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Scaffolds play a key role in cultured meat production by providing an optimal environment for efficient cell attachment, growth, and development. This study investigated the effects of gelatin coating on the adhesion, proliferation, and adipogenic differentiation of adipose tissue-derived stem cells (ADSCs) cultured on soy protein-agarose scaffolds. Gelatin-coated scaffolds were prepared using 0.5% and 1.0% (w/v) gelatin solutions. The microstructure, water absorption rate, mechanical strength, cytotoxicity, cell adhesion, proliferation, and differentiation capabilities of the scaffolds were analyzed. Field emission scanning electron microscopy revealed the porous microstructure of the scaffolds, which was suitable for cell growth. Gelatin-coated scaffolds exhibited a significantly higher water absorption rate than that of non-coated scaffolds, indicating increased hydrophilicity. In addition, gelatin coating increased the mechanical strength of the scaffolds. Gelatin coating did not show cytotoxicity but significantly enhanced cell adhesion and proliferation. The gene expression levels of peroxisome proliferator-activated receptor gamma, CCAT/enhancer-binding protein alpha, and fatty acid-binding protein 4 were upregulated, and lipid accumulation was increased by gelatin coating. These findings suggest that gelatin-coated scaffolds provide a supportive microenvironment for ADSC growth and differentiation, highlighting their potential as a strategy for the improvement of cultured meat production and adipose tissue engineering.
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Chronic kidney disease (CKD) commonly occurs in old dogs and cats. Oligo-fucoidan, fucoxanthin, and L-carnitine (OFL) compounds have a variety of reno-protective properties, including anti-inflammatory, anti-oxidative, and anti-fibrotic effects. Because their effects have not been investigated in naturally occurring canine CKD, we examined their reno-protective activities in dog patients with CKD. A total of 50 patients (OFL, n = 28; control, n = 22) were included in the analysis. A significant difference was identified in serum blood urea nitrogen and creatinine concentrations between the control and OFL groups at 6 months. No significant difference in electrolytes was found between the groups. A significant difference was identified in serum creatinine concentration between the control and OFL groups in azotemic (CKD IRIS stage 2-4) at 6 months. The OFL compounds showed a reno-protective effect, consistent with previous animal studies. The OFL combination can potentially delay the progression of canine CKD and be used as an adjuvant therapy.
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BACKGROUND: Pamidronate is used for the treatment of hypercalcemia. However, a rare but potential adverse event of pamidronate treatment is hypocalcemia. This report describes an unusual case of severe, irreversible hypocalcemia after a single injection of pamidronate for the treatment of hypercalcemia due to glucocorticoid withdrawal in a dog. CASE PRESENTATION: An 11-year-old castrated male Maltese dog presented with anorexia, vomiting, and diarrhea (day 0). The patient had calcinosis cutis throughout the body, calcification of intraabdominal organs, mild azotemia, and severe hypercalcemia. The severe calcification was attributed to long-term glucocorticoid administration, which was discontinued 1 month before presentation. Fluid therapy, diuretics, calcitonin, and a single intravenous injection of pamidronate were used for the treatment of hypercalcemia. On day 14, normocalcemia was achieved, but renal failure occurred. On day 20, severe and irreversible hypocalcemia occurred, and on day 42, the patient was euthanized at the owner's request because of worsened hypocalcemia and renal failure. CONCLUSIONS: Although hypocalcemia is an extremely rare adverse event of bisphosphonate treatment, bisphosphonates like pamidronate can result in potentially life-threatening conditions according to the patient's underlying conditions. Therefore, the patient's condition should be closely monitored and any underlying conditions should be carefully evaluated before initiating the treatment for hypercalcemia using pamidronate.
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Conservadores da Densidade Óssea , Doenças do Cão , Glucocorticoides , Hipercalcemia , Hipocalcemia , Pamidronato , Animais , Cães , Pamidronato/uso terapêutico , Hipocalcemia/veterinária , Hipocalcemia/induzido quimicamente , Masculino , Hipercalcemia/induzido quimicamente , Hipercalcemia/veterinária , Doenças do Cão/induzido quimicamente , Doenças do Cão/tratamento farmacológico , Glucocorticoides/uso terapêutico , Glucocorticoides/efeitos adversos , Glucocorticoides/administração & dosagem , Conservadores da Densidade Óssea/efeitos adversos , Conservadores da Densidade Óssea/uso terapêutico , Difosfonatos/efeitos adversos , Difosfonatos/uso terapêuticoRESUMO
The strategic integration of multi-functionalities within a singular nanoplatform has received growing attention for enhancing treatment efficacy, particularly in chemo-photothermal therapy. This study introduces a comprehensive concept of Janus nanoparticles (JNPs) composed of Au and Fe3O4 nanostructures intricately bonded with ß-cyclodextrins (ß-CD) to encapsulate 5-Fluorouracil (5-FU) and Ibuprofen (IBU). This strategic structure is engineered to exploit the synergistic effects of chemo-photothermal therapy, underscored by their exceptional biocompatibility and photothermal conversion efficiency (â¼32.88 %). Furthermore, these ß-CD-conjugated JNPs enhance photodynamic therapy by generating singlet oxygen (1O2) species, offering a multi-modality approach to cancer eradication. Computer simulation results were in good agreement with in vitro and in vivo assays. Through these studies, we were able to prove the improved tumor ablation ability of the drug-loaded ß-CD-conjugated JNPs, without inducing adverse effects in tumor-bearing nude mice. The findings underscore a formidable tumor ablation potency of ß-CD-conjugated Au-Fe3O4 JNPs, heralding a new era in achieving nuanced, highly effective, and side-effect-free cancer treatment modalities. STATEMENT OF SIGNIFICANCE: The emergence of multifunctional nanoparticles marks a pivotal stride in cancer therapy research. This investigation unveils Janus nanoparticles (JNPs) amalgamating gold (Au), iron oxide (Fe3O4), and ß-cyclodextrins (ß-CD), encapsulating 5-Fluorouracil (5-FU) and Ibuprofen (IBU) for synergistic chemo-photothermal therapy. Demonstrating both biocompatibility and potent photothermal properties (â¼32.88 %), these JNPs present a promising avenue for cancer treatment. Noteworthy is their heightened photodynamic efficiency and remarkable tumor ablation capabilities observed in vitro and in vivo, devoid of adverse effects. Furthermore, computational simulations validate their interactions with cancer cells, bolstering their utility as an emerging therapeutic modality. This endeavor pioneers a secure and efficacious strategy for cancer therapy, underscoring the significance of ß-CD-conjugated Au-Fe3O4 JNPs as innovative nanoplatforms with profound implications for the advancement of cancer therapy.
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Ouro , Camundongos Nus , beta-Ciclodextrinas , Animais , Ouro/química , Ouro/farmacologia , beta-Ciclodextrinas/química , Humanos , Camundongos , Fluoruracila/farmacologia , Fluoruracila/química , Ibuprofeno/farmacologia , Ibuprofeno/química , Terapia Fototérmica , Linhagem Celular Tumoral , Fotoquimioterapia/métodos , Camundongos Endogâmicos BALB C , Compostos Férricos/química , Compostos Férricos/farmacologiaRESUMO
Superoxide dismutase (SOD) is an antioxidant enzyme that protects the body from free radicals. It has both antioxidant and immunomodulatory properties, inducing macrophage polarization from M1 to M2. Macrophages, key mediators of the innate immune response, are divided into the M1 (pro-inflammatory) and M2 (anti-inflammatory) subtypes. In this study, we aimed to assess the antioxidant and neuroprotective effects of SOD on nerve cells and its immunomodulatory effects on macrophages. We observed that SOD inhibited the accumulation of reactive oxygen species and enhanced the viability of H2O2-treated nerve cells. Furthermore, SOD reduced the degree of necrosis in nerve cells treated with the conditioned medium from macrophages, which induced inflammation. In addition, SOD promoted the M1 to M2 transition of macrophages. Our findings suggest that SOD protects nerve cells and regulates immune responses.
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Macrófagos , Fármacos Neuroprotetores , Espécies Reativas de Oxigênio , Superóxido Dismutase , Animais , Superóxido Dismutase/metabolismo , Camundongos , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Macrófagos/metabolismo , Humanos , Fármacos Neuroprotetores/farmacologia , Células RAW 264.7 , Espécies Reativas de Oxigênio/metabolismo , Neuroblastoma/imunologia , Neuroblastoma/patologia , Linhagem Celular Tumoral , Peróxido de Hidrogênio/farmacologia , Sobrevivência Celular/efeitos dos fármacos , Antioxidantes/farmacologiaRESUMO
BACKGROUND: Tracheal collapse (TC), a common disease in dogs, is characterized by cough; however, little is known about the serum biomarkers that can objectively evaluate the severity of cough in canine TC. Furthermore, studies elucidating the relationship of fluoroscopic characteristics with the severity of cough are lacking. Therefore, this study aimed to evaluate the relationship between cough severity and clinical characteristics, fluoroscopic images, and new serum biomarkers in canine TC. RESULTS: Fifty-one client-owned dogs diagnosed with TC based on fluoroscopic and clinical signs were enrolled in this study and divided into three groups according to the severity of cough (grade of cough: 0, 1, and 2). Signalments, comorbidities, and fluoroscopic characteristics were compared among the groups retrospectively. The serum matrix metalloproteinase-9 (MMP-9), interleukin-6 (IL-6), surfactant protein-A (SP-A), and syndecan-1 (SDC-1) levels were measured in all groups. No significant differences in age, breed, sex, or clinical history were observed among the groups. Concomitant pharyngeal collapse increased significantly with the severity of cough (p = .031). Based on the fluoroscopic characteristics, the TC grade of the carinal region increased significantly and consistently with the grade of cough (p = .03). The serum MMP-9 level was significantly higher in the grade 2 group than that in the grade 0 group (p = .014). The serum IL-6 level was significantly lower in the grade 1 group than that in the grade 0 group (p = .020). The serum SP-A and SDC-1 levels did not differ significantly among the groups. CONCLUSIONS: The severity of cough with the progression of TC can be predicted with the fluoroscopic TC grade at the carinal region. MMP-9 may be used as an objective serum biomarker that represents cough severity to understand the pathogenesis.
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Doenças do Cão , Metaloproteinase 9 da Matriz , Humanos , Cães , Animais , Estudos Transversais , Estudos Retrospectivos , Interleucina-6 , Tosse/veterinária , Biomarcadores , Doenças do Cão/diagnóstico por imagem , Doenças do Cão/etiologiaRESUMO
BACKGROUND: Axitinib, a potent and selective inhibitor of vascular endothelial growth factor (VEGF) receptor (VEGFR) tyrosine kinase 1,2 and 3, is used in chemotherapy because it inhibits tumor angiogenesis by blocking the VEGF/VEGFR pathway. In veterinary medicine, attempts have been made to apply tyrosine kinase inhibitors with anti-angiogenic effects to tumor patients, but there are no studies on axitinib in canine mammary gland tumors (MGTs). OBJECTIVES: This study aimed to confirm the antitumor activity of axitinib in canine mammary gland cell lines. METHODS: We treated canine MGT cell lines (CIPp and CIPm) with axitinib and conducted CCK, wound healing, apoptosis, and cell cycle assays. Additionally, we evaluated the expression levels of angiogenesis-associated factors, including VEGFs, PDGF-A, FGF-2, and TGF-ß1, using quantitative real-time polymerase chain reaction. Furthermore, we collected canine peripheral blood mononuclear cells (PBMCs), activated them with concanavalin A (ConA) and lipopolysaccharide (LPS), and then treated them with axitinib to investigate changes in viability. RESULTS: When axitinib was administered to CIPp and CIPm, cell viability significantly decreased at 24, 48, and 72 h (p < 0.001), and migration was markedly reduced (6 h, p < 0.05; 12 h, p < 0.005). The apoptosis rate significantly increased (p < 0.01), and the G2/M phase ratio showed a significant increase (p < 0.001). Additionally, there was no significant change in the viability of canine PBMCs treated with LPS and ConA. CONCLUSION: In this study, we confirmed the antitumor activity of axitinib against canine MGT cell lines. Accordingly, we suggest that axitinib can be applied as a new treatment for patients with canine MGTs.
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Glândulas Mamárias Humanas , Fator A de Crescimento do Endotélio Vascular , Animais , Cães , Humanos , Axitinibe/farmacologia , Axitinibe/uso terapêutico , Fator A de Crescimento do Endotélio Vascular/metabolismo , Leucócitos Mononucleares/metabolismo , Lipopolissacarídeos , Glândulas Mamárias Humanas/metabolismo , Indazóis/farmacologia , Indazóis/uso terapêutico , Linhagem Celular TumoralRESUMO
BACKGROUND: Canine mammary gland cancer (CMGC) is a common neoplasm in intact bitches. However, the benefit of adjuvant chemotherapy is unclear. The aim of this study was to investigate the anti-proliferative effects of paclitaxel on CMGC in in-vitro and in-vivo settings. RESULTS: Paclitaxel dose-dependently inhibited viability and induced G2/M phase cell cycle arrest and apoptosis in both primary and metastatic CMGC cell lines (CIPp and CIPm). In animal experiments, the average tumour volume decreased significantly in proportion to the administered oral paclitaxel dose. By examining tumour tissue using a TUNEL assay and immunohistochemical staining with anti-CD31 as a marker of endothelial differentiation, respectively, it was confirmed that oral paclitaxel induced apoptosis and exerted an anti-angiogenetic effect in tumour tissues. Further, downregulation of cyclin D1 in tumour tissues suggested that oral paclitaxel induced cell cycle arrest in tumour tissues in-vivo. CONCLUSIONS: Our results suggest that paclitaxel may have anti-cancer effects on CMGC through cell cycle arrest, induction of apoptosis, and anti-angiogenesis. This study could provide a novel approach to treat CMGC.
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Neoplasias da Mama , Doenças do Cão , Animais , Cães , Camundongos , Apoptose , Pontos de Checagem do Ciclo Celular , Linhagem Celular Tumoral , Proliferação de Células , Doenças do Cão/tratamento farmacológico , Paclitaxel/farmacologia , Paclitaxel/uso terapêutico , Neoplasias da Mama/veterináriaRESUMO
Cortisol is a steroid hormone that is released from the body in response to stress. Although a moderate level of cortisol secretion can help the body maintain homeostasis, excessive secretion can cause various diseases, such as depression and anxiety. Conventional methods for cortisol measurement undergo procedures that limit continuous monitoring, typically collecting samples of bodily fluids, followed by separate analysis in a laboratory setting that takes several hours. Thus, recent studies demonstrate wearable, miniaturized sensors integrated with electronic modules that enable wireless real-time analysis. Here, the primary focus is on wearable and implantable electronic devices that continuously measure cortisol concentration. Diverse types of cortisol-sensing techniques, such as antibody-, DNA-aptamer-, and molecularly imprinted polymer-based sensors, as well as wearable and implantable devices that aim to continuously monitor cortisol in a minimally invasive fashion are discussed. In addition to the cortisol monitors that directly measure stress levels, other schemes that indirectly measure stress, such as electrophysiological signals and sweat are also summarized. Finally, the challenges and future directions in stress monitoring and management electronics are reviewed.
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Técnicas Biossensoriais , Dispositivos Eletrônicos Vestíveis , Hidrocortisona , Monitorização Fisiológica , Suor , Eletrônica , Técnicas Biossensoriais/métodosRESUMO
The generation of an active phase through dynamic surface reconstruction is a promising strategy for improving the activity of electrocatalysts. However, studies investigating the reconstruction process and its impact on the intrinsic properties of the catalysts are scarce. Herein, the surface reconstruction of NiFe2 O4 interfaced with NiMoO4 (Ru-NFO/NMO) facilitated by Ru doping is reported. The electrochemical and material characterizations demonstrate that Ru doping can regulate the electronic structure of NFO/NMO and induce the high-valence state of Ni3.6+ δ , facilitating the surface reconstruction to highly active Ru-doped NiFeOOH/NiOOH (SR-Ru-NFO/NMO). The optimized SR-Ru-NFO/NMO exhibits promising performance in the oxygen evolution reaction, displaying a low overpotential of 229 mV at 10 mA cm-2 and good stability at varying current densities for 80 h. Density functional theory calculations indicate that Ru doping can increase the electron density and optimize intermediate adsorption by shifting the d-band center downward. This work provides valuable insights into the tuning of electrocatalysts by surface reconstruction and offers a rational design strategy for the development of highly active oxygen evolution reaction electrocatalysts.
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BACKGROUND: Reactive oxygen species (ROS) have been shown to promote tumour growth and metastasis in human cell lines. The superoxide anion (â¢O2 - ) is produced during ROS formation and is involved in tumour cell signalling. OBJECTIVES: Superoxide dismutase (SOD) has been applied to canine mammary gland tumours to investigate its antitumour effects in vitro. METHODS: Cell proliferation, cell cycle cell migration assays, reverse transcription-quantitative polymerase chain reaction, and western blot analysis were performed to determine the effects of SOD on canine mammary tumour cell line. RESULTS: SOD treatment resulted in anti-proliferative effects and mediated cell cycle arrest in the canine mammary gland tumour cell lines (CIPp and CIPm). It also downregulated the expression of N-cadherin and Vimentin. CONCLUSIONS: The results confirmed that SOD inhibits tumour cell proliferation and migration, thus supporting the potential applications of SOD as a chemotherapeutic agent for canine mammary gland tumours.
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Glândulas Mamárias Humanas , Superóxido Dismutase , Animais , Cães , Humanos , Espécies Reativas de Oxigênio/metabolismo , Glândulas Mamárias Humanas/metabolismo , Linhagem Celular TumoralRESUMO
Aggressive end-of-life care in patients with advanced cancer is associated with poor experiences and outcomes. The purpose of the study was to examine the impact of aggressive end-of-life care on caregiver satisfaction for caregivers of bereaved advanced cancer patients. Data of 101 caregivers were gathered using a longitudinal, descriptive correlational design study. Postdeath interviews were conducted 2 months after the patient's death. The most common end-of-life care indicators were patient not enrolled in hospice or enrolled within 3 days of death, >1 hospitalization, and intensive care unit admission. More than one-third of patients received at least one of the aggressive end-of-life care indicators in the last 30 days of life. From the multiple linear regression analyses, patient intensive care unit admission and having more than one hospitalization significantly affected caregiver satisfaction with care. Understanding caregiver satisfaction with care may improve the clinical practice of nurses who have crucial role in patients' end-of-life care.
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Cuidados Paliativos na Terminalidade da Vida , Neoplasias , Assistência Terminal , Humanos , Cuidadores , Satisfação do Paciente , Neoplasias/terapia , Satisfação PessoalRESUMO
BACKGROUND/AIM: Nuclear matrix protein-22 (NMP-22) is widely used in human medicine as a prognostic and diagnostic tool for urothelial carcinoma (UC). In addition, the use of urinary exosomes as a liquid biopsy tool is emerging for the diagnosis of certain types of cancer in human medicine. This study aimed to investigate the change in urinary exosomal NMP-22 for the diagnosis of UC in dogs. PATIENTS AND METHODS: Among canine patients who visited the veterinary hospital, urine was collected from those whose owners provided consent. A total of 23 dogs (UC group, n=6; control group, n=17) were included in the analysis. After exosomes were isolated from the urine, NMP-22 was measured using enzyme-linked immunosorbent assay. RESULTS: In the UC group, the expression of NMP-22 in urinary exosomes was significantly higher than that in non-UC groups (p<0.0001). CONCLUSION: NMP-22 is significantly increased in exosomes in the urine of dogs diagnosed with UC, suggesting that urinary exosome NMP-22 can be considered as one of the liquid biopsy tools for diagnosing UC in dogs.
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Carcinoma de Células de Transição , Neoplasias da Bexiga Urinária , Humanos , Cães , Animais , Neoplasias da Bexiga Urinária/patologia , Carcinoma de Células de Transição/diagnóstico , Carcinoma de Células de Transição/veterinária , Carcinoma de Células de Transição/patologia , Projetos Piloto , Biomarcadores Tumorais/urina , Proteínas Associadas à Matriz NuclearRESUMO
BACKGROUND: Meningoencephalomyelitis of unknown etiology (MUE) is a comprehensive term for non-infectious inflammatory brain diseases of the central nervous system (CNS) caused by abnormal autoimmune responses. This study aims to compare the differences in survival and clinical response of MUE according to the adjuvant immunosuppressant use. Medical records of 82 dogs diagnosed with MUE were reviewed retrospectively. RESULTS: The overall survival time was 769 days (range 14-2687 days). The median survival time for each adjunctive was: leflunomide 1035 days (range 126-2163 days), mycophenolate mofetil 865 days (range 39-2191 days), cyclosporin 441 days (range 11-2176 days), cytosine arabinoside 754 days (range 6-1898 days) and a combination of mycophenolate mofetil and cytosine arabinoside 132 days (range 23-1227 days). There was no significant difference in the incidence rate of adverse events according to the immunosuppressants, but moderate to severe anemia was confirmed in 3 patients (18.7%) in the leflunomide group. CONCLUSIONS: The survival time and response rate of MUE dogs differed depending on which adjunctive immunosuppressants were used. Leflunomide showed a long survival time and a relatively good response rate in dogs with MUE. However, a large-scale further study with standardized doses of immunosuppressants and supportive treatment and constant monitoring interval is needed.
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Doenças do Cão , Encefalomielite , Meningoencefalite , Humanos , Cães , Animais , Imunossupressores/efeitos adversos , Estudos Retrospectivos , Ácido Micofenólico/efeitos adversos , Leflunomida/uso terapêutico , Prognóstico , Meningoencefalite/tratamento farmacológico , Meningoencefalite/veterinária , Citarabina/efeitos adversos , Encefalomielite/veterinária , Doenças do Cão/diagnósticoRESUMO
Hydroxyapatite (HAp), a well-known biomaterial, has witnessed a remarkable evolution over the years, transforming from a simple biocompatible substance to an advanced functional material with a wide range of applications. This abstract provides an overview of the significant advancements in the field of HAp and its journey towards becoming a multifunctional material. Initially recognized for its exceptional biocompatibility and bioactivity, HAp gained prominence in the field of bone tissue engineering and dental applications. Its ability to integrate with surrounding tissues, promote cellular adhesion, and facilitate osseointegration made it an ideal candidate for various biomedical implants and coatings. As the understanding of HAp grew, researchers explored its potential beyond traditional biomaterial applications. With advances in material synthesis and engineering, HAp began to exhibit unique properties that extended its utility to other disciplines. Researchers successfully tailored the composition, morphology, and surface characteristics of HAp, leading to enhanced mechanical strength, controlled drug release capabilities, and improved biodegradability. These modifications enabled the utilization of HAp in drug delivery systems, biosensors, tissue engineering scaffolds, and regenerative medicine applications. Moreover, the exceptional biomineralization properties of HAp allowed for the incorporation of functional ions and molecules during synthesis, leading to the development of bioactive coatings and composites with specific therapeutic functionalities. These functionalized HAp materials have demonstrated promising results in antimicrobial coatings, controlled release systems for growth factors and therapeutic agents, and even as catalysts in chemical reactions. In recent years, HAp nanoparticles and nanostructured materials have emerged as a focal point of research due to their unique physicochemical properties and potential for targeted drug delivery, imaging, and theranostic applications. The ability to manipulate the size, shape, and surface chemistry of HAp at the nanoscale has paved the way for innovative approaches in personalized medicine and regenerative therapies. This abstract highlights the exceptional evolution of HAp, from a traditional biomaterial to an advanced functional material. The exploration of novel synthesis methods, surface modifications, and nanoengineering techniques has expanded the horizon of HAp applications, enabling its integration into diverse fields ranging from biomedicine to catalysis. Additionally, this manuscript discusses the emerging prospects of HAp-based materials in photocatalysis, sensing, and energy storage, showcasing its potential as an advanced functional material beyond the realm of biomedical applications. As research in this field progresses, the future holds tremendous potential for HAp-based materials to revolutionize medical treatments and contribute to the advancement of science and technology.
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Nanopartículas , Nanoestruturas , Materiais Biocompatíveis/farmacologia , Materiais Biocompatíveis/química , Durapatita/química , Nanopartículas/química , Osso e OssosRESUMO
Mercury is a widespread pollutant of increasing global concern that exhibits a broad range of deleterious effects on organisms, including birds. Because the developing brain is well-known to be particularly vulnerable to the neurotoxic insults of mercury, many studies have focused on developmental effects such as on the embryonic brain and resulting behavioral impairment in adults. It is not well understood how the timing of exposure, for example exclusively in ovo versus throughout life, influences the impact of mercury. Using dietary exposure to environmentally relevant methylmercury concentrations, we examined the role that timing and duration of exposure play on spatial learning and memory in a model songbird species, the domesticated zebra finch (Taeniopygia guttata castanotis). We hypothesized that developmental exposure was both necessary and sufficient to disrupt spatial memory in adult finches. We documented profound disruption of memory for locations of hidden food at two spatial scales, cage- and room-sized enclosures, but found that both developmental and ongoing adult exposure were required to exhibit this behavioral impairment. Methylmercury-exposed birds made more mistakes before mastering the spatial task, because they revisited unrewarded locations repeatedly even after discovering the rewarded location. Contrary to our prediction, hippocampal volume was not affected in birds exposed to methylmercury over their lifetimes. The disruption of spatial cognition that we detected is severe and would likely have implications for survival and reproduction in wild birds; however, it appears that individuals that disperse or migrate from a contaminated site might recover later in life if no longer exposed to the toxicant.
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Tentilhões , Mercúrio , Compostos de Metilmercúrio , Humanos , Adulto , Animais , Mercúrio/toxicidade , Compostos de Metilmercúrio/toxicidade , Cognição , EncéfaloRESUMO
BACKGROUND: Mesenchymal stem cells (MSCs) have been investigated as therapeutic agents for inflammatory bowel disease (IBD). Stimulation of MSCs with pro-inflammatory cytokines is an approach to enhance their immunomodulatory effects. However, further investigation is required to support their application in immune-mediated disorders and companion animals. OBJECTIVES: This study aimed to assess the therapeutic effect of tumor necrosis factor (TNF)-α-stimulated feline adipose tissue-derived MSCs (fAT-MSCs) in a dextran sulfate sodium (DSS)-induced colitis mouse model. METHODS: Colitis mice was made by drinking water with 3% DSS and fAT-MSCs were injected intraperitoneally. Colons were collected on day 10. The severity of the disease was evaluated and compared. Raw 264.7 cells were cultured with the conditioned medium to determine the mechanism, using quantitative real-time polymerase chain reaction and enzyme-linked immunosorbent assay. RESULTS: TNF-α-stimulated fAT-MSCs more improved severity of DSS-induced colitis in disease activity, colon length, histologic score, and inflammatory cytokine. In sectionized colon tissues, the group comprising TNF-α-stimulated fAT-MSCs had higher proportion of CD11b+CD206+ macrophages than in the other groups. In vitro, TNF-α-stimulation increased cyclooxygenase-2 (COX-2) expression and prostaglandin E2 (PGE2) secretion from fAT-MSCs. The conditioned medium from TNF-α-stimulated fAT-MSCs enhanced the expression of interleukin-10 and arginase-1 in LPS-activated Raw 264.7 cells. CONCLUSIONS: These results represent that TNF-α-stimulated fat-mscs ameliorate the inflamed colon more effectively. Furthermore, we demonstrated that the effectiveness was interlinked with the COX-2/PGE2 pathway.
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Doenças do Gato , Colite , Transplante de Células-Tronco Mesenquimais , Células-Tronco Mesenquimais , Animais , Gatos , Camundongos , Tecido Adiposo , Doenças do Gato/metabolismo , Colite/induzido quimicamente , Colite/terapia , Colite/metabolismo , Colite/veterinária , Meios de Cultivo Condicionados/efeitos adversos , Ciclo-Oxigenase 2/genética , Citocinas/metabolismo , Sulfato de Dextrana/toxicidade , Dinoprostona/metabolismo , Modelos Animais de Doenças , Transplante de Células-Tronco Mesenquimais/veterinária , Células-Tronco Mesenquimais/fisiologia , Camundongos Endogâmicos C57BL , Fator de Necrose Tumoral alfa/metabolismoRESUMO
BACKGROUND/AIM: Recently, novel studies on the pivotal role of B cells in the tumor-microenvironment and anti-tumor immunity have been conducted. Additionally, Interleukin-21 (IL-21) and anti-B cell receptor (BCR) have been reported to stimulate B cells to secrete granzyme B, which exhibits cytotoxic effects on tumor cells. However, the direct anti-tumor effect of B cells is not yet fully understood in the veterinary field. This study is the first attempt in veterinary medicine to identify the immediate effect of B cells on tumor suppression and the underlying mechanisms involved. MATERIALS AND METHODS: Canine B cells were isolated from peripheral blood and activated with IL-21 and anti-B cell receptor (BCR). The canine leukemia cell line GL-1 was co-cultured with B cells, and the anti-tumor effect was confirmed by assessing the changes in cell viability and apoptotic ratio. RESULTS: When B cells were activated with IL-21 and anti-BCR, the secretion of granzyme B and tumor necrosis factor-related apoptosis-inducing ligand (TRAIL) increased. Simultaneously, the viability of GL-1 cells decreased, and the apoptotic ratio increased, particularly when co-cultured with activated B cells. CONCLUSION: The results demonstrated the direct anti-tumor effect of granzyme B-and TRAIL and its enhanced potential of B cells to inhibit tumor cell growth after activation with IL-21 and anti-BCR. This study is the first study dealing with immunomodulation in the canine tumor micro-environment.
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Linfócitos B , Neoplasias , Animais , Cães , Granzimas , Interleucinas/farmacologia , Fator de Necrose Tumoral alfa , Microambiente TumoralRESUMO
Recently, various nanomaterials based on hydroxyapatite (HAp) have been developed for bioimaging applications. In particular, HAp doped with rare-earth elements has attracted significant attention, owing to its enhanced bioactivity and imaging properties. In this study, the wet precipitation method was used to synthesize HAp codoped with Yb and Gd. The synthesized Ybx-Gdx-HAp nanoparticles (NPs) were characterized via various techniques to analyze the crystal phase, functional groups, thermal characteristics, and particularly, the larger surface area. The IR783 fluorescence dye and a folic acid (FA) receptor were conjugated with the synthesized Ybx-Gdx-HAp NPs to develop an effective imaging contrast agent. The developed FA/IR783/Yb-Gd-HAp nanomaterial exhibited improved contrast, sensitivity, and tumor-specific properties, as demonstrated by using the customized LUX 4.0 fluorescence imaging system. An in vitro cytotoxicity study was performed to verify the biocompatibility of the synthesized NPs using MTT assay and fluorescence staining. Photodynamic therapy (PDT) was also applied to determine the photosensitizer properties of the synthesized Ybx-Gdx-HAp NPs. Further, reactive oxygen species generation was confirmed by Prussian blue decay and a 2',7'-dichlorofluorescin diacetate study. Moreover, MDA-MB-231 breast cancer cells were used to evaluate the efficiency of Ybx-Gdx-HAp NP-supported PDT.
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Nanopartículas Metálicas , Itérbio/química , Gadolínio/química , Durapatita/química , Meios de Contraste/química , Nanopartículas Metálicas/química , Humanos , Neoplasias da Mama/diagnóstico por imagem , Neoplasias da Mama/terapiaRESUMO
Tumor-associated macrophages (TAMs) play an important role in the tumor microenvironment by producing cytokines and growth factors. Furthermore, TAMs play multifunctional roles in tumor progression, immune regulation, metastasis, angiogenesis, and chemoresistance. Hypoxia in the tumor microenvironment induces tumor-supporting transformation of TAMs, which enhances tumor malignancy through developing anti-cancer resistance, for example. In this study, a hybrid spheroid model of canine mammary gland tumor (MGT) cell lines (CIPp and CIPm) and canine macrophages (DH82) was established. The effects of hypoxia induced by the spheroid culture system on the anti-cancer drug resistance of canine MGT cells were investigated. A hybrid spheroid was created using an ultralow-adhesion plate. The interactions between canine MGT cells and DH82 were investigated using a co-culture method. When co-cultured with DH82, cell viability and expression levels of tumor growth factors and multi-drug resistance genes were increased in canine MGT cells under doxorubicin. Additionally, doxorubicin-induced apoptosis and G2/M cell cycle arrest were attenuated in canine MGT cells co-cultured with DH82. In conclusion, the hybrid spheroid model established in this study reflects the hypoxic TME, allowing DH82 to induce anti-cancer drug resistance in canine MGT cells.