Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents / A Rubiadina exerce um efeito anti-inflamatório agudo e crônico em roedores

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukey’s) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF-α e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1β foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF α e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1β nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents / A Rubiadina exerce um efeito anti-inflamatório agudo e crônico em roedores

Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF-α level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1β level was assessed in the chronic model. One-way ANOVA (post hoc Tukeys) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF α level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadin's anti-inflammatory effects were associated with a significant IL-1β decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.(AU)

A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF-α e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1β foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF α e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1β nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.(AU)

Analgesia perioperatória de gatas submetidas a ovariohisterectomia eletiva - uso preemptivo de carprofeno ou grapiprant / Perioperative analgesia in cats undergoing elective ovariohysterectomy - preemptive use of carprofen or grapiprant

Background: The nonsteroidal anti-inflammatory drugs (NSAIDs) exert their analgesic effect through peripheral inhibition of prostaglandin synthesis and a variety of other peripheral and central mechanisms. However, NSAIDs are associated with some adverse effects, mainly related to the gastrointestinal, renal, and hepatic systems, highlighting the need for research to develop safer drugs. Therefore, the aim of this study was to evaluate the efficacy of preoperative oral administration of carprofen or grapiprant in female cats submitted to elective ovariohysterectomy on the quality of perioperative analgesia and the need for hypnotic and analgesic drugs. Materials, Methods & Results: Thirty-three adult female cats were selected, without defined breed and healthy based on physical examination, routine laboratory analyses (complete blood count, total protein, Heinz body investigation and serum quantification of alanine transaminase [ALT], aspartate transaminase [AST], gamma glutamyl transpeptidase [GGT], alkaline phosphatase [ALP], urea, frutosamine, and glucose) and negative tests for feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). After 3 days of adaptation, they were submitted to ovariohysterectomy by celiotomy and randomly allocated into 2 groups according to the preoperative drug used: GCAR [carprofen - 4 mg/kg, VO, 2 h before surgery; n = 11] and GGRA (grapiprant - 2 mg/kg IV, 2 h before surgery; n = 21]. The cats were pre-medicated with acepromazine 0.05 mg/ kg IV and later submitted to general anesthesia with propofol intravenously. Anesthesia was maintained with isoflurane in 100% oxygen. After anesthetic induction, a continuous infusion of remifentanil at a rate of 10 µg/kg/h was initiated. During the transanesthetic period, the parameters of heart rate; respiratory rate; systolic, mean, and diastolic arterial pressure using the oscillometric method; electrocardiogram; rectal temperature; partial pressure of CO2 at the end of expiration: and partial saturation of O2 in hemoglobin were continuously monitored. The evaluation of nociception was based on the changes in the aforementioned physiological parameters. The rate of remifentanil used did not change over time with the use of carprofen. However, animals that received grapiprant required a lower remifentanil dose at 20, 25, and 30 min during the procedure. The female cats that received carprofen showed an increase in mean heart rate at 30 min compared to that at 20 and 25 min. In the Grapiprant group, the heart rate at 35 min was higher only than that observed at 25 min. Discussion: The remifentanil rate did not differ between the groups, even between the times for GCAR. However, the remifentanil rate was lower from 20 min of the procedure for GGRA. This decrease may be related to a decrease in the need for anesthetics and analgesics by decreasing temperature, which causes decreases in metabolism and surgical stimulation. The increase in systolic, mean, diastolic, and heart rate arterial pressure parameters observed in both treatments after 15 min of anesthesia is related to the nociceptive stimulus resulting from traction and ligation of the ovarian pedicles and maneuvers for exteriorization of the uterus. These are considered the moments of greater surgical stimulus during ovariohysterectomy, evidenced by the greater release of cortisol and increase in physiological parameters. The results of this study show that the administration of carprofen or grapiprant was clinically similar when used preemptively for perioperative analgesia in cats submitted to elective ovariohysterectomy.

Effect of tolfenamic acid in postpartum gilts and the performance of their piglets / Efeito do ácido tolfenâmico no pós-parto de leitoas e no desempenho da leitegada

Postpartum dysgalactia syndrome (PPDS) is a common disorder affecting sows in intensive production systems. In most cases, hypogalactia is not clearly identified and assumes a subclinical aspect. Therefore, the present study aimed to evaluate the effect of a nonsteroidal anti-inflammatory drug (NSAID) based on tolfenamic acid as a prophylactic treatment for PPDS and the performance of suckling piglets. Gilts (n = 319) were randomly divided into two groups: a tolfenamic acid group (n = 157) and a control (n = 162). The tolfenamic acid group received a single intramuscular injection (1 ml/20 kg of 4% tolfenamic acid) after farrowing, whereas the control group received no treatment. The occurrence of PPDS was confirmed. All piglets (n = 4,466) were weighed at 1, 4, and 18 days of age. All litters were evaluated for weight gain, the occurrence of diarrhea, and mortality between 4 and 18 days of age. PPDS variables were analyzed using logistic regression. Piglet weights were analyzed based on covariance while considering the effects of initial weight and the presence of diarrhea. Tolfenamic acid had no significant effect on the incidence of PPDS. The tolfenamic acid group had a 0.41% lower piglet mortality rate until 18 days of age. Tolfenamic acid administered prophylactically to gilts after farrowing reduced piglet mortality during lactation and promoted weight gain.

A síndrome da disgalactia pós-parto (PPDS) é uma doença comum e importante que afeta as matrizes suínas em sistemas intensivos de produção. Na maioria dos casos, a hipogalactia não é claramente identificada, assumindo um aspecto subclínico. Portanto, o presente estudo teve como objetivo avaliar o efeito de um medicamento anti-inflamatório não esteroide (AINE) baseado em ácido tolfenâmico como tratamento profiláctico para PPDS e o desempenho de leitões em aleitamento. As leitoas (n = 319) foram divididas aleatoriamente em dois grupos de tratamento: um grupo de ácido tolfenâmico (n = 157) e um grupo de controle (n = 162). O grupo tratado recebeu uma única injeção intramuscular (1 ml/20 kg de 4% de ácido tolfenâmico) após o parto, enquanto que o grupo de controle não recebeu nenhum tratamento. A ocorrência de PPDS foi então verificada. Todos os leitões (n = 4466) foram pesados com 1, 4, e 18 dias de idade. Todas as leitegadas foram avaliadas quanto ao ganho de peso, ocorrência de diarreia e mortalidade entre os 4 e 18 dias de idade. As variáveis PPDS foram analisadas através de regressão logística. Os pesos de leitões foram analisados com base na covariância, considerando os efeitos do peso inicial e a presença de diarreia. Não houve efeito significativo do ácido tolfenâmico sobre a ocorrência de PPDS. O grupo do ácido tolfenâmico teve menos 0,41% de mortalidade dos leitões até aos 18 dias de idade. O ácido tolfenâmico administrado profilaticamente nas leitoas após o parto reduziu a mortalidade dos leitões durante a lactação e aumentou o ganho de peso nos leitões.

Rubiadin exerts an acute and chronic anti-inflammatory effect in rodents

Abstract: Rubiadin is identified as a bioactive anthraquinone that exists in some quinone rich plants. The current research was carried out to evaluate the potential anti-inflammatory impact of Rubiadin in acute and chronic inflammation test models in rodents. The anti-inflammatory activity of Rubiadin was examined in cotton pellet-induced granuloma and carrageenan-induced edema as chronic and acute inflammation models in rats. TNF- level and histopathological changes were assessed using sampled foot tissue of rat in the acute model. Also, the IL-1 level was assessed in the chronic model. One-way ANOVA (post hoc Tukeys) analysis was used for comparing the groups. Rubiadin (0.5 mg/kg, i.p.) induced a significant reduction in TNF level and the paw edema compared to the control group in carrageenan test. Also, it was observed that the anti-inflammatory activity of Rubiadin (0.5 mg/kg, i.p.) is comparable to mefenamic acid (30 mg/kg, i.p.) as the standard drug. Rubiadin was effective in granuloma induced by cotton pellet concerning the granuloma and transudate formation amount. Rubiadins anti-inflammatory effects were associated with a significant IL-1 decrease in this model. The results suggest that Rubiadin as a natural compound can possess significant peripheral anti-inflammatory impacts.

Resumo A rubiadina é identificada como uma antraquinona bioativa que existe em algumas plantas ricas em quinonas. A presente pesquisa foi realizada para avaliar o potencial impacto anti-inflamatório da rubiadina em modelos de teste de inflamação aguda e crônica em roedores. A atividade anti-inflamatória da rubiadina foi examinada em granuloma induzido por pellet de algodão e edema induzido por carragenina como modelos de inflamação crônica e aguda em ratos. O nível de TNF- e as alterações histopatológicas foram avaliados usando amostra de tecido do pé de rato no modelo agudo. Além disso, o nível de IL-1 foi avaliado no modelo crônico. A análise ANOVA de uma via (post hoc de Tukey) foi usada para comparar os grupos. A rubiadina (0,5 mg / kg, i.p.) induziu uma redução significativa no nível de TNF e no edema da pata em comparação com o grupo de controle no teste de carragenina. Além disso, foi observado que a atividade anti-inflamatória da rubiadina (0,5 mg / kg, i.p.) é comparável ao ácido mefenâmico (30 mg/kg, i.p.) como o fármaco padrão. A rubiadina foi eficaz no granuloma induzido por pellet de algodão no que diz respeito à quantidade de granuloma e formação de transudato. Os efeitos anti-inflamatórios da rubiadina foram associados a uma redução significativa de IL-1 nesse modelo. Os resultados sugerem que a rubiadina como um composto natural pode ter impactos anti-inflamatórios periféricos significativos.

Deeper exploration of inflammatory cell populations in milk to monitor udder health in dairy cows

The present study explored the predictive values of milk leukocyte differentials (MLD) as a basis for improving the diagnosis of intramammary infections (IMIs) and subclinical mastitis. Quarter milk samples were collected for bacteriological analysis, quarter somatic cell count (qSCC), and MLD. The MLD were assessed using the cytospin technique, direct microscopic smears, and flow cytometry. The predictive values of each single leukocyte population and useful potential indices that could better reflect immune complexity were also calculated. Changes in the percentage of any leukocyte alone failed to substantially improve the predictive value of qSCC in diagnosing IMIs. Although certain parameters increased the area under the receiver operating characteristic curve (ROC curve) as a result of increased specificity values, a slight reduction in sensitivity was observed. The so-called CD8 complex was a unique parameter which improved both the sensitivity (78.79 %) and the specificity (80.77 %) in IMI diagnosis, resulting in the highest area under the ROC curve (0.87). To diagnose subclinical mastitis, the percentage of macrophages and the sum of the percentage PMNLs and T CD8+ cells divided by the percentage of macrophages showed the highest predictive values (sensitivity = 79.63, specificity = 73.68, and area under the ROC curve = 0.83) in the differentiation of the inflammatory condition status of cows. In conclusion, this study provides further insights into using T CD8+ lymphocytes in diagnosing bovine IMIs, combined with PMNLs and macrophages. The antidromic trend of macrophages vs. PMNLs and T CD8+ lymphocytes due to the increasing qSCCs was crucial to differentiating quarters under both inflammatory and non-inflammatory conditions.

Evaluation of histo-toxicity of nimesulide in black kites (Milvus migrans): a pharmacodynamic study / Avaliação da histotoxicidade da nimesulida em milhafre-preto (Milvus migrans): um estudo farmacodinâmico

The present experimental work was conducted to elucidate the toxicity of nimesulide at three different doses in black kites (Milvus migrans). M. migrans is one of the most common raptors near human habitations. The goal of the current investigation was to determine whether nimesulide is similarly hazardous to raptors as was diclofenac sodium and to investigate the acute oral toxicity of nimesulide in these birds. For this study, eight adult male black kites (M. migrans) were randomly divided into four groups. M. migrans in the control group (n = 02) were not treated with nimesulide. The other three groups were given nimesulide doses. The birds in the first (n = 02) were declared the control group. The second (n = 02), third (n = 02), and fourth groups were administered nimesulide at a low, medium, and high dose of 2, 4, and 6 mg/kg live body weight of bird/day, respectively, for 10 days. Nimesulide-addled birds became listless and despondent, then anorexic. The birds were standing there with their eyes closed and showing no signs of life. There was an increase in saliva production, a slowing of breathing, and dilated pupils. No clinical signs were observed in the control group. No mortality was seen in the control or treated groups. The control group did not show lesions of gout, but black kites intoxicated with nimesulide at 2, 4, and 6 mg/kg live body weight of bird/day showed inflammation, apoptosis, hemorrhage, necrosis, and leukocytic infiltration tissues of the liver, kidney, and heart of black kites (M. migrans) treated with different concentrations of nimesulide. The treated groups also showed apoptosis of myofibrils and hyperplasia. The hypertrophy, atrophy, fibrosis, necrosis of skeletal muscles and hemorrhage were prominent in the muscles of black kites (M. migrans) intoxicated with nimesulide. All observed histological alterations got worse in a dose-related way. There was no significant difference in AST, ALT, ALP, serum uric acid, but a significant difference was observed in the values of serum urea (p = 0.001) and serum creatinine (p = 0.019).

O presente trabalho experimental foi conduzido para elucidar a toxicidade da Nimesulida em três doses diferentes em milhafres (Milvus migrans). M. migrans é uma das aves de rapina mais comuns perto de habitações humanas. O objetivo da presente investigação foi determinar se a Nimesulida é igualmente perigosa para as aves de rapina como foi o diclofenaco sódico e investigar a toxicidade oral aguda do fármaco nessas aves. Para este estudo, 8 milhafres machos adultos (M. migrans) foram aleatoriamente divididos em 4 grupos. M. migrans no grupo controle (n = 2) não foram tratados com Nimesulida. Os outros 3 grupos receberam doses do fármaco. As aves do primeiro grupo (n = 2) foram declaradas o grupo controle. O segundo (n = 2), terceiro (n = 2) e quarto grupos receberam Nimesulida nas doses baixa, média e alta de 2, 4 e 6 mg/kg de peso corporal vivo da ave/dia, respectivamente, por 10 dias. Aves confusas com Nimesulida tornaram-se apáticas e desanimadas, depois anoréxicas. Os pássaros estavam parados com os olhos fechados e sem sinais de vida. Houve um aumento na produção de saliva, lentidão na respiração e pupilas dilatadas. Nenhum sinal clínico foi observado no grupo controle. Nenhuma mortalidade foi observada nos grupos de controle ou tratados. O grupo controle não apresentou lesões de gota, mas os milhafres intoxicados com Nimesulida nas doses de 2, 4 e 6 mg/kg peso vivo da ave/dia apresentaram inflamação, apoptose, hemorragia, necrose e infiltração leucocitária nos tecidos do fígado, rim e coração de milhafre-preto tratados com diferentes concentrações de Nimesulida. Os grupos tratados também apresentaram apoptose de miofibrilas e hiperplasia. A hipertrofia, atrofia, fibrose, necrose da musculatura esquelética e hemorragia foram proeminentes nos músculos de milhafres negros intoxicados com o fármaco. Todas as alterações histológicas observadas pioraram de forma dose-dependente. Não houve diferença significativa em AST, ALT, ALP, ácido úrico sérico, no entanto, foi observada diferença significativa nos valores de ureia sérica (p = 0,001) e creatinina sérica (p = 0,019).

Benefícios do matcha: um estudo de revisão / Benefits of matcha: a review study

O Chá Verde matcha é uma erva muito utilizada na culinária japonesa, produzida a partir das folhas da planta Camellia sinensis. A sua forma tradicional de cultivo, em ambiente sombreado por bambu natural, potencializa o teor de polifenóis, cafeína e clorofila. Suas propriedades promotoras de saúde são atribuídas ao alto teor de antioxidantes e substâncias antiinflamatórias. O objetivo do estudo foi realizar uma revisão narrativa acerca dos efeitos benéficos do matcha para a saúde humana, por meio de buscas nas bases de dados Google Acadêmico, Scientific Electronic Library Online (Scielo), Literatura Latino-americana e do National Library of Medicine (Pubmed), utilizando as palavras-chave: chá verde, matcha, benefícios, matcha tea. Os estudos indicam que o matcha presenta propriedades antioxidantes e antiinflamatórias, melhora as funções imunológicas, atua na prevenção do declínio cognitivo e apresenta potencial de impactar a microbiota intestinal, alterando a composição das bactérias presentes. Diante das evidências encontradas, notase a necessidade de realizar mais estudos para elucidar as propriedades e os mecanismos de ação de cada um dos compostos desta bebida.(AU)

Matcha green tea is an herb widely used in Japanese cuisine, produced from the leaves of the Camellia sinensis plant. Its traditional way of cultivation, in an environment shaded by natural bamboo, enhances the content of polyphenols, caffeine and chlorophyll. Its healthpromoting properties are attributed to its high content of antioxidants and anti inflammatory substances. The aim of the study was to perform a narrative review about the beneficial effects of matcha on human health, through searches in the databases Google Scholar, Scientific Electronic Library Online (Scielo) and Latin American Literature and the National Library of Medicine (Pubmed), using the keywords: green tea, matcha, benefits, matcha tea. Studies indicate that matcha has antioxidant and anti-inflammatory properties, improves immune functions, acts to prevent cognitive decline and has the potential to impact the intestinal microbiota, changing the composition of the bacteria present. In view of the evidence found, there is a need to carry out further studies to elucidate the properties and mechanisms of action of each of the compounds in this drink.(AU)

Down-regulation of complement genes in lipopolysaccharidechallenged zebrafish (Danio rerio) larvae exposed to Indonesian propolis / Regulação negativa dos genes do complemento em larvas de peixe-zebra (Danio rerio) desafiadas com lipopolissacarídeo expostas à própolis indonésia

Although propolis has been reported for having anti-inflammatory activities, its effects on complement system has not been much studied. This research was conducted to find out the effects of Indonesian propolis on the expression levels of C3, C1r/s, Bf, MBL, and C6 in zebrafish larvae which were induced by lipopolysaccharide (LPS). Counting of macrophages migrating to yolk sac and liver histology were carried out. Larvae were divided into four groups: CON (cultured in E3 medium only), LPS (cultured in a medium containing 0.5 μg/L LPS), LPSIBU (cultured in a medium containing LPS, and then treated with 100 μg/L ibuprofen for 24 hours), and LPSPRO (cultured in a medium containing LPS, and then immersed in 14,000 μg/L propolis for 24 hours) groups. The results showed that complement gene expression in larvae from the LPSIBU and LPSPRO groups were generally lower than in larvae from the LPS group. The number of macrophage migrations to the yolk in the LPSPRO group was also lower than in the LPS group. Histological structure of liver in all groups were considered normal. This study shows that Indonesian propolis has the potential to be used as an alternative to the substitution of NSAIDs.

Embora a própolis tenha sido relatada por ter atividade anti-inflamatória, seus efeitos no sistema complemento, uma parte do sistema imunológico inato, não foram muito estudados. Esta pesquisa foi conduzida para descobrir os efeitos da própolis da Indonésia nos níveis de expressão de C3, C1r/s, Bf, MBL e C6 em larvas de peixe-zebra induzidas por lipopolissacarídeo (LPS). Foram realizadas contagens de macrófagos que migram para o saco vitelino e histologia do fígado. As larvas foram divididas em quatro grupos: CON (cultivadas apenas em meio E3), LPS (cultivadas em meio contendo 0,5 μg/L de LPS), LPSIBU (cultivadas em meio contendo LPS e, em seguida, tratadas com 100 μg/L de ibuprofeno por 24 horas) e LPSPRO (cultivado em meio contendo LPS, e então imerso em própolis 14,000 μg/L por 24 horas). Os resultados mostraram que a expressão do gene do complemento em larvas dos grupos LPSIBU e LPSPRO foi geralmente menor que em larvas do grupo LPS. O número de migrações de macrófagos para a gema no grupo LPSPRO também foi menor que no grupo LPS. A estrutura histológica do fígado em todos os grupos foi considerada normal. Este estudo mostra que a própolis indonésia tem potencial para ser utilizada como alternativa na substituição dos AINEs (anti-inflamatórios não esteroides).

Down-regulation of complement genes in lipopolysaccharidechallenged zebrafish (Danio rerio) larvae exposed to Indonesian propolis / Regulação negativa dos genes do complemento em larvas de peixe-zebra (Danio rerio) desafiadas com lipopolissacarídeo expostas à própolis indonésia

Although propolis has been reported for having anti-inflammatory activities, its effects on complement system has not been much studied. This research was conducted to find out the effects of Indonesian propolis on the expression levels of C3, C1r/s, Bf, MBL, and C6 in zebrafish larvae which were induced by lipopolysaccharide (LPS). Counting of macrophages migrating to yolk sac and liver histology were carried out. Larvae were divided into four groups: CON (cultured in E3 medium only), LPS (cultured in a medium containing 0.5 μg/L LPS), LPSIBU (cultured in a medium containing LPS, and then treated with 100 μg/L ibuprofen for 24 hours), and LPSPRO (cultured in a medium containing LPS, and then immersed in 14,000 μg/L propolis for 24 hours) groups. The results showed that complement gene expression in larvae from the LPSIBU and LPSPRO groups were generally lower than in larvae from the LPS group. The number of macrophage migrations to the yolk in the LPSPRO group was also lower than in the LPS group. Histological structure of liver in all groups were considered normal. This study shows that Indonesian propolis has the potential to be used as an alternative to the substitution of NSAIDs.(AU)

Embora a própolis tenha sido relatada por ter atividade anti-inflamatória, seus efeitos no sistema complemento, uma parte do sistema imunológico inato, não foram muito estudados. Esta pesquisa foi conduzida para descobrir os efeitos da própolis da Indonésia nos níveis de expressão de C3, C1r/s, Bf, MBL e C6 em larvas de peixe-zebra induzidas por lipopolissacarídeo (LPS). Foram realizadas contagens de macrófagos que migram para o saco vitelino e histologia do fígado. As larvas foram divididas em quatro grupos: CON (cultivadas apenas em meio E3), LPS (cultivadas em meio contendo 0,5 μg/L de LPS), LPSIBU (cultivadas em meio contendo LPS e, em seguida, tratadas com 100 μg/L de ibuprofeno por 24 horas) e LPSPRO (cultivado em meio contendo LPS, e então imerso em própolis 14,000 μg/L por 24 horas). Os resultados mostraram que a expressão do gene do complemento em larvas dos grupos LPSIBU e LPSPRO foi geralmente menor que em larvas do grupo LPS. O número de migrações de macrófagos para a gema no grupo LPSPRO também foi menor que no grupo LPS. A estrutura histológica do fígado em todos os grupos foi considerada normal. Este estudo mostra que a própolis indonésia tem potencial para ser utilizada como alternativa na substituição dos AINEs (anti-inflamatórios não esteroides).(AU)

Antioxidant, anti-inflammatory and anti-obesity effects of onion and its by-products in high-fat fed rodents: a systematic review / Efeitos antioxidantes, anti-inflamatórios e anti-obesidade da cebola e seus subprodutos em roedores alimentados com alto teor de gordura: uma revisão sistemática

The effects of onion and its by-products on metabolic changes induced by excessive consumption of a high fat diet have been the focus of many studies. The aim of this study was to systematically review the effects of onion and its by-products antioxidant, anti-inflammatory and anti-obesity in rats exposed to a high-fat diet. Five databases were used: Pubmed, EMBASE, Science Direct, Web of science and Scopus until June 2020 updated December 1, 2022. Research of the articles was carried out by two reviewers, searching and selecting studies after an initial reading of the titles and abstracts. In total, 2,448 papers were found and, after assessing against the inclusion and exclusion criteria, 18 papers were selected for this review. The findings of this review show the beneficial effects of onion and its by-products on inflammatory parameters, obesity, cardiovascular disease, thermogenesis and hepatic alterations generally associated with the consumption of a high-fat diet.

Os efeitos da cebola e seus subprodutos nas alterações metabólicas induzidas pelo consumo excessivo de uma dieta rica em gordura têm sido foco de muitos estudos. O objetivo deste estudo foi revisar sistematicamente os efeitos da cebola e seus subprodutos antioxidantes, anti-inflamatórios e anti-obesidade em ratos expostos a uma dieta hiperlipídica. Foram utilizadas cinco bases de dados: Pubmed, EMBASE, Science Direct, Web of science e Scopus até junho de 2020, atualizado em 01 de dezembro de 2022. A pesquisa dos artigos foi realizada por dois revisores, buscando e selecionando os estudos após leitura inicial dos títulos e resumos. No total, 2.448 artigos foram encontrados e, após avaliação de acordo com os critérios de inclusão e exclusão, 18 artigos foram selecionados para esta revisão. Os achados desta revisão mostram os efeitos benéficos da cebola e seus subprodutos sobre parâmetros inflamatórios, obesidade, doenças cardiovasculares, termogênese e alterações hepáticas geralmente associadas ao consumo de uma dieta hiperlipídica.

Propolis anti-inflammatory effects on MAGE-1 and retinoic acid-treated dendritic cells and on Th1 and T regulatory cells

Background: Propolis exhibits huge potential in the pharmaceutical industry. In the present study, its effects were investigated on dendritic cells (DCs) stimulated with a tumor antigen (MAGE-1) and retinoic acid (RA) and on T lymphocytes to observe a possible differential activation of T lymphocytes, driving preferentially to Th1 or Treg cells. Methods: Cell viability, lymphocyte proliferation, gene expression (T-bet and FoxP3), and cytokine production by DCs (TNF-α, IL-10, IL-6 and IL-1ß) and lymphocytes (IFN-γ and TGF-ß) were analyzed. Results: MAGE-1 and RA alone or in combination with propolis inhibited TNF-α production and induced a higher lymphoproliferation compared to control, while MAGE1 + propolis induced IL-6 production. Propolis in combination with RA induced FoxP3 expression. MAGE-1 induced IFN-γ production while propolis inhibited it, returning to basal levels. RA inhibited TGF-ß production, what was counteracted by propolis. Conclusion: Propolis affected immunological parameters inhibiting pro-inflammatory cytokines and favoring the regulatory profile, opening perspectives for the control of inflammatory conditions.(AU)

Bisacurone gel ameliorated burn wounds in experimental rats via its anti-inflammatory, antioxidant, and angiogenic properties

Purpose: To investigate putative mechanism of wound healing for chitosan-based bisacurone gel against secondary burn wounds in rats. Methods: A second-degree burn wound with an open flame using mixed fuel (2 mL, 20 seconds) was induced in Sprague Dawley rats (male, 180-220 g, n = 15, each) followed by topical treatments with either vehicle control (white petroleum gel, 1%), silver sulfadiazine (1%) or bisacurone gel (2.5, 5, or 10%) for 20 days. Wound contraction rate and paw withdrawal threshold were monitored on various days. Oxidative stress (superoxide dismutase, glutathione, malondialdehyde, and nitric oxide), pro-inflammatory cytokines (tumour necrosis factor-alpha, interleukins by enzyme-linked immunosorbent assay), growth factors (transforming growth factor-ß, vascular endothelial growth factor C using real time polymerase chain reaction and Western blot assay) levels, and histology of wound skin were assessed at the end. Results: Bisacurone gel showed 98.72% drug release with a 420.90­442.70 cps viscosity. Bisacurone gel (5 and 10%) significantly (p < 0.05) improved wound contraction rate and paw withdrawal threshold. Bisacurone gel attenuated oxidative stress, pro-inflammatory cytokines, and water content. It also enhanced angiogenesis (hydroxyproline and growth factor) and granulation in wound tissue than vehicle control. Conclusions: These findings suggested that bisacurone gel can be a potential candidate to treat burn wounds via its anti-inflammatory, antioxidant, and angiogenic properties.

Astragaloside IV alleviates stroke-triggered early brain injury by modulating neuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway

Purpose: Stroke is an acute cerebrovascular disease. Astragaloside IV (AS-IV) is an active ingredient extracted from Astragalus membranaceus with an established therapeutic effect on central nervous system diseases. This study examined the neuroprotective properties and possible mechanisms of AS-IV in stroke-triggered early brain injury (EBI) in a rat transient middle cerebral artery occlusion (MCAO) model. Methods: The neurological scores and brain water content were analyzed. 2,3,5-triphenyl tetrazolium chloride (TTC) staining was utilized to determine the infarct volume, neuroinflammatory cytokine levels, and ferroptosis-related genes and proteins, and neuronal damage and molecular mechanisms were evaluated by terminal deoxynucleotidyl transferase dutp nickend labeling (TUNEL) staining, western blotting, and real-time polymerase chain reaction. Results: AS-IV administration decreased the infarct volume, brain edema, neurological deficits, and inflammatory cytokines TNF-α, interleukin-1ß (IL-1ß), IL-6, and NF-κB, increased the levels of SLC7A11 and glutathione peroxidase 4 (GPX4), decreased lipid reactive oxygen species (ROS) levels, and prevented neuronal ferroptosis. Meanwhile, AS-IV triggered the Nrf2/HO-1 signaling pathway and alleviated ferroptosis due to the induction of stroke. Conclusion: Hence, the findings of this research illustrate that AS-IV administration can improve delayed ischemic neurological deficits and decrease neuronal death by modulating nuroinflammation and ferroptosis via the Nrf2/HO-1 signaling pathway.

Diarrhea in cats infected with Cystoisospora spp. - evaluation of the neutrophil-to-lymphocyte ratio and monocyte-to-lymphocyte ratio

Background: Cystoisospora spp. is considered a potential pathogen to cause diarrhoea in cats, and the disease occurs clinically, especially in young, weak and immunocompromised cats. The present study aimed to evaluate the clinical utility and diagnostic roles of neutrophil-to-lymphocyte ratio (NLR) and monocyte-to-lymphocyte (MLR) ratios in diarrheal cats infected with Cystoisospora spp. Materials, Methods & Results: Twenty-five cats with diarrhea due to infection caused by Cystoisospora spp. and 15 healthy cats were included in this study. The anamnesis, clinical and laboratory findings of all cats were recorded. A clinical severity score was generated for diarrheal cats, which included activity, appetite, presence of vomit, and faecal consistency. Also, cats infected with Cystoisospora spp. were classified as systemic inflammatory response syndrome (SIRS) positive (+) and SIRS (-) group according to the presence of at least 3 of the SIRS criteria. The Cystoisospora spp. oocysts were diagnosed by direct smear and simple faecal flotation. Cats found positive for other parasitic and protozoal agents by faeces examination were excluded from the study. Complete blood counts (CBC) were performed with an automated blood cell counter for all cats. Blood smears were prepared (with May-Grunwald Giemsa) from samples, and the CBC results were confirmed microscopically (obj.100x). White blood cell (WBC), neutrophil, lymphocyte and monocyte counts were recorded directly from the CBC. The neutrophil-to-lymphocyte ratio was calculated as the ratio of the absolute neutrophil count to the absolute lymphocyte count. The monocyte-to-lymphocyte was calculated as the absolute monocyte count ratio to the absolute lymphocyte count. White blood cell (P = 0.015), neutrophil (P = 0.001), monocyte (P = 0.033), NLR (P = 0.000) and MLR (P = 0.042) of diarrheal cats infected with Cystoisospora spp. were significantly higher than in the healthy group. There was no significant difference between groups in the lymphocyte counts (P > 0.05). SIRS (+) group had statistically significantly higher WBC (P = 0.014), neutrophil counts (P = 0.000), NLR (P = 0.000) and MLR (P = 0.037) than the healthy group. Also, neutrophil counts and NLR of the SIRS (+) group were statistically significantly higher than the SIRS (-) group (P = 0.032; P = 0.001, respectively). However, there was no significant difference SIRS (+), SIRS (-), and healthy groups regarding lymphocyte and monocyte counts (P > 0.05). The clinical severity of the disease positively correlated with NLR and MLR. Also, the best cut-off value of NLR to predict SIRS was > 1.67, with 92.86% sensitivity and 84.62% specificity. MLR was not a useful predictor for SIRS. Discussion: NLR and MLR are parameters derived from complete blood count. In recent years, they have been used in human and veterinary medicine as a biomarker in the diagnosis, prognosis and treatment follow-up of various diseases and provide valuable information about inflammation. In cats, there are limited studies on NLR, and to our knowledge, there are no studies on MLR. The current study suggests that NLR and MLR may be used to determine the severity of the inflammatory condition in diarrheal cats infected with Cystoisospora spp., and NLR is a useful marker for predicting SIRS status in these cats. In addition, this study also will contribute to larger-scale studies in the future.

Circular RNA protein tyrosine kinase 2 aggravates pyroptosis and inflammation in septic lung tissue by promoting microRNA-766/eukaryotic initiation factor 5A axis-mediated ATP efflux

Purpose: Sepsis is characterized by an acute inflammatory response to infection, often with multiple organ failures, especially severe lung injury. This study was implemented to probe circular RNA (circRNA) protein tyrosine kinase 2 (circPTK2)-associated regulatory mechanisms in septic acute lung injury (ALI). Methods: A cecal ligation and puncture-based mouse model and an lipopolysaccharides (LPS)-based alveolar type II cell (RLE-6TN) model were generated to mimic sepsis. In the two models, inflammation- and pyroptosisrelated genes were measured. Results: The degree of lung injury in mice was analyzed by hematoxylin and eosin (H&E) staining and the apoptosis was by terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling staining. In addition, pyroptosis and toxicity were detected in cells. Finally, the binding relationship between circPTK2, miR-766, and eukaryotic initiation factor 5A (eIF5A) was detected. Data indicated that circPTK2 and eIF5A were up-regulated and miR-766 was down-regulated in LPS-treated RLE-6TN cells and lung tissue of septic mice. Lung injury in septic mice was ameliorated after inhibition of circPTK2. Conclusion: It was confirmed in the cell model that knockdown of circPTK2 effectively ameliorated LPS-induced ATP efflux, pyroptosis, and inflammation. Mechanistically, circPTK2 mediated eIF5A expression by competitively adsorbing miR-766. Taken together, circPTK2/ miR-766/eIF5A axis ameliorates septic ALI, developing a novel therapeutic target for the disease.

Steroid-responsive myelitis in dogs - comparison with steroid-responsive meningitis-arteritis

Background: Myelitis is the inflammation of the spinal cord parenchyma alone, whereas meningitis is the inflammation of the meninges. Steroid-responsive meningitis-arteritis (SRMA) is a meningomyelitis in which the major lesions involve the meninges, not the spinal cord parenchyma, and respond well to glucocorticoid treatment. However, myelitis in dogs has rarely been reported, and myelitis with a good response to glucocorticoid treatment without relapse has not been reported. This report describes 5 cases of steroid-responsive myelitis (SRM) in dogs. Cases: Case 1. A 8-year-old intact female Cocker Spaniel presented with progressive nonambulatory paraplegia. Whole spinal parenchymal lesions were identified using magnetic resonance imaging (MRI) scan. Mononuclear pleocytosis with increased total protein levels was the only abnormal finding on cerebrospinal fluid (CSF) analysis. Prednisolone (PDS) was administered followed by dose tapering according to therapeutic response. Cyclosporine was administered until the termination of PDS. Since then, no recurrence of neurological symptoms has been observed. Follow-up MRI and CSF analysis revealed resolution of previously observed abnormal findings. Case 2. A 2-year-old intact female Maltese presented with non-progressive paraparesis. A spinal parenchymal lesion in the lumbosacral region was observed on MRI. PDS was administered and slowly tapered at approximately 3-week intervals. No recurrence of neurological symptoms was observed after the treatment. Case 3. A 6-year-old intact female Miniature Pinscher presented with neck pain, along with leukocytosis and neutrophilia. Cervical spinal parenchyma lesions were revealed through MRI. Increased total protein concentration with mixed cell pleocytosis was observed on CSF analysis. Immunomodulatory therapy, similar to that in case 2, was initiated. A second MRI and CSF analysis revealed an improvement in the previously observed abnormalities. Case 4. A 2-year-old, intact female Toy Poodle presented with acute paraplegia and back pain. Lesions were observed in the spinal parenchyma at the T12-L3 levels on MRI. The treatment was conducted as in case 2. During treatment, neurological symptoms, including paraplegia and back pain, were not observed. Follow-up MRI revealed improvement in the spinal lesion. Case 5. A 6-month-old, castrated male Standard Poodle presented with progressive paraparesis. On MRI, lesions were observed in the T11-T13 regions. Immunomodulation therapy, similar to that in case 2, was initiated. No recurrence of neurological symptoms was observed after treatment initiation Discussion: SRM is similar to SRMA in terms of good steroid-responsiveness and noninfectious inflammation etiology; however, it does not exactly satisfy the diagnostic criteria for SRMA, nor does it progress similarly. The characteristics of SRM that do not satisfy the diagnostic criteria of SRMA include the absence of fever, C-reactive protein elevation, hyperglobulinemia, and relapse, and the presence of spinal parenchymal lesions without parenchymal or meningeal enhancement on MRI. It is also a seemingly different from spinal cord-only meningoencephalomyelitis of unknown origin due to its better treatment response and prognosis. However, the dogs in the present report with SRM satisfied the diagnostic criteria for transverse myelitis in human patients. Therefore, SRM, including good steroid responsiveness and good prognosis without relapse, may represent a novel type of meningomyelitis.

Naringenin attenuates cerebral ischemia/reperfusion injury by inhibiting oxidative stress and inflammatory response via the activation of SIRT1/FOXO1 signaling pathway in vitro

Purpose: To explore the protection of naringenin against oxygen-glucose deprivation/reperfusion (OGD/R)-induced HT22 cell injury, a cell model of cerebral ischemia/reperfusion (I/R) injury in vitro, focusing on SIRT1/FOXO1 signaling pathway. Methods: Cytotoxicity, apoptosis, reactive oxygen species (ROS) generation, malondialdehyde (MDA) content, 4-hydroxynonenoic acid (4-HNE) level, superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) activities were measured by commercial kits. Inflammatory cytokines levels were determined by enzyme-linked immunosorbent assay (ELISA). The protein expressions were monitored by Western blot analysis. Results: Naringenin significantly ameliorated OGD/Rinduced cytotoxicity and apoptosis in HT22 cells. Meanwhile, naringenin promoted SIRT1 and FOXO1 protein expressions in OGD/R-subjected HT22 cells. In addition, naringenin attenuated OGD/R-induced cytotoxicity, apoptosis, oxidative stress (the increased ROS, MDA and 4-HNE levels, and the decreased SOD, GSH-Px and CAT activities) and inflammatory response (the increased tumor necrosis factor-α, interleukin [IL]-1ß, and IL-6 levels and the decreased IL-10 level), which were blocked by the inhibition of the SIRT1/FOXO1 signaling pathway induced by SIRT1-siRNA transfection. Conclusion: Naringenin protected HT22 cells against OGD/R injury depending on its antioxidant and anti-inflammatory activities via promoting the SIRT1/FOXO1 signaling pathway.

Dry-eye syndrome in Shih Tzu dog: Ocular surface clinical and morphological aspects in the different stages of keratoconjunctivitis sicca / Síndrome do olho seco em Shih Tzu: aspectos clínicos e morfológicos da superfície ocular nas diferentes fases da ceratoconjuntivite seca

ABSTRACT: This study analyzed clinical and cyto-histomorphological parameters of the ocular surface of Shih Tzu dogs, non-carriers and carriers of quantitative keratoconjunctivitis sicca (KCS) at different stages. Thirty-five eyes from 23 male and female Shih Tzu dogs between two and eight years were evaluated in four groups: control group (CG - without KCS), mild KCS group (KCS1), moderate KCS group (KCS2), and severe KCS group (KCS3). Most clinical variables among KCS carrier groups worsened at the more advanced stages of the disease, with a negative correlation between the Schirmer tear test (STT-1) and tear film break-up time (TBUT). Squamous metaplasia, lymphoplasmacytic inflammatory infiltrate, and decrease in conjunctival goblet cells on histopathological examination comprised disease severity parameters. Quantitative KCS non-carried Shih Tzu dogs have qualitative and tear film distribution changes. The cytomorphological exam is limited to evaluating the inflammatory infiltrate and quantifying conjunctival goblet cells. However, intermediate epithelial cells were higher in healthy eyes compared to eyes with KCS in Shih Tzu dogs. Also, moderate and severe KCS carrier Shih Tzu dogs have qualitative dysfunction of the tear film. KCS in Shih Tzu dogs is common and chronic and may be responsible for the loss of vision of these animals. Early identification of the disease and routine evaluation can improve these dogs' quality of life and ocular health.

RESUMO: Este estudo analizou os parâmetros clinicos e cito-histomorfológicos da superfície ocular de cães da raça Shih Tzu, portadores e não portadores de ceratoconjuntivite seca quantitative (CCS) em diferentes estágios. Trinta e cinco olhos de 23 cães da raça Shih Tzu, machos e fêmeas, entre as idades de dois e oito anos foram avaliados em quatro grupos: grupo controle (GC - sem CCS), grupo CCS inicial (CCS1), grupo CCS moderada (CCS2) e grupo CCS severa (CCS3). A maioria das variáveis clínicas dentro os grupos portadores de CCS pioraram a medida que os estágios da doença avançam, com correlações negativas entre o teste lacrimal de Schirmer (TLS) e o tempo de ruptura do filme lacrimal (TRFL). Metaplasia escamosa, infiltrado inflamatório linfoplasmocítico e diminuição das células caliciformes no exame histopatológico compreenderam parâmetros de severidade da doença. Cães Shih Tzu não portadores de CCS quantitativa tem alterações qualitativas e na distribuição do filme lacrimal. O exame citomorfológico é limitado para a avaliação do infiltrado inflamatório e quantificação de células caliciformes. Entretanto, células inermediárias epiteliais são mais presents nos olhos saudáveis quando comparados aos olhos portadores de CCS em Shih Tzus. Também, Shih Tzus portadores de CCS nos estágios moderados e severos possuem disfunções qualitativas da lágrima. A CCS em Shih Tzu é comum, crônica e pode ser responsável pela perda de visão dos animais. A identificação precoce da doença e avaliações rotineiras podem aumentar a qualidade de vida e a saúde ocular nesses cães.

Effect of Bacillus Subtilis on Immune Function of Hd11 Chicken Macrophages

Poultry is frequently contaminated by Salmonella, a pathogen leading to human health concern worldwide. This study aimed to evaluate the effect of Bacillus subtilis (BS)strain 048 (BS048) on the activation, phagocytosis, sterilization, cytokine secretion, and nitrogen oxide synthesis of HD11 chicken macrophages subjected to Salmonella enteritidis challenge, using lipopolysaccharide treatment as a negative control. The results showed: (1) BS048 had no significant effect on extracellular lactate dehydrogenase activity (p>0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p >0.05), while lipopolysaccharide treatment significantly increased extracellular lactate dehydrogenase activity (p 0.05);(2)BS048 significantly upregulated the expression levels of pro-inflammatory cytokines (interleukin (IL)- 1â and IL-6), anti-inflammatory cytokines(IL-10 and transforming growth factor-â1), and anti-viral cytokine, interferon-â (p<0.01); ; (3) BS048 significantly upregulated the mRNA expression level of the inducible nitric oxide synthase and its activity as well as extracellular nitrogen oxide level (p <0.01). In conclusion, BS048 could improve antiinflammatory and immune functions of HD11 chicken macrophages, without cytotoxic effects on these cells.(AU)