RESUMO
Aryl Hydrocarbon Receptor (AHR) ligands, upon binding, induce distinct gene expression profiles orchestrated by the AHR, leading to a spectrum of pro- or anti-inflammatory effects. In this study, we designed, synthesized and evaluated three indole-containing potential AHR ligands (FluoAHRL: AGT-4, AGT-5 and AGT-6). All synthesized compounds were shown to emit fluorescence in the near-infrared. Their AHR agonist activity was first predicted using in silico docking studies, and then confirmed using AHR luciferase reporter cell lines. FluoAHRLs were tested in vitro using mouse peritoneal macrophages and T lymphocytes to assess their immunomodulatory properties. We then focused on AGT-5, as it illustrated the predominant anti-inflammatory effects. Notably, AGT-5 demonstrated the ability to foster anti-inflammatory regulatory T cells (Treg) while suppressing pro-inflammatory T helper (Th)17 cells in vitro. AGT-5 actively induced Treg differentiation from naïve CD4+ cells, and promoted Treg proliferation, cytotoxic T-lymphocyte-associated antigen 4 (CTLA-4) expression and interleukin-10 (IL-10) production. The increase in IL-10 correlated with an upregulation of Signal Transducer and Activator of Transcription 3 (STAT3) expression. Importantly, the Treg-inducing effect of AGT-5 was also observed in human tonsil cells in vitro. AGT-5 showed no toxicity when applied to zebrafish embryos and was therefore considered safe for animal studies. Following oral administration to C57BL/6 mice, AGT-5 significantly upregulated Treg while downregulating pro-inflammatory Th1 cells in the mesenteric lymph nodes. Due to its fluorescent properties, AGT-5 could be visualized both in vitro (during uptake by macrophages) and ex vivo (within the lamina propria of the small intestine). These findings make AGT-5 a promising candidate for further exploration in the treatment of inflammatory and autoimmune diseases.
Assuntos
Receptores de Hidrocarboneto Arílico , Linfócitos T Reguladores , Animais , Receptores de Hidrocarboneto Arílico/metabolismo , Receptores de Hidrocarboneto Arílico/agonistas , Linfócitos T Reguladores/efeitos dos fármacos , Linfócitos T Reguladores/imunologia , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/síntese química , Humanos , Peixe-Zebra , Corantes Fluorescentes/química , Ligantes , Camundongos Endogâmicos C57BL , Indóis/farmacologia , Indóis/química , Diferenciação Celular/efeitos dos fármacosRESUMO
Ethyl pyruvate (EP) is a redox-active compound that has been previously shown to be effective in restraining immune hyperactivity in animal models of various autoimmune and chronic inflammatory diseases. Importantly, EP has also been proven to have a potent tolerogenic effect on dendritic cells (DCs). Here, the influence of EP on the signaling pathways in DCs relevant for their tolerogenicity, including anti-inflammatory NRF2 and pro-inflammatory NF-κB, was explored. Specifically, the effects of EP on DCs obtained by GM-CSF-directed differentiation of murine bone marrow precursor cells and matured under the influence of lipopolysaccharide (LPS) were examined via immunocytochemistry and RT-PCR. EP counteracted LPS-imposed morphological changes and down-regulated the LPS-induced expression of pro-inflammatory mediators in DCs. While it reduced the activation of NF-κB, EP potentiated NRF2 and downstream antioxidative molecules, thus implying the regulation of NRF2 signaling pathways as the major reason for the tolerizing effects of EP on DCs.
Assuntos
Células Dendríticas , Lipopolissacarídeos , Fator 2 Relacionado a NF-E2 , NF-kappa B , Piruvatos , Transdução de Sinais , Fator 2 Relacionado a NF-E2/metabolismo , Células Dendríticas/efeitos dos fármacos , Células Dendríticas/metabolismo , Células Dendríticas/imunologia , Piruvatos/farmacologia , Animais , Camundongos , NF-kappa B/metabolismo , Lipopolissacarídeos/farmacologia , Transdução de Sinais/efeitos dos fármacos , Diferenciação Celular/efeitos dos fármacos , Camundongos Endogâmicos C57BL , Tolerância Imunológica/efeitos dos fármacos , Células CultivadasRESUMO
Complete Freund's adjuvant (CFA) is used as a standard adjuvant for the induction of experimental autoimmune encephalomyelitis (EAE), the most commonly used animal model in multiple sclerosis studies. Still, CFA induces glial activation and neuroinflammation on its own and provokes pain. In addition, as CFA contains Mycobacteria, an immune response against bacterial antigens is induced in parallel to the response against central nervous system antigens. Thus, CFA can be considered as a confounding factor in multiple sclerosis-related studies performed on EAE. Here, we discuss the effects of CFA in EAE in detail and present EAE variants induced in experimental animals without the use of CFA. We put forward CFA-free EAE variants as valuable tools for studying multiple sclerosis pathogenesis and therapeutic approaches.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Animais , Adjuvante de Freund , Esclerose Múltipla/complicações , Adjuvantes Imunológicos/farmacologia , Antígenos de BactériasRESUMO
We have recently characterized experimental autoimmune encephalomyelitis (EAE) induced in DA rats with spinal cord homogenate without complete Freund's adjuvant (CFA). The main advantage of this multiple sclerosis model is the lack of CFA-related confounding effects which represent the major obstacles in translating findings from EAE to multiple sclerosis. Here, antigen specificity of the cellular and humoral immune response directed against the central nervous system was explored. The reactivity of T and B cells to myelin basic protein, myelin oligodendrocyte glycoprotein, and ß-synuclein was detected. Having in mind that reactivity against ß-synuclein was previously associated with autoimmunity against the brain, the infiltration of immune cells into different brain compartments, i.e. pons, cerebellum, hippocampus, and cortex was determined. T cell infiltration was observed in all structures examined. This finding stimulated investigation of the effects of immunization on DA rat behavior using the elevated plus maze and the open field test. Rats recovered from EAE displayed increased anxiety-like behavior. These data support CFA-free EAE in DA rats as a useful model for multiple sclerosis research.
Assuntos
Encefalomielite Autoimune Experimental , Medula Espinal , Animais , Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Encefalomielite Autoimune Experimental/metabolismo , Ratos , Medula Espinal/imunologia , Medula Espinal/metabolismo , Medula Espinal/patologia , Modelos Animais de Doenças , Glicoproteína Mielina-Oligodendrócito/imunologia , Linfócitos T/imunologia , Linfócitos T/metabolismo , Esclerose Múltipla/imunologia , Esclerose Múltipla/patologia , Esclerose Múltipla/metabolismo , Linfócitos B/imunologia , Linfócitos B/metabolismo , Proteína Básica da Mielina/imunologia , Proteína Básica da Mielina/metabolismo , Encéfalo/patologia , Encéfalo/imunologia , Encéfalo/metabolismo , Feminino , Encefalite/imunologia , Encefalite/etiologia , Encefalite/patologia , Encefalite/metabolismo , Adjuvante de Freund/imunologia , Doenças Neuroinflamatórias/imunologia , Doenças Neuroinflamatórias/etiologia , Doenças Neuroinflamatórias/patologiaRESUMO
The goal of this study conducted in Serbia was to detect HEV in pig liver samples from slaughterhouses, retail outlets, and environmental swabs over the course of a year. All positive HEV samples were measured and expressed as HEV gene copy numbers per gram of sample, and a representative number of samples were sequenced using the Sanger approach. A total of 45 HEV-positive samples were re-amplified using nested RT-PCR employing CODEHOP primers targeting ORF2 (493 nucleotides). The average prevalence of the HEV genotype 3 in all pig liver samples from the slaughterhouses was 29%, while HEV prevalence was 44% in liver samples from animals younger than 3 months. HEV RNA was found in thirteen out of sixty (22%) environmental swab samples that were taken from different surfaces along the slaughter line. Our findings confirmed seasonal patterns in HEV prevalence, with two picks (summer and winter periods) during the one-year examination. Among HEV-positive samples, the average viral particles for all positive liver samples was 4.41 ± 1.69 log10 genome copies per gram. Phylogenetic analysis revealed the majority of HEV strains (43/45) from Serbia were grouped in the HEV-3a subtype, while two strains were classified into the HEV-3c subtype, and one strain could not be classified into any of the HEV-3 subtypes.
RESUMO
Experimental autoimmune encephalomyelitis (EAE) induced in inbred rodents, i.e., genetically identical animals kept under identical environmental conditions, shows variable clinical outcomes. We investigated such variations of EAE in Dark Agouti rats immunized with spinal cord homogenate and identified four groups: lethal, severe, moderate, and mild, at day 28 post immunization. Higher numbers of CD4+ T cells, helper T cells type 1 (Th1) and 17 (Th17) in particular, were detected in the spinal cord of the severe group in comparison with the moderate group. In addition, increased proportion of Th1 and Th17 cells, and heightened levels of interferon (IFN)-γ and interleukin (IL)-6 were detected in the small intestine lamina propria of the severe group. A selective agonist of free fatty acid receptor type 2 (Ffar2) applied orally in the inductive phase of EAE shifted the distribution of the disease outcomes towards milder forms. This effect was paralleled with potentiation of intestinal innate lymphoid cells type 3 (ILC3) regulatory properties, and diminished Th1 and Th17 cell response in the lymph nodes draining the site of immunization. Our results suggest that different clinical outcomes in DA rats are under determinative influence of intestinal ILC3 activity during the inductive phase of EAE.
Assuntos
Encefalomielite Autoimune Experimental , Ratos , Animais , Camundongos , Encefalomielite Autoimune Experimental/induzido quimicamente , Encefalomielite Autoimune Experimental/prevenção & controle , Imunidade Inata , Medula Espinal/patologia , Microglia , Células Th17 , Células Th1 , Camundongos Endogâmicos C57BLRESUMO
Gallic acid is a phenolic acid present in various plants, nuts, and fruits. It is well known for its anti-oxidative and anti-inflammatory properties. The phenethyl ester of gallic acid (PEGA) was synthesized with the aim of increasing the bioavailability of gallic acid, and thus its pharmacological potential. Here, the effects of PEGA on encephalitogenic cells were examined, and PEGA was found to modulate the inflammatory activities of T cells and macrophages/microglia. Specifically, PEGA reduced the release of interleukin (IL)-17 and interferon (IFN)-γ from T cells, as well as NO, and IL-6 from macrophages/microglia. Importantly, PEGA ameliorated experimental autoimmune encephalomyelitis, an animal model of chronic inflammatory disease of the central nervous system (CNS)-multiple sclerosis. Thus, PEGA is a potent anti-inflammatory compound with a perspective to be further explored in the context of CNS autoimmunity and other chronic inflammatory disorders.
Assuntos
Encefalomielite Autoimune Experimental , Animais , Camundongos , Encefalomielite Autoimune Experimental/tratamento farmacológico , Ácido Gálico/farmacologia , Ácido Gálico/uso terapêutico , Sistema Nervoso Central , Microglia , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Camundongos Endogâmicos C57BLRESUMO
Rosmarinic acid is a polyphenolic compound, abundantly present in herbs of the Lamiaceae family. The aim of the study was to evaluate the immunomodulatory properties of a recently developed phenethyl ester derivative of rosmarinic acid (PERA), with enhanced ability of diffusion through biological membranes, in an animal model of the central nervous system (CNS) autoimmunity. To this end, experimental autoimmune encephalomyelitis (EAE), an animal model of multiple sclerosis was used. Daily subcutaneous administration of PERA (30 mg/kg) from day 7 to day 22 after immunization successfully ameliorated EAE induced in Dark Agouti rats, shortening the disease duration and reducing maximal, cumulative and mean clinical score. PERA efficiently reduced production of major encephalitogenic cytokines, interferon (IFN)-γ and interleukin (IL)-17, in immune cells from the CNS or the lymph nodes draining the site of immunization of EAE rats, as well as in CD4+ T cells purified from the lymph nodes. Also, PERA inhibited NO production in the CNS and the lymph nodes, as well as in macrophages and microglial cells. Finally, microglial ability to produce pro-inflammatory cytokines IL-6, and tumor necrosis factor (TNF) were also reduced by PERA. Our results clearly imply that PERA possesses anti-encephalitogenic properties. Thus, further studies on the relevance of the observed effects for the therapy of multiple sclerosis are warranted.
Assuntos
Encefalomielite Autoimune Experimental , Esclerose Múltipla , Ratos , Animais , Camundongos , Ésteres/uso terapêutico , Citocinas , Modelos Animais de Doenças , Camundongos Endogâmicos C57BL , Ácido RosmarínicoRESUMO
A survey was undertaken to determine the overall prevalence of Yersinia enterocolitica in pigs of slaughter age and to characterize the isolates in relation to bio-serotype, the presence of virulence genes, genetic diversity, and antimicrobial resistance. Moreover, possible risk factors associated with Y. enterocolitica infection during the pre-harvested and harvested phase of pig production were studied. The overall Y. enterocolitica prevalence in the pigs was 10.4% (95% confidence interval, CI = 8.5-12.3%). The most common Y. enterocolitica bio-serotype was 4/O:3, accounting for 81.6% of investigated isolates. The pathogenicity of 63 Y. enterocolitica 4/O:3 isolates, originating from all infected farms, was confirmed by the presence of both the ail and ystA virulence-associated genes and the absence of ystB gene (100%). Characterization with PFGE of 63 confirmed Y. enterocolitica 4/O:3 isolates identified five different genotypes with shared identical genetic profiles (100% similarity) within each genotype. Isolates originating from farrow-to-finish farms were only resistant to ampicillin, while resistance to nalidixic acid, tetracycline, and chloramphenicol at fattening farms was also observed. Risk factors related to Y. enterocolitica pig infection include fattening farms (odds ratio, OR = 2.3, 95% CI = 1.4-3.8, P < 0.001), a 3-6 h lairage period (OR = 1.6, 95% CI = 1.0-2.6, P = 0.035) and winter season (OR = 3.8, 95% CI = 2.0-7.4, P < 0.001). In addition to the overall characterization of Y. enterocolitica isolates, identification of the main risks associated with infection allows better application of preventive measures to reduce the occurrence and distribution of Y. enterocolitica infection.
Assuntos
Doenças dos Suínos , Yersiniose , Yersinia enterocolitica , Suínos , Animais , Yersinia enterocolitica/genética , Yersiniose/epidemiologia , Yersiniose/veterinária , Sérvia , Doenças dos Suínos/epidemiologia , Tonsila Palatina , Fatores de RiscoRESUMO
The incidence of multiple sclerosis (MS) and susceptibility of animals to experimental autoimmune encephalomyelitis (EAE), the most commonly used experimental model of MS, decrease with aging. Generally, autoimmune diseases develop as the ultimate outcome of an imbalance between damaging immune responses against self and regulatory immune responses (keeping the former under control). Thus, in this review the age-related changes possibly underlying this balance were discussed. Specifically, considering the central role of T cells in MS/EAE, the impact of aging on overall functional capacity (reflecting both overall count and individual functional cell properties) of self-reactive conventional T cells (Tcons) and FoxP3+ regulatory T cells (Tregs), as the most potent immunoregulatory/suppressive cells, was analyzed, as well. The analysis encompasses three distinct compartments: thymus (the primary lymphoid organ responsible for the elimination of self-reactive T cells - negative selection and the generation of Tregs, compensating for imperfections of the negative selection), peripheral blood/lymphoid tissues ("afferent" compartment), and brain/spinal cord tissues ("target" compartment). Given that the incidence of MS and susceptibility of animals to EAE are greater in women/females than in age-matched men/males, sex as independent variable was also considered. In conclusion, with aging, sex-specific alterations in the balance of self-reactive Tcons/Tregs are likely to occur not only in the thymus/"afferent" compartment, but also in the "target" compartment, reflecting multifaceted changes in both T-cell types. Their in depth understanding is important not only for envisaging effects of aging, but also for designing interventions to slow-down aging without any adverse effect on incidence of autoimmune diseases.
Assuntos
Envelhecimento/imunologia , Encefalomielite Autoimune Experimental/imunologia , Esclerose Múltipla/imunologia , Subpopulações de Linfócitos T/imunologia , Linfócitos T Reguladores/imunologia , Fatores Etários , Idoso , Animais , Suscetibilidade a Doenças/imunologia , Encefalomielite Autoimune Experimental/epidemiologia , Encefalomielite Autoimune Experimental/patologia , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Esclerose Múltipla/epidemiologia , Esclerose Múltipla/patologia , Prevalência , Ratos , Fatores de Risco , Fatores Sexuais , Subpopulações de Linfócitos T/metabolismo , Linfócitos T Reguladores/metabolismo , Timo/crescimento & desenvolvimento , Timo/imunologiaRESUMO
Gut immune cells have been increasingly appreciated as important players in the central nervous system (CNS) autoimmunity in animal models of multiple sclerosis (MS). Among the gut immune cells, innate lymphoid cell type 3 (ILC3) is of special interest in MS research, as they represent the innate cell counterpart of the major pathogenic cell population in MS, i.e. T helper (Th)17 cells. Importantly, these cells have been shown to stimulate regulatory T cells (Treg) and to counteract pathogenic Th17 cells in animal models of autoimmune diseases. Besides, they are also well known for their ability to stabilize the intestinal barrier and to shape the immune response to the gut microbiota. Thus, proper maintenance of the intestinal barrier and the establishment of the regulatory milieu in the gut performed by ILC3 may prevent activation of CNS antigen-specific Th17 cells by the molecular mimicry. Recent findings on the role of ILC3 in the gut-CNS axis and their relevance for MS pathogenesis will be discussed in this paper. Possibilities of ILC3 functional modulation for the benefit of MS patients will be addressed, as well.
Assuntos
Encéfalo/metabolismo , Trato Gastrointestinal/metabolismo , Imunidade Inata , Subpopulações de Linfócitos/imunologia , Subpopulações de Linfócitos/metabolismo , Esclerose Múltipla/etiologia , Esclerose Múltipla/metabolismo , Animais , Autoimunidade , Biomarcadores , Encéfalo/imunologia , Comunicação Celular/imunologia , Gerenciamento Clínico , Suscetibilidade a Doenças , Retroalimentação Fisiológica , Trato Gastrointestinal/imunologia , Humanos , Sistema Imunitário/imunologia , Sistema Imunitário/metabolismo , Imunomodulação , Esclerose Múltipla/patologia , Esclerose Múltipla/terapiaRESUMO
Experimental autoimmune encephalomyelitis (EAE) is classically induced with complete Freund's adjuvant (CFA). The immune response against CFA has a confounding influence on the translational capacity of EAE as a multiple sclerosis model. Here, we compare clinical, cellular and molecular properties between syngeneic spinal cord homogenate (SCH)- and SCH + CFA-immunized Dark Agouti rats. EAE signs were observed earlier and the cumulative clinical score was higher without CFA. Also, a higher number of immune cells infiltrates in the spinal cords was noticed at the peak of EAE without CFA. High spinal cord abundance of CD8+CD11bc+MHC class II+ cells was detected in SCH-immunized rats. Myelin basic protein -specific response can be elicited in the cells from the lymph nodes draining the site of SCH immunization. This CFA-free EAE is a reliable multiple sclerosis model.
Assuntos
Encefalomielite Autoimune Experimental/imunologia , Encefalomielite Autoimune Experimental/patologia , Imunização/métodos , Animais , Feminino , Adjuvante de Freund , Masculino , Ratos , Medula Espinal/imunologiaRESUMO
The development of collagen type II (CII)-induced arthritis (CIA), a model of rheumatoid arthritis, in rats housed in cages with bedding composed of Celliant fibres containing ceramic particles, which absorb body heat and re-emit the energy back to the body in the form of infrared radiation (+IRF rats), and those housed in cages with standard wooden shaving bedding (-IRF control rats) was examined. The appearance of the first signs of CIA was postponed, while the disease was milder (judging by the arthritic score, paw volume, and burrowing behaviour) in +IRF compared with -IRF rats. This correlated with a lower magnitude of serum anti-CII IgG antibody levels in +IRF rats, and lower production level of IL-17, the Th17 signature cytokine, in cultures of their paws. This could be partly ascribed to impaired migration of antigen-loaded CD11b + dendritic cells and their positioning within lymph nodes in +IRF rats reflecting diminished lymph node expression of CCL19 /CCL21. Additionally, as confirmed in rats with carrageenan-induced paw inflammation (CIPI), the infrared radiation from Celliant fibres, independently from immunomodulatory effects, exerted anti-inflammatory effects (judging by a shift in pro-inflammatory mediator to anti-inflammatory/immunoregulatory mediator ratio towards the latter in paw cultures) and ameliorated burrowing behaviour in CIA rats.
Assuntos
Artrite Experimental/imunologia , Artrite Reumatoide/imunologia , Autoimunidade/efeitos da radiação , Roupas de Cama, Mesa e Banho/veterinária , Raios Infravermelhos/uso terapêutico , Animais , Artrite Experimental/diagnóstico , Artrite Experimental/radioterapia , Artrite Reumatoide/diagnóstico , Artrite Reumatoide/radioterapia , Carragenina/administração & dosagem , Carragenina/imunologia , Colágeno Tipo II/administração & dosagem , Colágeno Tipo II/imunologia , Abrigo para Animais , Humanos , Masculino , Ratos , Índice de Gravidade de DoençaRESUMO
Sremski kulen is a wide diameter dry fermented sausage, produced from pork, seasoned with red spicy paprika, stuffed into pork cecum, and preserved by smoking, fermentation and drying. Due to specific ripening process, Sremski kulen is suitable for the accumulation of biogenic amines. Therefore, the aminogenesis was studied in traditionally produced Sremski kulen, taking into account the physicochemical parameters and microbial counts. The content of six biogenic amines (tryptamine, phenylethylamine, tyramine, histamine, putrescine, and cadaverine) was analyzed using high-performance liquid chromatography. The ripening process of Sremski kulen was slow followed by changes in aw and pH value as well as expressed proteolysis. The autochthonous microbiota showed pronounced decarboxylase activity. Tryptamine and phenylethylamine were detected at each examined ripening stage while histamine was not detected until the end of ripening (16.55 ± 2.33 mg/kg). Tyramine, cadaverine, and putrescine content significantly increased during the ripening period (p < .05). In the final product, cadaverine was the dominant biogenic amine (132.40 ± 5.05 mg/kg), followed by tyramine (115.80 ± 15.46 mg/kg) and putrescine (68.55 ± 2.39 mg/kg). Although the long ripening period greatly contributed to the accumulation of biogenic amines in final product, their content are not of concern from product safety aspects, but requires improvement in hygiene of production process.
Assuntos
Aminas Biogênicas/análise , Fermentação , Análise de Alimentos/métodos , Manipulação de Alimentos/métodos , Conservação de Alimentos/métodos , Qualidade dos Alimentos , Produtos da Carne/análise , Carne de Porco , Animais , Cadaverina/análise , Fenômenos Químicos , Cromatografia Líquida de Alta Pressão , Microbiologia de Alimentos , Inocuidade dos Alimentos , Concentração de Íons de Hidrogênio , Produtos da Carne/microbiologia , Proteólise , Putrescina/análise , Suínos , Tiramina/análiseRESUMO
Monocytes' plasticity has an important role in the development of rheumatoid arthritis (RA), an autoimmune disease exhibiting greater prevalence in women. Contribution of this phenomenon to sex bias in RA severity was investigated in rat collagen-induced arthritis (CIA) model of RA. The greater severity of CIA in females (exhibiting signs of bone resorption) was accompanied by the higher blood level of advanced oxidation protein products and a more pro-oxidant profile. Consistently, in females, the greater density of giant multinuclear cells (monocytes/macrophages and osteoclasts) in inflamed joint tissue was found. This correlated with the higher frequencies of CCR2- and CX3CR1- expressing cells (precursors of inflammatory monocytes/macrophages and osteoclasts) among CD11b+ splenocytes. This in conjunction with the enhanced migratory capacity of CD11b+ monocytic cells in females compared with males could be linked with the higher frequencies of CCR2+CX3CR1-CD43lowCD11b+ and CCR2-CX3CR1+CD43hiCD11b+ cells (corresponding to "classical" and "non-classical" monocytes, respectively) and the greater density of CD68+ cells (monocytes/macrophages and osteoclast precursors/osteoclasts) in blood and inflamed paws from female rats, respectively. Consistently, the higher levels of GM-CSF, TNF-α and IL-6, IL-1ß (driving Th17 cell differentiation), and IL-17 followed by the lower level of IL-10 were measured in inflamed paw cultures from female compared with male rats. To the greater IL-17 production (associated with enhanced monocyte immigration and differentiation into osteoclasts) most likely contributed augmented Th17 cell generation in the lymph nodes draining arthritic joints from female compared with male rats. Overall, the study suggests the sex-specific contribution of monocytic lineage cells to CIA, and possibly RA development.
Assuntos
Artrite Experimental/metabolismo , Linhagem da Célula , Colágeno/efeitos adversos , Monócitos/metabolismo , Animais , Antioxidantes/metabolismo , Artrite Experimental/induzido quimicamente , Adesão Celular , Diferenciação Celular , Modelos Animais de Doenças , Feminino , Inflamação , Macrófagos/metabolismo , Masculino , Osteoclastos/metabolismo , Oxidantes/metabolismo , Fagocitose , Ratos , Fatores Sexuais , EspectrofotometriaRESUMO
This study assessed the effects of season on health, behaviour, physiological stress parameters, and carcass and meat quality in a total of 480 slaughter pigs. The following health indicators were recorded: pneumonia, pleurisy, milk spots, and pericarditis. Behaviour was monitored during unloading (slipping, falling, turning back, reluctance to move, panting, shivering) and lairaging (panting, shivering, huddling). Blood lactate and glucose concentrations were determined at exsanguination. Performance indices (live weight, daily weight gain), carcass (carcass weight, backfat and loin thickness, lean meat content, carcass lesion score), and meat quality (pH, temperature, drip, thawing and cooking losses, colour, marbling) traits were measured postmortem. Pigs slaughtered in winter had the highest live weight, carcass weight, loin thickness, and carcass lesion score, while the lowest live weight, carcass weight, and backfat thickness were recorded in pigs slaughtered in summer. The highest lactate and glucose concentrations were recorded in pigs slaughtered in summer. The highest prevalence of red, soft, and exudative meat was recorded in pigs slaughtered in winter. Pigs slaughtered in summer had the lowest pH, the highest thawing loss, L* value, b* value, and occurrence of pale, soft, and exudative meat. Pigs slaughtered in autumn had the lowest drip loss, cooking loss, L* value, b* value, and the greatest percentage of red, firm, and nonexudative meat. In conclusion, the summer and winter temperatures compromised health and welfare and reduced carcass and meat quality in slaughter pigs, indicating that protection against heat and cold stress is not yet effective.
Assuntos
Carne , Estresse Fisiológico , Animais , Cor , Estações do Ano , Suínos , TemperaturaRESUMO
This study assessed the potential use of various physiological stress biomarkers as indicators of carcass and meat quality traits in 240 pigs subjected to the standard marketing conditions and minimal stressful antemortem handling using Pearson correlations. The most important pork quality traits (pH and temperature, water holding capacity, and color) had limited correlations with stress metabolites (lactate, glucose), stress hormones (cortisol, adrenocorticotropic hormone), stress enzymes (creatine kinase, aspartate amino transferase, alanine amino transferase), electrolytes (sodium, chloride), and acute-phase proteins (haptoglobin, C-reactive protein, albumin), indicating poor reliability in predicting pork quality. Albumin level was moderately positively correlated with live weight, hot carcass weight, cold carcass weight, and back fat thickness. Alanine amino transferase level was moderately positively correlated with live weight, hot carcass weight, and cold carcass weight. Cortisol level was moderately positively correlated with live weight, hot carcass weight, cold carcass weight, and back fat thickness, and moderately negatively correlated with the lean carcass content. Increased lactate dehydrogenase level was moderately correlated with decreased drip and cooking loss. In conclusion, lactate dehydrogenase could help pork producers predict pork quality variation, while cortisol, alanine amino transferase, and albumin could be useful in prediction of carcass quality.
RESUMO
The study examined germinal centre (GC) reaction in lymph nodes draining inflamed joints and adjacent tissues (dLNs) in male and female Dark Agouti rat collagen type II (CII)-induced arthritis (CIA) model of rheumatoid arthritis. Female rats exhibiting the greater susceptibility to CIA mounted stronger serum CII-specific IgG response than their male counterparts. This correlated with the higher frequency of GC B cells in female compared with male dLNs. Consistently, the frequency of activated/proliferating Ki-67+ cells among dLN B cells was higher in females than in males. This correlated with the shift in dLN T follicular regulatory (Tfr)/T follicular helper (Tfh) cell ratio towards Tfh cells in females, and greater densities of CD40L and CD40 on their dLN T and B cells, respectively. The higher Tfh cell frequency in females was consistent with the greater dLN expression of mRNA for IL-21/27, the key cytokines involved in Tfh cell generation and their help to B cells. Additionally, in CII-stimulated female rat dLN cell cultures IFN-γ/IL-4 production ratio was shifted towards IFN-γ. Consistently, the serum IgG2a(b)/IgG1 CII-specific antibody ratio was shifted towards an IgG2a(b) response in females. Thus, targeting T-/B-cell interactions should be considered in putative further sex-based translational pharmacology research.
Assuntos
Artrite Experimental/patologia , Linfócitos B/metabolismo , Fatores Sexuais , Animais , Artrite Experimental/sangue , Artrite Experimental/metabolismo , Linfócitos B/imunologia , Células Cultivadas , Colágeno Tipo II/imunologia , Colágeno Tipo II/metabolismo , Citocinas/sangue , Citocinas/imunologia , Modelos Animais de Doenças , Feminino , Centro Germinativo/imunologia , Centro Germinativo/metabolismo , Linfonodos/metabolismo , Masculino , Ratos , Caracteres Sexuais , Linfócitos T Reguladores/imunologia , Células Th1/imunologia , Células Th1/metabolismo , Células Th17/imunologia , Células Th17/metabolismoRESUMO
The fatty acid (FA) profiles of lamb muscle and adipose tissue originating from ten different grazing areas in North Macedonia and an assessment of whether the meat origin could be distinguished on the basis of FA profile are presented. Muscle and adipose tissues of three-month-old male lambs (crossbreds of autochthonous Ovcepolian and Württemberg) reared on spring pastures were studied. Statistically significant differences in the individual FA contents, FA groups and FA ratios were observed between lamb tissues from the different geographic regions. Canonical discriminant analysis showed there was a significant linear divergence between tissues from almost all examined regions. The greatest weight in the differentiation of the different areas showed fatty acid ratios, C18:3n3, C18:1n9c and C20:5n3 for the muscle tissue, as well as C18:1n9c, C18:2n6c, C16:1 and C17:1 for the adipose tissue. This showed that the FA composition of muscle and adipose tissue obtained from lambs reared on pasture could serve as a useful indicator to aid differentiation of its geographic origin but it should be confirmed through further replicated studies.
Assuntos
Ácidos Graxos/análise , Carne Vermelha/análise , Carneiro Doméstico/fisiologia , Tecido Adiposo/química , Animais , Dieta/veterinária , Masculino , Músculos/química , República da Macedônia do NorteRESUMO
The aim of this study was to identify the prevalence of pathological lesions in pigs from small-scale farms and to determine associations between pathological lesions and hematological parameters, and carcass and meat quality in slaughtered pigs. The study was conducted on 625 pigs (~115 kg) originating from 20 small-scale farms. Any signs of pneumonia, pleurisy, pericarditis, and liver milk spots were recorded as present or absent. Complete blood count was investigated. The following carcass quality parameters were measured: live, hot and cold carcass weights, cooling loss, dressing percentage, backfat thickness, and meatiness. Meat pH and temperature were measured 45 min postmortem. Of the 625 examined pigs, 41.8% had pneumonia, 23.5% pleurisy, 2.7% pericarditis, and 29.9% liver milk spots. The presence of pathological lesions in slaughtered pigs adversely affected hematological parameters, reduced live, hot and cold carcass weights, and meatiness and had deleterious effects on meat quality (higher pH45min and higher prevalence of dark, firm and dry meat). In conclusion, this study showed a high prevalence of pathological lesions in slaughtered pigs, indicating serious health problems in smallholder pig production systems. The presence of single and, especially, multiple pathological lesions in slaughtered pigs negatively affected hematological parameters, and carcass and meat quality.