Animal models and experimental medicine最新文献

Background: The current understanding of diabetic kidney disease (DKD) has significant gaps regarding the underlying pathogenesis. In this study, we aimed to characterize the temporal progression of DKD using a state-of-the-art mouse model of hypertension-accelerated disease, integrating kidney biomarker analysis, histopathology, and glomerular transcriptomic profiling.

Methods: Female diabetic db/db mice received a single intravenous dose of adeno-associated virus-mediated renin overexpression (ReninAAV, week 5) and underwent uninephrectomy (UNx, week 4). db/db UNx-ReninAAV mice were terminated at weeks 1, 4, 8, and 12 (n = 7-8 per group). Female db/m mice were used as healthy controls. Study endpoints included plasma and urine biochemistry, glomerulosclerosis scoring, quantitative kidney histology, and RNA sequencing of glomeruli isolated using laser-capture microdissection.

Results: db/db UNx-ReninAAV mice developed progressive albuminuria (from week 4) and glomerulosclerosis (from week 8). A pathway analysis of clustered gene regulations revealed broad glomerular transcriptome perturbations with signatures of increased extracellular matrix (ECM) turnover from week 8 and early onset of metabolic dysfunction. Markers of glomerular cell types and injury exhibited temporal regulation over the course of DKD, with early and sustained downregulation of endothelial markers, heterogeneous regulation of podocyte markers, and significant mesangial and parietal epithelial aberrations. Furthermore, the upregulation of cell injury markers confirmed progressive glomerular injury in the model.

Conclusion: The db/db UNx-ReninAAV mouse model exhibits distinct temporal dynamics in glomerular cell markers, metabolic dysregulation, ECM remodeling, and injury. Together, these results highlight the utility of the db/db UNx-ReninAAV model as a relevant preclinical platform for studying progressive DKD.

Frontiers in Laboratory Animal Handling and Experimental Design: Bridging Ethics and Excellence Theme: Good Science with Good Care Ethical Framework: CCSEA & IAEC oversight | 3Rs (Replacement, Reduction, Refinement) | Transparent documentation Animal Handling & Anatomy: Mice • Rats • Rabbits • Guinea pigs Gentle restraint • Anatomical landmarks Administration routes-SC, IM, IP, IV (tail vein, ear vein) Blood sampling-tail vein, saphenous, submandibular/orbital sinus, ear vein/artery Husbandry & Nutrition: Balanced diet • Clean water • Environmental enrichment • Hygiene Health indicators-weight, coat condition, hydration, activity Experimental Design: Hypothesis development • Control vs. treatment groups Randomization • Blinding Statistical power analysis for ethical sample size Reproducibility assurance Pathology & Bio-Methodology: Routine health monitoring • Early disease detection Confounder reduction • Humane techniques Hands-On Training: Handling & restraint practice • Injection simulation Cage management & enrichment selection Ethical documentation • Endpoint assessment OUTCOME Enhanced animal welfare • Improved data reliability • Ethical compliance •Skilled personnel • Responsible research culture CORE MESSAGE GOOD SCIENCE WITH GOOD CARE Ethics + Expertise + Experimental Rigor = Responsible Research Excellence.

Background: Diabetes, a metabolic disease marked by endocrine dysfunctions, significantly impacts oxidative stress pathways. This study explores the protective effects of lemongrass extract (LE), citral, and lemongrass extract-synthesized silver nanoparticles (LE-AgNP) against hyperglycemia-induced oxidative stress by modulating the Nrf2 pathway, which is crucial for antioxidant responses.

Methods: Various techniques characterized the nanoparticles, including ultraviolet-visible spectroscopy, dynamic light scattering, zeta potential analysis, Fourier-transform infrared spectroscopy, scanning electron microscopy and transmission electron microscopy. Seventy rats, divided into seven groups, were used for in vivo experiments. Type 2 diabetes was induced using streptozotocin (65 mg/kg) and nicotinamide (90 mg/kg). After six weeks, biochemical parameters such as total antioxidant capacity, malondialdehyde, Nrf2, and Nrf2 miRNA were evaluated in pancreas tissue and blood serum, along with serum blood glucose levels.

Results: LE-AgNP significantly improved weight gain, reduced food and water intake, and lowered blood glucose levels in diabetic rats. LE and citral did not significantly alter these parameters but prevented the decline in Nrf2 gene expression. LE-AgNP showed a significant increase in Nrf2 gene expression compared to the diabetic control group.

Conclusions: This study highlights the potential of LE, citral, and especially LE-AgNP in mitigating oxidative stress induced by diabetes. LE-AgNP demonstrated superior therapeutic benefits, including improved oxidative stress conditions and hypoglycemic effects.

Background: Although widely used in periodontal research, rodents are naturally resistant to periodontitis. Conventional models, such as ligature-induced periodontitis, often fail to sustain defects due to spontaneous tissue regeneration after ligature removal. To address this, we refined a rat ligature-induced model of experimental periodontitis to better mimic the chronic, progressive nature of human periodontitis.

Methods: As a first step, following a split-mouth design, we compared the effectiveness of 3/0 silk thread and 0.008-inch orthodontic wire as ligature materials. Ligatures were applied around the left mandibular first molar for 6, 10, and 14 days. Periodontal pocket irrigation was performed every second day using a suspension of P. gingivalis, P. intermedia, and S. gordonii. As a second step, we evaluated whether silk-ligature alone, without human periopathogens, would be sufficient to induce a stable and progressive periodontal lesion. For that purpose, a silk ligature was removed on day 14, and the bone defect dynamics were monitored at 14-, 21-, and 28-days post-removal using micro-CT.

Results: Both wire and silk ligatures, in combination with bacterial irrigation, effectively induced rapid interproximal alveolar bone loss. However, silk ligature only, without periodontopathogen colonization, resulted in significantly lower bone loss (1.076 ± 0.22 mm vs. 2.012 ± 0.374 mm; p = 0.003) and the induced alveolar bone defects gradually resolved again over time.

Conclusions: The proposed rat model of periodontitis is well characterized and replicates human disease by sustaining colonization with viable periopathogens, leading to progressive disease with alveolar bone loss. The suggested model is straightforward, easy to establish and can be used reliably in preclinical studies.

ZSF1 lean rats are widely used as controls in cardiometabolic studies involving ZSF1 obese rats, which develop a cardiometabolic syndrome and diastolic dysfunction at a young age due to a double leptin receptor mutation (Lepr^cp and Lepr^fa). Although, lean littermates show no overt signs of cardiometabolic disease or diastolic impact, they belong to one of three genotypic variants, two of which carry one of the mutant Lepr alleles and, thus, doubt has been raised about their suitability as healthy controls. We compared 32-week-old female ZSF1 lean and Wistar rats regarding physiological, myocardial, vascular, skeletal muscle, and mitochondrial characteristics. Lean rats showed lower body weight but increased heart, kidney, and skeletal muscle mass. Despite thicker ventricular walls, systolic and diastolic function were preserved. Hemodynamically measured contractility was higher as underpinned by a higher mitochondrial respiratory capacity of LV fibers. However, left ventricular filling pressure was elevated, accompanied by increased ventricular stiffness. Endothelial function was preserved, but smooth muscle responsiveness was reduced, indicated by impaired SNP-induced relaxation. Passive vascular stiffness mediated by collagenous fibers was significantly higher in lean rats. Skeletal muscle function was mostly preserved, though maximal specific force of the EDL was reduced. Taken together, ZSF1 lean rats are physiologically different from Wistar rats as they display enlarged myocardial dimensions accompanied by increased blood pressure and an incipient diastolic and vascular stiffness. Therefore, our data indicate an early phase of passive compliance disorder in ZSF1 lean animals, which might become more pronounced at an advanced age.

RNA molecules play diverse and essential roles in cellular processes beyond their well-known functions in gene expression and regulation. While ribosomal RNAs (rRNAs) have long been recognized as structural components of ribosomes, recent research has highlighted the importance of a distinct group of RNAs which directly compose the structures or organelles in mammalian cells. We refer to these as 'organelle formation RNAs'. Specifically, the discovery of tubulin-associated lncRNA (TubAR), the first identified cytoskeleton-forming RNA, has expanded our understanding of RNA functionality; we now recognize 'organelle formation RNAs' not only as regulatory molecules but also as direct structural components within cellular subunits. Other 'organelle formation RNAs' include paraspeckle-forming RNAs, nuclear speckle-forming RNAs, and nucleolus-forming RNAs. Various RNAs contribute to the formation of distinct cellular structures, while also participating in intricate intermolecular interactions. Understanding these molecules not only uncovers their fundamental roles in cellular physiology but also suggests potential applications in the treatment of related diseases. By examining the latest advancements and methodologies in organelle formation RNA research, this review provides a comprehensive overview of the intricate mechanisms of these RNAs and future directions in the field.

Background: Diabetes mellitus (DM), a metabolic disorder that leads to chronic hyperglycemia, is one of the topmost global public health concerns according to the International Diabetes Federation. Adropin is a peptide hormone that is primarily involved in energy homeostasis, but its involvement in other biological activities such as lowering hyperlipidemia, and diminishing insulin resistance has also been reported. In this study, we aimed to explore additional effects of adropin on oxidative stress, inflammation, and cell proliferation in an animal model of type 1 DM.

Methods: To achieve our aim, normal and diabetic Wistar rats were treated with adropin (2.1 μg/kg/day) for a period of 10 days. Pancreatic tissue samples were collected for histomorphological analysis and inflammation assay, while blood was collected for oxidative stress assay.

Results: Our results showed that diabetes induction stimulated cell proliferation in both exocrine and endocrine pancreas, and adropin dramatically attenuated this effect in pancreatic exocrine tissue, but not in the islet of Langerhans. In addition, adropin significantly increased glutathione reductase expression in pancreatic tissue, and augmented serum total glutathione in the diabetic rats compared to diabetic untreated rats.

Conclusion: Our study indicates the potential role of adropin in alleviating oxidative stress in DM.

The FELASA 2025 Congress, themed "Reducing Severity in Animal Research," convened global experts in laboratory animal sciences to discuss ethical advancements, welfare standards, and innovative practices. Key sessions highlighted the integration of the 3R principles (Replacement, Reduction, Refinement), with presentations addressing challenges in immunology, AI-driven animal monitoring, and aseptic surgical techniques. Notable lectures, including Prof. Stasinos Stavrianeas' exploration of zoology's origins and Dr. David Anderson's award-winning talk on squid welfare, emphasized cultural relevance and ethical responsibility. The congress also prioritized sustainability through waste-reduction measures and digital tools like an official app for enhanced networking. Exhibitions showcased cutting-edge technologies, while workshops fostered hands-on skill development. By advocating openness and interdisciplinary collaboration, FELASA 2025 aimed to advance humane and scientifically rigorous animal research practices globally.