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BACKGROUNDS: Progranulin (PGRN) is a growth factor-like molecule with diverse roles in homeostatic and pathogenic processes including the control of immune and inflammatory responses. Pathogenic inflammation is a hallmark of systemic lupus erythematosus (SLE) and elevated serum levels of PGRN has been evaluated as a biomarker of disease activity in SLE. However, the role of PGRN in SLE has not been fully investigated. This study is aimed to determine the potential involvements of PGRN in SLE. METHODS: Wild type (WT) and PGRN knockout (PGRN-/-) C57BL/6 mice received intraperitoneal injection of pristane for induction of a murine model of SLE. Sera were collected every biweekly and levels of anti-dsDNA antibody, IgG, and inflammatory factors were measured. Mice were sacrificed 5 months later and the renal lesions, as well as the proportions of T cell subtypes in the spleen were analyzed. RESULTS: Following exposure to pristane, PGRN-/- mice generated significantly lower levels of anti-dsDNA antibody and IgG relative to WT mice. PGRN-/- mouse kidneys had less IgG and collagen deposition compared with WT mice after pristane injection. CONCLUSION: The results indicate that PGRN participates in inflammatory response and renal damage in pristane induced SLE models, suggesting that PGRN mediates the onset of SLE.
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Anticuerpos Antinucleares , Modelos Animales de Enfermedad , Inmunoglobulina G , Péptidos y Proteínas de Señalización Intercelular , Lupus Eritematoso Sistémico , Ratones Endogámicos C57BL , Ratones Noqueados , Progranulinas , Terpenos , Animales , Lupus Eritematoso Sistémico/inmunología , Ratones , Inmunoglobulina G/sangre , Anticuerpos Antinucleares/sangre , Riñón/metabolismo , Riñón/inmunología , Bazo/inmunología , Bazo/metabolismo , ColágenoRESUMEN
A patient who had sickle cell disease and had spleen uptake on bone scans is described, and additional causes for that finding are discussed.
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Anemia de Células Falciformes , Huesos , Bazo , Anemia de Células Falciformes/diagnóstico por imagen , Anemia de Células Falciformes/complicaciones , Humanos , Bazo/diagnóstico por imagen , Huesos/diagnóstico por imagen , Huesos/metabolismo , Transporte Biológico , MasculinoRESUMEN
The histological changes in the liver, kidney, spleen, and gills of Syacium papillosum from the continental shelf of the Yucatan Peninsula, Gulf of Mexico, and their statistical associations with environmental conditions and pollutants were assessed in 2010, 2011, and 2012. We evaluated the extension and severity of the lesions through a degree of tissue change (DTC), and, with the sum of the number of lesion types within each of their DTC stages, we determined the histological alteration index (HAI). The liver and kidney were the most affected organs, with HAI values > 100. Fish with the most severe damage were observed on the Campeche Bank and the Caribbean Sea, contrasting with those collected from the northern Yucatan continental shelf. The presence of foci cellular alteration and abundant melanomacrophage centers indicated that these flatfishes were chronically exposed to environmental stress factors. Redundancy analyses showed strong associations between HAI values and hydrocarbon and heavy metal concentrations in muscle. Our results provide evidence for the first time of a differential health condition of the Yucatan shelf through the histopathology shown in S. papillosum, establishing the baseline for future monitoring programs in the region.
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Monitoreo del Ambiente , Lenguado , Branquias , Riñón , Hígado , Contaminantes Químicos del Agua , Animales , Contaminantes Químicos del Agua/análisis , Riñón/patología , Branquias/patología , Hígado/patología , Estrés Fisiológico , Golfo de México , Bazo/patología , Metales Pesados/análisisRESUMEN
OBJECTIVE: To investigate the accuracy and reproducibility of diaphragmatic excursion (DE) measurements through hepato-renal/spleno-renal section as a novel method for assessing diaphragmatic function. METHODS: Twelve healthy participants were recruited. Each participant underwent DE measurements performed by four operators with varying levels of experience using traditional methods (liver/spleen section) and novel methods (hepato-renal/spleno-renal section), respectively. Among them, two experienced operators were critical care clinicians, and diaphragmatic ultrasound was performed in more than 50 cases. The other two inexperienced operators were respiratory therapists, with less than 10 cases of diaphragmatic ultrasound operations, who received a 2-hour theoretical and operational training before the study. Operators initially used the conventional method with a 1.5-6.0 MHz convex probe in M-mode, placing the sampling line perpendicular to the diaphragm at the point of maximum excursion, and the liver/spleen section DE was determined during normal breathing of participant. Then, they used the novel method with a 1.6-4.5 MHz phased array probe to observe diaphragmatic movement cranio-caudally along the mid-axillary line, employing anatomic M-mode with the sampling line placed perpendicular to the diaphragm at the level of the renal midpoint, and the DE of the hepato-renal/spleno-renal section was measured during normal breathing. The liver and hepato-renal sections were used to assess the right diaphragm, and spleen and spleno-renal sections were used to assess the left diaphragm. Correlation analysis of DE measurements from different sections was conducted using the Deming method, while consistency was assessed using the Bland-Altman method. The consistency of clinical acceptability was defined as the absence of fixed and proportional bias, with a difference of two standard deviations less than 40% of the mean measurement value. Percentage consistency limit = two standard deviations of the differences between measurements/mean measurement value×100%. RESULTS: Four operators performed image scans of DE in all four sections for each of the twelve subjects, with a high DE acquisition rate of 100% (48/48) for hepato-renal and spleno-renal sections, followed by the liver section [91.7% (44/48)] and the spleen section [66.7% (32/48)], particularly for the left diaphragm assessment, where the DE acquisition rate of spleno-renal section was significantly higher than that of traditional spleen section (P < 0.01). The overall measurement results showed that no significant difference was found in DE determined via the hepato-renal and spleno-renal sections using the novel method (cm: 1.64±0.10 vs. 1.55±0.14, P > 0.05), and they were significantly higher than those determined via the conventional liver and spleen sections (cm: hepato-renal section vs. liver section was 1.64±0.10 vs. 1.44±0.09, spleno-renal section vs. spleen section was 1.55±0.14 vs. 1.09±0.14, both P < 0.01). Correlation analysis revealed good correlations of DE between hepato-renal section and spleno-renal section, between liver section and hepato-renal section, between liver section and spleno-renal section (r values were 0.62, 0.59, and 0.42, all P < 0.01). Consistency analysis showed that the consistency in DE between hepato-renal section and spleno-renal section, as well as between liver section and hepato-renal section was good (both % consistency limits < 40%). However, the DE measured in the spleen section were not correlated with the other three sections, and there was no inconsistency (all % consistency limits > 40%). There was no statistically significant difference in DE measured by the four operators in the liver, spleen, hepato-renal, and spleno-renal sections (cm: 1.49±0.34, 1.44±0.37, 1.43±0.30, and 1.40±0.27 in liver section; 1.10±0.36, 1.05±0.18, 1.09±0.22, and 1.06±0.26 in spleen section; 1.67±0.43, 1.57±0.34, 1.63±0.32, and 1.66±0.36 in hepato-renal section; 1.45±0.33, 1.48±0.34, 1.50±0.24, and 1.65±0.26 in spleno-renal section; all P > 0.05). According to the clinically acceptable range of consistency limits, the DE measured by the four operators in all four sections showed good consistency (all % consistency limits < 40%). CONCLUSIONS: The novel method of measuring DE through hepato-renal/spleno-renal sections is accurate, highly reproducible, and has a high acquisition rate, serving as a viable alternative to the conventional method involving the liver/spleen section.
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Diafragma , Bazo , Ultrasonografía , Humanos , Diafragma/diagnóstico por imagen , Diafragma/fisiología , Adulto , Masculino , Ultrasonografía/métodos , Femenino , Bazo/diagnóstico por imagen , Hígado/diagnóstico por imagen , Adulto Joven , Riñón/diagnóstico por imagen , Reproducibilidad de los ResultadosRESUMEN
Objective: To observe the effects of targeting and blocking cannabinoid receptor 1 (CB1R) on mouse spleen immune function and inflammatory response under chronic intermittent hypoxia (CIH) conditions, and to explore its regulatory effort. Methods: Forty SPF male C57BL/6 mice aged 4 to 5 weeks,from May 2021 to August 2021 in Experimental Animal Center of the Second Hospital of Shanxi Medical University, were randomly divided into normal oxygen control group (NC), 6-week CIH group (6w CIH), 10-week CIH group (10w CIH), 6-week CIH+CB1R group (6w CIH+AM251) and 10-week CIH+CB1R group (10w CIH+AM251) according to the method of random number table. The advanced programmable intermittent low oxygen chamber was used to prepare the CIH mouse model. The morphological structure of spleen tissue of CIH mice was stained by hematoxylin-eosin (HE) staining. The expression levels of M1 and M2 macrophage surface markers CD86, CD206 were determined by immunofluorescence. The mRNA expression levels of CB1R, CD86, CD206 and the relative expression levels of RORγt and Foxp3,which are characteristic transcriptional regulators of T helper 17(Th17) and Treg cells were detected by quantitative reverse transcriptase PCR(qRT-PCR). The expression of inflammatory factors IL-6 and IL-10 was determined by ELISA. SPSS 26.0 and Graphpad prism 8.3 were used to analyze the data. Results: (1) Compared with NC group, spleen tissue structure was disordered, fibrous tissue hyperplasia, lymphocyte proliferation and disordered arrangement in periarteriole lymphatic sheath in CIH group. The expression of CB1R in CIH group was higher than that in NC group (P<0.05), and with the prolongation of CIH time, the expression of 10w CIH group was higher than that in 6w CIH group(P<0.05). The expression of CB1R in CIH+AM251 group was lower than that in the corresponding CIH group(all P<0.05). (2) Compared with NC group, the expression level of CD86 in macrophages in CIH group was higher than that in NC group(all P<0.05). The relative expression of RORγt in 6w and 10w CIH groups was 0.76±0.03 and 0.91±0.04, respectively, which was higher than that in NC group (0.65±0.06)(all P<0.05). The relative expression levels of inflammatory factor IL-6 were 10.80±1.73 and 14.86±0.01, respectively, which were higher than 6.69±0.23 in the NC group (all P<0.05). The expression level of CD206 in macrophages in the CIH+AM251 group was higher than that in the CIH group(all P<0.05). The relative expression levels of Foxp3 in 6w and 10w CIH+AM251 groups were 0.62±0.05 and 0.32±0.21, respectively, which were higher than those in 6w CIH group (0.28±0.02) and 10w CIH group (0.02±0.01)(P<0.05). The relative expression levels of anti-inflammatory factor IL-10 were 668.45±15.71 and 379.15±56.84, respectively, which were higher than those in CIH group (all P<0.05). Conclusion: Targeted sealing of CB1R may alleviate inflammatory response of mouse spleen under CIH conditions by regulating macrophage polarization and the expression of inflammatory factors, and may have some protective effect.
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Hipoxia , Inflamación , Receptor Cannabinoide CB1 , Bazo , Animales , Masculino , Ratones , Modelos Animales de Enfermedad , Hipoxia/metabolismo , Interleucina-10/metabolismo , Interleucina-6/metabolismo , Ratones Endogámicos C57BL , Piperidinas/farmacología , Pirazoles/farmacología , Receptor Cannabinoide CB1/metabolismo , Bazo/metabolismo , Linfocitos T Reguladores/inmunologíaRESUMEN
Littoral cell angioma is a very rare benign splenic neoplasm with typical morphological features. It is difficult to differentiate this angioma from other benign or malignant splenic tumors. It is a unique vascular tumor followed by abdominal pain or detected incidentally during examination. Incidence of this tumor is small, as only few appropriate cases were described in the literature. We present successful surgical treatment of littoral cell angioma of the spleen. The issues of clinical course, diagnosis, therapeutic tactics, morphologic and histochemical features are discussed.
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Hemangioma , Bazo , Esplenectomía , Neoplasias del Bazo , Humanos , Neoplasias del Bazo/cirugía , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/patología , Hemangioma/cirugía , Hemangioma/diagnóstico , Esplenectomía/métodos , Bazo/cirugía , Bazo/patología , Resultado del Tratamiento , Diagnóstico Diferencial , Femenino , Masculino , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodosRESUMEN
Maintaining peripheral immune tolerance and preventing harmful autoimmune reactions is a fundamental task of the immune system. However, these essential functions are significantly compromised during autoimmune disorders, creating a major challenge in treating these conditions. In this context, we provide an overview of research on small spleen polypeptides (SSPs) that naturally regulate peripheral immune tolerance. Alongside outlining the observed effects of SSPs, we summarize here the findings on the cellular and molecular mechanisms that underlie their regulatory impact. Specifically, SSPs have demonstrated remarkable effectiveness in halting the progression of developing or established autoimmune disorders like psoriasis or arthritis in animal models. They primarily target dendritic cells (DCs), swiftly prompting the production of extracellular ATP, which is then degraded and sensed by adenosine receptors. This process triggers the mTOR signaling cascade, similar to powerful immune triggers, but instead of a rapid and intense reaction, it leads to a moderate yet significant activation of the mTOR signaling cascade. This induces a tolerogenic state in dendritic cells, ultimately leading to the generation of Foxp3+ immunosuppressor Treg cells. In addition, SSPs may indirectly attenuate the autoimmune response by reducing extracellular ATP synthesis in non-immune cells, such as endothelial cells, when exposed to elevated levels of proinflammatory cytokines. SSPs thus have the potential to contribute to the restoration of peripheral immune tolerance and may offer valuable therapeutic benefits in treating autoimmune diseases.
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Tolerancia Inmunológica , Bazo , Humanos , Animales , Bazo/inmunología , Bazo/metabolismo , Enfermedades Autoinmunes/inmunología , Enfermedades Autoinmunes/tratamiento farmacológico , Células Dendríticas/inmunología , Péptidos/inmunología , Péptidos/farmacología , Antiinflamatorios/farmacología , Antiinflamatorios/uso terapéutico , Transducción de Señal , Serina-Treonina Quinasas TOR/metabolismo , Linfocitos T Reguladores/inmunologíaRESUMEN
Splenic nodular lesions in dogs can be either benign or malignant. They might be discovered incidentally or, in case of rupture, they may lead to hemoabdomen. Nevertheless, splenectomy followed by histopathology is essential for diagnosis and to prevent rupture. Yet, this invasive procedure might be postponed for dogs with benign splenic nodular lesions. Conversely, owners may opt for euthanasia over surgery for malignancies with poor prognosis like hemangiosarcoma. Thus, anticipating diagnosis with non-invasive biomarkers is crucial for proper patient management. In this prospective study, plasma samples were collected from 66 dogs with histologically confirmed splenic nodular lesions. A canine-specific ELISA kit was applied to assess nucleosome concentration, with histopathology of the spleen serving as the gold standard. Nucleosome concentration was found to be significantly higher in dogs with malignant splenic nodular lesions, particularly in those with hemangiosarcoma and other malignancies. The presence of hemoabdomen, more prevalent in dogs with splenic malignancy, also resulted in increased plasmatic nucleosome concentrations. Plasma nucleosomes could serve as a biomarker for detecting malignant splenic nodular lesions in dogs. More research is needed to understand how nucleosome concentration relate to disease stage and prognosis in dogs with hemangiosarcoma.
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Biomarcadores de Tumor , Enfermedades de los Perros , Hemangiosarcoma , Nucleosomas , Neoplasias del Bazo , Animales , Perros , Nucleosomas/metabolismo , Enfermedades de los Perros/sangre , Enfermedades de los Perros/diagnóstico , Enfermedades de los Perros/patología , Neoplasias del Bazo/veterinaria , Neoplasias del Bazo/sangre , Neoplasias del Bazo/diagnóstico , Neoplasias del Bazo/patología , Biomarcadores de Tumor/sangre , Masculino , Estudios Prospectivos , Femenino , Hemangiosarcoma/veterinaria , Hemangiosarcoma/sangre , Hemangiosarcoma/patología , Hemangiosarcoma/diagnóstico , Bazo/patología , Ensayo de Inmunoadsorción Enzimática/veterinariaRESUMEN
Pulmonary agenesis is a very rare congenital abnormality that can be missed in a routine radiographic examination, which delays diagnosis until adulthood. It can be associated with other congenital malformations, such as valvular heart disease and gastrointestinal organ abnormalities. Computed tomography (CT) is a useful modality for its better delineation of pulmonary and vascular structures. The reported case here is for an adult male who presented with dextroposition of the heart and was found to have a unilobed right lung associated with polysplenia. This has not been previously reported in the literature.
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Pulmón , Bazo , Tomografía Computarizada por Rayos X , Humanos , Masculino , Pulmón/anomalías , Pulmón/diagnóstico por imagen , Bazo/anomalías , Bazo/diagnóstico por imagen , Enfermedades Pulmonares/diagnóstico por imagen , Anomalías Múltiples/diagnóstico por imagen , AdultoRESUMEN
Precise regulation of B cell differentiation is essential for an effective adaptive immune response. Here, we show that B cell development in mice with B cell-specific Maf deletion is unaffected, but marginal zone B cells, germinal centre B cells, and plasmablasts are significantly more frequent in the spleen of naive Maf-deficient mice compared to wild type controls. In the context of a T cell-dependent immunization, Maf deletion causes increased proliferation of germinal centre B cells and extrafollicular plasmablasts. This is accompanied by higher production of antigen-specific IgG1 antibodies with minimal modification of early memory B cells, but a reduction in plasma cell numbers. Single-cell RNA sequencing shows upregulation of genes associated with DNA replication and cell cycle progression, confirming the role of Maf in cell proliferation. Subsequent pathway analysis reveals that Maf influences cellular metabolism, transporter activity, and mitochondrial proteins, which have been implicated in controlling the germinal centre reaction. In summary, our findings demonstrate that Maf acts intrinsically in B cells as a negative regulator of late B cell differentiation, plasmablast proliferation and germinal centre B cell formation.
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Linfocitos B , Diferenciación Celular , Proliferación Celular , Centro Germinal , Células Plasmáticas , Proteínas Proto-Oncogénicas c-maf , Animales , Centro Germinal/inmunología , Centro Germinal/metabolismo , Centro Germinal/citología , Ratones , Células Plasmáticas/inmunología , Células Plasmáticas/metabolismo , Células Plasmáticas/citología , Diferenciación Celular/inmunología , Linfocitos B/inmunología , Linfocitos B/metabolismo , Proteínas Proto-Oncogénicas c-maf/metabolismo , Proteínas Proto-Oncogénicas c-maf/genética , Ratones Noqueados , Ratones Endogámicos C57BL , Bazo/citología , Bazo/metabolismo , Bazo/inmunología , Inmunoglobulina G/inmunología , Inmunoglobulina G/metabolismo , FemeninoRESUMEN
Immune checkpoint blockade (ICB) enhances T cell responses against cancer, leading to long-term survival in a fraction of patients. CD8+ T cell differentiation in response to chronic antigen stimulation is highly complex, and it remains unclear precisely which T cell differentiation states at which anatomic sites are critical for the response to ICB. We identified an intermediate-exhausted population in the white pulp of the spleen that underwent substantial expansion in response to ICB and gave rise to tumor-infiltrating clonotypes. Increased systemic antigen redirected differentiation of this population toward a more circulatory exhausted KLR state, whereas a lack of cross-presented tumor antigen reduced its differentiation in the spleen. An analogous population of exhausted KLR CD8+ T cells in human blood samples exhibited diminished tumor-trafficking ability. Collectively, our data demonstrate the critical role of antigen density within the spleen for the differentiation and expansion of T cell clonotypes in response to ICB.
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Linfocitos T CD8-positivos , Inhibidores de Puntos de Control Inmunológico , Bazo , Linfocitos T CD8-positivos/inmunología , Inhibidores de Puntos de Control Inmunológico/uso terapéutico , Bazo/inmunología , Humanos , Animales , Ratones , Femenino , Ratones Endogámicos C57BL , Masculino , Diferenciación Celular/inmunología , Neoplasias/inmunologíaRESUMEN
BACKGROUND: Spectral imaging of photon-counting detector CT (PCD-CT) scanners allows for generating virtual non-contrast (VNC) reconstruction. By analyzing 12 abdominal organs, we aimed to test the reliability of VNC reconstructions in preserving HU values compared to real unenhanced CT images. METHODS: Our study included 34 patients with pancreatic cystic neoplasm (PCN). The VNC reconstructions were generated from unenhanced, arterial, portal, and venous phase PCD-CT scans using the Liver-VNC algorithm. The observed 11 abdominal organs were segmented by the TotalSegmentator algorithm, the PCNs were segmented manually. Average densities were extracted from unenhanced scans (HUunenhanced), postcontrast (HUpostcontrast) scans, and VNC reconstructions (HUVNC). The error was calculated as HUerror=HUVNC-HUunenhanced. Pearson's or Spearman's correlation was used to assess the association. Reproducibility was evaluated by intraclass correlation coefficients (ICC). RESULTS: Significant differences between HUunenhanced and HUVNC[unenhanced] were found in vertebrae, paraspinal muscles, liver, and spleen. HUVNC[unenhanced] showed a strong correlation with HUunenhanced in all organs except spleen (r = 0.45) and kidneys (r = 0.78 and 0.73). In all postcontrast phases, the HUVNC had strong correlations with HUunenhanced in all organs except the spleen and kidneys. The HUerror had significant correlations with HUunenhanced in the muscles and vertebrae; and with HUpostcontrast in the spleen, vertebrae, and paraspinal muscles in all postcontrast phases. All organs had at least one postcontrast VNC reconstruction that showed good-to-excellent agreement with HUunenhanced during ICC analysis except the vertebrae (ICC: 0.17), paraspinal muscles (ICC: 0.64-0.79), spleen (ICC: 0.21-0.47), and kidneys (ICC: 0.10-0.31). CONCLUSIONS: VNC reconstructions are reliable in at least one postcontrast phase for most organs, but further improvement is needed before VNC can be utilized to examine the spleen, kidneys, and vertebrae.
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Tomografía Computarizada por Rayos X , Humanos , Femenino , Masculino , Reproducibilidad de los Resultados , Persona de Mediana Edad , Tomografía Computarizada por Rayos X/métodos , Anciano , Bazo/diagnóstico por imagen , Hígado/diagnóstico por imagen , Algoritmos , Neoplasias Pancreáticas/diagnóstico por imagen , Adulto , Interpretación de Imagen Radiográfica Asistida por Computador/métodos , Anciano de 80 o más Años , Músculos Paraespinales/diagnóstico por imagen , Fotones , Columna Vertebral/diagnóstico por imagenRESUMEN
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.
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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/inmunologíaRESUMEN
Systemic lupus erythematosus is an autoimmune disease characterized by excessive inflammation and production of pathogenic Abs. Histone deacetylase 6 (HDAC6) is a class IIb histone deacetylase. It has been reported that selective HDAC6 inhibition decreases inflammation in lupus mouse models. In this study, sex- and age-matched wild-type (WT) and HDAC6-/- mice on the C57BL/6 background were administered 0.5 ml of pristane or PBS i.p. at 8-12 wk of age and were euthanized 10 d later. At sacrifice, body weight and spleen weight were measured, sera were collected, and splenocytes and peritoneal cells were harvested for flow cytometry. We found pristane administration increased the spleen weight with no difference between WT and HDAC6-/- mice. Pristane administration promoted the population of CD11b+Ly6C++ inflammatory monocytes and CD11b+Ly6G+ neutrophils. Peritoneal recruitment of these inflammatory monocytes and neutrophils was significantly decreased in HDAC6-/- mice compared with the WT mice. Flow cytometry results showed that the number of CD69+ T and B cells was increased in HDAC6-/- mice. Pristane administration also induced the IFN signature genes as determined by RT-qPCR. Furthermore, IFN signature genes were not affected in HDAC6-/- mice compared with the WT mice. In vitro studies in J774A.1 cells revealed that the selective HDAC6 inhibitor (ACY-738) increased acetylation of NF-κB while increasing Stat1 phosphorylation, which resulted in inducible NO synthase production in LPS/IFN-γ-stimulated cells. Taken together, these results demonstrate that although HDAC6 inhibition may inhibit some inflammatory pathways, others remain unaffected.
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Histona Desacetilasa 6 , Inflamación , Ratones Endogámicos C57BL , Ratones Noqueados , Terpenos , Animales , Histona Desacetilasa 6/antagonistas & inhibidores , Histona Desacetilasa 6/genética , Histona Desacetilasa 6/metabolismo , Terpenos/farmacología , Ratones , Lupus Eritematoso Sistémico/genética , Lupus Eritematoso Sistémico/inmunología , Bazo/inmunología , Bazo/metabolismo , Bazo/citología , Monocitos/metabolismo , Monocitos/inmunología , Monocitos/efectos de los fármacos , Femenino , Modelos Animales de Enfermedad , Neutrófilos/inmunología , Neutrófilos/metabolismo , Factor de Transcripción STAT1/metabolismo , Masculino , Linfocitos B/inmunología , Linfocitos B/metabolismoRESUMEN
In the past decade, the increasing distribution of pollutants in the aquatic environment has been observed, causing integrative effects on fish. Likewise, due to anthropogenic activities, the southern gulf of Lake Tana is an impacted region, and the production of Nile tilapia fish is reduced. For this reason, the aim of this study was to conduct a histopathological-based study of 48 Nile tilapia fishes' health status at the southern gulf of Lake Tana and aquaculture using a cross-sectional study from February 2023 to May 2023. The study evaluated the histopathology of the gill, liver, gonads, and spleen organs using descriptive statistics accompanied by a 2 × 2 contingency table and t-test analysis. During the study, different histological alterations were detected, and the numbers of fish affected by a specific histological alteration were presented as percentage prevalence; hence, from the total fish examined, hyperplasia (54.15%), followed by pigment deposits (52%), hemorrhage (50%), and immune cell infiltration (50%), respectively, were the most frequently detected alterations. However, Nile tilapias from the southern gulf of Lake Tana were 1.4 (odds ratio) times more likely to show histopathological alterations than those from aquaculture, although statistically, was not significant (p > 0.05). In addition, the study found the mean value of the fish index (95.3) and regressive indices of the gill (13.6), liver (14.8), and gonad (12.3); moreover, the inflammatory indices of the spleen organ (11.3) and mean severity grade value of the gill (2.35) and gonad (1.7) organs, respectively, were obtained from the southern gulf of Lake Tana, and all those values were significantly higher (p < 0.05) from this site as compared to the aquaculture. In general, it has been found that tilapias from the southern gulf of Lake Tana showed higher pathological severity as compared with aquaculture. Among the four target organs evaluated, liver organs were observed to be the most damaged, while gonads were the least impacted organs. Therefore, it has been concluded that tilapia fish are living in abnormal conditions, so to ensure a sustainable fishery, water pollutant sources from Bahirdar city must receive proper attention, and future studies should consider age differences, seasonal variation, and the detection of specific pollutants.
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Cíclidos , Lagos , Hígado , Bazo , Animales , Etiopía/epidemiología , Estudios Transversales , Hígado/patología , Bazo/patología , Masculino , Femenino , Branquias/patología , Gónadas/patología , Biomarcadores/análisis , Contaminación del Agua/efectos adversos , Contaminación del Agua/análisis , Enfermedades de los Peces/patología , Enfermedades de los Peces/epidemiología , Acuicultura , Monitoreo del Ambiente , Contaminantes Químicos del Agua/análisisRESUMEN
Iron is a vital element involved in a plethora of metabolic activities. Mammalian systemic iron homeostasis is mainly modulated by hepcidin, the synthesis of which is regulated by a number of proteins, including the hemochromatosis-associated proteins Hfe and Transferrin Receptor 2 (TfR2). Macrophages play versatile functions in iron homeostasis by storing iron derived from the catabolism of erythrocytes and supplying iron required for erythropoiesis. The absence of Hfe in macrophages causes a mild iron deficiency in aged mice and leads to an overproduction of the iron exporter Ferroportin 1 (Fpn1). Conversely, TfR2 gene silencing in macrophages does not influence systemic iron metabolism but decreases transcription of the macrophage Fpn1 in adult mice and modulates their immune response. This study investigated cellular and systemic iron metabolism in adult and aged male mice with macrophage-specific Hfe and TfR2 silencing (double knock-out, DKO). Serum iron parameters were significantly modified in aged animals, and significant differences were found in hepatic hepcidin transcription at both ages. Interestingly, splenic iron content was low in adult DKOs and splenic Fpn1 transcription was significantly increased in DKO animals at both ages, while the protein amount does not reflect the transcriptional trend. Additionally, DKO macrophages were isolated from mice bone marrow (BMDMs) and showed significant variations in the transcription of iron genes and protein amounts in targeted mice compared to controls. Specifically, Tranferrin Receptor 1 (TfR1) increased in DKO adult mice BMDMs, while the opposite is observed in the cells of aged DKO mice. Fpn1 transcript was significantly decreased in the BMDMs of adult DKO mice, while the protein was reduced at both ages. Lastly, a significant increase in Erythropoietin production was evidenced in aged DKO mice. Overall, our study reveals that Hfe and TfR2 in macrophages regulate hepatic Hepc production and affect iron homeostasis in the spleen and BMDMs, leading to an iron deficiency in aged animals that impairs their erythropoiesis.
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Proteína de la Hemocromatosis , Hierro , Macrófagos , Ratones Noqueados , Receptores de Transferrina , Bazo , Animales , Receptores de Transferrina/metabolismo , Receptores de Transferrina/genética , Bazo/metabolismo , Hierro/metabolismo , Macrófagos/metabolismo , Ratones , Masculino , Proteína de la Hemocromatosis/genética , Proteína de la Hemocromatosis/metabolismo , Médula Ósea/metabolismo , Proteínas de Transporte de Catión/metabolismo , Proteínas de Transporte de Catión/genética , Hepcidinas/metabolismo , Hepcidinas/genética , Ratones Endogámicos C57BL , Homeostasis , Hígado/metabolismoRESUMEN
Early-life nutrition significantly impacts vaccination efficacy in infants, whose immune response to vaccines is weaker compared to adults. This study investigated vaccination efficacy in female C57Bl/6JOlaHsd mice (6 weeks old) fed diets with 0.7% galacto-oligosaccharides (GOS)/long-chain fructo-oligosaccharides (lcFOS) (9:1), 0.3% human milk oligosaccharides (HMOS), or a combination (GFH) for 14 days prior to and during vaccination. Delayed-type hypersensitivity (DTH) was measured by assessing ear swelling following an intradermal challenge. Influvac-specific IgG1 and IgG2a levels were assessed using ELISAs, while splenic T and B lymphocytes were analyzed for frequency and activation via flow cytometry. Additionally, cytokine production was evaluated using murine splenocytes co-cultured with influenza-loaded dendritic cells. Mice on the GFH diet showed a significantly enhanced DTH response (p < 0.05), increased serological IgG1 levels, and a significant rise in memory B lymphocytes (CD27+ B220+ CD19+). GFH-fed mice also exhibited more activated splenic Th1 cells (CD69+ CXCR3+ CD4+) and higher IFN-γ production after ex vivo restimulation (p < 0.05). These findings suggest that GOS/lcFOS and HMOS, particularly in combination, enhance vaccine responses by improving memory B cells, IgG production, and Th1 cell activation, supporting the potential use of these prebiotics in infant formula for better early-life immune development.
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Vacunas contra la Influenza , Ratones Endogámicos C57BL , Leche Humana , Oligosacáridos , Animales , Oligosacáridos/farmacología , Leche Humana/inmunología , Leche Humana/química , Femenino , Vacunas contra la Influenza/inmunología , Humanos , Ratones , Vacunación , Inmunoglobulina G/sangre , Galactosa , Linfocitos B/inmunología , Bazo/inmunología , Citocinas/metabolismo , Modelos Animales de Enfermedad , Anticuerpos Antivirales/sangreRESUMEN
OBJECTIVE: Collagen-induced arthritis (CIA) model was induced in C57BL/6 wild-type (wt) and C57BL/6 miR-204/-211 double-knockout (dKO) mice to investigate the role of miR-204/-211 in suppressing splenic inflammation in rheumatoid arthritis (RA). METHODS: Differences of miR-204/-211 and structure-specific recognition protein 1 (SSRP1) in the spleen of DBA/1J wt and CIA mice were detected via PCR and immunohistochemistry. CIA was induced in both C57BL/6 wt and C57BL/6 miR-204/-211 dKO mice, and the onset of CIA and disease severity were statistically analyzed. Immunohistochemistry staining of interleukin-1ß (IL-1ß), tumor necrosis factor-α (TNF-α), and SSRP1 in spleen or knee joints was performed and analyzed. In CIA miR-204/-211 dKO mice, AAV-shSSRP1 was intra-articularly injected, with both the AAV-shRNA Ctrl and AAV-shRNA Ctrl CIA groups receiving the same dose of AAV-shRNA. Spleen sections were stained with hematoxylin and eosin (H&E). RESULTS: Compared to wt mouse spleens, aberrant expression of miR-204/-211 and SSRP1 was observed in the spleens of CIA mice. Immunized dKO mice exhibited a higher incidence of CIA onset and a more exacerbated RA disease phenotype, characterized by increased spleen inflammation score and elevated levels of IL-1ß, TNF-α, and SSRP1 expression. AAV-shSSRP1 injection in CIA dKO mice significantly reduced spleen inflammation scores, IL-1ß and TNF-α expression levels, and down-regulated Ki-67 expression compared to CIA dKO mice. CONCLUSION: Knockout of miR-204/-211 exacerbated the onset of CIA in C57BL/6 mice, while miR-204/-211 played a protective role against the progression of splenic inflammatory and proliferative progression in RA by targeting SSRP1.
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Artritis Experimental , Artritis Reumatoide , MicroARNs , Bazo , Animales , Masculino , Ratones , Artritis Experimental/inmunología , Artritis Experimental/patología , Artritis Experimental/genética , Artritis Reumatoide/genética , Artritis Reumatoide/inmunología , Progresión de la Enfermedad , Inflamación , Interleucina-1beta/metabolismo , Ratones Endogámicos C57BL , Ratones Endogámicos DBA , Ratones Noqueados , MicroARNs/genética , Bazo/patología , Bazo/inmunología , Factor de Necrosis Tumoral alfa/metabolismoRESUMEN
γδ T cells facilitate the CD4+ T helper 1 (Th1) cell response against Plasmodium infection by activating conventional dendritic cells (cDCs), although the underlying mechanism remains elusive. Our study revealed that γδ T cells promote the complete maturation and production of interleukin-12 and CXCR3-ligands specifically in type 1 cDCs (cDC1), with minimal impact on cDC2 and monocyte derived DCs (Mo-DCs). During the initial infection phase, γδ T cell activation and temporal accumulation in the splenic white pulp, alongside cDC1, occur via CCR7-signaling. Furthermore, cDC1/γδ T cell interactions in the white pulp are amplified through CXCR3 signaling in γδ T cells, optimizing Th1 cell priming by cDC1. We also demonstrated how transitional Th1 cells arise in the white pulp before establishing their presence in the red pulp as fully differentiated Th1 cells. Additionally, we elucidate the reciprocal activation between γδ T cells and cDC1s. These findings suggest that Th1 cell priming is orchestrated by this reciprocal activation in the splenic white pulp during the early phase of blood-stage Plasmodium infection.
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Células Dendríticas , Activación de Linfocitos , Malaria , Células TH1 , Células TH1/inmunología , Células Dendríticas/inmunología , Células Dendríticas/metabolismo , Animales , Ratones , Activación de Linfocitos/inmunología , Malaria/inmunología , Malaria/parasitología , Ratones Endogámicos C57BL , Receptores CXCR3/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/metabolismo , Receptores de Antígenos de Linfocitos T gamma-delta/inmunología , Receptores CCR7/metabolismo , Receptores CCR7/inmunología , Transducción de Señal , Bazo/inmunología , Diferenciación Celular/inmunología , FemeninoRESUMEN
ETHNOPHARMACOLOGICAL RELEVANCE: Ulcerative colitis (UC) is a chronic inflammatory bowel condition that is frequently related with Spleen-Kidney Yang Deficiency Syndrome (SKYD) in Chinese medicine. Fuzi Lizhong Pill (FLZP), a traditional medicine for SKYD, has been utilized in China for generations, although the exact mechanism by which it treats UC is unknown. AIM OF THE STUDY: The goal of this study is to further understand FLZP's therapeutic mechanism in SKYD-associated UC. MATERIALS AND METHODS: To investigate the impact of FLZP on SKYD-associated UC, we used a comprehensive method that included serum metabolomics and gut microbiota profiling. The chemical composition of FLZP was determined using mass spectrometry. UC rats with SKYD were induced and treated with FLZP. Serum metabolomics and 16S rRNA microbial community analysis were used to evaluate FLZP's effects on endogenous metabolites and gut microbiota, respectively. Correlation analysis investigated the association between metabolites and intestinal flora. A metabolic pathway analysis was undertaken to discover putative FLZP action mechanisms. RESULTS: FLZP contains 109 components, including liquiritin (584.8176 µg/g), benzoylaconine (16.3087 µg/g), benzoylhypaconine (31.9583), and hypaconitine (8.1160 µg/g). FLZP predominantly regulated seven metabolites and eight metabolic pathways involved in amino acid and nucleotide metabolism, with an emphasis on energy metabolism and gastrointestinal digestion. FLZP also influenced intestinal flora variety, increasing probiotic abundance while decreasing pathogenic bacteria prevalence. An integrated investigation identified associations between changes in certain gut flora and energy metabolism, specifically the tricarboxylic acid (TCA) cycle. CONCLUSIONS: FLZP successfully cures UC in SKYD rats by regulating amino acid and energy metabolism. Its positive effects may include altering microbiota composition and metabolite profiles in UC rats with SKYD. These findings shed light on FLZP's mode of action and its implications for UC management.