搜索结果：Translational animal science

Translation failure, in which promising animal study results cannot be reproduced in human trials, is a challenge in biomedical research. Metrics for replication success are widely used to evaluate reproducibility, that is the extent to which the results of a study agree with those of replication studies. The relevance of these metrics in assessing animal-to-human translation success (or failure) is unclear. We conducted a simulation study to examine whether these metrics can quantify translation success, and how their performance varies under different conditions. Using parameters from a meta-analysis on prenatal amino acid supplementation and maternal blood pressure, we simulated animal and human studies under 648 scenarios, varying effect sizes, heterogeneity, animal sample sizes, and number of pooled animal studies. Nine metrics were assessed, namely the two-trials rule, meta-analysis, replication Bayes factor, unweighted and weighted Edgington's methods, golden skeptical p-value, and three versions of controlled skeptical p-value. Most metrics, except meta-analysis and replication Bayes factor, controlled false positive rates under no heterogeneity, but became liberal as heterogeneity increased, particularly between human studies. Translation power (i.e. the probability of true positive translation success) was constrained by the weaker evidence of the two findings; for example, small sample size in the animal studies resulted in lower translation power. The metric based on meta-analysis frequently indicated success when either of the species found strong evidence, while skeptical p-values were more conservative. The skeptical p-value that controls overall type-one error and the weighted version of Edgington's method performed relatively consistently across scenarios. However, no metric was uniformly optimal. Metrics developed for replication studies can inform assessments of translation, but their utility depends on the underlying evidence and assumptions. Using multiple metrics in combination, with attention to their strengths and limitations, is recommended for evaluating the translation of animal findings to human outcomes.

Metabolic dysfunction-associated steatotic liver disease (MASLD) has become the most prevalent chronic liver disease worldwide, yet no pharmacological therapy has achieved regulatory approval. Flavonoids, plant-derived polyphenols encompassing seven structural subclasses, exhibit considerable preclinical promise through multi-target mechanisms but face translational barriers owing to poor oral bioavailability and insufficient clinical validation. This review systematically evaluates 33 structurally characterized single flavonoids for their therapeutic mechanisms, pharmacological targets, and translational prospects in MASLD, integrating evidence from cellular models, diverse rodent models, and available clinical trials. A tiered evidence classification (Levels A-C) was applied based on clinical data availability, multi-model validation, mechanistic depth, and study design rigor. Mechanistically, flavonoids restore hepatic lipid homeostasis by concurrently inhibiting SREBP-1c-mediated de novo lipogenesis and promoting PPARα-driven fatty acid β-oxidation via AMPK activation; ameliorate insulin resistance through IRS-1/PI3K/Akt signaling; attenuate hepatic inflammation by suppressing NF-κB/NLRP3 inflammasome cascades; reinforce antioxidant defenses via Nrf2/ARE-mediated induction of HO-1, SOD, and GPX4 with concomitant ferroptosis inhibition; enhance autophagic-lysosomal lipid clearance through TFEB nuclear translocation and Sirt1-dependent lipophagy; and remodel gut microbiota composition to fortify intestinal barrier integrity. Genistein, dihydromyricetin, quercetin, and kaempferol exemplify polypharmacological engagement across multiple pathways. Despite robust mechanistic evidence, oral bioavailability remains limited to 1%-5% owing to poor aqueous solubility, extensive phase II conjugation, and food-matrix interactions. Emerging strategies-carbamate prodrugs, nanoliposomes, biomimetic nanoemulsions, and colon-targeted nanoparticles-demonstrate feasibility in surmounting these barriers. Clinical evidence reveals compound-specific efficacy profiles: hesperidin reduces steatosis and transaminases; genistein improves insulin sensitivity; naringenin ameliorates lipid profiles without altering fibrosis markers. Critical appraisal identifies persistent limitations including small sample sizes, predominant reliance on male animals, short intervention durations, and absence of biopsy-confirmed endpoints. Future research must prioritize rigorous multicenter randomized controlled trials with optimized formulations, comparative efficacy studies, systematic safety evaluations, and multi-omics integration to bridge the translational gap toward evidence-based flavonoid therapeutics for MASLD.

Aortic aneurysm (AA) and aortic dissection (AD) are catastrophic aortic disorders characterized by progressive structural weakening or acute medial tearing, often resulting in rupture and high mortality. Their complex and heterogeneous pathogenesis-spanning extracellular matrix degradation, vascular smooth muscle cell dysfunction, inflammation, and dysregulated signaling-necessitates robust experimental systems. Diverse animal and engineered models have been developed to capture key features of these diseases, yet each recapitulates only specific aspects of human pathology. This review aims to: (1) systematically summarize current experimental models of AA and AD, including chemical, genetic, and combined systems; (2) provide a decision tree for selecting mouse models of AA and AD for vascular research; (3) evaluate model-specific strengths, limitations, and translational relevance, while highlighting emerging technologies such as vascular organoids and engineered 3D platforms that may bridge gaps between preclinical research and human disease. This review presents an integrated framework linking aortic pathology to model-specific mechanisms, illustrating how extracellular matrix (ECM) failure, smooth muscle cell remodeling, inflammation, and biomechanical stress drive AA and AD. We further emphasize the translational hierarchy across mouse, large-animal, and organoid models, providing guidance for rational model selection in therapeutic discovery. By systematically summarizing classical and emerging mouse models of AA and AD, this review provides a structured framework to guide model selection and future mechanistic studies in the field.

Nonalcoholic fatty liver disease (NAFLD) is a major metabolic liver disorder with limited pharmacological options. Paeoniflorin (PF), a bioactive compound from Paeonia lactiflora, has shown hepatometabolic effects in experimental studies, but its overall efficacy in NAFLD models remains unclear. We searched PubMed, Embase, Web of Science, the Cochrane Library, CNKI, Wanfang, VIP, and CBM from inception to January 2026 for controlled animal studies evaluating PF in diet-induced NAFLD models. Two reviewers independently performed study selection, data extraction, and risk-of-bias assessment using SYRCLE's tool. Weighted mean differences or standardized mean differences with 95% confidence intervals were pooled using random-effects models. Ten studies were included, all using diet-induced models. PF treatment was associated with improvements in lipid metabolism, liver injury, glucose homeostasis, inflammation, and oxidative stress, including reductions in total cholesterol, triglycerides, low-density lipoprotein cholesterol, alanine aminotransferase, aspartate aminotransferase, body weight, fasting blood glucose, insulin resistance indices, tumor necrosis factor-α, and malondialdehyde, together with increased superoxide dismutase activity. High-density lipoprotein cholesterol showed no consistent improvement. Mechanistic findings suggested that PF may activate AMP-activated protein kinase, inhibit sterol regulatory element-binding protein-1c/fatty acid synthase-mediated lipogenesis, and modulate inflammatory and oxidative-stress pathways. However, substantial heterogeneity and incomplete reporting of randomization, allocation concealment, and blinding limited confidence in the evidence. PF showed promising preclinical effects in NAFLD, but further well-designed animal studies and clinical investigations are needed to clarify dose-response relationships, safety, and translational relevance.

Acute right ventricular failure (ARVF) is a life-threatening condition commonly encountered in the intensive care unit. The treatment of ARVF profoundly changed in the last years, with a growing number of mechanical circulatory support (MCS) devices that have been deployed in clinical practice to support patients with severe forms of ARVF. However, comparative clinical data addressing the superiority of the different MCS strategies are lacking. Several animal models addressing ARVF have been proposed in the literature, and they have been crucial to increase the knowledge on right ventricular (RV) pathophysiology and response to different stressors. Nevertheless, models that reliably mimic acute RV severe failure, ventricular-pulmonary artery uncoupling, and cardiogenic shock are comparatively scarce. Furthermore, only a limited number of experimental studies have incorporated MCS devices in this setting, and direct head-to-head comparisons between different support strategies are largely lacking. This gap in preclinical experiences significantly limits the development of evidence-based algorithms for right-sided MCS deployment. In this review, we summarize currently available animal models of ARVF, critically highlighting their methodological strengths and limitations, and examining the evidence supporting the use of MCS within these frameworks. By highlighting the translational limitations of the existing preclinical experiences, we underscore the urgent need for standardized, reproducible, and clinically relevant ARVF models. Such efforts are essential to improve the current treatment of ARVF, and they could be particularly relevant in developing and optimizing MCS devices and their selection, ultimately enhancing outcomes in patients with ARVF.

Metabolic disorders, especially obesity, type 2 diabetes mellitus, and metabolic dysfunction-associated steatotic liver disease, are becoming increasingly prevalent and have imposed a growing burden on public health systems. These diseases are commonly associated with insulin resistance and abnormal lipid metabolism, and increasing evidence indicates that immune imbalance and chronic low-grade inflammation are involved in their development. Natural polysaccharides are important bioactive components derived from plants, fungi, algae, and other natural sources. Current evidence supporting their beneficial effects in metabolic diseases is predominantly preclinical, mainly from cell-based and animal studies, while clinical evidence remains limited and heterogeneous. Natural polysaccharides have attracted interest as candidate bioactive compounds because some preparations have shown immunomodulatory and metabolic regulatory activities in experimental models. Their activities are closely related to structural features, including monosaccharide composition, glycosidic linkage types, molecular weight, branching structure, and chemical modification. Current preclinical evidence suggests that natural polysaccharides may alleviate metabolic inflammation by regulating macrophage polarization, suppressing pro-inflammatory cytokine production, modulating MAPK, NF-κB, AMPK, and related signaling pathways, and reshaping the gut microbiota-immune axis. These compounds may help improve several pathological features of metabolic disorders, such as insulin resistance, abnormal lipid metabolism, inflammatory injury, and tissue dysfunction. However, several challenges still limit their translation, including unclear structure-activity relationships, inconsistent preparation standards, limited bioavailability, and insufficient well-designed clinical trials. Therefore, this review provides an overview of the natural sources, structural properties, immunomodulatory actions, and therapeutic prospects of natural polysaccharides in metabolic diseases, with a focus on their involvement in immune regulation and metabolic inflammation.

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Avascular necrosis (AVN) is a progressive bone disorder characterized by impaired blood supply, osteocyte death, and structural collapse, most commonly affecting the femoral head. In recent years, growing evidence has suggested that gut microbiota may influence skeletal health through immune, metabolic, and vascular pathways. This scoping review aimed to systematically map current evidence on the relationship between gut microbiota and AVN and to identify key knowledge gaps. Following Joanna Briggs Institute methodology and PRISMA-ScR guidelines, a comprehensive search of PubMed, EMBASE, ScienceDirect, Web of Science Core Collection, ClinicalTrials.gov, and Cochrane CENTRAL was conducted. Thirteen eligible studies, including experimental, clinical, multi-omics, and Mendelian randomization analyses, were included. The available evidence indicates that AVN, particularly glucocorticoid- and alcohol-associated forms, is consistently associated with intestinal dysbiosis, reduced production of short-chain fatty acids, immune activation, vascular impairment, and altered bone remodeling. Animal and translational studies demonstrate partial reversal of pathological changes through microbiota-targeted interventions, while human studies reveal etiology-specific microbiota-metabolome signatures. Genetic analyses further support a potential causal contribution of selected microbial taxa and pathways. Overall, current data support the existence of a multidimensional gut-bone axis in AVN. However, most evidence remains indirect - derived from animal models, cross-sectional human studies, and genetic inference rather than from direct interventional testing in patients. Well-designed longitudinal and interventional investigations are needed to clarify causality and therapeutic potential.

Pancreatic β-cells are vulnerable to glucotoxicity, lipotoxicity, oxidative and endoplasmic reticulum stress, chronic inflammation, sustained secretory demand, and loss of cellular identity. This narrative review critically evaluates the mechanistic, preclinical, and translational evidence for Panax ginseng, Curcuma longa, Withania somnifera, and Rhodiola rosea as modulators of β-cell function. A focused search of PubMed, Scopus, Web of Science, and Google Scholar prioritized studies that used β-cell lines, isolated islets, pancreatic tissue, and diabetic animal models, and that reported clinical outcomes related to glycemic control and β-cell function. The available evidence remains predominantly preclinical. Ginseng provides pancreas-level evidence for islet preservation and endocrine-cell remodeling; curcumin shows the strongest evidence for pancreatic and isolated-islet cytoprotection, although its translational relevance is limited by poor and formulation-dependent bioavailability. In a 9-month trial, curcumin reduced progression from prediabetes to type 2 diabetes, but HOMA-β remained an indirect endpoint. Salidroside has direct MIN6 and isolated-islet evidence supporting AMPK-dependent preservation of β-cell function, whereas ashwagandha is supported mainly by pancreatic findings in diabetic animals and by systemic metabolic or neuroendocrine outcomes. PI3K/Akt-, Nrf2-, NF-κB-, JNK-, UPR-, and incretin-related mechanisms have been reported, but their confirmation in β-cells is uneven and often derives from non-pancreatic models. Evidence for prevention of β-cell dedifferentiation, clinically relevant DPP-IV inhibition, and synergistic adaptogen combinations remains limited or hypothetical. Overall, these phytochemicals provide biological plausibility as adjunctive strategies, but standardized extracts, clinically achievable dosing, pharmacokinetic assessment, and β-cell-centered clinical endpoints are required before therapeutic conclusions can be established.

To systematically examine and quantitatively synthesize preclinical studies assessing the impacts of dental pulp stem cell-derived extracellular vesicles (DPSC-EVs) on dentin-pulp complex (DPC) regeneration and related regenerative outcomes. Preclinical in-vitro and in-vivo studies assessing the effects of DPSC-EVs on regenerative outcomes associated with DPC regeneration, including odontogenic differentiation, immunoregulation, extracellular matrix (ECM) remodeling, angiogenesis, and neurovascular regeneration. Electronic searches were conducted in PubMed, Scopus, and Web of Science, without limitations on publication year or language. Preclinical studies assessing DPSC-EVs for DPC regeneration were selected via duplicate removal, title/abstract screening, and full-text evaluation following PRISMA guidelines. In-vitro, EV exposure upregulated BMP2 (5.2-fold), DSPP (4.9-fold), OCN (4.4-fold), DMP1 (2.7-fold), RUNX2 (2.0-fold), and ALP (2.3-fold) compared to controls. Angiogenic effect was significantly improved, with VEGF upregulated by nearly 2.5-fold and endothelial junction development by 2.9-fold. Additionally, EV treatment alleviated pro-inflammatory cytokine expression by 44% while elevating anti-inflammatory signaling almost 2.0-fold. In-vivo, EV treatment significantly enhanced odontogenic regeneration, angiogenesis, ECM formation, and neurovascular tissue development, with COL1A1 and DSPP exhibiting the highest reported regenerative outcomes. Odontogenically triggered, hypoxia-treated, and engineered EVs consistently showed superior biological functionality compared to traditional EVs. Existing preclinical evidence indicates that DPSC-EVs exhibit substantial capacity for DPC regeneration. Nonetheless, significant methodological heterogeneity and the lack of clinical evidence presently preclude conclusions concerning clinical effectiveness. Standardization of EV manufacturing, characterization, dosing, and translational assessment remains necessary before clinical implementation can be considered. Existing preclinical evidence reflects that DPSC-EVs improve several biological pathways related to DPC regeneration, such as odontogenic differentiation, angiogenesis, ECM deposition, and immunoregulation. These outcomes support continued translational research of DPSC-EVs as a promising cell-free regenerative approach; nonetheless, clinical implementation awaits validation via large-animal and human clinical studies. Open Science Framework registration number: 10.17605/OSF.IO/MTP9.

Corneal blindness remains a major global health burden, limited by donor shortage and graft-related complications. Tissue-engineered corneal substitutes have emerged as a promising alternative, aiming to restore corneal structure and function through bioengineered constructs. To systematically review recent advances (2020-2025) in tissue-engineered corneal substitutes, classifying them according to the corneal layer replaced and evaluating their biological, optical, and functional performance, as well as their translational potential for clinical application. A systematic review. A systematic review was conducted following Preferred Reporting Items for Systematic Review and Meta-Analyses (PRISMA) 2020 guidelines. Searches were performed in PubMed/MEDLINE, Scopus, and Web of Science using predefined keywords related to corneal tissue engineering. Eligible studies included experimental, preclinical, or clinical studies published between January 2020 and June 2025 describing cell-based corneal substitutes. Studies focused on keratoprostheses (KPros), acellular scaffolds, or non-cellular biomaterials were excluded. Fourteen studies met the inclusion criteria: five endothelial, three stromal, one epithelial, and five epithelium-stroma substitutes. Endothelial models demonstrated cell viability, expression of tight junction proteins (ZO-1, Na+/K+-ATPase), and partial restoration of corneal transparency in animal and ex vivo systems. Stromal models incorporated advanced biofabrication techniques such as 3D bioprinting and neuronal co-culture, achieving > 80% optical transmittance and adequate biomechanical properties. The single epithelial model achieved complete re-epithelialization in a rabbit limbal deficiency model. Multilayered epithelium-stroma substitutes, including the NANOULCOR (Tissue Engineering Group, University of Granada, Granada, Spain) construct, exhibited safety and feasibility in preclinical and early clinical studies. Recent progress in corneal tissue engineering has yielded increasingly functional and biocompatible substitutes that replicate native corneal architecture. However, most studies remain limited by small sample sizes, short follow-up, and reliance on animal models. Further standardized clinical trials are required for clinical translation. Not applicable. New laboratory-made corneal tissues that could replace damaged corneas in the future: a review of recent scientific advances Corneal diseases are one of the main causes of vision loss worldwide. Many patients can recover their sight through a corneal transplant, but donated corneas are limited and not always suitable. For this reason, scientists are developing new laboratory-made corneal tissues using advanced techniques in tissue engineering. These artificial corneal substitutes could one day help patients who cannot receive a standard transplant. This article reviews the most important scientific advances made between 2020 and 2025 in the creation of tissue-engineered corneal substitutes. The studies included in this review explored different ways of rebuilding the cornea depending on the layer that is damaged: the epithelium (the surface), the stroma (the middle layer), or the endothelium (the inner layer). Some research groups also created substitutes that combine several layers at once. The methods used to create these tissues include 3D bioprinting, modified biological scaffolds, stem cells, and ultra-thin natural membranes. In laboratory tests and animal studies, many of these substitutes showed good transparency, healthy cell growth, and the ability to integrate with the host cornea. One model, called NANOULCOR, has already been tested in a small group of patients with severe corneal disease and showed promising safety and healing results. Although the progress is encouraging, most studies were small and had short follow-up periods. More research is needed to confirm long-term safety, transparency, and vision outcomes before these substitutes can become a routine treatment for patients. This review provides an accessible overview of how tissue-engineered corneal substitutes are evolving and how they may help address the global shortage of donor corneas in the coming years.

The complex, interconnected nature of dental, oral, and craniofacial tissues poses significant challenges for conventional in vitro models. Oral and maxillofacial organoids have emerged as advanced three-dimensional technologies capable of reproducing selected microstructures and biological functions of native tissues. This review aimed to summarize recent advances in these technologies and evaluate their potential clinical applications in dentistry. A narrative literature review was conducted using PubMed, Web of Science, Scopus, and Google Scholar, with particular focus on studies published between 2020 and 2026. The search terms included 'organoids', 'oral and maxillofacial diseases', 'tissue engineering', 'regeneration', and 'precision medicine'. Relevant studies addressing organoid development, bioengineering strategies, and clinical applications in dentistry were analysed. Recent advances have enabled the development of various oral and maxillofacial organoids, including tooth-germ, salivary gland, taste bud, oral cancer, lingual epithelial, and maxillofacial cartilage organoids. Advances in patient-derived organoids through construction strategies, such as spontaneous self-assembly of stem cells, biomaterial-assisted fabrication, and precision engineering, enhance their physiological properties and support personalized medicine. Despite these advances, several challenges remain that restrict clinical translation, including limited vascularization, lack of immune system integration, structural variability, scalability, and standardization issues. Oral and maxillofacial organoids represent promising experimental platforms for regenerative dentistry, disease modelling, drug screening, and tissue regeneration. Combining organoids with microfluidic technologies to create organ-on-a-chip devices and linking multiple chips represents important advances towards the reliable, large-scale generation of physiologically relevant oral and maxillofacial organoids for both research and clinical applications. Oral organoid systems may provide clinical platforms for personalized therapy, regenerative applications, and translational research while reducing reliance on conventional animal models. Among current models, oral cancer and salivary gland organoids demonstrate promising translational potential, given their functional validation and scalability.

Antimicrobial resistance (AMR) poses a global health crisis and necessitates novel therapeutic strategies beyond traditional antibiotic, driving interest in anti-virulence (AV) strategies that disable pathogenicity rather than bacterial viability. This review provides an integrated overview of emerging AV approaches targeting quorum sensing, type III secretion systems, biofilm development, adhesion, toxin activity, iron acquisition, and host-pathogen interactions. We highlight representative phytochemicals, repurposed drugs, engineered inhibitors, nanomaterial-enabled formulations, and antibiotic-combination strategies that have shown promise across Gram-positive and Gram-negative pathogens. Across the literature, quorum sensing inhibitors and biofilm-disrupting agents are the most extensively explored, with many candidates demonstrating robust in vitro attenuation of virulence phenotypes. Type III secretion system inhibitors stand out for their mechanistic precision and, in several instances, stronger in vivo support, whereas host-directed and toxin-neutralizing strategies expand the therapeutic landscape but require cautious translational assessment. Importantly, the evidentiary strength of AV candidates is highly variable, ranging from docking-based hypotheses to animal-model validation, underscoring the need to distinguish preliminary leads from more advanced therapeutics. Collectively, the reviewed studies suggest that AV therapy is best positioned as a precision anti-infective strategy, particularly for chronic, device-associated, and multidrug-resistant infections where conventional antibiotics are less effective. Future progress will depend on improved mechanistic validation, rigorous safety and pharmacokinetic assessment, and translational frameworks that capture virulence suppression, host recovery, and treatment durability beyond bacterial killing alone.

Dietary polyphenols are gaining attention as regulators of gut-brain-liver (GBL) signaling in metabolic disease. The objective of this narrative review is to examine how polyphenols affect neuro-metabolic and immune pathways across the gut-brain-liver axis in obesity, type 2 diabetes, and metabolic dysfunction-associated steatotic liver disease. The review covers literature from 2000 to 2025 indexed in PubMed, Scopus, and Web of Science, with emphasis on mechanistic, multi-omics, preclinical, and human studies. Most polyphenols show poor absorption in the gastrointestinal tract and depend on liver enzymes and intestinal microorganisms for conversion into active metabolites, including urolithins, phenyl-γ-valerolactones, equol, and other phenolic acids. These metabolites influence microbial composition, bile acid signaling, gut hormone secretion, and host processes related to oxidative stress, inflammation, energy balance, and mitochondrial function. In animal and cell models, polyphenols reduce hepatic fat accumulation, improve insulin sensitivity, strengthen gut barrier integrity, and lower endotoxemia. Human evidence remains limited, derived mainly from short-term trials with considerable inter-individual variability. This variability appears linked to metabotype, metabolic capacity, habitual diet, sex, and medication use. Overall, current evidence supports polyphenols as multi-target regulators of gut-brain-liver communication. Larger, well-designed clinical and translational studies are needed to confirm their therapeutic relevance.

Current rodent models for anxiety and depression assessment face methodological challenges compromising both scientific rigor and animal welfare. This study introduced a novel approach using the Lévy flight (LF) statistical method to analyze spontaneous movement in open spaces. We employed three models: Chronic unpredictable mild stress (CUMS), Electric shock stress (ES), and Chronic Restraint Stress (CRS)-utilizing a total of 540 mice for LF fitting. A support vector machine algorithm was applied to distinguish each model group based on the two-dimensional distribution of the variables γ and μ in the LF. Statistical analysis was performed using a two-dimensional Kolmogorov-Smirnov test before and after drug administration. We found that the ES model primarily exhibited anxiety-like behaviors, the CRS model predominantly exhibited depression-like behaviors, and the CUMS model displayed both depression-like and anxiety-like behaviors. All three stress models were suitable for LF fitting, with the distribution of CUMS in the γ-μ plane lying between the ES and CRS groups. To assess the therapeutic effect of fluoxetine (FXT) on CUMS, we excluded the CUMS-resistant mice and performed LF analysis. Following FXT treatment, the mice gradually shifted toward the normal area in the γ-μ plane, with a more pronounced shift toward the depression area observed as the modeling time increased. This study identifies a previously unrecognized statistical locomotor pattern in mice with anxiety and depression. By integrating scientific rigor with ethical considerations, this approach also presents a humane paradigm shift in preclinical assessment, accelerating translational breakthroughs in neuroscience research.

Personality disorders (PDs) are increasingly recognized and highly prevalent, yet remarkably poorly understood, diagnosed and treated mental conditions. Common PDs include antisocial, avoidant, borderline, dependent, histrionic, narcissistic, obsessive-compulsive personality, and paranoid disorders. Experimental (animal) models are a valuable tool to study various brain illnesses, including PDs. However, characterized by complex and frequently overlapping aberrant behaviors, PDs pose major challenges for their preclinical modeling. Here, we discuss the potential utility of zebrafish (Danio rerio) as complementary translational models relevant to studying PDs. Paralleling clinical symptoms and traits of PDs to specific behavioral phenotypes, biomarkers and paradigms in these fish, we critically evaluate the existing challenges and limitations of such models, and provide a conceptual framework for further research in this field. Despite clear conceptual and practical challenges, we argue that zebrafish models not only provide a powerful platform for elucidating neurobiological mechanisms of a wide range of key PD traits (e.g., impulsivity, aggression, emotional dysregulation), but may markedly accelerate both translational modeling of these disorders and therapeutic discovery.

Chronic kidney disease (CKD) affects ~ 850 million people globally. The NOD-like receptor protein 3 (NLRP3) inflammasome has emerged as a central regulator of inflammatory, fibrotic, and mitochondrial injury during CKD pathogenesis. Nevertheless, its consistency across disease models and translational status has not been systematically evaluated to date. We conducted a PubMed and Scopus search for research articles examining NLRP3 inflammasome activation across various CKD models, following PRISMA guidelines, and selected 17 animal studies for further analysis. We found that across all model types, NLRP3 activation was consistently associated with upregulated caspase-1, elevated IL-1β and IL-18, and a decline in renal function, tubular injury, interstitial fibrosis, and mitochondrial dysfunction. Inflammation was reported in renal tubular epithelial cells, infiltrating macrophages, and glomerular cells. Furthermore, both genetic and pharmacological inhibition of NLRP3 reproducibly attenuated CKD, establishing a causal role rather than association of NLRP3 inflammasome in CKD progression. Surprisingly, although pyroptosis is the canonical effector arm of NLRP3 signalling, no included CKD study directly assessed pyroptosis or gasdermin D-mediated cell death, highlighting a fundamental mechanistic gap. Furthermore, despite multiple preclinical studies, only AZD4144, an AstraZeneca NLRP3 inhibitor, is currently in clinical trials for CKD. Overall, NLRP3 is a validated driver of CKD progression across diverse models. The lack of evaluation of NLRP3-mediated pyroptosis in CKD, along with limited clinical trials evaluating NLRP3 inflammasome inhibitors, highlights key research and translational gaps in CKD treatment.

Fragile X syndrome (FXS), the most common inherited form of intellectual disability and the leading monogenic cause of autism, results from the loss of the fragile X mental retardation protein (FMRP). Dysregulated translation of FMRP target mRNAs is believed to underlie the aberrant synaptic plasticity observed in FXS. Identification of these targets is critical for elucidating disease mechanisms and developing therapeutic strategies. We confirmed the interaction between FMRP and FYN mRNA by RNA immunoprecipitation in HEK293 and SH-SY5Y cells and assessed FYN translational regulation via polyribosome profiling in FXS and control lymphoblastoid cells. The role of FYN in ERK hyperactivation was examined in FXS lymphoblastoid cells, FMR1-knockdown SH-SY5Y cells, and dfmr1 mutant flies. Additionally, we tested whether reducing or inhibiting Src64B, a Drosophila Src family kinase with homology to human FYN, could rescue neural and behavioral defects in dfmr1 mutants. FMRP bound to FYN mRNA and suppressed its translation without affecting mRNA stability. Phosphorylated ERK1/2 levels were markedly elevated in FXS lymphoblastoid cells, and this hyperactivation was largely reversed by either the Src family kinase inhibitor PP2 or siRNA-mediated FYN knockdown, supporting an important role for FYN in ERK1/2 dysregulation. Similar changes were observed in FMR1-knockdown SH-SY5Y cells, with increased FYN expression and ERK1/2 phosphorylation, and PP2 treatment attenuated the abnormal ERK1/2 phosphorylation. Furthermore, genetic or pharmacological suppression of Src64B restored ERK signaling and rescued mushroom body defects and memory deficits in dfmr1 mutants. This study identifies FYN as a novel translational target of FMRP and suggests that its upregulation may contribute to hyperactivation of ERK1/2 signaling in FXS.

Fish cell lines are indispensable in vitro systems that support diverse research areas, including virology, immunology, ecotoxicology, and biomedical science. Fish represent the most species-rich vertebrate group with remarkable genomic diversity, providing valuable resources for specialised cellular models. Since the establishment of the first fish cell line (RTG-2) in 1962, the global repository has expanded to approximately 918 authenticated cell lines derived from over 211 species. This review presents a comprehensive overview of the historical progression, global repositories, and current standards for cell line authentication. It summarises methodological advances in primary culture initiation, the development of continuous cell lines, and improvements in cryopreservation techniques. This review also critically explains the wide-ranging applications of fish cell lines in aquatic virology, vaccine development, and standardised ecotoxicological assays. The translational potential in biomedical research is also highlighted, particularly in cancer biology, regenerative medicine, and drug discovery, largely driven by the use of genetically tractable model species such as zebrafish (Danio rerio) and medaka (Oryzias latipes). Key challenges are also discussed, including mycoplasma contamination, cross-species misidentification, limitations in cryopreservation protocols for marine-derived cells, and the need for robust, open-access digital biobanking systems. Future perspectives encompass emerging technologies such as 3D organoids, organ-on-a-chip platforms, CRISPR-based genome editing, and serum-free culture systems. Integration of these innovations with omics approaches and adverse outcome pathway frameworks is expected to enhance the utility of fish cell lines, advancing research in aquaculture, environmental monitoring, and food security, while aligning with the principles of the 3Rs and the United Nations Sustainable Development Goals.