural damage to gills. Biochemical analysis revealed Na⁺-K⁺-ATPase activity decreased, and the levels of reactive oxygen species, 8-hydroxy-2′-deoxyguanosine, and malondialdehyde increased, inducing oxidative damage to DNA and lipids of gills. Meanwhile, the inflammatory and immune function of the gill was significantly influenced, as evidenced by the alteration of the expression of tumor necrosis factor-α, interleukin-1β, complement 3, and immunoglobulin M. RNA-seq results revealed that GLY and/or MC-LR treatment induced transcriptional changes in the fish gills, which may affect various biological functions, and the lipid metabolism disruption potentially involved in the aforementioned process. Integrating histopathological, biochemical, and transcriptomic analyses, this study revealed that both individual and combined exposures to GLY and MC-LR had adverse effects on zebrafish gills, with combined exposure appears to result in more pronounced adverse effects, potentially compromising fish health. Full article

The present work evaluates the influence of two prebiotic formulations—P1 (ColonX) and P4 (a product containing AnXietate extract), at concentrations of 3 and 6 mg/L—on scopolamine (SCOP, 100 μM)-induced cognitive dysfunction and anxiety-related behaviors in adult zebrafish (Danio rerio). To assess behavioral alterations, wild-type fish were subjected to the novel tank assay (NTT), Y-maze study, and novel object recognition test protocol (NOR). The formulations were examined for potential anti-inflammatory activity and cytotoxicity. In parallel, in vitro assays were performed to evaluate cytotoxic and anti-inflammatory effects. The results indicate that both prebiotic formulations effectively mitigated SCOP-induced behavioral impairments and improved cognitive performance in zebrafish. Furthermore, the prebiotic formulation P4 showed significant anti-inflammatory activity without inducing cytotoxicity. The study was conducted following ethical guidelines, ensuring scientific rigor and integrity. These findings highlight the therapeutic potential of prebiotics in alleviating anxiety and cognitive deficits, with promising implications for the management of neuropsychiatric disorders. Full article

Photophores are light-producing organs found in many fish species living in the mesopelagic, bathypelagic, and abyssal layers of the ocean. They function to attract prey, confuse predators, and communicate with other individuals of the same species. Understanding the structure and function of photophores is crucial to exploring bioluminescence and the ecological adaptations of marine life in deep-sea environments. The present study is the first to investigate the photophore anatomy of the mesopelagic fish Ichthyococcus ovatus (Cocco, 1838), using specimens naturally stranded along the coast of the Strait of Messina. The morphology of the ventral photophores of I. ovatus includes four functional parts: a tank containing photogenic cells, a lens filter, a reflector surrounding the entire organ, and a pigmented layer. An immunohistochemical assay was conducted using anti-nNOS and anti-S100p antibodies. The presence of nNOS/NOS type I immunolabeling the pigmented layer surrounding the photophores and the nerve fibers reaching the lens suggests a potential role of neuronal nitric oxide signaling in modulating light shielding by the pigment sheath, controlling light exposure, and adjusting light focusing though the lens-associated nerves. S100p immunostaining was observed in the nerve fibers reaching the photophores, highlighting its potential involvement in regulating neuronal calcium levels and, consequently, influencing signal transmission to control bioluminescence output. A sensory feedback pathway from the photophore to the CNS is suggested. Within the lens and in the irregularly shaped cells located in the photophore’s lens, S100p immunolabeling could indicate active signaling and differentiation processes. These findings expand our understanding of light-emitting systems in mesopelagic fishes and offer a valuable foundation for future studies on the functional and evolutionary significance of photophores. Full article

Plastics have become integral to modern life; however, their widespread use and persistent nature have resulted in significant environmental contamination, especially by microplastics (MPs < 5 mm) and nanoplastics (NPs < 100 nm). These plastic particles can enter the human body via ingestion, inhalation, or dermal absorption, raising substantial concerns about their potential health impacts. Recent studies using zebrafish, rodent models, and human cell lines have begun to elucidate the mechanisms underlying micro- and nanoplastics (MNPs)-induced toxicity. These mechanisms include oxidative stress, inflammation, disruption of metabolic processes, neurotoxicity, reproductive dysfunction, and carcinogenicity. Despite these advances, significant knowledge gaps remain. There remains a lack of comprehensive reviews that systematically evaluate these effects across major human organ systems and address how MNPs cross biological barriers in the human body. This review addresses these gaps by summarizing the available evidence on MNPs’ toxicity, critically discussing their absorption, distribution, metabolism, and the associated cellular and molecular mechanisms of action. Furthermore, it outlines urgent research priorities, emphasizing the need for standardized analytical protocols, realistic exposure models, and extended epidemiological research to evaluate human health risks posed by MNPs accurately. In addition, the adoption of precautionary regulatory actions is recommended to mitigate exposure and safeguard public health. Full article

Background: Glioblastoma, the most common malignant primary brain tumor in adults, continues to present a major therapeutic challenge, with a median survival of only 12–15 months and a 5-year survival rate below 2%. Despite aggressive treatment—including maximal surgical excision, radiation, and temozolomide (TMZ) chemotherapy—recurrent disease is nearly universal due to the tumor’s infiltrative nature. Objectives: To address the critical need for improved diagnostic and therapeutic strategies for glioblastoma multiforme (GBM), we have developed an innovative theranostic molecule, [^99mTc]Tc-AGT-7. Methods: AGT-7 integrates diagnostic and therapeutic modalities comprising [^99mTc]Tc-TF (a nuclear medicine imaging agent) and TMZ. The diagnostic component has been tailored to selectively accumulate in glioma mitochondria. A chelating moiety enables radiolabeling with technetium-99m (^99mTc) for precise Single-Photon Emission Computed Tomography (SPECT) imaging. The therapeutic arm includes the tethering of a TMZ moiety for localized cytotoxicity. Conclusions: In vitro studies illustrated that AGT-7 has potent cytotoxic effects in GBM cell lines (T98 and U87), with greater efficacy than TMZ, and toxicity assays in zebrafish embryos indicated a favorable safety profile. Biodistribution studies in CFW mice demonstrated that [^99mTc]Tc-AGT-7 exhibited a ~10-fold lower heart uptake compared to [^99mTc]Tc-TF, implying reduced off-target cardiac localization. This significantly lowers the risk of cardiotoxicity and enhances AGT-7’s potential as a glioma-targeted theranostic agent. Full article

This study comprehensively evaluated how the inclusion of the inner shell and the choice of extraction method influence the antioxidant activity of Quercus Fructus (QF). Eight QF extracts were prepared with or without the inner shell using stirring (S) and ultrasonication (U) with 80% ethanol, boiled water (B) and autoclave (A) with distilled water. Among them, the ultrasonication extract with inner shell (IU) exhibited the highest antioxidant capacity, showing strong DPPH radical scavenging (228.8 mg TEAC/g), ABTS activity (162.9 mg TEAC/g), reducing power (380.9 mg TERP/g), and SOD-like activity (38.1%). HPLC-UV profiling identified quercetin-7-glucoside (Q7G) as a major detectable compound, although several polar phenolics remained unidentified. In LPS-stimulated Raw 264.7 cells, IU significantly suppressed nitric oxide production and iNOS expression without cytotoxicity. Additionally, IU treatment markedly reduced ROS accumulation in H₂O₂-exposed zebrafish embryos. These findings suggest that including the inner shell with ultrasonication extraction synergistically enhances QF’s antioxidant efficacy, suggesting a practical strategy for maximizing the functional potential of QF in natural antioxidant development. Full article