Despite intensive studies on developing therapies for Alzheimer’s disease (AD), there is still a need to improve the treatment efficacy. Results of recent studies indicated that genistein (4′,5,7-trihydroxyisoflavone) was effective in an autophagy stimulation-dependent improving of cognitive deficits and reducing levels of amyloid-beta and hyperphosphorylated tau protein in brains, when employing a streptozotocin-induced rat model of the sporadic form of AD. Despite those encouraging results, the above-mentioned model has its limitations, mainly related to the rapid and inducible character of the symptoms caused by streptozotocin, induction of other effects (like diabetes) by this toxin, and the requirement for invasive administration of this compound to the brain, in contrast to naturally occurring AD. Thus, in this study, we hypothesized that genistein might be effective in reducing symptoms of AD in well-defined genetic models of this disease and tested the efficacy of this compound. Three genetic models of AD were employed, including mouse lines 5xFAD, THY-Tau22, and 3xTg-AD. Orally administered genistein (at the dose of 150 mg/kg/day) considerably alleviated cognitive deficits (in spatial memory, learning, and long-term memory) of AD animals as estimated using the Morris water maze and the novel object recognition tests. Moreover, significantly reduced levels of amyloid-beta and hyperphosphorylated tau protein in plasma and brains were detected in genistein-treated AD animals relative to those treated with water. We conclude that genistein revealed significant efficacy in ameliorating symptoms occurring in murine genetic models of AD. Thus, further studies towards the development of a genistein-based treatment for this disease are substantiated. Not applicable.
Osteoarthritis (OA) is characterized by progressive articular cartilage degeneration, in which inflammatory mediators drive MMP-mediated matrix breakdown and chondrocyte apoptosis, ultimately leading to pain and functional impairment. Although often described as a “wear-and-tear” disease, increasing evidence highlights immune/inflammatory signaling as a key contributor to OA progression. Gastrodia elata Blume (GEB) has reported anti-inflammatory and immunomodulatory activities, but its preventive potential in OA remains unclear. This study evaluated GEB extract in a widely used monosodium iodoacetate (MIA)-induced OA rat model. Male Sprague–Dawley rats (5 weeks old) were assigned to CON, OA, OA + L-GEB, and OA + H-GEB groups; GEB was administered orally once daily for 5 weeks, and OA was induced by intra-articular MIA (3 mg/50 µL) at day 21. GEB improved gross cartilage surface appearance and histopathological outcomes (HE, Safranin O, Alcian blue; Mankin and OARSI scores), showing reduced cartilage damage and better preservation of proteoglycan staining compared with the OA group. Consistently, GEB decreased IL-6, MMP-13, and cleaved caspase-3 in cartilage (IHC) and reduced TUNEL-positive cells, indicating suppression of inflammatory signaling and chondrocyte apoptosis. RT-qPCR further showed downregulation of NF-κB, IL-6, MMP-9, MMP-13, and TIMP-1 mRNA levels in GEB-treated groups versus OA. GEB extract attenuated inflammatory and catabolic responses and inhibited chondrocyte apoptosis in MIA-induced OA, supporting its potential as a prophylactic strategy for localized inflammatory pathology such as osteoarthritis.
Urinary tract reconstruction is a key technical barrier in murine kidney transplantation due to the tiny ureteral caliber. Conventional methods are technically demanding with high morbidity. This study assesses a refined intraluminal stenting approach for better surgical stability, fewer complications, and preserved anti-reflux structural anatomy of the ureterovesical junction. We performed 88 orthotopic mouse kidney transplantations using three distinct reconstruction modalities: bladder patch (n = 31), ureter implantation (n = 28), and intraluminal stenting (n = 29). The stenting protocol utilized a micro-polyethylene (PE) stent to achieve end-to-end ureteral alignment. Outcomes included operative efficiency, learning curve trajectories, postoperative survival, and urinary-related morbidity. The stenting cohort achieved a 14-day survival rate of 96.6
Abstract Background Balanced injectable anesthesia combining an α2-adrenoceptor agonist, a benzodiazepine, and an opioid is widely used in laboratory rodents because it provides sedation, muscle relaxation, and analgesia through complementary pharmacological mechanisms. In Japan, a mixture of medetomidine, midazolam, and butorphanol (MMB) is commonly used as an injectable anesthetic regimen in mice and rats. Remimazolam is an ultra-short-acting benzodiazepine that is rapidly metabolized by tissue esterases and produces no active metabolites. Because of its rapid metabolism and predictable pharmacokinetic profile, remimazolam has attracted attention as a sedative agent in clinical anesthesia and procedural sedation. Replacing midazolam with remimazolam generates a novel balanced anesthetic combination consisting of medetomidine, remimazolam, and butorphanol (MRB). Although this regimen has been investigated in mice, its anesthetic characteristics in rats have not yet been fully evaluated. The present study aimed to compare the anesthetic and physiological effects of MMB and MRB anesthesia in Sprague–Dawley (SD) rats. Results Both mixtures induced anesthesia in all animals. The MRB regimen produced faster immobilization than the MMB regimen, whereas the time to loss of righting reflex did not differ significantly between regimens. Reflex-based anesthetic depth during the observation period was comparable between the two regimens. Physiological monitoring revealed regimen-dependent differences in time-course dynamics, particularly for oxygen saturation and respiratory rate. For oxygen saturation, pointwise comparisons showed no significant difference after Holm correction, whereas the area under the curve (AUC) analysis did show a significant difference. Linear mixed-effects modeling (LMM) further demonstrated significant group, time, and group × time interaction effects for oxygen saturation, and significant time and group × time interaction effects for respiratory rate. Recovery after atipamezole (ATI) administration was faster in the MRB group, as shown by both return of righting reflex and behavioral recovery score analyses. Conclusions MRB produced a reflex-score profile comparable to that of MMB while accelerating early immobilization and antagonist-assisted recovery. Substitution of midazolam with remimazolam also altered SpO₂ and respiratory-rate trajectories. MRB may therefore be useful when rapid recovery is desired. However, comparability was limited to the reflex-based scoring system; these findings do not establish equivalence for painful or invasive surgical procedures.
Abstract Background Natural disasters, infrastructure failures, and infectious disease outbreaks can disrupt the operations of laboratory animal facilities and threaten both research continuity and animal welfare. Previous events, including Tropical Storm Allison and the Great East Japan Earthquake, demonstrated the vulnerability of laboratory animal populations during emergencies and highlighted the need to incorporate animal welfare considerations into emergency preparedness planning. The aim of this study was to identify key elements of emergency preparedness programs for laboratory animal facilities and to propose a framework to support the development of practical Standard Operating Procedures (SOPs) in which animal welfare considerations are integrated into facility operations and decision-making processes during emergencies. Results Regulatory frameworks and guidance documents from the United States, Europe, Canada, and Korea were reviewed and compared to identify approaches applicable to laboratory animal facility management. The analysis included definitions of emergencies, core program components, veterinary oversight systems, and decision-making structures across these four regulatory contexts. Despite differences in regulatory approaches and institutional contexts, common elements were identified and organized into three functional domains: continuity of facility operations, protection of animal welfare, and institutional response capacity. Based on these findings, we propose an integrated emergency preparedness framework and a stepwise operational checklist intended to facilitate the integration of welfare priorities into emergency planning and response. Conclusions Emergency preparedness should not be regarded solely as an operational requirement. In laboratory animal facilities, it should be understood as an extension of the animal welfare program that, while prioritizing personnel safety and institutional resilience, also seeks to minimize animal suffering and preserve the value of ongoing research when normal operating conditions cannot be maintained.
