Observation of Giardia duodenalis infection in Mongolian gerbils: Cysts isolated from bovine feces.

Following peripheral nerve injury (PNI), the ferroptosis-inflammation axis restricts the neural repair process. As a critical neuroregenerative factor, the mechanism by which CXCL12 promotes nerve repair by regulating the ferroptosis-inflammation axis remains unclear. This study systematically investigated the mechanism of CXCL12 using a combination of clinical samples, as well as cellular and animal experimental models. Clinical data showed that CXCL12 levels in the serum of PNI patients were significantly elevated at 72 hours post-surgery, suggesting its potential involvement in the early regulatory process following nerve injury. In an LPS-induced Schwann cell (SC) injury model, CXCL12 effectively inhibited the occurrence of ferroptosis by activating the ERK/Nrf2 signaling pathway, which led to reduced cellular Fe2+ accumulation, downregulation of ACSL4, and upregulation of GPX4 and FSP1 expression. Further investigation revealed that the alleviation of cellular ferroptosis was accompanied by a decrease in NF-κB pathway activity, characterized by reduced levels of p-NF-κB and p-IκBα, as well as decreased secretion of TNF-α and IL-1β, indicating that CXCL12 possesses anti-inflammatory effects. Rescue experiments demonstrated that the ERK inhibitor U0126 partially reversed the anti-ferroptotic effect of CXCL12. Iron overload experiments (FAC) weakened the anti-inflammatory effect of CXCL12, whereas Ferrostatin-1 mimicked its anti-inflammatory action, suggesting that ferroptosis plays a pivotal role in the anti-inflammatory effects of CXCL12. Additionally, overexpression of NF-κB also diminished the anti-inflammatory efficacy of CXCL12. Animal experiments further confirmed that CXCL12 improved the mitochondrial structure of nerve tissues following PNI, reduced the accumulation of Fe2+ and lipid peroxidation, and promoted axonal and myelin regeneration. In conclusion, CXCL12 inhibits SC ferroptosis and reduces intracellular Fe2+ accumulation via the ERK/Nrf2 pathway, thereby attenuating the NF-κB-mediated inflammatory response and promoting nerve repair after PNI.

Diabetic retinopathy (DR) is the most significant manifestation of diabetic microangiopathy. The existing tree shrew model of DR has dysfunctional retinal short wave sensitivity (SWS) cones and retinal ganglion cells, but it remains unclear whether the retinal microvessels are also compromised. In this study, we established a tree shrew diabetes model to investigate the characteristics of retinal microvascular disease observed in early human DR. A high-fat and high-sugar diet combined with streptozotocin was used to establish the tree shrew diabetes model. After 20 weeks of sustained high glucose levels, we measured the thickness of each retinal layer and the number of ghost pericyte cells and acellular capillaries, and examined the ultrastructural changes in the retina. We also performed RNA sequencing (RNA-seq) and evaluated the protein expression levels of vascular endothelial growth factor (VEGF) and Bcl-2-related X protein (Bax). The tree shrew model exhibited the characteristics of diabetes, including hyperglycemia, hyperlipidemia, and insulin resistance. The retinal nerve fiber layer and ganglion cell layer exhibited significant thinning (36% and 30%, respectively). Retinal capillaries exhibited ghost pericytes and acellular capillaries, whereas the retinal ultrastructure exhibited signs of damage. VEGF and Bax protein levels in the retina were significantly upregulated. RNA-seq revealed downregulation of phosphoserine aminotransferase 1 (PSAT1). Overexpression of PSAT1 in retinal microvascular endothelial cells restored their lumen formation ability and mobility in a high-glucose environment, and reduced the expression of VEGF. Our results indicate that the tree shrew may be a suitable experimental animal model for studying the pathogenesis of early DR. Furthermore, PSAT1 may be a promising molecular target for DR treatment.

Background/Objectives: Adequate peri-implant soft tissue thickness is essential for long-term peri-implant health and esthetics. Horizontal platelet-rich fibrin (H-PRF) has been proposed to support soft tissue regeneration; however, experimental and translational evidence for its application in peri-implant soft tissue augmentation remains limited. This study aimed to evaluate a H-PRF membrane block approach primarily through an experimental animal model, with clinical cases presented to illustrate translational feasibility. Methods: A customized compression device was used to fabricate the H-PRF membrane block. The biological performance of the H-PRF membrane block was first evaluated in a rabbit model, with histologic assessment of peri-implant soft tissue thickness and integration at 8 weeks. Representative clinical cases requiring peri-implant mucosal thickening were subsequently treated with H-PRF membrane block on the buccal aspect of the alveolar bone beneath a supra-periosteal flap to demonstrate clinical applicability. Results: In the animal model, the H-PRF membrane block resulted in a significant increase in peri-implant soft tissue thickness by increasing the lamina propria compared with control sites demonstrated by histologic analysis. The clinical illustrations showed stable buccal soft tissue volume and contour with minimal patient morbidity. Conclusions: Within the limitations of this experimental study, the horizontal H-PRF membrane block technique demonstrated promising biological performance for peri-implant soft tissue augmentation in an animal model. The accompanying clinical illustrations support the translational feasibility of this approach. Clinical relevance: This experimental study provides biological and translational insight into a minimally invasive strategy for peri-implant soft tissue thickening and may inform future controlled clinical investigations.

Cryptococcal meningitis remains the top cause of death from an invasive fungal infection in humans, responsible for ~100,000 deaths annually of vulnerable patients with underlying immune deficiencies. Animal models of cryptococcal meningitis are important for understanding the immune parameters that correlate with protection. However, modeling this infection in mice is challenging. There is wide variability in infection routes, doses, and mouse background used in the field, which makes understanding phenotypes of mutants and immune interventions difficult to broadly apply. Our intention was to create an observational data set for the field on how Cryptococcus neoformans strain influences analysis of organ-specific immune responses in an intravenous mouse model of cryptococcal meningitis, focusing on impact of the fungal strain while keeping mouse genetic background (C57BL/6J) and infection route constant. We quantified myeloid and lymphoid cell recruitment and fungal-specific CD4 T-cell activation, correlating these results with fungal burdens in mice infected with the commonly used reference strain H99 or with two recently isolated clinical strains that were the same molecular type (VNI) or an unrelated type (VNB). We also analyzed how dose used in murine infection models affected brain immune responses during C. neoformans infection. Our work reveals intriguing patterns of organ-specific immunity that are dependent on C. neoformans strain but not always explained by virulence potential, raising important future questions for the field regarding the impact of C. neoformans strain on cellular immune responses in experimental animal models.IMPORTANCECryptococcal meningitis is a fungal infection that causes a wide variation of clinical disease in patients. This variation is thought to be partly due to the diversity of fungal strains that cause the infection. In this work, we have provided an in-depth analysis of immune responses to different clinical isolates of the fungus using mouse models of the infection. Our work reveals intriguing patterns of organ-specific immunity that are dependent on C. neoformans strain but not always explained by virulence potential, raising important future questions for the field regarding the impact of C. neoformans strain on cellular immune responses in experimental animal models.

Decoding the extracts of Lippia alnifolia Schauer (Verbenaceae): Chemical composition and its impacts on nociception and inflammation.

Antiulcer and laxative potential of polysaccharides from the ripe seed pulp of Delonix regia: A preliminary study.

Smart hydrogels embedding mesenchymal stromal cells are receiving increasing attention as a potential solution for preventing articular cartilage degeneration in knee osteoarthritis (OA). In this work we demonstrate that an injectable piezoelectric hydrogel embedding autologous adipose tissue-derived mesenchymal stromal cells (ASCs), stimulated by low-intensity pulsed ultrasound (LIPUS), is effective in reducing knee OA in two preclinical surgically induced OA models. A medium-sized rabbit model was used to evaluate sex differences in treatment efficacy, while a large-sized sheep model was employed to assess the translatability of this innovative approach to a scenario with similarities to human conditions. We developed computational models to ensure reliable and precise delivery of a specific ultrasound dose to the target, modelling wave propagation through tissues and considering the anatomy of the two experimental animal models. Sex-based differences in therapy effectiveness were observed in rabbits, with better macroscopic and microscopic outcomes in counteracting OA in female animals. Furthermore, we found that the combination of ASC-laden piezoelectric hydrogel and LIPUS can be scaled in a large-sized sheep model, proving effective in counteracting OA.

IgM-enriched immunoglobulin treatment significantly improves coagulation dysbalance in an experimental animal model of fulminant sepsis.

Liver transplantation (LTx) is among the most technically challenging procedures in abdominal surgery, especially for patients with severe liver fibrosis and cirrhosis. Constraints in surgical exposure, ethical considerations, and patient safety requirements have expedited the implementation of structured, competency-based training programs. Experimental animal models are crucial for advanced transplant training, offering physiological realism, procedural practice, and translational understanding of surgical problems associated with fibrosis. This narrative review critically synthesizes material from 1990 to 2024 sourced from PubMed/MEDLINE, Scopus, and Google Scholar, concentrating on the pedagogical utilization of rodent, porcine, and non-human primate models. We explicitly associate each model with specified training objectives, evaluative assessment instruments, and the incorporation of contemporary simulation technologies. The review additionally contrasts global training norms and suggests a unified, hybrid architecture to enhance skill acquisition, ethical governance, and patient outcomes.

Piriform sinus fistula (PSF) is a rare congenital anomaly derived from the third or fourth pharyngeal pouch. However, its developmental mechanisms remain poorly understood owing to the absence of suitable animal models. Cotton rats (Sigmodon hispidus) spontaneously develop PSF, providing a unique opportunity to investigate its anatomical origin and postnatal remodeling. In this study, we performed a three-dimensional reconstruction of serial histological sections from two inbred strains, HIS/Mz with third-pouch-derived PSF and HIS/Hiph with fourth-pouch-derived PSF. The third-pouch PSF opened dorsally at the base of the piriform sinus and terminated outside the thyroid gland, whereas the fourth-pouch PSF opened ventrally at the apex and extended into the thyroid parenchyma. Focusing on the fourth-pouch PSF in the HIS/Hiph, we further identified progressive epithelial stratification and age-dependent inflammation leading to suppurative thyroiditis. This remodeling was accompanied by marked alterations in epithelial marker expression, including a shift from Nkx2-1+/CK8+/UEA-I- to p63+/CK5+/UEA-I+ cell populations. Together, these features resemble the known characteristics of ultimobranchial body remnants and highlight the dynamic inflammation-associated transformation of the PSF epithelium. Collectively, our findings establish the cotton rat as a biologically informative experimental animal model for elucidating the developmental origin and pathological progression of PSF. This study provides new insights that may improve understanding, diagnosis, and clinical management of congenital cervical anomalies in humans.

Preeclampsia (PE) is a major cause of maternal and perinatal morbidity, with its pathogenesis involving, in particular, impaired mineral homeostasis. Recent evidence suggest that fibroblast growth factor 23 (FGF23), a key regulator of phosphate balance and vitamin D3 metabolism, may contribute to pregnancy complications, however, its role in PE remains poorly understood. This study aimed to evaluate serum FGF23 level and its relationship with vitamin D3 and calcium–phosphate balance at preeclampsia development in animal experimental model. Thirty-five Wistar female rats were divided into three groups: controls on a standard­ diet; vitamin D3-deficient rats; vitamin D3-deficient rats supplemented with cholecalciferol. Within each group, PE was induced by Nω-nitro-L-arginine methyl ester administration. Serum concentrations of 25(OH)D3, FGF23, parathyroid hormone (PTH), total calcium, inorganic phosphate, and alkaline phosphatase (ALP) activity were determined by ELISA and biochemical assays. It was shown that vitamin D3 deficiency was accompanied by hypocalcemia, hypophosphatemia, elevated FGF23 and increased ALP activity in the serum. Supplementation with vitamin D3 increased 25(OH)D3, markedly reduced FGF23 levels and normalized mine­ral parameters. Induction of PE caused significant disturbances in calcium–phosphate status, hypertension, and 100% mortality of vitamin D3-deficient animals. In the presence of preeclampsia vitamin D3 efficacy was limited. In PE group, despite of vitamin D3 supplementation, serum FGF23 was markedly elevated, indicating impaired vitamin D3 metabolism. Our findings demonstrate that vitamin D3 deficiency amplifies PE severity through disruption of mineral homeostasis and FGF23 dependent signaling. Keywords: 25OHD3, calcium–phosphate metabolism, L-NAME, preeclampsia, vitamin D3 deficiency

Marburg virus (MARV) is a highly pathogenic zoonotic filovirus. The Orthomarburgvirus marburgense species includes MARV and Ravn virus (RAVV), which differs from MARV by 21% at the nucleotide level and 22% at the protein level. This review offers fresh discussions of the epidemiology, genetics and natural reservoir transmission of RAVV, summarizes experimental animal models, outlines current vaccine development and raises outstanding questions about RAVV life history, transmission and pathogenicity.

Background: Colorectal cancer (CRC) remains one of the leading causes of cancer-related morbidity and mortality worldwide. Besides tumor-intrinsic factors, CRC risk and progression are strongly influenced by metabolic dysfunction - including obesity, insulin resistance, and T2DM. These implications emphasize the need for therapeutic strategies that address both tumor biology and the metabolic context. Objectives: This review examines the emerging role of glucagon-like peptide-1 receptor agonists (GLP-1RAs) in colorectal cancer biology, synthesizing mechanistic, preclinical, and human evidence to evaluate their potential relevance beyond well-known glycemic control. Methods: We integrate experimental studies, animal models, and epidemiologic and clinical data to evaluate the effects of GLP-1RAs on colorectal cancer–related pathways, tumor growth and progression, and resulting clinical outcomes, with special attention given to metabolic and signaling mechanisms. Key Findings: Preclinical evidence suggests that GLP-1RAs may modulate pathways involved in cancer cell proliferation, survival, metabolism, angiogenesis, and invasion, including PI3K/Akt/mTOR, ERK, and hypoxia-associated signaling. In vivo models showcase inhibitory effects on tumor growth and metastatic potential, heightened in metabolically dysregulated settings. Human observational studies report heterogeneous but generally neutral to protective associations between GLP-1RA exposure and CRC risk, while randomized trials have primarily addressed cardiometabolic outcomes rather than being tumor-focused. Conclusions: Collectively, current evidence supports a biologically plausible role for GLP-1 receptor signaling in colorectal cancer growth and progression. Definitive clinical data are lacking, but evidence regarding GLP-1RAs justifies further investigation into their potential relevance.

Alcohol-associated liver disease (ALD) is a major cause of chronic liver injury, in which disruption of the gut-liver axis plays a key pathogenic role. Probiotics have been proposed as a potential therapeutic strategy to mitigate alcohol-induced liver damage; however, the preclinical evidence has not been systematically synthesised. This systematic review aimed to evaluate and summarise the hepatoprotective effects of probiotic supplementation in experimental animal models of ALD. The review protocol was pre-registered in PROSPERO (CRD420250653666) and followed PRISMA guidelines. A systematic search was conducted across PubMed, EMBASE and AGRICOLA databases using relevant keywords from inception to 30 April 2025. We included preclinical randomised controlled trials evaluating single-strain probiotic interventions against placebo or untreated controls in animal models of ALD. Risk of bias was assessed using SYRCLE's tool, and the certainty of evidence for critical outcomes was evaluated using the GRADE framework. A narrative synthesis was performed, as a quantitative meta-analysis was precluded by incomplete numerical outcome reporting. From initial 628 records, 36 studies were included in the final synthesis. Probiotic supplementation consistently attenuated alcohol-induced liver injury, as evidenced by marked reductions in serum ALT and AST levels and improved liver histology. Mechanistically, probiotics restored gut barrier integrity, reduced systemic endotoxemia, and suppressed pro-inflammatory pathways. Furthermore, probiotic treatment effectively counteracted alcohol-induced gut dysbiosis by increasing microbial diversity and restoring taxonomic balance, notably by reversing the alcohol-induced expansion of Proteobacteria. Despite these consistent directional effects, the overall certainty of evidence for the critical outcomes was rated as very low. Although the preclinical literature suggests hepatoprotective effects of probiotics in experimental ALD, these findings should be interpreted with caution due to the very low certainty of evidence. The observed benefits are limited by methodological shortcomings, indirectness inherent to animal models, and incomplete outcome reporting. This review provides a structured preclinical framework to inform the design of future translational studies and well-controlled clinical trials evaluating probiotics as potential adjunctive therapies in human ALD.

Land directly affects people's health and well-being. Soil is essential for social and economic growth. It is impossible to overstate the urgency of conserving soil, as it is crucial for fostering the development of an ecological civilization and maintaining household stability. A new significant threat to soil health and fertility has emerged in the form of contaminants of emerging concern (CECs). Unlike other pollutants, these CECs (e.g., pharmaceuticals, cosmetics, PFAS, and microplastics) are resistant to microbial degradation; therefore, they persist in soil and can enter the food chain or pollute groundwater supplies. Several researchers worldwide have shown that CECs destroy soil microflora, impair ecological balance, and reduce soil fertility and agricultural productivity. Recent experimental studies have confirmed their presence in cell culture and experimental animal models at concentrations ranging from nanomolar (nM) to millimolar (mM) levels. The unrestricted use of these CECs has resulted in their bioaccumulation at higher levels in the food chain, ultimately reaching human beings. Despite their hazardous nature, no definite environmental laws or FDA regulations exist, adding fuel to the fire. Therefore, we aim to highlight the environmental implications of these CECs and the steps needed to prevent them from transforming into an environmental catastrophe. This review focuses on five key CECs, including nanoparticles, cosmetic additives (phthalates and biphenyls), flame retardants, and microplastics, along with their environmental implications.

Experimental autoimmune uveitis (EAU) in rats is a pivotal model for understanding the immunological mechanisms of human uveitis and developing therapies. In humans, optical coherence tomography (OCT) allows for the in vivo detection of characteristic findings in active uveitis, as well as sequelae of inflammation. The objective of this study was to correlate OCT findings in patients with uveitis with retinal histologies from two rat models of EAU caused by T cells with different autoantigen specificities and well-known underlying immunological pathomechanisms. Patients with various noninfectious uveitis subtypes underwent imaging using an ultra-widefield swept source or conventional OCT. Histological cryosections from rat eyes with experimental autoimmune uveitis were stained for T cell and/or macrophage markers. Typical human OCT findings were reproduced in the experimental animal model. Hyperreflective signals observed on OCT corresponded to lymphocyte infiltration in histological sections. This infiltration was typically found as vasculitis in the perivascular regions and snowballs in the posterior hyaloid. There was lymphocyte and macrophage infiltration of the retina through the retinal vessels and the retinal pigment epithelium. Comparing in vivo OCT imaging of human uveitis with corresponding histologies from rat models improves our understanding of the type of inflammation, extent of tissue destruction, and immunopathogenesis.

Fever, or pyrexia, is defined as an elevation in body temperature beyond normal physiological limits and pain an unpleasant sensory and emotional experience occur in some types of fever. Dioscorea bulbifera leaves are traditionally used for managing fever with aches and pain as per Siddha Literature. Based on these traditional claims, the present study aimed to scientifically evaluate the antipyretic and analgesic activities of Diacorea bulbifera leaf decoction using experimental animal models. For antipyretic activity, 18 male Wistar albino rats were divided into three groups: control, standard, and test. Fever was induced using 15% w/v Brewer's yeast administered subcutaneously. After 18 hours, rectal temperatures were recorded at 30, 60, 90, and 120 minutes following treatment. The control group received 1 ml/kg normal saline, the standard group received paracetamol syrup, and the test group received Diacorea bulbifera leaf decoction according to standard dose calculation. For analgesic activity, 18 female Wistar albino rats were divided similarly, and the tail immersion method was used. Tail withdrawal times were recorded at 30, 60, 90, and 120 minutes after administering saline, diclofenac and diascorea bulbifera decoction. The Dioscorea bulbifera decoction significantly reduced fever, showing effects comparable to paracetamol after 90 minutes. It also exhibited notable analgesic activity from the 60th minute onward, with stronger and longer-lasting effects than diclofenac. Dioscorea bulbifera leaf decoction demonstrates significant antipyretic and analgesic effects, supporting its traditional use in treating fever and pain.

Dietary supplementation of pickering emulsions as functional foods: fabrication, in vitro gastrointestinal bioaccessibility and in vivo animal experimental model

The aim of this study was to compare recombinant and urinary follicle stimulating hormone (FSH) with each other in terms of endometrial receptivity for the purpose of controlled ovarian stimulation. Twenty-four female albino mice (Mus musculus, C/C; 6-8 weeks, 18-22g) and six males (8-10 weeks) were divided into four groups: control (no mating), spontaneous mating, urinary FSH (uFSH), and recombinant FSH (rFSH). Females in estrus received 5 IU of uFSH or rFSH, followed by mating after 48h. Implantation sites were evaluated using histopathology and immunohistochemistry with anti-LIF, anti-Laminin, and integrin αVβ3 antibodies. LIF levels in serum collected from the tail vein were measured using ELISA. The Tukey multiple comparison test showed significant group differences in Laminin and Integrin αVβ3 staining intensity (p < 0.001). rFSH treatment significantly increased Laminin and Integrin αVβ3 expression compared with both uFSH and spontaneous conception groups (p < 0.001), while uFSH also showed higher levels than the spontaneous group (p < 0.001). For LIF, no difference was found between the control and spontaneous groups (p > 0.05), but both rFSH and uFSH groups exhibited higher expression than the spontaneous group, with the highest levels in the rFSH group (p < 0.001). rFSH treatment was associated with the greatest enhancement of endometrial receptivity markers, both immunohistochemically and biochemically, suggesting that rFSH may exert a more favorable effect on implantation potential compared with uFSH.