RESUMEN

IgG4-Related Ophthalmic Disease (IgG4-ROD) is a chronic autoimmune-mediated fibrotic disease that predominantly affects the lacrimal glands, often leading to loss of function in the involved tissues or organs. Recent studies have demonstrated that MMP-12 is highly expressed in IgG4-ROD and plays a significant role in regulating immune responses. In this study, we reviewed nine patients diagnosed with IgG4-ROD based on clinical manifestations and histological analysis, and we investigated the expression of IL-33/ST2 and MMP-12 in IgG4-ROD lacrimal gland tissues using IHC. We found that IL-33 interacts with its specific receptor ST2, both of which are significantly overexpressed in IgG4-ROD tissues. Additionally, we successfully constructed a mouse model by introducing the LatY136F mutation into C57BL/6 mice to mimic IgG4-ROD lacrimal gland involvement, which helped elucidate the mechanisms involved in the induction of MMP-12. Furthermore, immunofluorescence staining confirmed that most MMP-12+ cells were derived from M2 macrophages, and an ELISA assay demonstrated that IL-33 upregulates MMP-12 in IgG4-ROD. Collectively, these data suggest that the IL-33/ST2/MMP-12 signaling pathway is activated in IgG4-ROD, with IL-33/ST2 potentially promoting M2 macrophage polarization and activation to produce MMP-12, which may serve as a novel therapeutic target for IgG4-ROD.

RESUMEN

Introduction: The severity of Coronavirus disease 2019 (COVID-19) caused by the severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) is often dictated by a range of comorbidities. A considerable literature suggests iron deficiency and iron overload may contribute to increased infection, inflammation and disease severity, although direct causal relationships have been difficult to establish. Methods: Here we generate iron deficient and iron loaded C57BL/6 J mice by feeding standard low and high iron diets, with mice on a normal iron diet representing controls. All mice were infected with a primary SARS-CoV-2 omicron XBB isolate and lung inflammatory responses were analyzed by histology, immunohistochemistry and RNA-Seq. Results: Compared with controls, iron deficient mice showed no significant changes in lung viral loads or histopathology, whereas, iron loaded mice showed slightly, but significantly, reduced lung viral loads and histopathology. Transcriptional changes were modest, but illustrated widespread dysregulation of inflammation signatures for both iron deficient vs. controls, and iron loaded vs. controls. Some of these changes could be associated with detrimental outcomes, whereas others would be viewed as beneficial. Discussion: Diet-associated iron deficiency or overload thus induced modest modulations of inflammatory signatures, but no significant histopathologically detectable disease exacerbations.

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OBJECTIVES: Current data suggests that Bacille Calmette-Guerin (BCG) vaccination contributes to nonspecific enhancement of resistance to various infections. Thus, BCG vaccination induces both specific immunity against mycobacteria and non-specific "trained immunity" against various pathogens. To understand the fundamental mechanisms of "trained" immunity, studies of transcriptome changes occurring during BCG vaccination in innate immunity cells, as well as in their precursors, are necessary. Furthermore, this data possesses important significance for practical applications associated with the development of recombinant BCG strains aimed to enhance innate immunity against diverse infectious agents. DATA DESCRIPTION: We performed RNA sequencing of innate immune cells derived from murine bone marrow and spleen three days after subcutaneous BCG vaccination. Using fluorescence-activated cell sorting we obtained three cell populations for each mouse from both control and BCG vaccinated groups: bone marrow monocytes and neutrophils and splenic NK-cells. Then double-indexed cDNA libraries for Illumina sequencing from the collected samples were prepared, the resulting cDNA library mix was subjected to NovaSeq 6000 sequencing. This paper describes the collection of 24 RNA sequencing samples comprising 4 sets of immune cell populations obtained from subcutaneously BCG-vaccinated and control mice.

Asunto(s)

Vacuna BCG , Inmunidad Innata , Bazo , Transcriptoma , Animales , Vacuna BCG/inmunología , Vacuna BCG/administración & dosificación , Ratones , Transcriptoma/genética , Bazo/inmunología , Vacunación/métodos , Células Asesinas Naturales/inmunología , Ratones Endogámicos C57BL , Inyecciones Subcutáneas , Monocitos/inmunología , Femenino , Neutrófilos/inmunología , Análisis de Secuencia de ARN/métodos , Células de la Médula Ósea/inmunología

RESUMEN

Binge eating disorder is the most prevalent eating disorder, affecting both sexes but more commonly found in women. Given the frequent co-occurrence of psychiatric disorders, this study aimed to establish a standardized experimental intermittent protocol to investigate overeating associated with depression. A 10-day protocol induced uncontrolled eating behavior in C57BL/6J female mice. The first experiment included the following groups: naive group (chow ad libitum), control group (chow and sucrose solution ad libitum), and fasting groups (16 and 20 h) exposed to an intermittent sucrose solution (10 %) and chow regimen. Subsequently, the feeding test, open field test, elevated plus maze test, tail suspension test, and light/dark conflict test were conducted. Furthermore, monoamine oxidase (MAO) A and B activities in brain structures and plasma corticosterone levels were assessed. Food overconsumption and depressive-like behavior were observed in both sucrose fasting groups, while risk-taking behaviors were specifically observed in the 20-hour fasting sucrose group. While both fasting sucrose groups caused reduced hippocampal MAO-A activity, only the F20 sucrose group inhibited MAO-B in the cortex and hypothalamus. Moreover, both fasting sucrose groups exhibited elevated corticosterone levels. In a separate design (Experiment 2), groups with 16 and 20 h of fasting alone (without sucrose) did not show the same behavioral results as the intermittent fasting sucrose groups, thus avoiding fasting bias. Based on these results, the 20-hour sucrose fasting group was chosen as the ideal protocol for mimicking overeating behavior associated with depression to investigate future therapeutic approaches for this comorbidity.

RESUMEN

Approximately 10% of patients without cardiovascular disorders suffer myocardial injury and have a 10% risk of death within 30 days after noncardiac surgery. Preoperative stress increases the risk of myocardial injury after noncardiac surgery (MINS). The mechanisms of MINS are poorly understood. Lack of physical activity and the development of weakness and fatigue are consequences of many noncardiac surgery types. The relationship between surgery and changes in the morphofunctional state of muscles in the postoperative period is still unclear now. The study showed for the first time that metabolic and hormonal changes caused by preoperative stress + surgery or surgery alone underlie MINC in the postoperative period in C57BL/6 mice. Minor increases in triglyceride-glucose (TyG) index were for the first time identified as indicative of ischemic/hypoxic damage to the myocardium and skeletal muscles. More research is necessary to perform to better understand the effects of preoperative stress and noncardiac surgery on the myocardium and muscle performance, as well as the risks and benefits of perioperative treatment.

RESUMEN

This study explores the potential of zinc and silver nanocomposites, synthesized with ß-lactoglobulin, a whey protein, in promoting wound healing, using the C57BL/6J mouse model. Our research is distinct in its dual focus: assessing the antimicrobial efficacy of these nanocomposites and their impact on wound healing processes. The antimicrobial properties were investigated through minimum inhibitory concentration (MIC) assessments and colony-forming unit (CFU) tests, providing insights into their effectiveness against wound-associated microorganisms. Notably, the formulation's effective antibacterial concentration did not exhibit toxicity to mouse fibroblasts. A key aspect of our methodology involved the use of a stereoscopic microscope for detailed monitoring of the wound closure process. Additionally, the distribution and potential systemic effects of the zinc and silver ions were analyzed using Inductively Coupled Plasma-Mass Spectrometry (ICP-MS). This analysis was crucial in evaluating metal ion absorption through the wound site and estimating any toxic effects on the body. Our findings are particularly significant in the field of regenerative medicine. Transmission electron microscopy (TEM) revealed that the tested nanocomposites notably enhanced collagen deposition, a vital component in the wound healing process. Furthermore, a reduction in glycogen levels in hepatocytes was observed following treatment with these metal-protein dressings. This novel finding warrants further investigation. Overall, our findings highlight the diverse roles of zinc and silver nanocomposites in wound healing. This study not only contributes to our understanding of metal-protein complexes in tissue regeneration but also opens new avenues for research into the delivery mechanisms of such treatments for hard-to-heal wounds.

RESUMEN

Staphylococcus aureus (SA) is a common Gram-positive bacterium that activates inflammatory cells, expressing various cytokines and inducing an inflammatory response. Recent research revealed aconitate decarboxylase 1 (ACOD1) as a regulator of the immune response through various metabolic pathways, playing a dual role in the inflammatory response. However, the mechanism by which ACOD1 participates in the regulation of SA-induced inflammatory responses in macrophages remains unknown. Therefore, this study aims to investigate the function and underlying regulatory mechanisms of ACOD1 in SA-induced inflammatory response. This study reveals that SA induced a macrophage inflammatory response and upregulated ACOD1 expression. ACOD1 knockdown significantly inhibited SA-induced macrophage inflammatory response, attenuated SA-induced nuclear envelope wrinkling, and plasma membrane rupture, and suppressed the TLR4/NF-κB signaling pathway. Furthermore, ACOD1 knockdown reduced the inflammatory response and alleviated lung tissue injury and cellular damage, leading to decreased bacterial loads in the lungs of SA-infected mice. Collectively, these findings demonstrate that SA induces an inflammatory response in macrophages and increases ACOD1 expression. ACOD1 enhances SA-induced inflammatory responses via the TLR4/NF-κB signaling pathway. Our findings highlight the significant role of ACOD1 in mediating the inflammatory response in SA-infected macrophages and elucidate its molecular mechanism in regulating the SA-induced inflammatory response.

Asunto(s)

Carboxiliasas , Macrófagos , Transducción de Señal , Infecciones Estafilocócicas , Staphylococcus aureus , Animales , Humanos , Ratones , Carboxiliasas/metabolismo , Carboxiliasas/genética , Inflamación/inmunología , Inflamación/metabolismo , Pulmón/inmunología , Pulmón/patología , Pulmón/microbiología , Macrófagos/inmunología , Macrófagos/metabolismo , Ratones Endogámicos C57BL , FN-kappa B/metabolismo , Células RAW 264.7 , Transducción de Señal/inmunología , Infecciones Estafilocócicas/inmunología , Staphylococcus aureus/inmunología , Receptor Toll-Like 4/metabolismo , Receptor Toll-Like 4/genética

RESUMEN

In Alzheimer's disease (AD), transgenic mouse models have established links between abnormalities in the retina and those in the brain. APPNL-F/NL-F is a murine, humanized AD model that replicates several pathological features observed in patients with AD. Research has focused on obtaining quantitative parameters from optical coherence tomography (OCT) in AD. The aim of this study was to analyze, in a transversal case-control study using manual retinal segmentation via SD-OCT, the changes occurring in the retinal layers of the APPNL/F-NF/L AD model in comparison to C57BL/6J mice (WT) at 6, 9, 12, 15, 17, and 20 months of age. The analysis focused on retinal thickness in RNFL-GCL, IPL, INL, OPL, and ONL based on the Early Treatment Diabetic Retinopathy Study (ETDRS) sectors. Both APPNL-F/NL-F-model and WT animals exhibited thickness changes at the time points studied. While WT showed significant changes in INL, OPL, and ONL, the AD model showed changes in all retinal layers analyzed. The APPNL-F/NL-F displayed significant thickness variations in the analyzed layers except for the IPL compared to related WT. These thickness changes closely resembled those found in humans during preclinical stages, as well as during mild and moderate AD stages, making this AD model behave more similarly to the disease in humans.

Asunto(s)

Enfermedad de Alzheimer , Modelos Animales de Enfermedad , Ratones Transgénicos , Retina , Tomografía de Coherencia Óptica , Animales , Enfermedad de Alzheimer/patología , Enfermedad de Alzheimer/diagnóstico por imagen , Enfermedad de Alzheimer/genética , Tomografía de Coherencia Óptica/métodos , Retina/patología , Retina/diagnóstico por imagen , Ratones , Ratones Endogámicos C57BL , Humanos , Envejecimiento/patología , Precursor de Proteína beta-Amiloide/genética , Precursor de Proteína beta-Amiloide/metabolismo , Masculino , Femenino , Estudios de Casos y Controles

RESUMEN

Three hyperimmune egg-based formulations rich in immunoglobulin Y (IgY) were orally administered (daily, for up to 90 days) to C57BL/6 mice that were not microbially challenged. The serum levels of 32 cytokines were quantified every 30 days. Histopathology, hematology, and serum biochemistry investigations were also performed. As a sign of increased immune activity, lymphohistiocytic infiltrates were detected in the digestive tract and the liver after 30, 60, and 90 days of treatment. These infiltrates were also present in the lungs after 30 and 60 days, but not at 90 days. Blood analysis indicated systemic inflammation after 30 days of treatment: increases in pro-inflammatory cytokines, glycemia, total serum proteins, ALT, and ALP. After 60 and 90 days of treatment, the analyzed blood parameters showed mixed signs of both increased and decreased inflammation. The increased cytokines, which varied with formulation and time of exposure, indicated a combination of mostly Th17- and Th2-type immune responses. As the mice were healthy and housed in standardized sanitary conditions, and were not microbially challenged, the data were consistent with an interaction of IgY with the gut-associated lymphoid tissue as the main mechanism of action. This interaction generated a local immune response, which subsequently induced a systemic response.

Asunto(s)

Citocinas , Inmunidad Mucosa , Inmunoglobulinas , Ratones Endogámicos C57BL , Células Th17 , Células Th2 , Animales , Inmunoglobulinas/metabolismo , Administración Oral , Citocinas/metabolismo , Células Th2/inmunología , Células Th2/metabolismo , Células Th17/inmunología , Células Th17/metabolismo , Ratones , Inmunidad Mucosa/efectos de los fármacos , Femenino , Huevos

RESUMEN

Melanoma has gained considerable attention due to its high mortality and morbidity rate worldwide. The currently available treatment options are associated with several limitations such as nonspecificity, drug resistance, easy clearance, low efficacy, toxicity-related issues, etc. To this end, nanotechnology has garnered significant attention for the treatment of melanoma. In the present manuscript, we have demonstrated the in vitro and in vivo anticancer activity of silver nitroprusside nanoparticles (abbreviated as AgNNPs) against melanoma. The AgNNPs exhibit cytotoxicity against B16F10 cells, which has been investigated by several in vitro experiments including [methyl 3H]-thymidine incorporation assay, cell cycle and apoptosis analysis by flow cytometry, and ROS generation through DCFDA, DHE, and DAF2A reagents. Further, the internalization of nanoparticles was determined by ICPOES analysis, while their colocalization was analyzed by confocal microscopy. Additionally, JC-1 staining is performed to examine mitochondrial membrane potential (MMP). Cytoskeleton integrity was observed by phalloidin staining. Expression of different markers (Ki-67, cytochrome c, and E-cadherin) was checked using an immunofluorescence assay. The in vivo therapeutic efficacy of AgNNPs has been validated in the melanoma model established by inoculating B16F10 cells into the dorsal right abdomen of C57BL/6J mice. The intraperitoneal administration of AgNNPs reduced melanoma growth and increased the survivability of tumor-bearing mice. The in vivo immunofluorescence studies (Ki-67, CD31, and E-cadherin) and TUNEL assay support the inhibitory and apoptotic nature of AgNNPs toward melanoma, respectively. Furthermore, the various signaling pathways and molecular mechanisms involved in anticancer activity are evaluated by Western blot analysis. These findings altogether demonstrate the promising anticancer potential of AgNNPs toward melanoma.

Asunto(s)

Antineoplásicos , Apoptosis , Proliferación Celular , Ensayos de Selección de Medicamentos Antitumorales , Ratones Endogámicos C57BL , Nitroprusiato , Plata , Animales , Ratones , Antineoplásicos/farmacología , Antineoplásicos/química , Nitroprusiato/farmacología , Nitroprusiato/química , Apoptosis/efectos de los fármacos , Plata/química , Plata/farmacología , Proliferación Celular/efectos de los fármacos , Tamaño de la Partícula , Ensayo de Materiales , Melanoma/tratamiento farmacológico , Melanoma/patología , Nanopartículas del Metal/química , Materiales Biocompatibles/química , Materiales Biocompatibles/farmacología , Nanopartículas/química , Supervivencia Celular/efectos de los fármacos , Potencial de la Membrana Mitocondrial/efectos de los fármacos , Línea Celular Tumoral , Especies Reactivas de Oxígeno/metabolismo , Melanoma Experimental/tratamiento farmacológico , Melanoma Experimental/patología , Melanoma Experimental/metabolismo

RESUMEN

Bilharzia is a parasitic flatworm that causes schistosomiasis, a neglected tropical illness worldwide. Praziquantel (PZQ) is a commercial single treatment of schistosomiasis so alternative drugs are needed to get rid of its side effects on the liver. The current study aimed to estimate the effective role of Ficus carica nanoparticles (Fc-NPCs), silver nanoparticles (Ag-NPCs) and Ficus carica nanoparticles loaded on silver nanoparticles (Fc-Ag NPCs) on C57BL/6 black female mice infected by Schistosoma mansoni and treated with PZQ treatment. It was proved that schistosomiasis causes liver damage in addition to the PZQ is ineffective as an anti-schistosomiasis; it is recorded in the infected mice group and PZQ treated group as in liver function tests, oxidative stress markers & anti-oxidants, pro-inflammatory markers, pro-apoptotic and anti-apoptotic markers also in liver cells' DNA damage. The amelioration in all tested parameters has been clarified in nanoparticle-protected mice groups. The Fc-Ag NPCs + PZQ group recorded the best preemptive effects as anti-schistosomiasis. Fc-NPCs, Ag-NPCs and Fc-Ag NPCs could antagonize PZQ effects that were observed in amelioration of all tested parameters. The study showed the phytochemicals' nanoparticles groups have an ameliorated effect on the health of infected mice.

Asunto(s)

Ficus , Nanopartículas del Metal , Praziquantel , Schistosoma mansoni , Esquistosomiasis mansoni , Plata , Animales , Ficus/química , Ratones , Praziquantel/farmacología , Femenino , Schistosoma mansoni/efectos de los fármacos , Nanopartículas del Metal/química , Plata/química , Plata/farmacología , Esquistosomiasis mansoni/tratamiento farmacológico , Esquistosomiasis mansoni/parasitología , Ratones Endogámicos C57BL , Hígado/parasitología , Hígado/efectos de los fármacos , Hígado/metabolismo , Cercarias/efectos de los fármacos , Estrés Oxidativo/efectos de los fármacos , Sinergismo Farmacológico , Nanopartículas/química , Extractos Vegetales/farmacología , Extractos Vegetales/química , Antihelmínticos/farmacología , Antihelmínticos/química , Antihelmínticos/uso terapéutico

RESUMEN

BACKGROUND: Water electrospray technology has been developed and extensively studied for its physical properties and potential application as a non-chemical biocide against airborne pathogens. However, there are still concerns regarding the safety and potential toxicity of inhaling water electrospray (WE) particles. To address these potential hazards and offer insights into the impact of WE on humans, we analyzed the immunopathological response to WE by employing an intranasal challenge C57BL/6 mouse model. This analysis aimed to compare the effects of WE with those of sodium hypochlorite (SH), a well-known biocidal agent. RESULTS: The study findings suggest that the WE did not trigger any pathological immune reactions in the intranasal-challenged C57BL/6 mouse model. Mice challenged with WE did not experience body weight loss, and there was no increase in inflammatory cytokine production compared to SH-treated mice. Histopathological analysis revealed that WE did not cause any damage to the lung tissue. In contrast, mice treated with SH exhibited significant lung tissue damage, characterized by the infiltration of neutrophils and eosinophils. Transcriptomic analysis of lung tissue further confirmed the absence of a pathological immune response in mice treated with WE compared to those treated with SH. Upon intranasal challenge with WE, the C57BL/6 mouse model did not show any evidence of immunopathological damage. CONCLUSIONS: The results of this study suggest that WE is a safe technology for disinfecting airborne pathogens. It demonstrated little to no effect on immune system activation and pathological outcomes in the intranasal challenge C57BL/6 mouse model. These findings not only support the potential use of WE as an effective and safe method for air disinfection but also highlight the value of the intranasal challenge of the C57BL/6 mouse model in providing significant immunopathological insights for assessing the inhalation of novel materials for potential use.

RESUMEN

OBJECTIVES: We here assessed whether typical pathogens of laboratory mice affect the development of diet-induced obesity and glucose intolerance, and whether colonization affects the efficacy of the GLP-1R agonist liraglutide and of the GLP-1/GIP co-agonist MAR709 to treat obesity and diabetes. METHODS: Male C57BL/6J mice were experimentally infected with Helicobacter hepaticus, Rodentibacter pneumotropicus and Staphylococcus aureus and compared to a group of uninfected specific and opportunistic pathogen free (SOPF) mice. The development of diet-induced obesity and glucose intolerance was monitored over a period of 26 weeks. To study the influence of pathogens on drug treatment, mice were then subjected for 6 days daily treatment with either the GLP-1 receptor agonist liraglutide or the GLP-1/GIP co-agonist MAR709. RESULTS: Colonized mice did not differ from SOPF controls regarding HFD-induced body weight gain, food intake, body composition, glycemic control, or responsiveness to treatment with liraglutide or the GLP-1/GIP co-agonist MAR709. CONCLUSIONS: We conclude that the occurrence of H. hepaticus, R. pneumotropicus and S. aureus does neither affect the development of diet-induced obesity or type 2 diabetes, nor the efficacy of GLP-1-based drugs to decrease body weight and to improve glucose control in mice.

Asunto(s)

Dieta Alta en Grasa , Intolerancia a la Glucosa , Incretinas , Liraglutida , Ratones Endogámicos C57BL , Obesidad , Staphylococcus aureus , Animales , Dieta Alta en Grasa/efectos adversos , Ratones , Masculino , Staphylococcus aureus/efectos de los fármacos , Incretinas/metabolismo , Obesidad/metabolismo , Liraglutida/farmacología , Intolerancia a la Glucosa/metabolismo , Receptor del Péptido 1 Similar al Glucagón/agonistas , Receptor del Péptido 1 Similar al Glucagón/metabolismo , Organismos Libres de Patógenos Específicos , Infecciones por Helicobacter/tratamiento farmacológico , Infecciones por Helicobacter/microbiología , Infecciones por Helicobacter/metabolismo

RESUMEN

Obesity continues to rise in prevalence and financial burden despite strong evidence linking it to an increased risk of developing several chronic diseases. Dopamine response and receptor density are shown to decrease under conditions of obesity. However, it is unclear if this could be a potential mechanism for treatment without drugs that have a potential for abuse. Therefore, the aim of this study was to investigate whether moderate-intensity exercise could reduce body weight gain and the associated decreases in dopamine signaling observed with high-fat diet-induced adiposity. We hypothesized that exercise would attenuate body weight gain and diet-induced inflammation in high-fat (HF)-fed mice, resulting in dopamine signaling (release and reuptake rate) comparable to sedentary, low-fat (LF)-fed counterparts. This hypothesis was tested using a mouse model of diet-induced obesity (DIO) and fast-scan cyclic voltammetry to measure evoked dopamine release and reuptake rates. Although the exercise protocol employed in this study was not sufficient to prevent significant body weight gain, there was an enhancement of dopamine signaling observed in female mice fed a HF diet that underwent treadmill running. Additionally, aerobic treadmill exercise enhanced the sensitivity to amphetamine (AMPH) in this same group of exercised, HF-fed females. The estrous cycle might influence the ability of exercise to enhance dopamine signaling in females, an effect not observed in male groups. Further research into females by estrous cycle phase, in addition to determining the optimal intensity and duration of aerobic exercise, are logical next steps.

Asunto(s)

Dieta Alta en Grasa , Dopamina , Ratones Endogámicos C57BL , Obesidad , Condicionamiento Físico Animal , Aumento de Peso , Animales , Dopamina/metabolismo , Obesidad/metabolismo , Femenino , Aumento de Peso/efectos de los fármacos , Aumento de Peso/fisiología , Dieta Alta en Grasa/efectos adversos , Condicionamiento Físico Animal/fisiología , Ratones , Transducción de Señal/fisiología , Transducción de Señal/efectos de los fármacos , Anfetamina/farmacología , Masculino , Modelos Animales de Enfermedad

RESUMEN

BACKGROUND: Obesity and consumption of high-fat diets (HFD) are associated with intestinal permeabilization and increased paracellular transport of endotoxins, which can promote neuroinflammation. Inflammation can affect the hypothalamic pituitary adrenal (HPA) axis, which controls responses to stress and downregulates the brain-derived neurotrophic factor (BDNF), which can promote anxiety and depression, conditions frequently found in obesity. We previously showed that consumption of anthocyanins (AC) mitigate HFD-induced insulin resistance, intestinal permeability, and inflammation. OBJECTIVES: This study investigated if a dietary supplementation with a cyanidin- and delphinidin-rich extract (CDRE) could counteract HFD/obesity-induced hippocampal inflammation in mice. METHODS: C57BL/6J male mice were fed for 14 wk on one of the following diets: 1) a control diet containing 10% total calories from fat (C), 2) a control diet supplemented with 40 mg AC/kg body weight (BW) (CAC), 3) a HFD containing 60% total calories from fat (lard) (HF), or 4) the HFD supplemented with 2, 20, or 40 mg AC/kg BW (HFA2, HFA20, and HFA40, respectively). In plasma and in the hippocampus, parameters of neuroinflammation and the underlying cause (endotoxemia) and consequences (alterations to the HPA and BDNF downregulation) were measured. RESULTS: Consumption of the HFD caused endotoxemia. Accordingly, hippocampal Tlr4 mRNA levels were 110% higher in the HF group, which were both prevented by CDRE supplementation. Consumption of the HFD also caused: 1) microgliosis and increased expression of genes involved in neuroinflammation, that is, Iba-1, Nox4, Tnfα, and Il-1ß, 2) alterations of HPA axis regulation, that is, with low expression of mineralocorticoid (MR) and glucocorticoid (GR) receptors; and 3) decreased Bdnf expression. Supplementation of HFD-fed mice with CDRE mitigated neuroinflammation, microgliosis, and MR and BDNF decreases. CONCLUSIONS: CDRE supplementation mitigates the negative effects associated with HFD consumption and obesity in mouse hippocampus, in part by decreasing inflammation, improving glucocorticoid metabolism, and upregulating BDNF.

Asunto(s)

Antocianinas , Dieta Alta en Grasa , Hipocampo , Inflamación , Ratones Endogámicos C57BL , Animales , Antocianinas/farmacología , Dieta Alta en Grasa/efectos adversos , Masculino , Hipocampo/metabolismo , Hipocampo/efectos de los fármacos , Ratones , Inflamación/prevención & control , Factor Neurotrófico Derivado del Encéfalo/metabolismo , Factor Neurotrófico Derivado del Encéfalo/genética , Obesidad , Suplementos Dietéticos

RESUMEN

This report evaluates the effects of chlordiazepoxide, a benzodiazepine commonly prescribed to manage anxiety-related disorders in adolescent/pediatric populations, on elevated plus maze (EPM) performance in juvenile mice. This approach was taken because chlordiazepoxide produces anxiolytic-like effects in multiple models in adult rodents, however, less is known about the behavioral effects of this benzodiazepine in juveniles. Thus, we administered a single intraperitoneal injection of chlordiazepoxide (0, 5, or 10 mg/kg) to postnatal day 35 male C57BL/6 mice. Thirty minutes later, mice were allowed to explore the EPM for 5-min. We found that chlordiazepoxide-treated mice (5 and 10 mg/kg) spent more time exploring the open arms of the EPM. No differences in velocity (cm/s) or distance traveled (cm) were observed between the groups. These results indicate that chlordiazepoxide induces anxiolytic-related behavior in adolescent male mice.

Asunto(s)

Ansiolíticos , Ansiedad , Clordiazepóxido , Ratones Endogámicos C57BL , Animales , Clordiazepóxido/farmacología , Masculino , Ratones , Ansiedad/tratamiento farmacológico , Ansiolíticos/farmacología , Conducta Animal/efectos de los fármacos , Aprendizaje por Laberinto/efectos de los fármacos , Prueba de Laberinto Elevado , Relación Dosis-Respuesta a Droga

RESUMEN

In lab settings, inbred mouse strains like BALB/c, C57BL/6J, and C57BL/6N are commonly used. Research in immunology and infectious diseases indicates that their Th1 and Th2 immune responses differ. However, the specific differences in the immune response to the vaccination still require investigation. In this study, ovalbumin (OVA) was used as an antigen and CpG-enriched recombinant plasmid (pUC18-CpG) as an adjuvant for immunisation. The level of serum-specific antibody IgG was detected by indirect ELISA. At 35dpi, serum cytokine levels were measured using MILLIPLEX®. T lymphocyte clusters from mouse spleen were examined using flow cytometry to investigate the immunological effects of the CPG-OVA vaccine on three different types of mice. The results showed that pUC18-CpG as an adjuvant could successfully enhance the immune response. BALB/c had the highest level of IgG antibody. In the OVA-only group, the CD4+/CD8+ ratio of the three types of mice was generally increased, and the BALB/c group had the highest ratio. After inoculation with CpG-OVA, the CD4+/CD8+ ratio of the three types of mice was lower than that of the OVA-only group, and C57BL/6J was the lowest. Compared with the CpG-OVA group of the three kinds of mice, the levels of Th2 cytokines IL-6 and IL-10 in BALB/c were increased compared with C57BL/6J and C57BL/6N. After OVA, the six cytokines secreted in C57BL/6J were higher than those in the C57BL/6N OVA group. Therefore, C57 is a better model for examining the function of the vaccine in cellular immunity, whereas BALB/c mice are more prone to humoral immunity. In addition to highlighting the CpG plasmid's ability to successfully activate the immune response of Th1 and Th2, as well as the expression of IgG in vivo and promote T cell immune typing, this study provides valuable insights into immunology and the selection of mouse models for infectious diseases, providing a valuable resource for designing more effective vaccines in the future.

Asunto(s)

Adyuvantes Inmunológicos , Citocinas , Inmunidad Celular , Inmunidad Humoral , Inmunoglobulina G , Animales , Femenino , Ratones , Adyuvantes Inmunológicos/administración & dosificación , Adyuvantes Inmunológicos/farmacología , Citocinas/metabolismo , Inmunidad Celular/efectos de los fármacos , Inmunidad Humoral/efectos de los fármacos , Inmunoglobulina G/sangre , Ratones Endogámicos BALB C , Ratones Endogámicos C57BL , Oligodesoxirribonucleótidos/farmacología , Oligodesoxirribonucleótidos/administración & dosificación , Oligodesoxirribonucleótidos/inmunología , Ovalbúmina , Células Th2/inmunología

RESUMEN

The effects of the novel synthetic peptide, A7-1, on wound healing and skin grafts were evaluated in a C57BL/6 mouse model. Two 15-mm wide circular skin excisions were made on the backs of mice and to each excision, 100 µM A7-1 or normal saline was applied daily. The treatments were applied and sutured for skin graft analysis. Digital photos were acquired on days 4, 7, 11, and 14 and fluorescein angiography was conducted. Wound sizes were verified using stereoscopic microscopy. Histological analysis was performed via hematoxylin and eosin staining and Masson's trichrome staining. Western blotting was performed using vascular endothelial growth factor. Using a stereoscopic microscope, significantly faster wound healing (17.3%) and skin graft healing (16.5%) were observed in the A7-1 treatment group in comparison to that of the control. The angiogenesis was significantly faster in fluorescein angiography examination in wound healing (11%) and skin grafts (15%). However, the average completion of epithelization (overall time for wound healing), did not show any significant differences. In comparison to the control, the new protein, A7-1, led to significantly faster wound healing in the initial angiogenesis.

Asunto(s)

Ratones Endogámicos C57BL , Péptidos , Cicatrización de Heridas , Animales , Cicatrización de Heridas/efectos de los fármacos , Ratones , Péptidos/farmacología , Péptidos/química , Piel/efectos de los fármacos , Masculino , Modelos Animales de Enfermedad , Trasplante de Piel , Neovascularización Fisiológica/efectos de los fármacos , Factor A de Crecimiento Endotelial Vascular/metabolismo

RESUMEN

In this study, we investigated the effects of flickering light on refractive development of mice and the changes of fundus structure and function during this process. C57BL/6 mice were randomly divided into control group and flickering light-induced myopia (FLM) group. Mice in the control group were fed under normal lighting. FLM group mice were fed under lighting with a duty cycle of 50% and flash frequency of 2 Hz. Refractive status, axial length (AL), corneal radius of curvature (CRC), and electroretinogram signals were measured in all animals before treatment and at 2 and 4 weeks after treatment. Retinal thickness (RT), choroidal thickness (ChT) and choroidal blood perfusion (ChBP) were measured by optical coherence tomography (OCT) and optical coherence tomography angiography (OCTA). After 4 weeks of flickering light stimulation, the mice became myopia, the AL increased, but the CRC remained constant. The induction of myopia reduced the implicit time and amplitude of a-wave and b-wave in electroretinogram, which affects the function of retina. Full-layer retinal thickness, ChT and ChBP decreased at both 2 and 4 weeks after flickering light induction. The superficial and middle layers of the retina were significantly thinner, while the deep layer was only slightly thinner without statistical significance. Calculated by the concentric circle algorithm, the decrease of choroidal blood perfusion in FLM was mainly concentrated in the concentric circle area with the optic disc as the center radius of 150-450 µm. In conclusion, the present study shows that flickering light can successfully induce myopia in C57BL/6 mice, affect the electrophysiological activity of retina, and cause changes in fundus tissue structure and blood flow.

Asunto(s)

Modelos Animales de Enfermedad , Electrorretinografía , Angiografía con Fluoresceína , Fondo de Ojo , Ratones Endogámicos C57BL , Miopía , Refracción Ocular , Retina , Tomografía de Coherencia Óptica , Animales , Ratones , Tomografía de Coherencia Óptica/métodos , Miopía/fisiopatología , Miopía/etiología , Refracción Ocular/fisiología , Retina/fisiopatología , Angiografía con Fluoresceína/métodos , Coroides/irrigación sanguínea , Estimulación Luminosa , Luz , Longitud Axial del Ojo , Masculino

RESUMEN

Ulcerative colitis (UC), an inflammatory disease affecting the colon and rectal mucosa, is characterized by chronic and heterogeneous behavior of unknown origin. The primary cause of UC is chronic inflammation, which is closely linked to the development of colorectal cancer. Sonchus arvensis L. (SAL), a plant consumed worldwide for its nutritional and medicinal properties, holds significance in this context. In this study, we employed the total flavone in SAL as a treatment for male C57BL/6 mice with UC. The cecal contents metabolic profile of C57BL/6 mice in different groups, including UC (group ML; n = 5), UC treated with aspirin (group AN; n = 5), UC treated with the total flavone in SAL (group FE; n = 5), and healthy male C57BL/6 mice (group CL; n = 5), was examined using UHPLC-Triple-TOF-MS. Through the identification of variations in key metabolites associated with UC and the exploration of their underlying biological mechanisms, our understanding of the pathological processes underlying this condition has been enhanced. This study identified a total of seventy-three metabolites that have a significant impact on UC. Notably, the composition of total flavone in SAL, a medication used for UC treatment, differs from that of aspirin due to the presence of four distinct metabolites (13,14-Dihydro-15-keto-PGE2, Prostaglandin I2 (PGI2), (20R,22R)-20,22-dihydroxycholesterol, and PS (18:1(9Z)/0:0)). These metabolites possess unique characteristics that set them apart. Moreover, the study identified a total of eleven pathways that were significantly enriched in mice with UC, including Aminoacyl-tRNA biosynthesis, Valine, leucine and isoleucine biosynthesis, Linoleic acid metabolism, PPAR signaling pathway, mTOR signaling pathway, Valine, leucine and isoleucine degradation, Lysine degradation, VEGF signaling pathway, Melanogenesis, Endocrine and other factor-regulated calcium reabsorption, and Cocaine addiction. These findings contribute to a better understanding of the metabolic variations in UC following total flavonoids of SAL therapy and provide valuable insights for the treatment of UC.Keywords: Ulcerative colitis; Total flavonoids of Sonchus arvensis L.; Key metabolites; Metabonomics; Cecal contents of male C57BL/6 mice.