Lapsi (Choerospondias axillaris), a plant native to Nepal, has been traditionally used in Asian countries to treat cardiovascular conditions. However, its effects on immune regulatory function remain largely unexplored. This study aimed to in vivo evaluate the immunoregulatory properties of Lapsi fruit extract in mice on immunotoxic responses with analysis on in vitro mechanism for immune suppression, oxidative stress, and inflammatory response. Male Balb/c mice were intragastrically administered various doses of the extract for 21 days. In some mice, immune suppression was induced with cyclophosphamide, and subsequent immune recovery was assessed. In addition, RAW264.7 cells and THP-1-derived macrophages were treated in vitro with lipopolysaccharide and different concentrations of the extract. Administration of extract increased the IgG2a/IgG1 ratio while reducing serum IgE and IgG1 level compared with control mice. Tumor necrosis factor (TNF)-α and interleukin (IL)-17 levels were lower in splenic culture supernatants of mice administered extract. Lapsi extract also effectively reversed cyclophosphamide (CP)-induced immunosuppression by enhancing serum levels of IgA and IgG2a, of interferon-γ and interleukin (IL)-4 secreted by splenic T cells, and of IgG1 and IgG2a secreted by B cells, as well as by increasing immune cell counts. In cell cultures, the extract decreased the levels of inflammation markers, including nitric oxide, reactive oxygen species, prostaglandin E2, and pro-inflammatory cytokines (IL-6, TNF-α, and IL-1β). Mechanistic analysis showed that Lapsi extract modulated the NF-κB p65, MAPK, and inflammasome pathways. Lapsi extract may act as both an immunostimulatory and anti-inflammatory agent, indicating its potential as a candidate immunomodulatory activity under polyclonal and CP-suppressed conditions; however, further disease-specific studies, along with isolation and characterization of active phytochemicals, are warranted to evaluate its therapeutic applicability.

Mpox, known before now as monkeypox, is a novel zoonotic disease that may infect both humans and animals. It usually spreads by direct contact with bodily fluids, lesion material, or fomites (such as contaminated linens) and prolonged face-to-face contact. Mpox can spread to laboratory animals in a research laboratory through either a general outbreak or during procedures. Animal models are essential as we learn more about how infections occur and how to treat illnesses in both humans and animals which require laboratory procedures with mpox virus. As drug-resistant organisms proliferate, bioterrorism becomes a greater danger, international trade and travel expand, and the number of newly developing infectious illnesses grows, the use of animals in infectious disease research has increased. Animal research offers a solid basis for clinical trials used in standard medication development. Animal studies must be planned to produce conclusive effectiveness evidence that is robust, rigorous, and repeatable per the animal rule so that the agency may depend on the results when making regulatory decisions. There is a need to understand the transmission risk and biosafety protocol to be in place in laboratory settings to prevent an outbreak and probably contain an outbreak. Hence, this review discussed the overview of mpox in animal research, biosafety protocols in mpox research, laboratory waste management methods, legal and ethical considerations in mpox research, challenges in carrying out mpox research and future directions.

Vitiligo is a skin disorder characterized by the loss of melanocytes (MCs), leading to depigmentation. While the exact mechanisms are unclear, the transcription factor Ets-1, known for its role in regulating matrix metalloproteinase expression and MC migration, is suspected to play a part. Ets-1 gene-deficient mice exhibit a vitiligo-like phenotype with spontaneous skin depigmentation, suggesting a direct link between Ets-1 deficiency and MC dysfunction. This study aimed to characterize the molecular and histological features of Ets-1 gene knockout (KO) mice to understand the underlying mechanisms of this depigmentation. Transcriptomic analysis of depigmented and normal skin from Ets-1 KO and wild-type mice revealed significant differentially expressed genes (DEGs). KEGG pathway enrichment analysis demonstrated alterations in metabolic and signal transduction pathways, notably the downregulation of melanogenesis-related genes. RT-qPCR and immunohistochemistry confirmed reduced tyrosinase expression at both transcript and protein levels in the depigmented skin of KO mice. Protein-protein interaction network analysis of the DEGs highlighted a central network involving keratin proteins and discrete interactions regulating melanogenesis, stress response, and cellular signaling pathways. These findings demonstrate that Ets-1 deficiency in mice leads to significant molecular and histological changes consistent with MC dysfunction and depigmentation. The observed downregulation of melanogenesis-related genes and alterations in key signaling pathways provide valuable insights into the molecular basis of Ets-1’s role in MC maintenance and suggest potential therapeutic targets for skin pigmentation disorders, including vitiligo.

BackgroundWith aging, the canonical histone H3.1/3.2 in skeletal muscle is progressively replaced by the non-canonical variant H3.3. Although H3.3 is thought to be involved in age-related epigenetic regulation due to its role as a histone variant, its functional characteristics remain largely unknown. Serine 31 (S31) is a unique amino acid residue of H3.3 that undergoes phosphorylation. Therefore, the present study aimed to investigate the relationship between skeletal muscle aging and H3.3 phosphorylation at S31 (H3.3S31ph).ResultsWe first demonstrated that H3.3S31ph levels were significantly reduced in the tibialis anterior muscle of 75-wk-old mice compared to 8-wk-old mice. We then examined the effects of viral vector–mediated expression of wild-type H3.3 or a phosphorylation-mimicking H3.3 mutant (H3.3S31E) on gene responsiveness to acute exercise in aging skeletal muscle. In muscles expressing wild-type H3.3, which simulates epigenetic alterations observed during skeletal muscle aging, the transcriptional response to acute exercise was lost by 30 weeks post-treatment (60 weeks of age). In contrast, expression of H3.3S31E successfully rescued the gene responses to acute exercise. This rescue was accompanied by increased enrichment of H3K4me3 and H3K27me3 following acute exercise in the H3.3S31E group, whereas no such histone modification changes were observed in the wild-type H3.3 group. Additionally, robust involvement of exogenous H3.3 in exercise-related histone turnover was observed in the wild-type H3.3 group, but not in the H3.3S31E group, suggesting that phosphorylation at S31 limits the dynamic behavior of H3.3.ConclusionsImpaired transcriptional responsiveness to exercise in a simulated epigenetic aging model induced by exogenous H3.3 expression was rescued by the phosphorylation-mimicking H3.3S31E variant in middle-aged skeletal muscle. The findings of the present study demonstrate that H3.3S31ph plays a critical role in regulating the stability of H3.3 within chromatin.Supplementary InformationThe online version contains supplementary material available at 10.1186/s42826-025-00254-6.

Asthma is a chronic and heterogeneous airway disease characterized by a variety of respiratory symptoms associated with airflow limitation. Asthma patients exhibit altered immunological and physiological features in the airways, including inflammation, hyperresponsiveness, and, in severe cases, permanent structural changes that lead to airway obstruction. Among the different types of asthma, allergic asthma mediated by Th2 cells is the most prevalent phenotype worldwide. The diversity of etiological factors involved, the variability in symptom intensity, and the high global incidence have increased interest in studying this phenomenon. Due to the ethical constraints associated with studying asthma in humans, the development of animal models has emerged as an alternative for investigating the disease’s pathophysiology. In particular, the guinea pig (Cavia porcellus) has become one of the most commonly used species, as it closely resembles the inflammatory, pharmacological, and physiological responses observed in the human airway. This article provides a comprehensive description of the development of an allergic asthma model in the guinea pig. The processes involved in each methodological phase are described in detail from an immunological and physiological perspective, emphasizing their importance in understanding the disease’s pathophysiological mechanisms. It is argued that the airway inflammation, obstructive responses, and remodeling processes observed in this model are consistent with features seen in asthma patients, establishing the guinea pig as a reliable model for studying allergic asthma in humans.

BackgroundAsian sand dust (ASD), generated from the deserts of China and Mongolia, mainly affects the human health of several countries in Northeast Asia including China, Korea, and Japan. In this study, we investigated the toxic effects of ASD on respiratory tract and explored the effects of ASD exposure on allergic asthma using ovalbumin-induced asthma model. C57BL/6 male mice were used for both the toxicity and allergic asthma studies. ASD (10, 20, and 40 mg/kg) was administered intranasally on days 1, 3, and 5. For allergic asthma, mice were sensitized with OVA (20 µg/mouse) and aluminum hydroxide (2 mg) on days 1 and 15, followed by OVA inhalation (1%, w/v) on days 22, 24, and 26, with subsequent ASD instillation on days 21, 23, and 25.ResultsASD exposure showed the elevation of respiratory inflammation including inflammatory cell infiltration, cytokine production, and mucus secretion with the increase in phosphorylated (p)-nuclear factor-kappa B (NF-κB) p65 expression. In addition, ASD exposure to asthma model significantly increased airway responsiveness, inflammatory cell count and mucus secretion with the elevation of cytokines and immunoglobulin E, which were accompanied with the increases in p-NF-κB p65, p-p38 and cyclooxygenase 2 (COX2).ConclusionsTherefore, ASD exposure induces respiratory inflammation and aggravates the progression of allergic asthma, which was closely associated with the phosphorylation of NF-κB. Respiratory exposure to ASD causes inflammation, upregulation of cytokines, p-NF-κB, and COX2, which can exacerbate asthma.

BackgroundObesity affects nearly a billion people globally and is associated with various health consequences. Current anti-obesity medications primarily target appetite, but drug candidates that modulate energy expenditure (EE) and substrate utilization based on respiratory exchange ratio (RER) are also essential to continuously improve the treatment modalities for people living with obesity. Selecting appropriate animal models and methods is crucial to improving translational value in preclinical research. While pig obesity models provide a relevant alternative to rodent models due to their similarities to humans, little is known about the assessment and translatability of EE in pigs. The aim of this study was to evaluate the translatability of minipigs for assessing the effect of EE-modulating drugs using indirect calorimetry and three positive control compounds that have known effects on EE and/or RER in humans. The study consisted of five sub-studies: Sub-study 1 assessed EE and RER based on sex (male/female) and diet (chow/high-fat diet) with and without correction for body composition; Sub-studies 2–4 evaluated changes in EE and RER after treatment with three positive control compounds: 2,4-dinitrophenol, DNP; a glucagon receptor agonist, GCG-RA; and a melanocortin receptor 4 agonist, MC4-RA; and sub-study 5 established three predictive equations for resting metabolic rate.ResultsSub-study 1 resulted in detectable differences in EE and RER based on diet/body sizes (P-value < 0.0001), while EE adjusted for body composition resulted in differences based on sex (P-value < 0.0001). Sub-studies 2–4 revealed that the three pharmacological interventions known to affect EE in humans, DNP, GCG-RA, and MC4-RA, showed similar effects in the Göttingen Minipigs by significantly increasing EE by 26.1% (P-value: 0.0014), 21.3% (P-value: 0.0491), and 25.4% (P-value: 0.0013), respectively, emphasizing the translational value of the model. In sub-study 5, three predictive equations were established for RMR based on body composition, demographic and anthropometric measurements, and the most accurate equation based on all variables. All three equations demonstrated acceptable accuracy (adjusted R2: 0.73–0.85).ConclusionsThe present study qualifies the use of Göttingen Minipigs for investigating EE in preclinical research and provides a framework for conducting such research.

Ischemic stroke (IS) is the most recorded case of stroke that is caused by decreased blood flow to the brain. Nowadays, therapeutical agents for IS are limited and they have not shown maximum clinical results. Therefore, the exploration of new candidates for IS treatment continues to be done. Zebrafish as one of the animal models has its advantages and currently is being developed to be incorporated into the drug discovery pipeline of IS. This review explores the latest applications of the zebrafish model in screening potential therapeutic agents for IS. Key factors related to the experimental design such as developmental stage and strain, routes of drug administration, induction methods, and experimental parameters are also elaborated. Finally, this review offers future recommendations for the use of zebrafish in the pre-clinical study of IS. This review is beneficial as a reference for establishing drug screening protocols using the zebrafish IS model.