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OBJECTIVE: Chronic graft-versus-host disease (cGVHD) is a significant complication following allogenic hematopoietic stem cell transplantation, often necessitating therapeutic interventions such as rituximab (RTX) and cyclosporin A (CsA). This study aims to elucidate the mechanisms by which RTX and CsA jointly address B-cell dysregulation in cGVHD, providing a theoretical foundation and scientific rationale for the treatment and prognostic evaluation of this condition. METHODS: A total of 30 cGVHD mouse models were established by subjecting recipient mice to total body irradiation followed by injection of a mixed suspension of bone marrow cells and splenocytes from donor mice. From Day 2 to Day 29 post-model establishment, the mice received subcutaneous administration of RTX and CsA. Throughout the study, body weight, clinical cGVHD scores, and survival rates were monitored. Blood samples were collected via the orbital venous plexus. Serum levels of B-cell activating factor (BAFF) and pro-inflammatory factors were measured using enzyme-linked immunosorbent assay (ELISA), and the ratio of regulatory B cells (Bregs) in the blood sample was assessed via flow cytometry. RESULTS: Mice with cGVHD exhibited a 14.5% decrease in body weight, elevated clinical scores, and more severe symptoms compared to the control group. Notably, all mice in both the cGVHD and control groups survived until the conclusion of the study. Induction of cGVHD resulted in B-cell dysregulation, evidenced by elevated serum BAFF levels and a decreased proportion of Bregs. However, treatment with RTX combined with CsA ameliorated B-cell dysregulation and significantly reduced serum levels of pro-inflammatory factors in cGVHD mice, with decreases of 39.78% in TNF-α and 37.89% in IL-6. CONCLUSION: The combination of RTX and CsA effectively mitigates B-cell dysregulation in cGVHD, thereby reducing the severity and progression of the disease.
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Objective: Physalis Peruviana Linnaeus (PPL) is an herbaceous species characterized by a wide variety of bioactive compounds to which anti-inflammatory properties have been attributed. This makes this fruit a possible complementary therapy for diseases that involve chronic inflammation, such as inflammatory bowel diseases (IBD). In the present study, the effect of a PPL extract on the expression of inflammatory markers in the Caco-2 cell line was evaluated.Methods: An in vitro gastric digest (50 g PPL pulp) was performed, obtaining an extract that was used to challenge Caco-2 cells for 24 and 72 hours. This extract was characterized by LC-MS/MS. Then, the relative mRNA expression of NF-kB, TLR4, IL-18 and MCP-1 was determined through qRT-PCR and the protein levels of TNF-α, IL-6, IL-8, IL-18 and MCP-1 through Luminex Immunoassay.Results: From the characterization of the extract, compounds with bioactive potential such as isothiocyanates, indoles and coumarins were found. Treatment of Caco-2 cells with PPL extract (80 µg/ml), particularly for 72 hours, produced a reduction of IL-18 and MCP-1 mRNA expression (p < 0.01), in addition to IL-18 (p < 0.01), IL-8 (p < 0.0001) and MCP-1 (p < 0.01) protein levels, however, no effects on NF-kB p65 (p = 0.09) and TLR4 (p = 0.20) mRNA expression were observed.Conclusion: The results obtained in this study open the possibility that the regular consumption of 50 g of PPL could constitute a possible complementary therapy for the treatment of IBD, improving the quality of life of these patients.
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Resumen La astrocitopatía autoinmune asociada a proteína ácida fibrilar glial (GFAP) fue descripta por primera vez en el año 2016. La manifestación clínica más frecuente es la meningoencefalomielitis asociado a un patrón imagenológico característico que permite la sospecha diagnóstica y su confirmación mediante la determina ción de los anticuerpos en suero y en líquido cefalorra quídeo (LCR). Presentamos el caso de una paciente de 35 años con compromiso del sistema nervioso a nivel central y periférico y un reciente diagnóstico de cáncer de tiroides, que frente al cuadro clínico compatible de meningoencefalomielitis, los hallazgos característicos en resonancia magnética y luego de la exclusión de enfermedades alternativas, finalmente se arribó al diag nóstico por la determinación positiva de anti GFAP en LCR. Realizó tratamiento quirúrgico y con iodo radio activo por su tumor hallado y posteriormente recibió tratamiento con corticoides con mejoría parcial de la signo-sintomatología neurológica. Destacamos que en esta enfermedad las imágenes por resonancia magnética presentan un patrón característico, aunque no patog nomónico, siendo necesario considerar otras causas. Ante una alta sospecha de esta entidad por el cuadro clínico e imagenológico, es conveniente realizar dosaje del anticuerpo en LCR, dada la mayor sensibilidad y especificidad en comparación con su pesquisa en suero, con el fin de arribar al diagnóstico etiológico definitivo como en el caso clínico presentado.
Abstract Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy was described for the first time in 2016. The most common clinical manifestation is menin goencephalomyelitis associated with a characteristic imaging pattern that allows diagnostic suspicion and its confirmation through determination of antibodies in serum and cerebrospinal fluid (CSF). We present a case of a 35-year-old patient with involvement of the central and peripheral nervous system and a recent diagnosis of thyroid cancer, which compared to the compatible clinical picture of meningoencephalomyelitis, characteristic findings on MRI and after the exclusion of alternative pathologies, we finally arrived at the diagnosis by the positive determination of anti-GFAP in CSF. The patient underwent surgical treatment and radioactive iodine for the diagnosed thyroid tumor and she subsequently received treatment with corticosteroids with partial improvement of the neurological symptomatology. We emphasize that in this pathology the MRI images usually depict a characteristic pattern, although not pathogno monic, it is necessary to consider other causes. Before a high suspicion of this entity due to the clinical and imaging picture, it is convenient to measure the anti body in CSF, given the greater sensitivity and specificity compared to its serum screening, in order to arrive to the definitive etiological diagnosis as it was done in the clinical case that is presented.
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Resolvin D5 (RvD5) is a lipid mediator that has been reported to present anti-inflammatory and pro-resolution properties. Evidence also supports its capability to enhance reactive oxygen species (ROS) production during bacterial infections, which would be detrimental in diseases driven by ROS. The biological activity of RvD5 and mechanisms against UVB irradiation skin pathology have not been investigated so far. Female hairless mice were treated intraperitoneally with RvD5 before UVB stimulus. RvD5 reduced skin edema in a dose-dependent manner as well as oxidative stress by increasing antioxidants (endogenous tissue antioxidant scavenging of cationic radical, iron reduction, catalase activity and reduced glutathione levels) and decreasing pro-oxidants (superoxide anion and lipid peroxidation). RvD5 antioxidant activity was accompanied by enhancement of Nrf2, HO-1 and NQO1 mRNA expression. RvD5 reduced the production of IL-1ß, TNF-α, TGF-ß, and IL-10. RvD5 also reduced the inflammatory cell counts, including mast cells and neutrophils/macrophages. The reduction of oxidative stress and inflammation resulted in diminished matrix metalloproteinase 9 activity, collagen degradation, epidermal thickening and sunburn cell development. Therefore, this study demonstrates, to our knowledge, the first body of evidence that RvD5 can be used to treat UVB skin pathology and unveils, at least in part, its mechanisms of action.
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INTRODUCTION: Influenza A is a virus from the Orthomixoviridae family responsible for high lethality rates and morbidity, despite clinically proven vaccination strategies and some anti-viral therapies. The eicosanoid Lipoxin A4 (LXA4) promotes the resolution of inflammation by decreasing cell recruitment and pro-inflammatory cytokines release, but also for inducing activation of apoptosis, efferocytosis, and macrophage reprogramming. OBJECTIVE: Here, we evaluated whether a synthetic lipoxin mimetic, designated AT-01-KG, would improve the course of influenza A infection in a murine model. METHOD: Mice were infected with influenza A/H1N1 and treated with AT-01-KG (1.7 µg/kg/day, i.p.) at day 3 post-infection. RESULTS: AT-01-KG attenuated mortality, reducing leukocyte infiltration and lung damage at day 5 and day 7 post-infection. AT-01-KG is a Formyl Peptide Receptor 2 (designated FPR2/3 in mice) agonist, and the protective responses were not observed in fpr2/3 -/- animals. In mice treated with LXA4 (50 µg/kg/day, i.p., days 3-6 post-infection), at day 7, macrophage reprogramming was observed, as seen by a decrease in classically activated macrophages and an increase in alternatively activated macrophages in the lungs. Furthermore, the number of apoptotic cells and cells undergoing efferocytosis was increased in the lavage of treated mice. Treatment also modulated the adaptive immune response, increasing the number of T helper 2 cells (Th2) and regulatory T (Tregs) cells in the lungs of the treated mice. CONCLUSION: Therefore, treatment with a lipoxin A4 analog was beneficial in a model of influenza A infection in mice. The drug decreased inflammation and promoted resolution and beneficial immune responses, suggesting it may be useful in patients with severe influenza.
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Pereskia aculeata has been widely investigated due to its anti-inflammatory potential. Among the metabolites found in this species are the phytosterols beta-sitosterol (ß-SIT) and stigmasterol (STIG). The objective of the study was to evaluate the anti-inflammatory and toxicity activities of the hexane partition of P. aculeata (PHEX), as well as ß-SIT and STIG. PHEX was prepared and the phytosterols were quantified. In terms of toxicity against L929 fibroblast cells, PHEX showed toxicity up to 200â µg/mL; STIG and ß-SIT showed toxicity up to 25â µg/mL. PHEX inhibited 66 % of nitric oxide radicals, while STIG and ß-SIT inhibited 33.73 % and 34.94 %, respectively. In an anti-inflammatory test against Zophobas morio larvae, all samples significantly reduced hemocyte levels. Additionally, the LD50 values were calculated: 229.6â mg/kg for PHEX, 101.5â mg/kg for STIG, and 103.8â mg/kg for ß-SIT. In conclusion, the study indicates that the phytosterols present in PHEX may contribute to its anti-inflammatory activity.
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Anti-Inflamatórios , Larva , Óxido Nítrico , Estigmasterol , Animais , Larva/efeitos dos fármacos , Camundongos , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/química , Anti-Inflamatórios/isolamento & purificação , Estigmasterol/farmacologia , Estigmasterol/química , Estigmasterol/isolamento & purificação , Óxido Nítrico/metabolismo , Óxido Nítrico/antagonistas & inibidores , Sitosteroides/farmacologia , Sitosteroides/química , Linhagem Celular , Fitosteróis/farmacologia , Fitosteróis/química , Sobrevivência Celular/efeitos dos fármacos , Relação Dose-Resposta a Droga , Extratos Vegetais/química , Extratos Vegetais/farmacologia , Extratos Vegetais/isolamento & purificaçãoRESUMO
Interferons (IFNs) are a family of cytokines that activate the JAK-STAT signaling pathway to induce an antiviral state in cells. Interleukin 27 (IL-27) is a member of the IL-6 and/or IL-12 family that elicits both pro- and anti-inflammatory responses. Recent studies have reported that IL-27 also induces a robust antiviral response against diverse viruses, both in vitro and in vivo, suggesting that IFNs and IL-27 share many similarities at the functional level. However, it is still unknown how similar or different IFN- and IL-27-dependent signaling pathways are. To address this question, we conducted a comparative analysis of the transcriptomic profiles of human monocyte-derived macrophages (MDMs) exposed to IL-27 and those exposed to recombinant human IFN-α, IFN-γ, and IFN-λ. We utilized bioinformatics approaches to identify common differentially expressed genes between the different transcriptomes. To verify the accuracy of this approach, we used RT-qPCR, ELISA, flow cytometry, and microarrays data. We found that IFNs and IL-27 induce transcriptional changes in several genes, including those involved in JAK-STAT signaling, and induce shared pro-inflammatory and antiviral pathways in MDMs, leading to the common and unique expression of inflammatory factors and IFN-stimulated genes (ISGs)Importantly, the ability of IL-27 to induce those responses is independent of IFN induction and cellular lineage. Additionally, functional analysis demonstrated that like IFNs, IL-27-mediated response reduced chikungunya and dengue viruses replication in MDMs. In summary, IL-27 exhibits properties similar to those of all three types of human IFN, including the ability to stimulate a protective antiviral response. Given this similarity, we propose that IL-27 could be classified as a distinct type of IFN, possibly categorized as IFN-pi (IFN-π), the type V IFN (IFN-V).
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Febre de Chikungunya , Dengue , Interleucina-27 , Janus Quinases , Macrófagos , Transdução de Sinais , Humanos , Células Cultivadas , Febre de Chikungunya/imunologia , Febre de Chikungunya/virologia , Vírus Chikungunya/imunologia , Dengue/imunologia , Dengue/virologia , Vírus da Dengue/fisiologia , Vírus da Dengue/imunologia , Interferons/metabolismo , Interleucina-27/metabolismo , Interleucinas/imunologia , Interleucinas/farmacologia , Janus Quinases/metabolismo , Macrófagos/imunologia , Macrófagos/virologia , Transdução de Sinais/genética , Fatores de Transcrição STAT/metabolismo , Transcriptoma , Replicação ViralRESUMO
Protectin DX (PDX), a specialized pro-resolving lipid mediator, presents potential therapeutic applications across various medical conditions due to its anti-inflammatory and antioxidant properties. Since type-1 diabetes mellitus (T1DM) is a disease with an inflammatory and oxidative profile, exploring the use of PDX in addressing T1DM and its associated comorbidities, including diabetic neuropathic pain, depression, and anxiety becomes urgent. Thus, in the current study, after 2 weeks of T1DM induction with streptozotocin (60 mg/kg) in Wistar rats, PDX (1, 3, and 10 ng/animal; i.p. injection of 200 µl/animal) was administered specifically on days 14, 15, 18, 21, 24, and 27 after T1DM induction. We investigated the PDX's effectiveness in alleviating neuropathic pain (mechanical allodynia; experiment 1), anxiety-like and depressive-like behaviors (experiment 2). Also, we studied whether the PDX treatment would induce antioxidant effects in the blood plasma, hippocampus, and prefrontal cortex (experiment 3), brain areas involved in the modulation of emotions. For evaluating mechanical allodynia, animals were repeatedly submitted to the Von Frey test; while for studying anxiety-like responses, animals were submitted to the elevated plus maze (day 26) and open field (day 28) tests. To analyze depressive-like behaviors, the animals were tested in the modified forced swimming test (day 28) immediately after the open field test. Our data demonstrated that PDX consistently increased the mechanical threshold throughout the study at the two highest doses, indicative of antinociceptive effect. Concerning depressive-like and anxiety-like behavior, all PDX doses effectively prevented these behaviors when compared to vehicle-treated T1DM rats. The PDX treatment significantly protected against the increased oxidative stress parameters in blood plasma and in hippocampus and prefrontal cortex. Interestingly, treated animals presented improvement on diabetes-related parameters by promoting weight gain and reducing hyperglycemia in T1DM rats. These findings suggest that PDX improved diabetic neuropathic pain, and induced antidepressant-like and anxiolytic-like effects, in addition to improving parameters related to the diabetic condition. It is worth noting that PDX also presented a protective action demonstrated by its antioxidant effects. To conclude, our findings suggest PDX treatment may be a promising candidate for improving the diabetic condition per se along with highly disabling comorbidities such as diabetic neuropathic pain and emotional disturbances associated with T1DM.
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Ansiedade , Diabetes Mellitus Experimental , Diabetes Mellitus Tipo 1 , Ácidos Docosa-Hexaenoicos , Ratos Wistar , Animais , Masculino , Diabetes Mellitus Experimental/complicações , Diabetes Mellitus Experimental/tratamento farmacológico , Diabetes Mellitus Experimental/psicologia , Ratos , Diabetes Mellitus Tipo 1/tratamento farmacológico , Diabetes Mellitus Tipo 1/complicações , Diabetes Mellitus Tipo 1/psicologia , Ácidos Docosa-Hexaenoicos/farmacologia , Ácidos Docosa-Hexaenoicos/uso terapêutico , Ansiedade/tratamento farmacológico , Ansiedade/etiologia , Depressão/tratamento farmacológico , Depressão/etiologia , Antioxidantes/farmacologia , Antioxidantes/uso terapêutico , Hiperalgesia/tratamento farmacológico , Comportamento Animal/efeitos dos fármacos , Hipocampo/efeitos dos fármacos , Hipocampo/metabolismo , Córtex Pré-Frontal/efeitos dos fármacos , Neuropatias Diabéticas/tratamento farmacológicoRESUMO
Resumen (analítico) En Colombia no existen estudios consolidados que muestren la existencia de conductas prosociales y menos indicadores que reflejen cómo estas conductas pueden influir en la reducción de los comportamientos agresivos. Lo que sí se sabe por estudios previos es que las conductas de naturaleza altruista parecen incompatibles con la agresividad. El artículo recoge los resultados de una investigación que describe las conductas prosociales de los niños de este contexto. El estudio de tipo transversal se realizó con 587 niños entre los 9 y 12 años. Los resultados evidencian niveles elevados de prosocialidad y diferencias significativas a favor de las niñas en casi todas las dimensiones evaluadas. Con la presencia de estos comportamientos se puede inferir que la prosocialidad representa un activo muy importante para prevenir manifestaciones agresivas en las escuelas.
Abstract (analytical) In Colombia there are no consolidated studies that evidence the existence of prosocial behavior. There are very few indicators that measure how these behaviors can help reduce levels of aggression and violence. What is known from previous studies is that altruistic behaviors seem incompatible with aggression. This article summarizes the results of an investigation that describes the prosocial behaviors of children in the Colombian context. A cross-sectional study was carried out with 587 children between 9 and 12 years of age. The results show high levels of prosocial behavior among girls and significant differences among members of this gender group in almost all of the dimensions that were evaluated. Based on these results, it can be inferred that prosocial behavior represents a very important asset that helps prevent acts of aggression in schools.
Resumo (analítico) Na Colômbia, não existem estudos consolidados que mostrem a existência de comportamentos pró-sociais e poucos indicadores que reflitam como esses comportamentos podem influenciar na redução de comportamentos agressivos. O que se sabe de estudos anteriores é que comportamentos de natureza altruísta parecem incompatíveis com a agressividade. O artigo recolhe os resultados de uma investigação que descreve os comportamentos pró-sociais de crianças neste contexto. O estudo transversal foi realizado com 587 crianças entre 9 e 12 anos de idade. Os resultados mostram altos níveis de pró-socialidade e diferenças significativas a favor das meninas em quase todas as dimensões avaliadas. Com a presença desses comportamentos, pode-se inferir que a pró-socialidade representa um recurso muito importante para prevenir manifestações agressivas nas escolas.
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BACKGROUND: Preterm birth accounts for 60% to 80% of neonatal mortality. Approximately one-third of preterm births are caused by the spontaneous onset of preterm labor. Nevertheless, 70% to 90% of women diagnosed with preterm labor will not deliver within 7 days. Thus, many women will be unnecessarily treated by preterm labor with risk medications. Better tools are needed to categorize women in preterm labor into high or low risk of preterm delivery. OBJECTIVE: This study aimed to evaluate the amino-terminal pro-brain natriuretic peptide concentration in the amniotic fluid as a prognostic test to predict the risk of delivery within 48 hours or 7 days and before 34 0/7 or 37 0/7 weeks of gestation in women in preterm labor. STUDY DESIGN: A total of 102 pregnant women presenting signs and symptoms of spontaneous preterm birth (22 0/7 to 34 0/7 weeks of gestation) were included. Amniotic fluid was obtained by amniocentesis, and amino-terminal pro-brain natriuretic peptide concentration was measured. Below normal concentration was defined as <0.5 multiples of the median of the standard curve according to gestational age. The risk of preterm delivery was estimated according to normal or lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations. The predictive capacity of the test (below normal amino-terminal pro-brain natriuretic peptide concentration) was evaluated to identify spontaneous preterm birth at 48 hours or 7 days from amniocentesis and less than 34 0/7 or 37 0/7 weeks at delivery. RESULTS: For the outcome delivery within 48 hours, lower-than-normal amino-terminal pro-brain natriuretic peptide concentration had 94.6% sensitivity, 73.8% specificity, 96.0% negative predictive value, 3.61 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcome delivery within 7 days, the test had 93.9% sensitivity, 88.7% specificity, 94.0% negative predictive value, 8.31 positive likelihood ratio, and 0.07 negative likelihood ratio. For the outcomes of spontaneous preterm birth before 34 0/7 and 37 0/7 weeks of gestation, below normal amino-terminal pro-brain natriuretic peptide concentrations had 80.0% sensitivity, 83.0% specificity, 78.0% negative predictive value, 4.70 positive likelihood ratio, and 0.24 negative likelihood ratio and 64.1% sensitivity, 91.7% specificity, 44.0% negative predictive value, 7.70 positive likelihood ratio, and 0.39 negative likelihood ratio, respectively. CONCLUSION: Among patients in spontaneous preterm labor, the detection of lower-than-normal amino-terminal pro-brain natriuretic peptide concentrations (<0.5 multiples of the median) in amniotic fluid has an excellent predictive capacity to identify those patients at low risk of preterm delivery within 48 hours or 7 days.
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BACKGROUND: The nasal vaccine HB-ATV-8 has emerged as a promising approach for NAFLD (non-alcoholic fatty liver disease) and atherosclerosis prevention. HB-ATV-8 contains peptide seq-1 derived from the carboxy-end of the Cholesteryl Ester Transfer Protein (CETP), shown to reduce liver fibrosis, inflammation, and atherosclerotic plaque formation in animal models. Beyond the fact that this vaccine induces B-cell lymphocytes to code for antibodies against the seq-1 sequence, inhibiting CETP's cholesterol transfer activity, we have hypothesized that beyond the modulation of CETP activity carried out by neutralizing antibodies, the observed molecular effects may also correspond to the direct action of peptide seq-1 on diverse cellular systems and molecular features involved in the development of liver fibrosis. METHODS: The HepG2 hepatoma-derived cell line was employed to establish an in vitro steatosis model. To obtain a conditioned cell medium to be used with hepatic stellate cell (HSC) cultures, HepG2 cells were exposed to fatty acids or fatty acids plus peptide seq-1, and the culture medium was collected. Gene regulation of COL1A1, ACTA2, TGF-ß, and the expression of proteins COL1A1, MMP-2, and TIMP-2 were studied. AIM: To establish an in vitro steatosis model employing HepG2 cells that mimics molecular processes observed in vivo during the onset of liver fibrosis. To evaluate the effect of peptide Seq-1 on lipid accumulation and pro-fibrotic responses. To study the effect of Seq-1-treated steatotic HepG2 cell supernatants on lipid accumulation, oxidative stress, and pro-fibrotic responses in HSC. RESULTS AND CONCLUSION: Peptide seq-1-treated HepG2 cells show a downregulation of COLIA1, ACTA2, and TGF-ß genes, and a decreased expression of proteins such as COL1A1, MMP-2, and TIMP-2, associated with the remodeling of extracellular matrix components. The same results are observed when HSCs are incubated with peptide Seq-1-treated steatotic HepG2 cell supernatants. The present study consolidates the nasal vaccine HB-ATV-8 as a new prospect in the treatment of NASH directly associated with the development of cardiovascular disease.
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Hepatopatia Gordurosa não Alcoólica , Vacinas , Animais , Inibidor Tecidual de Metaloproteinase-2/metabolismo , Inibidor Tecidual de Metaloproteinase-2/farmacologia , Metaloproteinase 2 da Matriz , Proteínas de Transferência de Ésteres de Colesterol/metabolismo , Regulação para Baixo , Hepatócitos/metabolismo , Fibrose , Cirrose Hepática/patologia , Hepatopatia Gordurosa não Alcoólica/genética , Hepatopatia Gordurosa não Alcoólica/prevenção & controle , Fator de Crescimento Transformador beta/metabolismo , Fator de Crescimento Transformador beta/farmacologia , Ácidos Graxos/metabolismo , Lipídeos/farmacologia , Fígado/metabolismoRESUMO
Introducción: la violencia no es un subproducto inherente de las relaciones humanas, pero los con-flictos sí lo son. En este artículo se examinan los factores y circunstancias que conducen a la tensión y los conflictos entre las personas que buscan atención médica y los establecimientos médicos nepalíes y los miembros del personal que trabajan allí. Desarrollo: embebido con una revisión de la literatura relevante, a través del análisis de datos etnográficos generada a partir de la investigación de campo y el análisis de contenido de la representación de noticias seleccionada, el artículo se desarrolla en cuatro secciones diferentes. La primera parte trata sobre el contexto de las consultas médicas que resultan en el desarrollo de una relación problemática. A esto le sigue el examen de los diferentes tipos de violencia, enfrentamientos y protestas que surgen a través de tales relaciones. En la tercera parte se analizan las implicaciones de las crecientes promesas médicas y el consiguiente aumento de las expectativas, mien-tras que la última parte destaca cómo las prácticas médicas típicas que existen en los propios hospitales nepaleses aumentan la posibilidad de enfrentamientos y violencia. Conclusión: la frecuente ocurrencia de peleas y violencia médica tanto en hospitales públicos como privados en Nepal sugiere que hay una bre-cha de comunicación entre los proveedores de servicios y el paciente debido a la naturaleza esotérica de la medicina. El conflicto y la violencia hacia los proveedores de servicios también pueden prosperar en el contexto de un modelo explicativo diferencial de las dos partes. La creciente animosidad también indica una disminución de la confianza entre los proveedores de atención médica y los solicitantes en Nepal
Introduction: Violence is not an inherent by-product of human relationships, but conflicts are. This arti-cle examines the factors and circumstances that lead to tension and conflicts between health seekers, and their counterpart Nepali medical establishments, and their staff members. Development: The article is divided into four sections by embedding a relevant literature review, analyzing ethnographic data generated from field research, and analyzing the content analysis of selected news portrayals. The first section discusses the context of the medical consultations that lead to the development of a problematic relationship. This is followed by examining the various types of violence, confrontations, and protests that arise from such relationships. The implications of rising medical promises and resulting height-ened expectations are discussed in the third section. The last section focuses on how common medical practices in Nepali hospitals increase the possibility of confrontations and violence. Conclusions: The prevalence of tussles and medical violence in Nepal's public and private hospitals suggests that they can occur in any hospital, regardless of ownership. Because of the esoteric nature of medicine, there is always a communication gap between service providers and patients. Conflict and violence against service providers can thrive in the context of a two-sided differential explanatory model. The growing hostility also indicates a decline in trust between healthcare providers and patients in Nepal
Introdução: a violência não é um subproduto inerente às relações humanas, mas o conflito é. Este artigo examina os fatores e circunstâncias que levam à tensão e ao conflito entre as pessoas que pro-curam cuidados médicos e os estabelecimentos médicos nepaleses e os funcionários que aí trabalham. Desenvolvimento: incorporada a uma revisão da literatura relevante, através da análise de dados etno-gráficos gerados a partir da pesquisa de campo e da análise de conteúdo da representação noticiosa selecionada, o artigo desenvolve-se em quatro seções distintas. A primeira parte trata do contexto das consultas médicas que resultam no desenvolvimento de uma relação problemática. Em seguida, exa-minamos os diferentes tipos de violência, confrontos e protestos que surgem através de tais relações. A parte três discute as implicações das crescentes promessas médicas e o consequente aumento das expectativas, enquanto a última parte destaca como as práticas médicas típicas que existem nos próprios hospitais nepaleses aumentam o potencial de confrontos e violência. Conclusão: a frequente ocorrência de brigas e violência médica em hospitais públicos e privados no Nepal sugere-nos que podem ocorrer em qualquer hospital, independentemente do proprietário. Sempre existe uma lacuna de comunicação entre os prestadores de serviços e o paciente devido à natureza esotérica da medicina. O conflito e a vio-lência contra os prestadores de serviços também podem florescer no contexto de um modelo explicativo diferencial das duas partes. A crescente animosidade também indica um declínio na confiança entre os prestadores de cuidados de saúde e os requerentes no Nepal
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Humanos , Violência , NepalRESUMO
Tritrichomonas foetus is a flagellated parasite that primarily infects the reproductive tissues of livestock, causing bovine trichomoniasis. The cytoplasmic membrane of T. foetus contains various compounds that contribute to adherence, colonization, and pathogenicity. Metronidazole (MTZ) is the main treatment for trichomoniasis, but the emergence of drug-resistant strains is a concern due to improper use and dosing. T. foetus infection induces inflammation, and macrophages are key players in the immune response. However, our understanding of the host's immune response to T. foetus is limited, and the specific mechanisms underlying these responses are not well understood. This study aimed to investigate the impact of T. foetus surface proteins from trophozoites cultured under different sublethal MTZ conditions (MTZ-treated T. foetus MPs) on macrophage activation. By analyzing cytokine levels and gene expression in murine macrophages, we demonstrated that MTZ-treated T. foetus MPs induce a specific proinflammatory response. MTZ-treated T. foetus MPs-exposed macrophages exhibited a higher NO and H2 O2 production and overexpression of iNOS and NOX-2 genes in comparison to untreated T. foetus. Additionally, MTZ-treated T. foetus MPs triggered a significant induction of the proinflammatory cytokines IL-1ß, IL-6, TNF-α, and IFN-γ, as well as the overexpression of the TLR4, MyD88, and NF-κB genes on murine macrophages. The study aimed to unravel the immunological response and potential proinflammatory pathways involved in T. foetus infection and MTZ stress. Understanding the immune responses and mechanisms through which T. foetus surface proteins activate macrophages can contribute to the development of new therapeutic strategies for controlling bovine trichomoniasis.
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Tricomoníase , Tritrichomonas foetus , Animais , Bovinos , Camundongos , Metronidazol/farmacologia , Citocinas , Macrófagos , Proteínas de MembranaRESUMO
Skeletal muscle tissue has the critical function of mechanical support protecting the body. In addition, its functions are strongly influenced by the balanced synthesis and degradation processes of structural and regulatory proteins. The inhibition of protein synthesis and/or the activation of catabolism generally determines a pathological state or condition called muscle atrophy, a reduction in muscle mass that results in partial or total loss of function. It has been established that many pathophysiological conditions can cause a decrease in muscle mass. Skeletal muscle innervation involves stable and functional neural interactions with muscles via neuromuscular junctions and is essential for maintaining normal muscle structure and function. Loss of motor innervation induces rapid skeletal muscle fiber degeneration with activation of atrophy-related signaling and subsequent disassembly of sarcomeres, altering normal muscle function. After denervation, an inflammation stage is characterized by the increased expression of pro-inflammatory cytokines that determine muscle atrophy. In this review, we highlighted the impact of some soluble factors on the development of muscle atrophy by denervation.
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Denervação Muscular , Atrofia Muscular , Humanos , Denervação Muscular/efeitos adversos , Atrofia Muscular/genética , Atrofia Muscular/metabolismo , Músculo Esquelético/metabolismo , Transdução de Sinais , Citocinas/metabolismoRESUMO
Diversos estudios han mostrado que existe una asociación entre el comportamiento prosocial y la habilidad empática. La forma más frecuente de evaluar ambos constructos es a través de escalas de autorreporte, siendo la Escala de Conducta Prosocial (ECP) y el Indice de Reactividad Interpersonal (IRI) las más utilizadas en población adulta. Hasta el momento, no hay reportes disponibles sobre la relación entre la empatía y la conducta prosocial en adultos de habla hispana evaluados con dichas escalas. Objetivo: Evaluar la conducta prosocial utilizando la ECP en personas adultas de habla hispana y analizar su interacción con la empatía evaluada con la escala IRI, así como también identificar su relación con otras variables de interés (edad, género y orden de presentación de las escalas durante la evaluación). Método: Se administró la ECP y el IRI a una muestra de 115 participantes, quienes fueron asignados de manera aleatoria a un orden específico de exposición a las escalas (IRI-ECP y ECP-IRI). Resultados: El rendimiento en la ECP mostró estar asociado a la edad y a la interacción entre el rendimiento en el IRI y el género, mientras que el orden de presentación de las escalas no mostró asociación con las puntuaciones. Conclusión: La empatía y variables sociodemográficas como el género y la edad se relacionan con las conductas prosociales de individuos adultos de habla hispana y por lo tanto deben considerarse en la evaluación.
Previous research has shown an association between prosocial behavior and empathic ability. These constructs are normally assessed in the adult population using self-report scales, such as Prosocial Behavior Scale (ECP) and Interpersonal Reactivity Index (IRI). Currently, there is no available data about the interaction between empathy and prosocial behavior assessed with these scales in Spanish-speaking adults. Objective: To assess prosocial behaviors using ECP in Spanish-speaking adults and analyze its interaction with empathy assessed with IRI, as well as identify the relationship with other variables of interest (age, gender and order of presentation of the scales during the assessment). Method: ECP and IRI were administered to a sample of 115 subjects, who were randomly assigned to a specific order of exposure to the scales (IRI-ECP and ECP-IRI). Results: Performance on ECP was associated with age and the interaction between IRI scores and gender. The order in which the scales were presented during assessment showed no association with ECP scores. Conclusion: Empathy and sociodemographic variables, such as gender and age, are associated with prosocial behaviors of Spanish-speaking adults and therefore need to be considered during the assessment.
Vários estudos mostraram que existe uma associação entre o comportamento pró-social e a capacidade empática. A forma mais comum de avaliar ambos os construtos é por meio de escalas de autorrelato, sendo a Escala de Comportamento Pró-Social (ECP) e o Índice de Reatividade Interpessoal (IRI) os mais utilizados na população adulta. Até o momento, não há relatos disponíveis sobre a relação entre empatia e Comportamento pró-social em adultos falantes de español avaliados com essas escalas. Objetivo: Avaliar o comportamento pró-social por meio da ECP em adultos falantes de español e analizar sua interação com a empatia availada com a escala IRI, bem como identificar sua relação com outras variáveis de interesse (idade, gênero e ordem de apresentação das escalas durante a avaliação). Método: A ECP e o IRI foram aplicados a uma amostra de 115 participantes, os quais foram aleatoriamente designados para uma ordem específica de exposição às escalas (IRI-ECP e ECP-IRI). Resultados: O desempenho na ECP mostrou-se associado à idade e à interação entre o desempenho no IRI e o gênero, enquanto a ordem de apresentação das escalas não apresentou associação com os escores. Conclusão: A empatia e variáveis ââsociodemográficas como gênero e idade estão relacionadas aos comportamentos pró-sociais de indivíduos adultos falantes de espanhol e, portanto, devem ser consideradas na avaliação.
RESUMO
The rapid fetal development and the increased demand for milk result in a catabolic state and oxidative stress in hyperprolific sows. Despite animal defense mechanisms, the dietary supplementation of antioxidants is being evaluated to reduce the impacts of excess free radicals. The aim of this study was to evaluate the short- and long-term effects of beta-carotene supplementation for sows on the reproductive response and performance of suckling piglets. A total of 120 sows were distributed in a 3 × 4 factorial arrangement of three supplementation levels (B0-no supplementation, B200-200 mg beta-carotene/day and B400-400 mg beta-carotene/day) and four groups of parity order (1st, 2nd, 3rd, above 4th). Beta-carotene supplementation during lactation resulted in a higher litter weight at weaning. A higher average weight of piglets and litter weight at birth were observed, as well as a greater number of piglets weaned and litter weight at weaning in sows supplemented with 400 mg of beta-carotene during gestation and lactation periods. Supplementation with 200 and 400 mg of beta-carotene resulted in a greater weight at weaning and daily weight gain in piglets. Daily supplementation with 400 mg of beta-carotene in the prepartum and lactation phases provides a greater litter weight at weaning and, when supplemented in the pre-gestation and gestation periods, results in a greater litter weight at birth and at weaning.
RESUMO
BACKGROUND: Previous studies have experimentally validated and reported that chemical constituents of marine sponges are a source of natural anti-inflammatory substances with the biotechnological potential to develop novel drugs. AIMS: Therefore, the aim of this study was to perform a systematic review to provide an overview of the anti-inflammatory substances isolated from marine sponges with therapeutic potential. METHODS: This systematic review was performed on the Embase, PubMed, Scopus and Web of Science electronic databases. In total, 613 were found, but 340 duplicate studies were excluded, only 100 manuscripts were eligible, and 83 were included. RESULTS: The results were based on in vivo and in vitro assays, and the anti-inflammatory effects of 251 bioactive compounds extracted from marine sponges were investigated. Their anti-inflammatory activities include inhibition of pro-inflammatory mediators, such as tumor necrosis factor- α (TNF-α), interleukin-6 (IL-6), nitrite or nitric oxide (NO), inducible nitric oxide synthase (iNOS), cyclooxygenase-2 (COX-2), interleukin 1ß (IL-1ß), prostaglandin E2 (PGE2), phospholipase A2 (PLA2), nuclear transcription factor-kappa B (NF-κB), leukotriene B4 (LTB4), cyclooxygenase- 1 (COX-1), and superoxide radicals. CONCLUSION: In conclusion, data suggest (approximately 98% of articles) that substances obtained from marine sponges may be promising for the development of novel anti-inflammatory drugs for the treatment of different pathological conditions.
Assuntos
NF-kappa B , Poríferos , Animais , NF-kappa B/metabolismo , Anti-Inflamatórios/farmacologia , Anti-Inflamatórios/uso terapêutico , Interleucina-6/metabolismo , Fator de Necrose Tumoral alfa/metabolismo , Poríferos/metabolismo , Lipopolissacarídeos/farmacologia , Óxido Nítrico Sintase Tipo II/metabolismo , Ciclo-Oxigenase 2/metabolismo , Óxido Nítrico/metabolismoRESUMO
Lupus nephritis (LN) is the most frequent and severe complication of systemic lupus erythematosus (SLE). A prospective cohort with a six-month follow-up was performed. Twelve SLE patients diagnosed with LN Class III, twelve NL Class IV patients, and twelve healthy control subjects (HC) were included. SLE data, renal function, oxidants, antioxidants, and inflammation were determined at baseline and six-month follow-up. During the six-month follow-up, the SLE Disease Activity Index (SLEDAI-2K) decreased in both LN Class III (20.08 ± 6.92 vs. 11.92 ± 5.87, p < 0.001) and LN Class IV (25.33 ± 6.01 vs. 13.83 ± 5.52, p < 0.001) patients. Furthermore, the values of the C4 component also increased during follow-up for LN Class III (25.36 ± 6.34 vs. 30.91 ± 9.22, p = 0.027) and LN Class IV (12.18 ± 3.90 vs. 20.33 ± 8.95, p = 0.008) groups. Regarding inflammation markers, both groups presented decreased C-reactive protein (CRP), but this was only significant for patients with LN class III (7.93 ± 1.77 vs. 4.72 ± 3.23, p = 0.006). Renal function remained stable in both groups, with no changes in eGFR. Patients with LN Class III and Class IV showed higher baseline levels for lipoperoxides (Class III p < 0.01, Class IV p < 0.1) and carbonyl groups in proteins (Class III p < 0.01, Class IV p < 0.1) compared to HC. Moreover, both groups presented lower baseline values of total antioxidant capacity (Class III p < 0.01, Class IV p < 0.1) and catalase (Class III p < 0.01, Class IV p < 0.1) compared to HCs. However, antioxidant and oxidant markers did not show significant differences between baseline values and at six months for either of the two study groups. In conclusion, patients show an imbalance in the oxidative state characterized by the increase in the oxidants LPO and protein carbonyl groups and the decrease in the activity of the antioxidant enzymes TAC and CAT compared to HC. However, the patients did not present an increase in disease activity and renal function improvement. The glomerular filtration rate did not change during the length of the study, and SLEDAI -2K, C3, and C4 improved. The early co-management between Rheumatologists and Nephrologists is essential to prevent the rapid progression of LN. It would be interesting to administer antioxidant supplements to patients with a recent diagnosis of LN and evaluate its effect in a follow-up study.
RESUMO
Glucose and lipid metabolism regulation by the peroxisome proliferator-activated receptors (PPARs) has been extensively reported. However, the role of their polymorphisms remains unclear. OBJECTIVE: To determine the relation between PPAR-γ2 rs1801282 (Pro12Ala) and PPAR-ß/δ rs2016520 (+294T/C) polymorphisms and metabolic biomarkers in adults with type 2 diabetes (T2D). MATERIALS AND METHODS: We included 314 patients with T2D. Information on anthropometric, fasting plasma glucose (FPG), HbA1c and lipid profile measurements was taken from clinical records. Genomic DNA was obtained from peripheral blood. End-point PCR was used for PPAR-γ2 rs1801282, while for PPAR-ß/δ rs2016520 the PCR product was digested with Bsl-I enzyme. Data were compared with parametric or non-parametric tests. Multivariate models were used to adjust for covariates and interaction effects. RESULTS: minor allele frequency was 12.42% for PPAR-γ2 rs1801282-G and 13.85% for PPAR-ß/δ rs2016520-C. Both polymorphisms were related to waist circumference; they showed independent effects on HbA1c, while they interacted for FPG; carriers of both PPAR minor alleles had the highest values. Interactions between FPG and polymorphisms were identified in their relation to triglyceride level. CONCLUSIONS: PPAR-γ2 rs1801282 and PPAR-ß/δ rs2016520 polymorphisms are associated with anthropometric, glucose, and lipid metabolism biomarkers in T2D patients. Further research is required on the molecular mechanisms involved.