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OBJECTIVE: To explore lung ultrasound (LUS) in the evolution of bronchopulmonary dysplasia (BPD) and the diagnostic value of LUS in BPD. METHODS: Newborn rats were randomly assigned to the room air (RA) group or the oxygen (O2) group. LUS were performed at 12 h and on the 3rd, 7th, and 10th days to explore the LUS in BPD rats. Hematoxylin-eosin staining and immunohistochemical were analyzed to evaluate pathological characteristics. RESULTS: LUS score (LUSs) in the O2 group was significantly increased on the 7th and 10th days. In the early stage, LUS revealed multiple B-lines and air bronchograms. In the late stage, LUS revealed anechoic echoic areas on the pleural surface and scattered dot-like hyperechoic patterns in the lung field. The LUS findings were consistent with the pathological results. CONCLUSION: There was a strong positive correlation between LUS and pathological findings. LUS can be used to monitor the evolution of BPD.
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Displasia Broncopulmonar , Pulmón , Animales , Pulmón/diagnóstico por imagen , Pulmón/patología , Displasia Broncopulmonar/diagnóstico por imagen , Displasia Broncopulmonar/patología , Ratas , Ultrasonografía , Animales Recién Nacidos , Modelos Animales de Enfermedad , Ratas Sprague-Dawley , FemeninoRESUMEN
In animals, low-dose-rate radiation induces cancer at a reduced rate compared with a high-dose-rate at an identical cumulative dose, although the underlying mechanism is not well understood. The immediate responses of cells to irradiation are well established, including DNA double-strand break repair, cell-cycle arrest and cell death; conversely, the changes in tissues weeks after irradiation are not well understood. We therefore analysed cellular dynamics in rat mammary tissue weeks after high- or low-dose-rate irradiation. We irradiated 5-week-old rats with 2 Gy (30 Gy/h) or 3- to 5-week-old rats with continuous 2 Gy (6 mGy/h). For histological analysis, luminal cells were identified with anti-cytokeratin (CK) 8 + 18; CK8 + 18Low cells are luminal progenitor cells, and CK8 + 18High cells are luminal mature cells. To evaluate cell composition by flow cytometry, epithelial cells were isolated from mammary tissue. The proliferative potential of luminal progenitor cells-as measured by Ki-67 on paraffin sections-decreased 2 weeks after irradiation at either the high- or low-dose rate but recovered to the control level by 4 weeks. No significant difference was observed in the S phase and total cell-cycle length identified by 5-ethynyl-2'-deoxyuridine and 5-bromo-2'-deoxyuridine or cell death marked by cleaved caspase-3 among the dose-rates. Furthermore, the composition of luminal mature cells changed 2-6 weeks after completing the high- and, to a lesser extent, low-dose-rate radiation exposure, indicating potential proliferative stimulation of luminal progenitor cells related to susceptibility to carcinogenesis. These findings suggest that the altered cell composition and dynamics of luminal cells for several weeks contribute to carcinogenesis.
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BACKGROUND: The aim of the study was to develop a non-human primate model of metabolic dysfunction in Macaca fascicularis using chronic high-fat diet (HFD) to mimic clinical disease progression. METHODS: Thirty-five male macaques aged 10-15 years underwent an 18-month HFD intervention. Physiological parameters (BMI, BP, hematology), liver fat fraction (evaluated by ultrasound/MRI), cardiac function (assessed by echocardiography), and histopathology (using liver biopsy) were measured before and after the intervention. Serum proteomics with KEGG/STRING analyses identified molecular mechanisms. RESULTS: Within 6 months, HFD induced dyslipidemia (elevated TG, TCHO, HDL-C, LDL-C). After 18 months, metabolic dysfunction-associated steatohepatitis (MASH) was confirmed by histopathology in 57.14% (16/28) of macaques, diabetes (elevated FPG/HbA1c) in 17.86% (5/28), and myocardial hypertrophy (elevated LVMass/LAD) in 46.43% (13/28). Proteomics identified Bile acid-CoA: amino acid N-acyltransferase (BAAT) as a MASH hallmark protein, the level of which was inversely correlated with the degree of fibrosis. For diabetes, citrate synthase (CS) and malate dehydrogenase 1 (MDH1) impaired glucose oxidation via the TCA cycle, while hexose-6-phosphate dehydrogenase (H6PD) disrupted gluconeogenesis. Myocardial hypertrophy was associated with the downregulation of SRC proto-oncogene, non-receptor tyrosine kinase (SRC), mitogen-activated protein kinase 14 (MAPK14), emerin (EMD), and integrin subunit beta 1 (ITGB1). CONCLUSIONS: An 18-month HFD successfully established a translational M. fascicularis model replicating key metabolic disorders (MASH, diabetes, cardiac hypertrophy). BAAT, CS/MDH1/H6PD, and SRC/MAPK14/EMD/ITGB1 were identified as mechanistic biomarkers for these conditions.
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PURPOSE: Osteoarthritis is a degenerative joint disease that causes painful inflammation with cartilaginous damage that highly impacts geriatric health, demanding advanced therapy with limited complications on treatment. Conventional therapies focused on associated pain only, thus failing to treat the root cause of inflammatory degenerative cartilaginous tissue of the joints. To overcome the related issues, a holistic approach is the combinatorial therapy of Oxaprozin (OXA) and Apricot kernel oil (AKO) which encompasses the excellent analgesic and restoration of lipid-balance activities. METHOD: The scalable targeted transcutaneous delivery of OXA-loaded Apricot oil-based nanoemulgel (OXA-NEG) was optimized and evaluated. Further, preclinical studies aligned with better therapeutic outcomes. RESULT: The GC-MS study of the AKO identified potential components, including vitamins, fatty acids, and antioxidants. The optimized nanoemulsion with an average globule size of 208.5 ± 5.97 nm, PDI 0.2502 ± 0.045, and zeta potential of -16.33 ± 0.241 mV, revealed promising delivery. The OXA-NEG exhibited good spreadability and extrudability in texture analysis. The in-vitro and ex-vivo studies demonstrated sustained release with high permeation flux compared to conventional gel. The therapeutic potential was assessed on an osteoarthritis-induced animal model, where radiographic examination revealed that the OXA-NEG group of rats showed prominent recovery of the swollen joint cartilage in contrast to the control group. The plasma TNF-α and IL-6 levels also showed substantial variation (p < 0.001) compared to the control group. CONCLUSION: It is concluded that the proposed formulation has promising dual therapeutic potential for transcutaneous delivery, meeting safety aspects and could be aligned with better clinical acceptance.
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Cor pulmonale, indicative of right heart failure (RHF), is precipitated by pulmonary conditions that escalate pulmonary arterial pressure. This complication is notably prevalent in patients with chronic obstructive pulmonary disease (COPD), and is recognized as an independent predictor of adverse outcomes. Despite its significance, the lack of appropriate animal models has hindered the development of therapies for cor pulmonale in COPD patients. Therefore, we aimed to establish a mouse model that mimics the essential pathological features of COPD-cor pulmonale. All mice underwent thoracic surgery, including left pulmonary artery ligation (LPAL) or sham surgery (artery exposed without ligation). Following a 2-week recuperation, the mice were exposed to cigarette smoke or room air for 28 weeks. At the end of the exposure, pulmonary function, right ventricular hemodynamics, and histological alterations were determined. CD31, α-SMA, and CD68 were detected by immunofluorescence and immunohistochemistry to show vascular and macrophage changes. Mice subjected to LPAL and cigarette smoke exposure exhibited COPD-like features, including impaired lung function, emphysematous alterations, pulmonary inflammatory cell infiltration, and airway remodeling, accompanied by the increase in right ventricular systolic pressure, right ventricular hypertrophy, fibrosis, macrophage aggregation, and reduced capillary density. This model, integrating cigarette smoke exposure with LPAL, effectively replicates the critical pathological features of COPD-cor pulmonale.
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Fumar Cigarrillos , Arteria Pulmonar , Enfermedad Pulmonar Obstructiva Crónica , Enfermedad Cardiopulmonar , Animales , Enfermedad Cardiopulmonar/etiología , Enfermedad Cardiopulmonar/patología , Enfermedad Cardiopulmonar/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/fisiopatología , Enfermedad Pulmonar Obstructiva Crónica/patología , Enfermedad Pulmonar Obstructiva Crónica/complicaciones , Arteria Pulmonar/cirugía , Modelos Animales de Enfermedad , Ratones , Masculino , Ratones Endogámicos C57BL , Ligadura , Pulmón/patología , Pulmón/fisiopatología , Fumar Cigarrillos/efectos adversosRESUMEN
BACKGROUND: Intervertebral disc degeneration (IVDD) is a primary cause of chronic low back pain. Recent evidence suggests a potential association between low-virulence infections, particularly by Cutibacterium acnes, and IVDD. However, the pathways and mechanisms by which this commensal skin bacterium infects intervertebral discs remain poorly understood. OBJECTIVE: The purpose of this study was to determine whether Cutibacterium acnes can enter the intervertebral disc through hematogenous or contiguous routes, and whether injury-induced damage to the annulus fibrosus and IVDD increases susceptibility to infection, using an animal model. METHODS: To investigate Cutibacterium acnes infection pathways, Sprague-Dawley rats underwent caudal disc annulus fibrosus puncture or remained intact (confirmed by 28-day MRI T2WI). After MRI, hematogenous and contiguous infections were modeled by daily Cutibacterium acnes injections for 7 days. Tail-vein injections were given in Groups A (intact discs) and C (punctured discs) to simulate hematogenous spread, while subcutaneous injections were given in Groups B (intact discs) and D (punctured discs) to simulate contiguous spread. Intervertebral disc samples were taken under very strict aseptic conditions after the intervention. Gram staining and Cutibacterium acnes-specific 16S rDNA PCR were used to confirm the presence of Cutibacterium acnes in these disc specimens cultured under aerobic and anaerobic conditions. The remaining segment was subjected to histological evaluation (H&E staining). RESULTS: Intervertebral disc puncture successfully induced IVDD, as evidenced by MRI and histology. Punctured discs exhibited significantly higher susceptibility to Cutibacterium acnes infection via both hematogenous (Group C: 17.5% vs. Group A: 0%; P = 0.012) and contiguous spread (Group D: 20% vs. Group B: 0%; P = 0.005), as confirmed by anaerobic culture. No bacteria were cultured in an aerobic environment, and the PBS group. CONCLUSIONS: Annulus fibrosus injury and IVDD significantly increase the risk of intervertebral disc Cutibacterium acnes infection through hematogenous and contiguous spread pathways.
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Infecciones por Bacterias Grampositivas , Degeneración del Disco Intervertebral , Disco Intervertebral , Propionibacteriaceae , Propionibacterium acnes , Punciones , Animales , Ratas Sprague-Dawley , Infecciones por Bacterias Grampositivas/etiología , Infecciones por Bacterias Grampositivas/microbiología , Ratas , Modelos Animales de Enfermedad , Degeneración del Disco Intervertebral/microbiología , Degeneración del Disco Intervertebral/diagnóstico por imagen , Disco Intervertebral/microbiología , Disco Intervertebral/diagnóstico por imagen , Masculino , Punciones/efectos adversos , Propionibacteriaceae/patogenicidad , Imagen por Resonancia MagnéticaRESUMEN
Novel treatment strategies are urgently needed to combat Mycobacterium avium complex pulmonary disease (MAC-PD). Animal models are important for screening therapeutic strategies, but their ability to reproduce human-like immunopathology, and impaired respiratory function is poorly characterised. We modeled chronic lung infection in BALB/c mice over 20 weeks with three isolates of MAC (MAC101, MAC104 and MAC2285R) to compare bacterial growth, histological injury, immune cellular dynamics and respiratory function. We found MAC101 caused a proliferative infection over 20 weeks, associated with a strong adaptive response, progressive granulomatous inflammation and increasing respiratory effort. For MAC104, lung bacterial burden rose initially but fell after week 12, accompanied by increased regulatory T-cell response and stabilization of pathological and respiratory changes. By contrast, MAC2285R caused a low-virulence, non-proliferative infection associated with a strong myeloid cell response, modest histopathological change and increased respiratory effort. Immune cell dynamics in chronic murine MAC-PD correlate with bacterial burden and pathology, and are strongly MAC-isolate dependent. These findings provide a spectrum of quantifiable and clinically-relevant disease outcomes to facilitate the preclinical screening of novel antimicrobial and host-directed therapies for MAC-PD.
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Tendinopathy is a common degenerative tendon disorder, characterized by extracellular matrix disorganization and progressive fibrosis. While macrophages play a role in fibrosis in other tissues, their specific function in tendon fibrosis remains unclear. This study aims to investigate the involvement of M2-polarized macrophages and their secretion of transforming growth factor-ß1 (TGF-ß1) in tendon fibrosis. A chronic Achilles tendinopathy rat model was established by combining repetitive acupuncture needle puncture with treadmill overuse. Immunofluorescence and molecular biology techniques were used to assess M2 macrophage infiltration, TGF-ß1 expression, and JNK pathway activation. Pharmacological intervention was performed using GW2580 (CSF-1R antagonist), and genetic knockout experiments were conducted in a mouse model. Results showed that the model group exhibited disrupted collagen structure and fibrotic matrix deposition in the tendon, accompanied by significant accumulation of CD206⺠M2 macrophages and elevated TGF-ß1 expression. Immunofluorescence co-localization revealed that TGF-ß1 was primarily produced by CD206⺠macrophages. Activation of the JNK signaling pathway was observed. GW2580 treatment significantly reduced M2 macrophage infiltration, suppressed TGF-ß1 levels, and improved histological fibrosis scores. Genetic deletion of Tgf-ß1 in myeloid cells also alleviated fibrotic changes. In conclusion, M2 macrophage-derived TGF-ß1 plays a crucial role in tendon fibrosis by activating the JNK signaling pathway, suggesting its potential as a therapeutic target.
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Tendón Calcáneo , Macrófagos , Tendinopatía , Factor de Crecimiento Transformador beta1 , Animales , Factor de Crecimiento Transformador beta1/metabolismo , Macrófagos/metabolismo , Macrófagos/fisiología , Tendinopatía/metabolismo , Tendinopatía/patología , Fibrosis , Ratas Sprague-Dawley , Masculino , Modelos Animales de Enfermedad , Tendón Calcáneo/patología , Tendón Calcáneo/metabolismo , Ratones , Ratas , Ratones Endogámicos C57BL , Ratones NoqueadosRESUMEN
Caprine herpesvirus 1 (CpHV-1), a member of the Herpesvirales order, Herpesviridae family, Alphaherpesvirinae subfamily, and Simplexvirus genus, is classically associated with two distinct clinical syndromes. In kids, CpHV-1 induces severe systemic disease with high morbidity and mortality, whereas in adult goats, the infection leads to genital lesions such as vulvovaginitis or balanoposthitis, with abortions occurring mainly in the second half of gestation. CpHV-1 shares several biological characteristics with human herpesvirus 2, including molecular features, tropism for vaginal epithelium, genital lesion nature, and latency in the sacral ganglia. These features make CpHV-1-infected goats a reliable animal model for studying human herpesvirus-induced genital disease, relevant for pathogenic research, as well as the development of new vaccines and antiviral agents. Recent full sequencing of the CpHV-1 genome has identified at least 10 genes encoding glycoproteins. Among these, glycoprotein D (gD) has been characterized but not yet exploited for immunogenic or diagnostic purposes. In this study, the structural features of CpHV-1 gD were predicted using in silico analysis. A truncated version of gD lacking the transmembrane domain (secreted glycoprotein D [Sec-gD]) was subsequently generated and expressed in mammalian cells, enabling its secretion into the culture medium. Despite the structural modifications, Sec-gD retained a conserved glycosylation pattern, as confirmed by N-glycosylation mutants generation and peptide-N-glycosidase F treatment. Furthermore, the antigenic properties of Sec-gD were preserved, as demonstrated by reverse serum neutralization assays. Notably, the culture supernatant containing Sec-gD was directly usable in diagnostic enzyme-linked immunosorbent assays, supporting its potential as a valuable tool for both diagnostic and immunization strategies.IMPORTANCECaprine herpesvirus 1 (CpHV-1)-infected goats represent a large animal model for studying human herpesvirus-induced genital disease and could be utilized for pathogenic research, as well as for the development of new vaccines and antiviral agents. CpHV-1 glycoprotein D can be efficiently produced and rescued from the supernatant of transfected mammalian cells, retaining its immunogenic properties, and could be used for immunogenic and diagnostic purposes.
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Infecciones por Herpesviridae , Varicellovirus , Proteínas del Envoltorio Viral , Animales , Cabras , Varicellovirus/genética , Varicellovirus/metabolismo , Proteínas del Envoltorio Viral/genética , Proteínas del Envoltorio Viral/inmunología , Proteínas del Envoltorio Viral/metabolismo , Proteínas del Envoltorio Viral/química , Enfermedades de las Cabras/virología , Humanos , Infecciones por Herpesviridae/virología , Infecciones por Herpesviridae/veterinaria , Modelos Animales de Enfermedad , Anticuerpos Antivirales/sangre , Anticuerpos Antivirales/inmunología , FemeninoRESUMEN
Following the publication of the above paper, it was drawn to the Editor's attention by a concerned reader that, regarding the bioluminescence and fluorescence images of the mouse shown in Fig. 2C and E respectively, the images/positioning of the mouse appeared to be unexpectedly similar, and the authors were asked to confirm whether the images were captured at the same time, but separate results were obtained for the luminescence and fluorescence readings. Similarly, in Fig. 3A, the same mouse image (re. its appearance and positioning) appeared to be shown for the 5aDLuc cell line on Days 14 and 28, albeit with different bioluminescence. Finally, upon analyzing the data independently in the Editorial Office, it came to light that, for the phase contrast images of the MDAMD231 and 5aDLuc cell lines shown in Fig. 1A, these appeared to be the same image, but with different lighting intensities and with the 5aDLuc image rotated through 90Ë. The authors were contacted by the Editorial Office to offer an explanation for these possible anomalies in the presentation of the data in this paper, although up to this time, no response from them has been forthcoming. Owing to the fact that the Editorial Office has been made aware of potential issues surrounding the scientific integrity of this paper, we are issuing an Expression of Concern to notify readers of this potential problem while the Editorial Office conitnues to investigate this matter further. [International Journal of Oncology 48: 525532, 2016; DOI: 10.3892/ijo.2015.3300].
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Proteínas Fluorescentes Verdes , Luciferasas , Animales , Ratones , Humanos , Línea Celular Tumoral , Proteínas Fluorescentes Verdes/genética , Proteínas Fluorescentes Verdes/metabolismo , Luciferasas/genética , Luciferasas/metabolismo , Mediciones Luminiscentes/métodos , Metástasis de la Neoplasia , FemeninoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Urtica dioica Linn. is a medicinal herb that belongs to the Urticaceae family. It is found in several countries worldwide and has numerous health-related benefits, including neuroprotection, anticancer, and anti-inflammatory effects. U. dioica has shown potential efficacy in treating diabetic neuropathy. AIM OF THE STUDY: This study aimed to systematically review the neuroprotective effects of U. dioica in diabetic models and explore the relationship between molecular and behavioral outcomes. MATERIALS AND METHODS: A comprehensive search was conducted in several databases, including PubMed, Web of Science, Scopus, Science Direct, and the Cochrane Library. Only preclinical studies conducted on diabetic animal models with neural dysfunction were included. Eligible studies were required to have specific controlled groups and evaluate neural outcomes through behavioral tests or molecular investigations. Two authors independently extracted data according to the predefined inclusion and exclusion criteria. Of the 1398 studies identified, 11 met the inclusion criteria and were included in this review. RESULTS: U. dioica has been demonstrated to have beneficial effects in mitigating diabetes-induced neural dysfunction. These effects are likely mediated through mechanisms such as reducing oxidative stress and neuroinflammation, modulating insulin signaling pathways, and promoting neurogenesis. Evidence has shown that U. dioica consumption has positive effects on neuronal density in diabetes-affected neural tissues. CONCLUSIONS: Preclinical findings suggest that U. dioica consumption may protect against diabetes-associated neural dysfunction. While these results highlight its potential as a complementary strategy for mitigating diabetic neuropathy, further research, including clinical trials, is required for validation.
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Diabetes Mellitus Experimental , Neuropatías Diabéticas , Fármacos Neuroprotectores , Extractos Vegetales , Urtica dioica , Animales , Diabetes Mellitus Experimental/complicaciones , Diabetes Mellitus Experimental/tratamiento farmacológico , Neuropatías Diabéticas/diagnóstico , Neuropatías Diabéticas/etiología , Neuropatías Diabéticas/prevención & control , Fármacos Neuroprotectores/farmacología , Fármacos Neuroprotectores/uso terapéutico , Fármacos Neuroprotectores/aislamiento & purificación , Estrés Oxidativo/efectos de los fármacos , Extractos Vegetales/farmacología , Extractos Vegetales/uso terapéutico , Extractos Vegetales/aislamiento & purificación , Urtica dioica/químicaRESUMEN
AIM: The aim of this study was to assess the dose-dependent effects of radiotherapy on the progression of apical periodontitis (AP) in rats. METHODS: Forty-five animals were divided into five groups based on radiation dose and apical periodontitis induction (nâ¯=â¯9): AP-RT7 (irradiated with a dose of 7.5â¯Gy + AP); AP-RT10 (10â¯Gy dose + AP); AP-RT15 (15â¯Gy dose + AP); AP (AP without radiation), and Control (no intervention). Radiation therapy was administered on the first day of the experiment. After seven days, the apical periodontitis induction was carried out in all groups except Control. All animals were euthanized after 21 days of AP progression (day 28), and the area and volume of AP were analyzed using radiography, micro-CT, and histological analyses. Inflammation intensity and extent were assessed histologically. Statistical analysis was performed using ANOVA and Student's t test for quantitative data, and Kruskal-Wallis for ordinal data (Pâ¯<â¯0.05). RESULTS: The AP-RT15 group exhibited significantly larger apical periodontitis lesions compared to the AP-RT7.5, AP-RT10, and AP groups, as demonstrated by radiographic (pâ¯<â¯0.05), micro-CT (pâ¯<â¯0.0001), and histological analyses (pâ¯<â¯0.0001). Histological examination further revealed a more extensive and intense inflammatory response in the AP-RT15 group (pâ¯<â¯0.01). Overall, radiotherapy contributed to increased apical bone resorption and exacerbated inflammation in a dose-dependent manner. CONCLUSIONS: The progression of apical periodontitis in irradiated animals follows a dose-dependent pattern, with higher radiation doses markedly amplifying the lesion's area, volume, and inflammatory severity.
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Periodontitis Periapical , Animales , Periodontitis Periapical/diagnóstico por imagen , Periodontitis Periapical/patología , Periodontitis Periapical/radioterapia , Periodontitis Periapical/etiología , Ratas , Progresión de la Enfermedad , Microtomografía por Rayos X , Relación Dosis-Respuesta en la Radiación , Dosificación Radioterapéutica , Masculino , Ratas Wistar , Modelos Animales de EnfermedadRESUMEN
Nitrosamines are classified as carcinogenic chemicals and are a growing public health concern. They have been widely documented in food, which is the main route of human exposure. However, there is little research on their appearance in biological samples, such as feces. This study presents a methodology for determining the concentration of 14 nitrosamines in cooked hams and fecal samples obtained from animals fed with them, allowing changes in the nitrosamine concentration during digestion to be identified. The novelty of this research lies in the fact that it is the first to evaluate whether incorporating polyphenols into cooked ham influences the levels of NAs in feces using an animal model. The proposed analytical method based on ultrasound-assisted extraction of the nitrosamine high-performance liquid chromatography and mass spectrometry using a triple quadrupole achieved low limits of quantification (in the 0.44-47 ng g-1 range), good precision (coefficient of variation of less than 12.4%), and trueness for both matrices. A total of 68 samples were analyzed, with five nitrosamines detected in the cooked ham samples and seven in the fecal samples. Statistical analysis revealed that the nitrosamine profile mainly depended on the biological matrix. While the preservative did not significantly affect the nitrosamine profile in cooked ham, it did modulate the nitrosamine concentration in feces. Specifically, diets containing polyphenols significantly reduced fecal nitrosamine levels compared to diets containing nitrites, suggesting a possible protective role against the formation of these compounds in the gut.
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Heces , Conservantes de Alimentos , Productos de la Carne , Nitrosaminas , Animales , Heces/química , Nitrosaminas/análisis , Ratas , Cromatografía Líquida de Alta Presión/métodos , Porcinos , Conservantes de Alimentos/análisis , Conservantes de Alimentos/química , Culinaria , Productos de la Carne/análisis , Límite de Detección , Espectrometría de Masas/métodosRESUMEN
Background: The pathogenesis of thymoma-associated myasthenia gravis (TAMG) remains unclear, and one of the key problems is the lack of an appropriate animal model. The present study aimed to investigate the feasibility of establishing an animal model of TAMG. Methods: Patient thymoma tissue specimens were transplanted into the left renal subcapsules of BALB/c nude mice under sterile conditions. The content of T lymphocytes and subsets, as well as total complement, in the mouse peripheral blood was detected using flow cytometry and enzyme-linked immunosorbent assay (ELISA) prior to and following transplantation. Furthermore, the tumor tissues were analyzed by immunohistochemistry (IHC). Results: Transplanted thymoma tissues survived in the mice with a success rate of 61%. Flow cytometry results indicated that the percentage of cluster of differentiation CD3+ and CD4+ T cells in the peripheral blood post-transplantation was significantly higher compared with pre-transplantation. By contrast, the percentage of CD8+ T cells and total complement cells was significantly reduced post-transplantation compared with pre-transplantation (P<0.05). Conclusions: This preliminary study demonstrates the feasibility of establishing an animal model for thymoma and myasthenia gravis (MG) pathogenesis research by transplanting human thymoma tissues into BALB/c nude mice. Nevertheless, several issues and challenges must be resolved and investigated in future research.
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The main aim of biological research is to bridge the gap between preclinical findings and clinical applications so that human health can be improved. Animal models are beneficial in replicating disease mechanisms, facilitating diagnosis, and assessing treatment efficacy for any disease. They play a vital role in drug discovery, toxicological assessments, dosage determination, and the evaluation of side effects, all while adhering to the ethical guidelines. These models are effectively used to treat a wide range of human diseases, including autoimmune disorders, rheumatoid arthritis, epilepsy, Alzheimer's disease, cardiovascular conditions, atherosclerosis, severe acute respiratory syndrome/Coronavirus disease 2019 (SARS/COVID-19), and diabetes. In disease modeling, they significantly contribute to drug development, medical device testing, tissue engineering, wound healing, and bone and cartilage regeneration. One cannot deny the fact that there are major significances of small and large animal models in scientific studies, apart from various advantages and challenges. Animal Models play an essential role in pharmaceutical research, biomedical research, genome editing, transgenic studies, and surgical applications. These models enable scientists and researchers to perform experiments that would be ethically or practically impossible in humans. In recent years, various animal species have been widely used to study health problems, including the 2019 Coronavirus pandemic, diabetes, and obesity. Mice, pigs, rabbits, rats, murine, primate, porcine, and aquatic models have played a crucial role in understanding the neurological, behavioral, cardiovascular, and oncological disorders while contributing to the development of innovative therapeutic approaches for their treatment. The studies in which pain is inflicted on animals must follow strict ethical standards. Whereas research involving painless animal death is often more accepted because of the fact that animals have limited awareness of their future. This review highlights the use of animal models in indispensable contributions to modern medicine and underscores their relevance in disease research, treatment development, and ethical considerations in experimental studies and their scientific advancements.
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BACKGROUND: With increased dermal filler use, hyaluronic acid (HA) injection-induced blindness reports emerge. The underlying mechanism of HA-induced ophthalmic artery occlusion (OAO)-associated blindness and effective treatment modalities are currently unknown, primarily due to the lack of an ideal HA embolization blindness animal model. OBJECTIVE: In this study, we aimed to establish a feasible and reproducible animal model of OAO-induced blindness using interventional, ophthalmological, and behavioral approaches, thereby serving as an ideal preclinical model for research aimed at developing treatments for blindness induced by hyaluronic acid injection. METHODS: We injected HA into the porcine ophthalmic artery (OA) to induce retinal artery ischemia, assessing blood flow and intraretinal structures using digital angiography and ophthalmologic examination, and vision using the obstacle course test. We performed hematoxylin and eosin staining to observe the retina structure two months after embolization. RESULTS: Compared with normal baseline observations, post-embolization angiography suggested no OA visualization, fundus photography revealing a pale fundus and optic disk edema. Obstacle course collisions and completion times were significantly lower in the post-embolization OX (blindfolded right eye) than in the post-embolization XX (both eyes blindfolded) group, higher in the post-embolization OO (no blindfolded) than in the preoperative OO group, and lower in the pre-embolization OO than in the pre-embolization XX group. Compared with control eyes, the hematoxylin and eosin staining demonstrated a disordered retinal structural arrangement, a lack of retinal ganglion cells, and severe fibrosis in the experimental eyes. CONCLUSION: In conclusion, we created a reproducible OAO blindness porcine model, which could serve as an ideal preclinical animal model for research on treatment strategies for patients with HA injection-induced blindness. NO LEVEL ASSIGNED: This journal requires that authors assign a level of evidence to each submission to which Evidence-Based Medicine rankings are applicable. This excludes Review Articles, Book Reviews, and manuscripts that concern Basic Science, Animal Studies, Cadaver Studies, and Experimental Studies. For a full description of these Evidence-Based Medicine ratings, please refer to the Table of Contents or the online Instructions to Authors www.springer.com/00266.
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Background: Proximal-distal orientation of nerve autografts (graft polarity) is an important consideration in peripheral nerve repair, but the literature is inconsistent on whether reversing graft polarity improves regeneration. With these disparities, we aimed to systematically review the effect of forward (normal proximal-to-distal) vs. reversed graft orientation on peripheral nerve regeneration or functional outcomes. Methods: We conducted a comprehensive search of PubMed, Scopus, Cochrane Library, EMBASE, and Google Scholar (January 1978-August 2025) for studies comparing autograft polarity in nerve regeneration. Of 90 articles identified, 9 studies met inclusion criteria (comparative studies directly evaluating graft orientation). Data on nerve conduction and functional recovery outcomes were extracted, and random-effects meta-analyses (using Hedges' g standardized mean differences) were performed to compare forward vs. reversed graft orientation, with heterogeneity assessed by I2 and τ2. Results: The nine included studies (all in animals) assessed histological, morphometric, electrophysiological (e.g., nerve conduction velocity, action potential amplitude), behavioral and functional outcomes. Three of the nine studies reported a significant outcome difference favoring one graft orientation, whereas six studies found no significant difference. Meta-analysis of five studies reporting nerve conduction velocity found no overall difference between forward and reversed orientation (Hedges' g = -0.57, 95% confidence interval -1.52 to 0.37; p = 0.23; I2 = 82.96%, τ2 = 0.935). Conclusions: This meta-analysis provides the first quantitative synthesis of experimental evidence assessing the impact of nerve autograft orientation, revealing no consistent advantage of forward or reversed polarity on regeneration outcomes. Although based on limited and heterogeneous animal data, the findings clarify existing trends and highlight areas for further experimental and clinical research.
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Hyperphosphatemia is a common complication of chronic kidney disease (CKD) and occurs in both high- and low-turnover bone disorders. While phosphate (P) control is known to reduce adverse effects, most supporting studies have focused on high-turnover models. This study evaluates the effects of two P binders-calcium carbonate (CaCO3) and sevelamer carbonate-on laboratorial markers and bone histomorphometry in a low-turnover bone disease model. Wistar rats underwent 5/6 nephrectomy and total parathyroidectomy (Nx + PTx) to induce low-turnover bone disease. Animals were assigned to 4 groups: Sham, untreated Nx + PTx, Nx + PTx + CaCO3, and Nx + PTx + sevelamer. After 8 weeks, we performed biochemical analysis, bone histomorphometry, gene expression (SOST, ß-catenin, DKK-1), immunohistochemistry (sclerostin, ß-catenin, FGF23, DKK-1), and apoptosis assays. Bone histology confirmed low-turnover disease in Nx + PTx rats, which also developed CKD and hyperphosphatemia. Both P binders effectively reduced serum P levels, but only CaCO3 corrected hypocalcemia. Notably, CaCO3 treatment led to increased osteoid parameters, elevated osteoblast surface and absence of tetracycline labeling - hallmarks of osteomalacia. Moreover, CaCO3 increased osteoblast apoptosis. In a rat model of low-turnover bone disease with normal dietary P, high-dose CaCO3 impaired bone mineralization and induced osteomalacia. These findings highlight potential risks of calcium-based phosphate binders in patients with low bone turnover and hyperphosphatemia, supporting the need for careful clinical consideration and monitoring.
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Enfermedades Óseas , Carbonato de Calcio , Osteomalacia , Animales , Osteomalacia/inducido químicamente , Osteomalacia/metabolismo , Ratas Wistar , Ratas , Carbonato de Calcio/efectos adversos , Carbonato de Calcio/farmacología , Modelos Animales de Enfermedad , Factor-23 de Crecimiento de Fibroblastos , Masculino , Sevelamer , Hiperfosfatemia/tratamiento farmacológico , Fosfatos/metabolismo , Insuficiencia Renal Crónica/complicaciones , Huesos/efectos de los fármacos , Huesos/metabolismo , Factores de Crecimiento de FibroblastosRESUMEN
Introduction: CD3, a surface antigen critical for T cell activation and signal transduction, serves as a key diagnostic marker for T cell-associated malignancies and a therapeutic target in immunotherapy. With canine models gaining prominence in translational immunology and oncology, reliable tools to study T cell-mediated immunity are essential. Methods and Results: In this study, recombinant canine CD3ε protein was generated via eukaryotic expression and used to immunize rabbits, yielding a novel rabbit anti-canine CD3ε monoclonal antibody (mAb), designated HORCF-CD3.1. Functional characterization confirmed its specificity through flow cytometry and Western blot, demonstrating robust binding to CD3 molecules. Furthermore, the mAb effectively induced T cell stimulation in vitro when applied as an anti-CD3 activator. These findings validate HORCF-CD3.1 as a versatile tool for ELISA, Western blot, and flow cytometry applications. Discussion: The successful development of this species-specific antibody provides a foundation for advancing diagnostic and therapeutic strategies targeting T cell-related diseases in both humans and dogs.