Search Results (855)

Several animal models of Alzheimer’s disease have been developed and tested for diagnostic and treatment purposes. [¹¹C]PIB is the gold-standard radiotracer for the detection of Aβ plaque deposits, a hallmark of the disease. This study aimed to evaluate the in vivo detection of Aβ plaques using [¹¹C]PIB microPET imaging across different animal models of Alzheimer’s disease. The study included 3xTg-AD transgenic mice, TgF344-AD transgenic rats and Aβ injection-based rat model. The results showed an age-related increase in [¹¹C]PIB uptake in 3xTg-AD mice, particularly in the midbrain and thalamus. In TgF344-AD rats, differences were also observed compared to WT controls, with the highest values observed in the hippocampus and cortex. In the injection-based model, inoculated rats showed greater uptake in the injection site than SHAM animals. Across all microPET studies, [¹¹C]PIB uptake was consistently higher in females than in their male counterparts. These findings support the value of transgenic and Aβ injection-based models in preclinical research on Aβ plaque deposition and highlight the importance of considering species, model type, sex, and age in experimental design. Full article

Mitochondrial dysfunction and oxidative stress are crucial contributors to the pathogenesis of Alzheimer’s disease (AD) and dementia exhibiting cognitive decline at the early stage of neurodegeneration. Natural vitamin antioxidants (NVAs) and novel mitochondria-targeted antioxidants (MTAs) are proposed as potential therapeutics though conclusive evidence is lacking. Objectives were to examine in vivo evidence on NVAs and MTAs for preventing and/or treating cognitive decline leading to dementia, to identify the most promising antioxidants, and highlight translational gaps. Methods followed PRISMA-ScR guidelines. MEDLINE, EMBASE and Scopus were searched for English language in vivo experiments assessing NVAs or MTAs in AD and dementia. A total of 25 studies (13 NVAs; 12 MTAs) met inclusion criteria. NVAs (Vitamin A, B, C, E) demonstrated mixed efficacy in reducing oxidative stress and improving cognitive outcomes, with Vitamin E showing the most consistent neuroprotective effects. MTAs (MitoQ, MitoTEMPO, SS31, SkQ1) improved mitochondrial dynamics and cognitive performance and reduced dementia-related pathology. Both NVAs and MTAs improved biomarker profiles and cognitive outcomes in vivo animal models of AD and dementia, but MTAs showed more robust and consistent efficacy by directly targeting mitochondrial pathways. Given the favourable safety profiles of MTAs in other clinical conditions, early-phase human trials in dementia and AD are warranted to evaluate their long-term cognitive benefits. Full article

Transmissible gastroenteritis (TGE), caused by the TGE virus (TGEV), is a highly contagious enteric disease characterized by vomiting, dehydration, and watery diarrhea. It mainly endangers piglets within two weeks of age, with a 100% mortality rate, inflicting severe economic losses on the global swine industry. Since enteric tropism of the virus and mucosa serves as the first line of defense against viral invasion, an oral vaccine inducing sufficient secretory immunoglobulin A (SIgA) antibodies in animals should be developed. Being a generally recognized as safe (GRAS) microorganism, Bacillus subtilis can form endospores under extreme environmental conditions, which confer resistance to the hostile gastric environment and have been widely employed as delivery vehicles for oral vaccines owing to their immunoadjuvant activity and non-specific antidiarrheal effects. In this study, the AD antigenic epitope of the TGEV S protein was selected as the immunogen. The mature peptide of the B subunit of the heat-labile enterotoxin from enterotoxigenic Escherichia coli served as a mucosal adjuvant, and B. subtilis WB800N was used as the delivery host to construct the recombinant strain pHT43-LTB-AD/WB800N. After confirming the successful expression of the target protein, oral immunization was performed using mice as a model. The results demonstrated that this recombinant strain induced robust mucosal, humoral, and cellular immunity, along with considerable levels of neutralizing antibodies. These findings indicate that recombinant B. subtilis could serve as an oral vaccine candidate to combat TGEV infections. Full article

Metabolic syndrome is a disorder of energy metabolism characterized by persistently high prevalence and significant medical and economic burden on society. An effective animal model that closely replicates the key features of the syndrome in humans is essential for evaluating therapeutic strategies aimed at improving health outcomes. High-calorie diet-induced animal models of metabolic syndrome are preferred by many research groups for studying its pathogenesis, prevention and therapy. However, there are numerous variations in the types and proportions of carbohydrates and/or fats in the diets used. In 2015, our research team developed a diet-induced model of metabolic syndrome in young adult male Wistar rats that was based on adding 17% animal fat and 17% fructose to the standard rat chow and 10% fructose to the drinking water. This model reliably induced the morphometric and biochemical alterations that represent the core diagnostic features of the syndrome in humans. Since its initial introduction, we have utilized the high-fat high-fructose diet-induced model of metabolic syndrome/obesity in ten experimental studies. The current paper provides a protocol for applying the model, presents its repeatability and discusses the variability in the morphometric, biochemical, histopathological, immunohistochemical, and behavioral data of 10 experimental studies on Wistar rats. Full article

Background/Objectives: GATA-binding protein 3 (GATA-3) is a crucial transcription factor that drives type 2 immune responses, and it is actively involved in allergic conditions such as asthma, allergic rhinitis (AR), and atopic dermatitis (AD). However, the molecular mechanisms GATA-3 uses to modulate immune responses and its potential therapeutic targeting are not fully understood. This systematic review aimed to summarize studies on the role of GATA-3 in immune responses, particularly in allergic diseases, and evaluate GATA-3’s potential as a therapeutic target. Methods: We searched PubMed, Scopus, Web of Science, Cochrane, and Science Direct for studies published before April 2025. Articles were sifted through using predefined criteria, and risk of bias was measured with RoB 2 for clinical trials and SYRCLE for animal models and in vitro studies; evidence was graded using the GRADE system. Results: Twenty-nine eligible studies reported that GATA-3 is a key regulator of Th2 and ILC2 differentiation, promoting the production of IL-4, IL-5, and IL-13. Animal models and in vitro studies demonstrated its role in exacerbating allergic inflammation and highlighted the promise of targeting strategies such as DNAzymes and nanocapsules. Clinical trials showed that targeting GATA-3, particularly with DNAzymes, can reduce allergic responses in asthma. Conclusions: GATA-3’s role in driving allergic inflammation through Th2 and ILC2 pathways suggests it as a promising therapeutic target. Understanding its broader regulatory mechanisms is imperative for designing effective GATA-3 targeting-based therapies. Full article

Overactivation of the renin–angiotensin–aldosterone system (RAAS) promotes haemodynamic overload, inflammation, and fibrosis in the heart and kidneys. Recently, sodium–glucose cotransporter-2 (SGLT2) inhibitors have emerged as a cornerstone therapy in cardiorenal protection. Emerging data indicate that adding SGLT2 inhibitors to angiotensin-converting enzyme (ACE) inhibitors, angiotensin receptor blockers, mineralocorticoid receptor antagonists, or angiotensin receptor–neprilysin inhibitors confers additional cardiorenal protection, yet their mechanistic basis and optimal clinical use in cardiovascular (CV) disease remain unclear. This review will integrate pre-clinical and clinical evidence on dual RAAS/SGLT2 modulation in CV disease, providing mechanistic insight into dual therapy. The review will finally outline priorities for future translational and outcome studies. Clinically, adding SGLT2 inhibitors to RAAS-based therapy reduces heart failure hospitalizations and slows kidney disease progression without new safety liabilities in type 2 diabetes, heart failure, and chronic kidney disease. Mechanistically, SGLT2 inhibition restores tubuloglomerular feedback and constricts the afferent arteriole; RAAS blockade dilates the efferent arteriole, and together, they lower intraglomerular pressure. Both classes also reduce oxidative stress, inflammatory signalling, and pro-fibrotic pathways, with SGLT2 inhibitors in several settings shifting RAAS balance toward the protective ACE2/angiotensin-(1–7)/Mas receptor axis. Key gaps include the scarcity of adequately powered trials designed to test combination therapy versus either component alone, limited evidence on timing and sequencing, incomplete characterization in high-risk groups, and mechanistic insight limited by study design in animal and cell models. Collectively, current data support layering SGLT2 inhibitors onto RAAS-based therapy, while definitive evidence from dedicated clinical trials is awaited. Full article

Background/Objectives: Non-melanoma skin cancer, which includes cutaneous squamous cell carcinoma (cSCC), ranks as the 5th most common cancer globally with high morbidity and more total deaths than melanoma despite having a lower mortality rate. While most cSCC cases can be treated with surgery, locally advanced, metastatic, and high-risk cSCC tumors are associated with a worse prognosis with higher rates of recurrence and require multimodality therapy. However, there is limited data on animal models of cutaneous squamous cell carcinoma for the use of combinatory immunotherapy and radiation. Methods: In this study, spontaneously generated tumors using DMBA/TPA were treated over three weeks with either IgG control, anti-PD1 antibody monotherapy, 8 Gy of localized radiation, or a combination of anti-PD1 and 8 Gy of radiation followed by anti-PD1 therapy. Results: We found that while anti-PD1 therapy showed a trend toward slowed tumor growth compared to controls, this difference was not statistically significant (p = 0.0775), with most mice showing continued tumor progression. Preliminary histological analysis suggested that anti-PD1 treatment increased CD8+ T cell infiltration, and the addition of radiation further enhanced CD8+ responses but added greater variability. A pathologic review revealed that irradiated tumors were associated with fibroblastic spindle-like cell morphology. Conclusions: This animal model represents a potential preclinical model for studying CSCC with limited responses to immunotherapy to understand potential mechanisms of resistance. Full article

In the breeding scene, limited by the small number of samples and environmental interference such as illumination occlusion, sika deer behavior recognition still faces challenges such as insufficient feature representation and weak cross-scale modeling ability. To this end, this study builds a lightweight improved model SDB-YOLO based on YOLOv11n. Firstly, the FPSC module is proposed to enhance the correlation between multi-scale features through the shared convolution mechanism, so as to significantly improve the quality of feature fusion under the condition of small samples. Secondly, the Ghost feature generation and dynamic convolution strategy are introduced into the C3k2 module to construct the C3_GDConv structure, so as to strengthen the fine-grained behavior pattern modeling ability and reduce redundant calculations. In addition, the CBAM attention mechanism is added to the neck of the network to further improve the ability of key information extraction and enhance the discrimination of feature expression. Finally, the EfficientHead was used to replace the original detection head to obtain a more robust training process and higher detection accuracy in small-sample scenarios. Experimental results show that SDB-YOLO achieves 90.2% detection accuracy with only 4.3 GFLOPs of calculation, which achieves significant performance improvement compared with YOLOv11n, and verifies the effectiveness and lightweight advantages of the proposed method in small-sample special animal behavior recognition tasks. Full article

Anthracycline’s clinical application is often hampered by severe life-threatening cardiotoxicity, which could result in death in approximately one-third of patients. Previous studies have found that during the anthracycline-induced cardiotoxicity (AIC), uric acid (UA) levels increase abnormally. However, the role of UA in AIC remains elusive. Here, we conducted a correlation analysis between UA and cardiac damage markers (NT-pro-BNP, hs-cTnT, LDH, CRP and hs-CRP) by using the National Health and Nutrition Examination Survey database (NHANES); the results revealed that the elevated UA levels showed significant positive associations with the levels of several cardiac damage markers. Secondly, molecular docking experiments suggested potential binding interactions between UA and BNP, cTnT, CRP, and LDH. Finally, animal experiments were performed to validate this correlation we explored and further validated the effect of UA on AIC by adding or lowering UA in animal models. We observed that under high uric acid (HUA) conditions, AIC not only manifested earlier but also progressed more severely. In contrast, AIC was alleviated under UA clearance conditions. Collectively, these results suggested that HUA might be an important contributing factor in the development and progression of AIC, supporting the further investigation of UA-lowering strategies for potential prevention. This work might offer new prevention and treatment strategies for AIC. Full article

This review examines a small interfering RNA (siRNA) designed for intrathecal (IT) injection, which reduces the formation of amyloid beta precursor protein (APP), a critical factor in the pathology of Alzheimer’s disease (AD). The siRNA, designated ALN-APP, incorporates a 16-carbon chain (C16-siRNA) to enhance its delivery to the central nervous system (CNS) while leveraging advancements in specificity and duration of action based on previously approved drugs by the Food and Drug Administration. The development of ALN-APP involved a comprehensive analysis of the optimal carbon chain length and its conjugation position to the siRNA. Preclinical studies conducted on male Sprague Dawley rats, mice, and non-human primates (NHPs) demonstrated the efficacy of ALN-APP. In rats, an IT injection of C16-siRNAs at a concentration of 30 mg/mL, delivering a dose of 0.9 mg, resulted in cranial distribution via cerebrospinal fluid and led to a 75% reduction in copper-zinc superoxide dismutase 1 (SOD1) mRNA levels. These effects were dose-dependent and persisted for three months across multiple brain regions. Furthermore, studies in NHPs indicated that soluble APP levels were reduced to below 25%, sustained for two months. In the cerebrovascular amyloid Nos2^−/− (CVN) mouse model of AD, administration of 120 µg of siRNA via the intracerebroventricular route produced reductions in APP expression, with mRNA levels remaining suppressed for 60 days in the ventral cortex. Indeed, ALN-APP controlled neuropathology in 5xFAD mice by significantly reducing amyloid levels and brain neuroinflammation, with improved behaviors in the elevated plus maze. Following these promising results in animal models, ALN-APP advanced to a Phase 1 trial, designated ALN-APP-001, which assessed its safety and efficacy in 12 participants with early-onset Alzheimer’s disease (EOAD). Initial findings revealed a 55% reduction in soluble APPα and a 69% reduction in APPβ by day 15. These exploratory findings require further validation with larger cohorts and proper statistical analysis. In a subsequent cohort of 36 patients, administration of the 75 mg dose via IT injection led to mean reductions of 61.3% in soluble APPα (sAPPα) and 73.5% in soluble APPβ (sAPPβ) after one month. These silencing effects persisted for six months and were associated with important decreases in Aβ42 and Aβ40 levels. These results highlight the potential of ALN-APPs to address Alzheimer’s pathology while maintaining a favorable safety profile. Whether ALN-APP succeeds in further clinical trials, key challenges include ensuring accessibility and affordability due to treatment costs, the need for specialized intrathecal administration, and establishing infrastructure for large-scale production of siRNAs. In conclusion, advancements in ALN-APP represent a promising strategy to reduce beta-amyloid formation in AD, with substantial biomarker reductions suggesting potential disease-modifying effects. Continued development may pave the way for innovative treatments for neurodegenerative diseases. Full article

Glucagon-like peptide-1 receptor agonists (GLP-1RAs) are widely used in the treatment of type 2 diabetes and obesity due to their metabolic effects. Emerging evidence suggests they may also have neuroprotective effects, indicating their potential as disease-modifying therapies in neurodegenerative disorders such as Alzheimer’s disease (AD) and Parkinson’s disease (PD). Preclinical studies in animal models have demonstrated that GLP-1RAs can reduce neuroinflammation, oxidative stress, neuronal apoptosis, and pathological protein aggregation, while enhancing glucose metabolism and mitochondrial function. This narrative review analyzed results from human clinical trials evaluating GLP-1RAs in AD and PD, based on a search of four databases (Web of Science, Medline, Embase, and Clinical Trials). The analysis included eleven studies. In AD, clinical trials suggest that GLP-1RAs such as liraglutide and semaglutide may enhance brain glucose metabolism, facilitate glucose transport across the blood–brain barrier, and benefit neuronal networks. However, most studies did not demonstrate improvements in cognitive functions or radiological markers. Short-term clinical trials of GLP-1RAs, including exenatide and lixisenatide, demonstrated promising effects on motor and selected non-motor symptoms in patients with PD, but their disease-modifying effects remain unproven. GLP-1RAs showed a favorable safety profile. Despite promising findings, small study populations, heterogeneous protocols, and short observation periods limit definitive conclusions. Further larger, long-term studies are needed, particularly to clarify the risk–benefit balance, weight control, and long-term outcomes. Full article

Saline–alkaline soils are increasingly reducing global forage productivity and may indirectly compromise the nutritional quality of animal-derived foods for human consumption. Alfalfa, grown under saline–alkaline conditions, often accumulates sodium, thereby altering its nutritional composition and digestibility. NaCl was added to an alfalfa-based total mixed ration (TMR) to model saline-alkaline alfalfa with high salt content. This method is a simplified modeling approach wherein sodium chloride is used to simulate saline stress. We have studied, using this model, changes in growth performance, nutrient digestibility, amino acid composition, and meat quality of AOHU (Hu × Australian White) lambs. The levels of dietary NaCl were set at 0.43% (to reflect the baseline NaCl content of standard alfalfa-based TMR and 1.71% (to reflect a level of high-salt alfalfa produced under saline–alkaline growing conditions). Compared to the control group, supplementation with NaCl enhanced the average daily gain, feed conversion efficiency, relative growth rate, and dry matter intake (p < 0.05). Apparent digestibility of dry matter, organic matter, crude protein, ether extract, fiber fractions (NDF and ADF), and gross energy was also improved (p < 0.001), reflecting enhanced nutrient utilization. Total saturated fatty acids had decreased, while meat redness increased, and the PUFA/SFA ratio increased, reflecting a leaner and healthier lipid profile. Moreover, essential amino acids-threonine, valine, methionine, isoleucine, leucine, and lysine-were significantly higher (p < 0.05), revealing a better meat nutritional quality. In summary, dietary NaCl supplementation in an alfalfa-based TMR effectively simulates saline–alkaline conditions that improve growth performance, nutrient digestibility, and meat nutritional composition. Results from this study show how NaCl supplementation in alfalfa-based rations—used here to mimic the elevated salt levels found in alfalfa grown on saline–alkaline soils—affects growth performance, nutrient digestibility, and meat quality in lambs, providing insight for feeding strategies in salt-affected production systems. Full article

Alzheimer’s disease (AD) is an age-related neurodegenerative disorder, characterised by the build-up of amyloid beta (Aβ) plaques and neurofibrillary tangles comprising hyper-phosphorylated tau. Increasing evidence indicates that in the early stages of AD, elevated levels of oligomeric forms of Aβ and phosphorylated tau (p-tau) gives rise to impaired synaptic function which ultimately drives AD-associated cognitive abnormalities. Thus, developing drugs that can limit the synaptic impairments that occur early in AD may have therapeutic benefits. Clinical evidence increasingly supports a link between lifestyle choices and AD risk. Indeed, there is an association between the circulating levels of the metabolic hormone leptin, mid-life obesity and disease risk, which has in turn stimulated interest in targeting the leptin system to treat AD. It is well-established that leptin readily accesses the brain, with the hippocampus, a key region that degenerates in AD, identified as a prime target for this hormone. Within the hippocampus, leptin has cognitive enhancing properties as it markedly influences the cellular events underlying hippocampal-dependent learning and memory, with significant impact on synaptic plasticity and trafficking of glutamate receptors at hippocampal excitatory CA1 synapses. Moreover, studies using a range of cell-based systems and animal models of disease indicate not only that leptin has powerful pro-cognitive effects, but also that leptin protects against the unwanted synapto-toxic effects of Aβ and tau, as well as enhancing neuronal cell viability. Moreover, recent studies have demonstrated that smaller leptin-based molecules replicate the full repertoire of protective features of whole leptin. Here we review the evidence that the leptin system is a potential novel avenue for drug discovery in AD. Full article

Beef production on chemically uniform grass monocultures can limit nutrient synchrony and contribute to uneven pasture use. We evaluated whether supplementing tannins with bioactive plant secondary compounds improves foraging dynamics and landscape use by beef cattle grazing a meadow bromegrass monoculture in ways aligned with rangeland sustainability. Twenty-four Angus cow–calf pairs were allocated to six 3.6-ha paddocks (four pairs/paddock), randomly assigned to Control (Ctrl; n = 3) or Tannin treatment (TT; n = 3). Animals received 1 kg/cow/day of DDGs, with TT receiving an added 0.4% tannins (2:1 condensed:hydrolyzable). Grazing occurred during four 15-day periods (July–September) across two years. Data were analyzed with mixed-effects models. Tannins did not alter biomass removal or cow weight loss (p > 0.05). However, TT cows exhibited longer evening grazing (2.9 vs. 2.1 h), fewer standing-to-lying transitions (5.7% vs. 7.3%), and more even spatial grazing distribution (CV = 1.861 vs. 2.13; p < 0.05), and greater water consumption (147 vs. 121 L/day; p < 0.01). Average daily gain of calves was numerically greater in TT compared to Ctrl (1.03 vs. 0.93 kg/day; p = 0.27). Collectively, these shifts promoted by tannins point to enhanced evening intake opportunities and reduced patch overuse, outcomes consistent with improved welfare and more uniform pasture utilization two pillars of sustainable grazing. Increased water demand under tannins highlights a management consideration for arid systems. Overall, moderate tannin inclusion was compatible with sustainable grazing by promoting even pasture use and potentially improving nutrient use efficiency without compromising intake. Full article

Atopic dermatitis (AD) is a chronic inflammatory skin disorder associated with immune dysregulation, skin barrier dysfunction, and microbial dysbiosis characterized by Staphylococcus aureus overcolonization and reduced bacterial diversity. Beyond its classical role in calcium homeostasis, Vitamin D (VD) influences skin immunity and microbial composition. This review summarizes current knowledge on VD metabolism, its immunological pathways in AD, and its interactions with the skin microbiome. Recent evidence positions the skin as an active immunological organ rather than a passive barrier. Commensal bacteria such as Staphylococcus epidermidis not only inhibit pathogens by producing bacteriocins and modulins but also generate ceramides and short-chain fatty acids (SCFAs) that stabilize the lipid barrier. Moreover, dermal fibroblasts and preadipocytes produce antimicrobial peptides, while resident γδ T cells release growth factors like fibroblast growth factor 7 (FGF7), linking host defense with tissue regeneration. VD modulates AD by suppressing T helper 2 cells/T helper 17 cell responses, enhancing regulatory T cell development, inducing antimicrobial peptides, and strengthening skin and gut barrier integrity. Its interaction with the microbiome and pathways such as SCFA and aryl hydrocarbon receptor (AhR) signaling supports its potential as an adjunctive therapy in AD management. Evidence from mechanistic studies and animal models suggests that VD supplementation may modulate inflammation and microbial diversity. Clinical implications, therapeutic perspectives, and future research directions highlight the potential of VD as a therapeutic adjunct in AD management. Full article