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1.
BMC Res Notes ; 17(1): 184, 2024 Jul 02.
Artigo em Inglês | MEDLINE | ID: mdl-38956715

RESUMO

OBJECTIVE: Bartonella are emerging bacterial zoonotic pathogens. Utilization of clotted blood samples for surveillance of these bacteria in wildlife has begun to supersede the use of tissues; however, the efficacy of these samples has not been fully investigated. Our objective was to compare the efficacy of spleen and blood samples for DNA extraction and direct detection of Bartonella spp. via qPCR. In addition, we present a protocol for improved DNA extraction from clotted, pelleted (i.e., centrifuged) blood samples obtained from wild small mammals. RESULTS: DNA concentrations from kit-extracted blood clot samples were low and A260/A280 absorbance ratios indicated high impurity. Kit-based DNA extraction of spleen samples was efficient and produced ample DNA concentrations of good quality. We developed an in-house extraction method for the blood clots which resulted in apposite DNA quality when compared to spleen samples extracted via MagMAX DNA Ultra 2.0 kit. We detected Bartonella in 9/30 (30.0%) kit-extracted spleen DNA samples and 11/30 (36.7%) in-house-extracted blood clot samples using PCR. Our results suggest that kit-based methods may be less suitable for DNA extraction from blood clots, and that blood clot samples may be superior to tissues for Bartonella detection.


Assuntos
Animais Selvagens , Infecções por Bartonella , Bartonella , DNA Bacteriano , Baço , Animais , Bartonella/isolamento & purificação , Bartonella/genética , DNA Bacteriano/sangue , DNA Bacteriano/genética , DNA Bacteriano/isolamento & purificação , Baço/microbiologia , Infecções por Bartonella/diagnóstico , Infecções por Bartonella/sangue , Infecções por Bartonella/microbiologia , Animais Selvagens/microbiologia , Reação em Cadeia da Polimerase em Tempo Real/métodos
2.
Nat Commun ; 15(1): 5752, 2024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38982135

RESUMO

The early-life organ development and maturation shape the fundamental blueprint for later-life phenotype. However, a multi-organ proteome atlas from infancy to adulthood is currently not available. Herein, we present a comprehensive proteomic analysis of ten mouse organs (brain, heart, lung, liver, kidney, spleen, stomach, intestine, muscle and skin) at three crucial developmental stages (1-, 4- and 8-weeks after birth) acquired using data-independent acquisition mass spectrometry. We detect and quantify 11,533 protein groups across the ten organs and obtain 115 age-related differentially expressed protein groups that are co-expressed in all organs from infancy to adulthood. We find that spliceosome proteins prevalently play crucial regulatory roles in the early-life development of multiple organs, and detect organ-specific expression patterns and sexual dimorphism. This multi-organ proteome atlas provides a fundamental resource for understanding the molecular mechanisms underlying early-life organ development and maturation.


Assuntos
Proteoma , Proteômica , Animais , Proteoma/metabolismo , Camundongos , Feminino , Masculino , Proteômica/métodos , Rim/metabolismo , Rim/crescimento & desenvolvimento , Spliceossomos/metabolismo , Especificidade de Órgãos , Camundongos Endogâmicos C57BL , Encéfalo/metabolismo , Encéfalo/crescimento & desenvolvimento , Fígado/metabolismo , Pulmão/metabolismo , Pulmão/crescimento & desenvolvimento , Regulação da Expressão Gênica no Desenvolvimento , Caracteres Sexuais , Baço/metabolismo , Baço/crescimento & desenvolvimento
3.
Egypt J Immunol ; 31(3): 28-40, 2024 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-38985532

RESUMO

The study aimed to assess the immunomodulatory effects of Phoenix dactylifera (dates) fruit, a traditional remedy used by Moroccans to enhance immunity against pathogens. This research sought to evaluate the impacts of this fruit on immune cells and their functions. To achieve this, we conducted tests using date extracts on splenocytes, thymocytes, and macrophages, focusing on their functions: antibody production, phagocytosis, and T-lymphocyte toxicity. The results obtained demonstrated that the aqueous extract of P. dactylifera fruit exhibited significant immunostimulatory effects on humoral immunity. It achieved this by enhancing complement activity and increasing splenocyte (including B-lymphocytes) proliferation by 142.5% compared to control cells. Similarly, in the same conditions, there was notable stimulation of cellular immunity through thymocyte activity, resulting in a remarkable increase in cell proliferation (225%) and a boost in thymocyte function (245.9%), which plays a role in safeguarding against cancer. Moreover, the date extract demonstrated anti-inflammatory properties. This was evident in the increased phagocytosis activity mediated by macrophages under the ethyl acetate extract, effectively eliminating pathogens. Assessing the cosmetic potential of date extracts showed that the ethyl acetate extract possesses both anti-inflammatory and strong antioxidant effects, exhibited high photo absorption of ultraviolet-B rays. Based on these findings, we propose to study the utilization of this extract for sun protection as a sunscreen. Furthermore, the Fourier-transform infrared spectroscopy analysis indicated that the most active compounds present were flavonoids. These outcomes substantiate the traditional usage of this fruit for reinforcing immunity.


Assuntos
Imunidade Celular , Imunidade Humoral , Phoeniceae , Extratos Vegetais , Animais , Imunidade Celular/efeitos dos fármacos , Imunidade Humoral/efeitos dos fármacos , Extratos Vegetais/farmacologia , Extratos Vegetais/imunologia , Camundongos , Phoeniceae/química , Adjuvantes Imunológicos/farmacologia , Fagocitose/efeitos dos fármacos , Fagocitose/imunologia , Macrófagos/efeitos dos fármacos , Macrófagos/imunologia , Baço/imunologia , Baço/efeitos dos fármacos , Baço/citologia , Linfócitos T/imunologia , Linfócitos T/efeitos dos fármacos , Frutas/química , Frutas/imunologia , Masculino , Proliferação de Células/efeitos dos fármacos
4.
Elife ; 122024 Jul 09.
Artigo em Inglês | MEDLINE | ID: mdl-38979889

RESUMO

Extramedullary erythropoiesis is not expected in healthy adult mice, but erythropoietic gene expression was elevated in lineage-depleted spleen cells from Cd47-/- mice. Expression of several genes associated with early stages of erythropoiesis was elevated in mice lacking CD47 or its signaling ligand thrombospondin-1, consistent with previous evidence that this signaling pathway inhibits expression of multipotent stem cell transcription factors in spleen. In contrast, cells expressing markers of committed erythroid progenitors were more abundant in Cd47-/- spleens but significantly depleted in Thbs1-/- spleens. Single-cell transcriptome and flow cytometry analyses indicated that loss of CD47 is associated with accumulation and increased proliferation in spleen of Ter119-CD34+ progenitors and Ter119+CD34- committed erythroid progenitors with elevated mRNA expression of Kit, Ermap, and Tfrc. Induction of committed erythroid precursors is consistent with the known function of CD47 to limit the phagocytic removal of aged erythrocytes. Conversely, loss of thrombospondin-1 delays the turnover of aged red blood cells, which may account for the suppression of committed erythroid precursors in Thbs1-/- spleens relative to basal levels in wild-type mice. In addition to defining a role for CD47 to limit extramedullary erythropoiesis, these studies reveal a thrombospondin-1-dependent basal level of extramedullary erythropoiesis in adult mouse spleen.


Assuntos
Antígeno CD47 , Eritropoese , Baço , Trombospondina 1 , Animais , Antígeno CD47/metabolismo , Antígeno CD47/genética , Trombospondina 1/metabolismo , Trombospondina 1/genética , Baço/metabolismo , Camundongos , Camundongos Knockout , Regulação da Expressão Gênica , Camundongos Endogâmicos C57BL , Células Precursoras Eritroides/metabolismo
5.
Chirurgia (Bucur) ; 119(3): 330-341, 2024 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-38982911

RESUMO

Background: multiple studies showed important benefices arising from splenic preservation in patients with digestive cancer in general and gastric cancer in particular. The minimally invasive approach remains controversial in locally advanced gastric cancer cases whilst the open approach still has an important role. This paper's aim is to describe and present the feasibility of an open surgical technique that allows removing stations 10 together with 11p and 11d with spleen and splenic vessels preservation in pacients operated upon by open surgery. Material and Methods: We present an open "Ex-situ" spleen and pancreas preserving surgical technique that removes the anterior and posterior ganglia from the splenic hilum, the splenic vessels and the distal pancreas in locally advanced gastric cancer cases of the upper two thirds of the stomach. Forty-three consecutive patients since 2003 were operated upon by the author in multiple centers. during upper two thirds gastric cancer resections requiring no. 10 lymphadenectomy. Results: no splenectomy was needed . All the spleens were viable at postoperative Doppler echography and CT scans. No spleen migrated nor caused mechanical complications. No clinically significant pancreatic leaks were noticed. Two patients died during hospital stay, one of miocardial infarction and one of massive stroke. Pertinent follow up data and survival were not available. Conclusions: The method enables the surgeon to remove the lymph nodes no. 10 along with 11p and 11d without needing to sacrifice the spleen. All spleens were reattached sucessfully using the preserved spleno-renal ligament fold, no wandering spleen was noticed.


Assuntos
Estudos de Viabilidade , Gastrectomia , Excisão de Linfonodo , Baço , Neoplasias Gástricas , Humanos , Excisão de Linfonodo/métodos , Resultado do Tratamento , Baço/cirurgia , Neoplasias Gástricas/cirurgia , Neoplasias Gástricas/patologia , Gastrectomia/métodos , Estadiamento de Neoplasias , Masculino , Tratamentos com Preservação do Órgão/métodos , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Idoso
6.
Zhongguo Zhen Jiu ; 44(7): 757-61, 2024 Jul 12.
Artigo em Chinês | MEDLINE | ID: mdl-38986587

RESUMO

OBJECTIVE: To observe the clinical effect of the row-like needling along the spleen meridian combined with autonomous functional exercise in treatment of postpartum diastasis recti abdominis. METHODS: A total of 72 patients with postpartum diastasis recti abdominis were randomly divided into an observation group (36 cases, 3 cases excluded) and a control group (36 cases, 3 cases dropped out). In the control group, the autonomous functional exercise was performed on the rectus abdominis. In the observation group, on the basis of the treatment as the control group, the row-like needling along the spleen meridian was delivered. Along the distribution of the spleen meridian on the abdomen, besides Daheng (SP 15), acupuncture was operated at the sites 3 cm and 6 cm directly above and below Daheng (SP 15) bilaterally. Five points on each side were stimulated along the meridian. Acupuncture was delivered once every two days, 3 interventions a week. One course of treatment, composed of 10 treatments, was required. Before treatment and after 5 and 10 treatments, the inter-rectus distance (IRD) and the score of the medical outcomes study 36-item short form health survey (SF-36) were observed in the two groups, respectively. RESULTS: After 5 and 10 treatments, the IRD at the sites 3 cm above the umbilicus, in the center of the umbilicus and below the umbilicus was reduced when compared with that before treatment in the observation group, respectively (P<0.01); and the IRD at the site 3 cm above the umbilicus was decreased in comparison with that before treatment in the control group (P<0.05). After treated for 5 times, compared with the control group, the IRD at the site 3 cm below the umbilicus was reduced in the observation group (P<0.05); and after treated for 10 times, compared with the control group, the IRD at the sites 3 cm above the umbilicus, in the center of the umbilicus and below the umbilicus was reduced in the observation group (P<0.01). After the completion of 5 and 10 treatments, the scores of physical functioning (PF), role-physical (RP), role-emotional (RE) and health change (HC), as well as the total score of SF-36 were all higher than those before treatment in the observation group (P<0.01); while in the control group, the scores of PF, RP and RE, as well as the total score of SF-36 were increased in comparison with those before treatment (P<0.01). After 5 treatments, the scores of general health (GH) and HC in the observation group were higher than those of the control group (P<0.05, P<0.01); and after 10 treatments, the score of PF, GH and HC, as well as the total score of SF-36 in the observation group were higher than those of the control group (P<0.01). CONCLUSION: On the basis of autonomous functional exercise, the row-like needling along the spleen meridian can promote the recovery of postpartum diastasis recti abdominis and improve the quality of life of the patients.


Assuntos
Terapia por Acupuntura , Reto do Abdome , Baço , Humanos , Feminino , Adulto , Baço/fisiopatologia , Adulto Jovem , Período Pós-Parto , Diástase Muscular/terapia , Pontos de Acupuntura , Terapia por Exercício , Gravidez
7.
Parasit Vectors ; 17(1): 288, 2024 Jul 06.
Artigo em Inglês | MEDLINE | ID: mdl-38971783

RESUMO

BACKGROUND: Currently, treatment regimens for visceral leishmaniasis (VL) are limited because of the presence of numerous adverse effects. Nicotinamide, a readily available and cost-effective vitamin, has been widely acknowledged for its safety profile. Several studies have demonstrated the anti-leishmanial effects of nicotinamide in vitro. However, the potential role of nicotinamide in Leishmania infection in vivo remains elusive. METHODS: In this study, we assessed the efficacy of nicotinamide as a therapeutic intervention for VL caused by Leishmania infantum in an experimental mouse model and investigated its underlying molecular mechanisms. The potential molecular mechanism was explored through cytokine analysis, examination of spleen lymphocyte subsets, liver RNA-seq analysis, and pathway validation. RESULTS: Compared to the infection group, the group treated with nicotinamide demonstrated significant amelioration of hepatosplenomegaly and recovery from liver pathological damage. The NAM group exhibited parasite reduction rates of 79.7% in the liver and 86.7% in the spleen, respectively. Nicotinamide treatment significantly reduced the activation of excessive immune response in infected mice, thereby mitigating hepatosplenomegaly and injury. Furthermore, nicotinamide treatment enhanced fatty acid ß-oxidation by upregulating key enzymes to maintain lipid homeostasis. CONCLUSIONS: Our findings provide initial evidence supporting the safety and therapeutic efficacy of nicotinamide in the treatment of Leishmania infection in BALB/c mice, suggesting its potential as a viable drug for VL.


Assuntos
Leishmania infantum , Leishmaniose Visceral , Metabolismo dos Lipídeos , Fígado , Camundongos Endogâmicos BALB C , Niacinamida , Baço , Animais , Leishmaniose Visceral/tratamento farmacológico , Leishmaniose Visceral/parasitologia , Leishmaniose Visceral/imunologia , Niacinamida/farmacologia , Niacinamida/uso terapêutico , Camundongos , Metabolismo dos Lipídeos/efeitos dos fármacos , Fígado/parasitologia , Fígado/efeitos dos fármacos , Fígado/patologia , Leishmania infantum/efeitos dos fármacos , Baço/parasitologia , Baço/efeitos dos fármacos , Citocinas/metabolismo , Modelos Animais de Doenças , Feminino , Inflamação/tratamento farmacológico , Antiprotozoários/farmacologia , Antiprotozoários/uso terapêutico
8.
FASEB J ; 38(14): e23807, 2024 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-38989570

RESUMO

Specialized proresolving mediators (SPMs) promote local macrophage efferocytosis but excess leukocytes early in inflammation require additional leukocyte clearance mechanism for resolution. Here, neutrophil clearance mechanisms from localized acute inflammation were investigated in mouse dorsal air pouches. 15-HEPE (15-hydroxy-5Z,8Z,11Z,13E,17Z-eicosapentaenoic acid) levels were increased in the exudates. Activated human neutrophils converted 15-HEPE to lipoxin A5 (5S,6R,15S-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), 15-epi-lipoxin A5 (5S,6R,15R-trihydroxy-7E,9E,11Z,13E,17Z-eicosapentaenoic acid), and resolvin E4 (RvE4; 5S,15S-dihydroxy-6E,8Z,11Z,13E,17Z-eicosapentaenoic acid). Exogenous 15-epi-lipoxin A5, 15-epi-lipoxin A4 and a structural lipoxin mimetic significantly decreased exudate neutrophils and increased local tissue macrophage efferocytosis, with comparison to naproxen. 15-epi-lipoxin A5 also cleared exudate neutrophils faster than the apparent local capacity for stimulated macrophage efferocytosis, so the fate of exudate neutrophils was tracked with CD45.1 variant neutrophils. 15-epi-lipoxin A5 augmented the exit of adoptively transferred neutrophils from the pouch exudate to the spleen, and significantly increased splenic SIRPa+ and MARCO+ macrophage efferocytosis. Together, these findings demonstrate new systemic resolution mechanisms for 15-epi-lipoxin A5 and RvE4 in localized tissue inflammation, which distally engage the spleen to activate macrophage efferocytosis for the clearance of tissue exudate neutrophils.


Assuntos
Lipoxinas , Macrófagos , Neutrófilos , Baço , Animais , Neutrófilos/metabolismo , Neutrófilos/efeitos dos fármacos , Macrófagos/metabolismo , Camundongos , Humanos , Lipoxinas/metabolismo , Lipoxinas/farmacologia , Baço/metabolismo , Baço/citologia , Ácido Eicosapentaenoico/análogos & derivados , Ácido Eicosapentaenoico/farmacologia , Ácido Eicosapentaenoico/metabolismo , Camundongos Endogâmicos C57BL , Fagocitose , Masculino , Inflamação/metabolismo , Ácidos Heptanoicos
9.
Front Immunol ; 15: 1415565, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38989285

RESUMO

How the microbiome regulates responses of systemic innate immune cells is unclear. In the present study, our purpose was to document a novel mechanism by which the microbiome mediates crosstalk with the systemic innate immune system. We have identified a family of microbiome Bacteroidota-derived lipopeptides-the serine-glycine (S/G) lipids, which are TLR2 ligands, access the systemic circulation, and regulate proinflammatory responses of splenic monocytes. To document the role of these lipids in regulating systemic immunity, we used oral gavage with an antibiotic to decrease the production of these lipids and administered exogenously purified lipids to increase the systemic level of these lipids. We found that decreasing systemic S/G lipids by decreasing microbiome Bacteroidota significantly enhanced splenic monocyte proinflammatory responses. Replenishing systemic levels of S/G lipids via exogenous administration returned splenic monocyte responses to control levels. Transcriptomic analysis demonstrated that S/G lipids regulate monocyte proinflammatory responses at the level of gene expression of a small set of upstream inhibitors of TLR and NF-κB pathways that include Trem2 and Irf4. Consistent with enhancement in proinflammatory cytokine responses, decreasing S/G lipids lowered gene expression of specific pathway inhibitors. Replenishing S/G lipids normalized gene expression of these inhibitors. In conclusion, our results suggest that microbiome-derived S/G lipids normally establish a level of buffered signaling activation necessary for well-regulated innate immune responses in systemic monocytes. By regulating gene expression of inflammatory pathway inhibitors such as Trem2, S/G lipids merit broader investigation into the potential dysfunction of other innate immune cells, such as microglia, in diseases such as Alzheimer's disease.


Assuntos
Monócitos , Transdução de Sinais , Monócitos/imunologia , Monócitos/metabolismo , Monócitos/efeitos dos fármacos , Animais , Camundongos , Microbiota/imunologia , Camundongos Endogâmicos C57BL , Imunidade Inata , Receptor 2 Toll-Like/metabolismo , Regulação da Expressão Gênica/efeitos dos fármacos , Glicoproteínas de Membrana/metabolismo , Glicoproteínas de Membrana/genética , Lipopeptídeos/farmacologia , Receptores Imunológicos/metabolismo , Receptores Imunológicos/genética , NF-kappa B/metabolismo , Inflamação/imunologia , Fatores Reguladores de Interferon/metabolismo , Fatores Reguladores de Interferon/genética , Masculino , Lipídeos , Baço/imunologia , Baço/metabolismo , Citocinas/metabolismo , Feminino
10.
BMJ Case Rep ; 17(7)2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38991575

RESUMO

We present a compelling case of an elderly male with a complex medical history who presented with sepsis secondary to a urinary tract infection. During admission, changes in his abdominal exam prompted imaging studies, which revealed a grade IV splenic laceration with a giant splenic artery pseudoaneurysm containing a suspected arteriovenous fistula component. Multidisciplinary discussion was had regarding patient management which resulted in the decision to perform an emergent splenectomy. Learning points from this case underscore the crucial role of interdisciplinary collaboration in the treatment of this pathology. Additionally, we discuss the decision-making process to support surgical intervention in the absence of clear guidelines in this exceedingly rare condition.


Assuntos
Falso Aneurisma , Fístula Arteriovenosa , Esplenectomia , Artéria Esplênica , Humanos , Falso Aneurisma/diagnóstico por imagem , Falso Aneurisma/terapia , Falso Aneurisma/etiologia , Falso Aneurisma/diagnóstico , Falso Aneurisma/cirurgia , Masculino , Artéria Esplênica/diagnóstico por imagem , Fístula Arteriovenosa/diagnóstico por imagem , Fístula Arteriovenosa/diagnóstico , Fístula Arteriovenosa/complicações , Fístula Arteriovenosa/cirurgia , Fístula Arteriovenosa/terapia , Fístula Arteriovenosa/etiologia , Baço/irrigação sanguínea , Baço/diagnóstico por imagem , Baço/lesões , Idoso , Tomografia Computadorizada por Raios X
11.
BMC Genomics ; 25(1): 684, 2024 Jul 11.
Artigo em Inglês | MEDLINE | ID: mdl-38992576

RESUMO

BACKGROUND: Integration of high throughput DNA genotyping and RNA-sequencing data enables the discovery of genomic regions that regulate gene expression, known as expression quantitative trait loci (eQTL). In pigs, efforts to date have been mainly focused on purebred lines for traits with commercial relevance as such growth and meat quality. However, little is known on genetic variants and mechanisms associated with the robustness of an animal, thus its overall health status. Here, the liver, lung, spleen, and muscle transcriptomes of 100 three-way crossbred female finishers were studied, with the aim of identifying novel eQTL regulatory regions and transcription factors (TFs) associated with regulation of porcine metabolism and health-related traits. RESULTS: An expression genome-wide association study with 535,896 genotypes and the expression of 12,680 genes in liver, 13,310 genes in lung, 12,650 genes in spleen, and 12,595 genes in muscle resulted in 4,293, 10,630, 4,533, and 6,871 eQTL regions for each of these tissues, respectively. Although only a small fraction of the eQTLs were annotated as cis-eQTLs, these presented a higher number of polymorphisms per region and significantly stronger associations with their target gene compared to trans-eQTLs. Between 20 and 115 eQTL hotspots were identified across the four tissues. Interestingly, these were all enriched for immune-related biological processes. In spleen, two TFs were identified: ERF and ZNF45, with key roles in regulation of gene expression. CONCLUSIONS: This study provides a comprehensive analysis with more than 26,000 eQTL regions identified that are now publicly available. The genomic regions and their variants were mostly associated with tissue-specific regulatory roles. However, some shared regions provide new insights into the complex regulation of genes and their interactions that are involved with important traits related to metabolism and immunity.


Assuntos
Estudo de Associação Genômica Ampla , Locos de Características Quantitativas , Animais , Suínos/genética , Polimorfismo de Nucleotídeo Único , Feminino , Fatores de Transcrição/genética , Fatores de Transcrição/metabolismo , Fígado/metabolismo , Especificidade de Órgãos/genética , Baço/metabolismo , Transcriptoma , Regulação da Expressão Gênica , Pulmão/metabolismo , Pulmão/imunologia , Genótipo
12.
Xi Bao Yu Fen Zi Mian Yi Xue Za Zhi ; 40(6): 494-500, 2024 Jun.
Artigo em Chinês | MEDLINE | ID: mdl-38952088

RESUMO

Objective To investigate the effect of Terminalia chebula water extract (TCWE) on the cellular immunity and PD-1/PD-L1 pathway in rats with collagen-induced arthritis (CIA). Methods SD rats were randomly divided into four groups: a control group, a CIA group, a TCWE group and a methotrexate (MTX) group, with 15 rats in each group. Except for the control group, SD rats in other groups were subcutaneously injected with type II collagen to establish the model of collagen-induced arthritis (CIA). The rats in the TCWE group were treated with 20 mg/(kg.d) TCWE and the rats in the MTX group were treated with 1.67 mg/(kg.d) MTX. After 14 days of treatment, the cartilage morphology was examined using hematoxylin-eosin (HE) staining, and splenic T lymphocyte apoptosis and Treg/Th17 cell ratio were detected by flow cytometry. The mRNA expressions of retinoid-related orphan nuclear receptor γt (RORγt), forkhead box P3 (FOXP3), PD-1 and PD-L1 in spleen were detected by reverse transcription PCR. The expression and localization of RORγt and FOXP3 were detected by immunohistochemical staining. The protein expressions of PD-1 and PD-L1 in splenic lymphocytes were detected by Western blot, and the levels of serum interleukin 17 (IL-17) and transforming growth factor ß (TGF-ß) in rats were detected by ELISA. Results Compared with CIA group, the pathological changes of cartilage and synovium were significantly alleviated in the TCWE group and the MTX group. Both the apoptosis rate of T lymphocytes in spleen and the ratio of Treg/Th17 cells increased. The expression of RORγt decreased, while the expressions of FOXP3, PD-1 and PD-L1 increased in spleen lymphocytes. The level of serum IL-17 decreased, while the level of serum TGF-ß increased. Conclusion TCWE treatment may activate PD-1/PD-L1 pathway in spleen cells to regulate cellular immunity, thus reducing cartilage injury in CIA rats.


Assuntos
Artrite Experimental , Antígeno B7-H1 , Receptor de Morte Celular Programada 1 , Ratos Sprague-Dawley , Baço , Terminalia , Animais , Artrite Experimental/imunologia , Artrite Experimental/tratamento farmacológico , Artrite Experimental/metabolismo , Baço/efeitos dos fármacos , Baço/imunologia , Baço/metabolismo , Antígeno B7-H1/genética , Antígeno B7-H1/metabolismo , Receptor de Morte Celular Programada 1/genética , Receptor de Morte Celular Programada 1/metabolismo , Ratos , Terminalia/química , Masculino , Imunidade Celular/efeitos dos fármacos , Regulação para Cima/efeitos dos fármacos , Extratos Vegetais/farmacologia , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/genética , Membro 3 do Grupo F da Subfamília 1 de Receptores Nucleares/metabolismo , Inflamação/tratamento farmacológico , Inflamação/imunologia , Inflamação/metabolismo , Linfócitos T Reguladores/imunologia , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/metabolismo , Células Th17/imunologia , Células Th17/efeitos dos fármacos , Células Th17/metabolismo
13.
PLoS One ; 19(7): e0292408, 2024.
Artigo em Inglês | MEDLINE | ID: mdl-38950025

RESUMO

Co-infections are a common reality but understanding how the immune system responds in this context is complex and can be unpredictable. Heligmosomoides bakeri (parasitic roundworm, previously Heligmosomoides polygyrus) and Toxoplasma gondii (protozoan parasite) are well studied organisms that stimulate a characteristic Th2 and Th1 response, respectively. Several studies have demonstrated reduced inflammatory cytokine responses in animals co-infected with such organisms. However, while general cytokine signatures have been examined, the impact of the different cytokine producing lymphocytes on parasite control/clearance is not fully understood. We investigated five different lymphocyte populations (NK, NKT, γδ T, CD4+ T and CD8+ T cells), five organs (small intestine, Peyer's patches, mesenteric lymph nodes, spleen and liver), and 4 cytokines (IFN©, IL-4, IL-10 and IL-13) at two different time points (days 5 and 10 post T. gondii infection). We found that co-infected animals had significantly higher mortality than either single infection. This was accompanied by transient and local changes in parasite loads and cytokine profiles. Despite the early changes in lymphocyte and cytokine profiles, severe intestinal pathology in co-infected mice likely contributed to early mortality due to significant damage by both parasites in the small intestine. Our work demonstrates the importance of taking a broad view during infection research, studying multiple cell types, organs/tissues and time points to link and/or uncouple immunological from pathological findings. Our results provide insights into how co-infection with parasites stimulating different arms of the immune system can lead to drastic changes in infection dynamics.


Assuntos
Coinfecção , Citocinas , Nematospiroides dubius , Toxoplasma , Animais , Coinfecção/imunologia , Coinfecção/parasitologia , Toxoplasma/imunologia , Camundongos , Citocinas/metabolismo , Nematospiroides dubius/imunologia , Infecções por Strongylida/imunologia , Infecções por Strongylida/parasitologia , Infecções por Strongylida/mortalidade , Toxoplasmose/imunologia , Toxoplasmose/mortalidade , Toxoplasmose/complicações , Feminino , Toxoplasmose Animal/imunologia , Toxoplasmose Animal/mortalidade , Toxoplasmose Animal/parasitologia , Baço/imunologia , Baço/patologia , Baço/parasitologia , Carga Parasitária , Tecido Linfoide/imunologia , Tecido Linfoide/patologia , Tecido Linfoide/parasitologia
14.
Sci Rep ; 14(1): 15264, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961124

RESUMO

This study evaluated the use of F-18 fluorodeoxyglucose (FDG) PET/CT imaging to differentiate between scrub typhus and systemic lupus erythematosus (SLE) in patients presenting with lymphadenopathy. We carried out a retrospective analysis of 18 scrub typhus patients and seven SLE patients, using various imaging parameters, including lymph node size, spleen and liver lengths, the distance between the two farthest lesions (Dmax), and assessments of glucose metabolism. On FDG PET images, we measured the maximum standardized uptake value (SUVmax) of the lymph nodes, spleen, and liver and the mean standardized uptake value (SUVmean) of the liver and spleen. The Dmax values of scrub typhus patients were significantly longer than those of SLE patients, indicating that lymphadenopathy is more generalized in the patients with scrub typhus. The SUVmax values for the lymph node, spleen, and liver were also higher in patients with scrub typhus, while the SUVmean of the liver and spleen did not differ between the two groups. This study is the first to compare FDG PET/CT images between these two conditions, suggesting the potential of this imaging modality to provide critical diagnostic distinctions.


Assuntos
Fluordesoxiglucose F18 , Lúpus Eritematoso Sistêmico , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada , Tifo por Ácaros , Humanos , Tifo por Ácaros/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/diagnóstico por imagem , Lúpus Eritematoso Sistêmico/complicações , Tomografia por Emissão de Pósitrons combinada à Tomografia Computadorizada/métodos , Feminino , Masculino , Pessoa de Meia-Idade , Adulto , Estudos Retrospectivos , Idoso , Linfonodos/diagnóstico por imagem , Linfonodos/patologia , Baço/diagnóstico por imagem , Baço/patologia , Fígado/diagnóstico por imagem , Fígado/patologia , Fígado/metabolismo , Diagnóstico Diferencial , Compostos Radiofarmacêuticos , Adulto Jovem
15.
Sci Rep ; 14(1): 15297, 2024 07 03.
Artigo em Inglês | MEDLINE | ID: mdl-38961187

RESUMO

Characteristics of livers and spleens of people with multiple sclerosis (pwMS) could constitute good biomarkers of MS-related characteristics such as the disability status. To test the hypothesis "the gross anatomical features of livers and spleens, are not similar between pwMS with different disease characteristics" a cross-sectional study was conducted on pwMS seen at the Isfahan MS clinic, Iran, from February until December 2023. Definitive, otherwise-healthy, pwMS were enrolled after an initial laboratory evaluation. Presence/absence and grading of non-alcoholic fatty liver disease (NAFLD) and the span of spleen were determined by a radiologist using high-resolution abdominopelvic ultrasonography. 193 pwMS (160 women) were enrolled. Of whom, 143 (74.1%) were receiving first-line disease-modifying therapies (DMTs), 24 (12.4%) fingolimod, and 26 (13.5%) rituximab. The span of spleen was negatively associated with EDSS (adjusted ß [SE] - 4.08 [1.52], p < 0.01), as well as 6 m-CDW (adjusted ß [SE] - 6.94 [3.56], p = 0.05), unlike age, DMTs, and MS duration (all with p > 0.05). Receiver operating characteristic analysis showed, spleen span performs significant but poor in discrimination of EDSS > 1 from EDSS = 1 (area under curve [AUC] 0.62, SE 0.05, p < 0.01), yet, significant and fair in discrimination of presence from absence of 6 m-CDW (AUC 0.72, SE 0.06, p < 0.01). Other findings were unremarkable. Further longitudinal, prospective studies are warranted to confirm whether smaller spleens are predictive of higher disability accrual rate in pwMS. Particularly, findings require further validation in untreated/treatment-naïve pwMS, and ones with higher EDSS scores.


Assuntos
Esclerose Múltipla , Baço , Ultrassonografia , Humanos , Feminino , Baço/diagnóstico por imagem , Estudos Transversais , Adulto , Masculino , Esclerose Múltipla/diagnóstico por imagem , Ultrassonografia/métodos , Pessoa de Meia-Idade , Hepatopatia Gordurosa não Alcoólica/diagnóstico por imagem , Fígado/diagnóstico por imagem , Fígado/patologia , Irã (Geográfico)
16.
BMC Vet Res ; 20(1): 294, 2024 Jul 05.
Artigo em Inglês | MEDLINE | ID: mdl-38970005

RESUMO

Since its identification in the vitreous humour of the eye and laboratory biosynthesis, hyaluronic acid (HA) has been a vital component in several pharmaceutical, nutritional, medicinal, and cosmetic uses. However, little is known about its potential toxicological impacts on aquatic inhabitants. Herein, we investigated the hematological response of Clarias gariepinus to nominal doses of HA. To achieve this objective, 72 adult fish were randomly and evenly distributed into four groups: control, low-dose (0.5 mg/l HA), medium-dose (10 mg/l HA), and high-dose (100 mg/l HA) groups for two weeks each during both the exposure and recovery periods. The findings confirmed presence of anemia, neutrophilia, leucopoenia, lymphopenia, and eosinophilia at the end of exposure to HA. In addition, poikilocytosis and a variety of cytomorphological disturbances were observed. Dose-dependent histological alterations in spleen morphology were observed in the exposed groups. After HA removal from the aquarium for 2 weeks, the groups exposed to the two highest doses still exhibited a notable decline in red blood cell count, hemoglobin concentration, mean corpuscular hemoglobin concentration, and an increase in mean corpuscular volume. Additionally, there was a significant rise in neutrophils, eosinophils, cell alterations, and nuclear abnormalities percentages, along with a decrease in monocytes, coupled with a dose-dependent decrease in lymphocytes. Furthermore, only the highest dose of HA in the recovered groups continued to cause a significant increase in white blood cells. White blood cells remained lower, and the proportion of apoptotic RBCs remained higher in the high-dose group. The persistence of most of the haematological and histological disorders even after recovery period indicates a failure of physiological compensatory mechanisms to overcome the HA-associated problems or insufficient duration of recovery. Thus, these findings encourage the inclusion of this new hazardous agent in the biomonitoring program and provide a specific pattern of hematological profile in HA-challenged fish. Further experiments are highly warranted to explore other toxicological hazards of HA using dose/time window protocols.


Assuntos
Peixes-Gato , Ácido Hialurônico , Baço , Animais , Ácido Hialurônico/sangue , Baço/efeitos dos fármacos , Baço/patologia , Relação Dose-Resposta a Droga
17.
Sci Rep ; 14(1): 13969, 2024 06 17.
Artigo em Inglês | MEDLINE | ID: mdl-38886503

RESUMO

Periodontitis is a chronic inflammatory disease that affects the periodontal tissues. Although it is associated with various systemic diseases, the impact of periodontitis on kidney transplantation (KT) outcomes, particularly allograft rejection, remains unclear. This study investigated the effect of periodontitis on transplant immunity, specifically examining Porphyromonas gingivalis-derived lipopolysaccharide (LPS-PG). In vitro experiments revealed that LPS-PG increased regulatory T cells (Tregs) in Lewis rat spleen cells. In a mixed lymphocyte reaction assay, concentrations of interferon-γ, indicative of alloreactivity, were lower than in controls when LPS-PG was added to the culture and when LPS-PG-administered Lewis rat spleen cells were used as responders. In a rat KT model, LPS-PG administration to recipients promoted mild tubulitis and low serum creatinine and blood urea nitrogen levels 5 days post-KT compared with PBS-administered controls. Furthermore, LPS-PG-administered recipients had an elevated Treg proportion in their peripheral blood and spleen cells, and increased infiltrating Tregs in kidney allografts, compared with controls. The elevated Treg proportion in peripheral blood and spleen cells had a significant negative correlation with serum creatinine, suggesting elevated Tregs modulated allograft rejection. These findings suggest that periodontitis might modulate alloimmune reactivity through LPS-PG and Tregs, offering insights to refine immunosuppressive strategies for KT recipients.


Assuntos
Rejeição de Enxerto , Transplante de Rim , Lipopolissacarídeos , Porphyromonas gingivalis , Ratos Endogâmicos Lew , Linfócitos T Reguladores , Animais , Porphyromonas gingivalis/imunologia , Transplante de Rim/efeitos adversos , Ratos , Linfócitos T Reguladores/imunologia , Masculino , Rejeição de Enxerto/imunologia , Aloenxertos , Periodontite/imunologia , Periodontite/microbiologia , Modelos Animais de Doenças , Baço/imunologia
18.
Int J Mol Sci ; 25(11)2024 May 25.
Artigo em Inglês | MEDLINE | ID: mdl-38891942

RESUMO

While considerable attention has been devoted to respiratory manifestations, such as pneumonia and acute respiratory distress syndrome (ARDS), emerging evidence underlines the significance of extrapulmonary involvement. In this study, we examined 15 hospitalized patients who succumbed to severe complications following SARS-CoV-2 infection. These patients were admitted to the Sibiu County Clinical Emergency Hospital in Sibiu, Romania, between March and October 2021. All patients were ethnic Romanians. Conducted within a COVID-19-restricted environment and adhering to national safety protocols, autopsies provided a comprehensive understanding of the disease's multisystemic impact. Detailed macroscopic evaluations and histopathological analyses of myocardial, renal, hepatic, splenic, and gastrointestinal tissues were performed. Additionally, reverse transcription-quantitative polymerase chain reaction (rt-qPCR) assays and immunohistochemical staining were employed to detect the viral genome and nucleocapsid within the tissues. Myocardial lesions, including ischemic microstructural changes and inflammatory infiltrates, were prevalent, indicative of COVID-19's cardiac implications, while renal pathology revealed the chronic alterations, acute tubular necrosis, and inflammatory infiltrates most evident. Hepatic examination identified hepatocellular necroinflammatory changes and hepatocytic cytopathy, highlighting the hepatic involvement of SARS-CoV-2 infection. Splenic parenchymal disorganization was prominent, indicating systemic immune dysregulation. Furthermore, gastrointestinal examinations unveiled nonspecific changes. Molecular analyses detected viral genes in various organs, with immunohistochemical assays confirming viral presence predominantly in macrophages and fibroblasts. These findings highlighted the systemic nature of SARS-CoV-2 infection, emphasizing the need for comprehensive clinical management strategies and targeted therapeutic approaches beyond respiratory systems.


Assuntos
COVID-19 , Genoma Viral , SARS-CoV-2 , Humanos , SARS-CoV-2/genética , COVID-19/virologia , COVID-19/genética , COVID-19/patologia , Masculino , Feminino , Pessoa de Meia-Idade , Idoso , Rim/virologia , Rim/patologia , Rim/metabolismo , Fígado/virologia , Fígado/patologia , Fígado/metabolismo , Adulto , Baço/virologia , Baço/patologia , Baço/metabolismo , Romênia , Nucleocapsídeo/genética , Nucleocapsídeo/metabolismo , Miocárdio/patologia , Miocárdio/metabolismo , Autopsia , Idoso de 80 Anos ou mais , Proteínas do Nucleocapsídeo de Coronavírus/genética , Proteínas do Nucleocapsídeo de Coronavírus/metabolismo
19.
Int J Mol Sci ; 25(11)2024 Jun 01.
Artigo em Inglês | MEDLINE | ID: mdl-38892297

RESUMO

The continuously expanding field of Alzheimer's disease (AD) research is now beginning to defocus the brain to take a more systemic approach to the disease, as alterations in the peripheral organs could be related to disease progression. One emerging hypothesis is organ involvement in the process of Aß clearance. In the present work, we aimed to examine the status and involvement of the kidney as a key organ for waste elimination and the spleen, which is in charge of filtering the blood and producing lymphocytes, and their influence on AD. The results showed morphological and structural changes due to acute amyloidosis in the kidney (glomeruli area) and spleen (red pulp area and red/white pulp ratio) together with reduced antioxidant defense activity (GPx) in 16-month-old male and female 3xTg-AD mice when compared to their age- and sex-matched non-transgenic (NTg) counterparts. All these alterations correlated with the anxious-like behavioral phenotype of this mouse model. In addition, forced isolation, a cause of psychological stress, had a negative effect by intensifying genotype differences and causing differences to appear in NTg animals. This study further supports the relevance of a more integrative view of the complex interplay between systems in aging, especially at advanced stages of Alzheimer's disease.


Assuntos
Doença de Alzheimer , Modelos Animais de Doenças , Glomérulos Renais , Camundongos Transgênicos , Estresse Oxidativo , Isolamento Social , Baço , Animais , Doença de Alzheimer/metabolismo , Doença de Alzheimer/patologia , Doença de Alzheimer/genética , Camundongos , Masculino , Feminino , Baço/metabolismo , Baço/patologia , Glomérulos Renais/patologia , Glomérulos Renais/metabolismo , Hipertrofia
20.
Int J Mol Sci ; 25(11)2024 Jun 03.
Artigo em Inglês | MEDLINE | ID: mdl-38892340

RESUMO

Severe malarial anemia (SMA) increases the morbidity and mortality of Plasmodium, the causative agent of malaria. SMA is mainly developed by children and pregnant women in response to the infection. It is characterized by ineffective erythropoiesis caused by impaired erythropoietin (EPO) signaling. To gain new insights into the pathogenesis of SMA, we investigated the relationship between the immune system and erythropoiesis, conducting comparative analyses in a mouse model of malaria. Red blood cell (RBC) production was evaluated in infected and reinfected animals to mimic endemic occurrences. Higher levels of circulating EPO were observed in response to (re)infection. Despite no major differences in bone marrow erythropoiesis, compensatory mechanisms of splenic RBC production were significantly reduced in reinfected mice. Concomitantly, a pronounced immune response activation was observed in erythropoietic organs of reinfected animals in relation to single-infected mice. Aged mice were also used to mimic the occurrence of malaria in the elderly. The increase in symptom severity was correlated with the enhanced activation of the immune system, which significantly impaired erythropoiesis. Immunocompromised mice further support the existence of an immune-shaping regulation of RBC production. Overall, our data reveal the strict correlation between erythropoiesis and immune cells, which ultimately dictates the severity of SMA.


Assuntos
Anemia , Eritropoese , Imunomodulação , Malária , Animais , Camundongos , Malária/imunologia , Malária/parasitologia , Anemia/imunologia , Eritrócitos/parasitologia , Eritrócitos/imunologia , Eritrócitos/metabolismo , Modelos Animais de Doenças , Eritropoetina/metabolismo , Feminino , Baço/imunologia , Baço/patologia , Baço/metabolismo , Camundongos Endogâmicos C57BL
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