Probiotics supplementation reduces cigarette smoke-induced damage in the respiratory micro-architecture of mice / Suplementação com probióticos reduz os danos causados pela fumaça de cigarro na microarquitetura respiratória de camundongos

This study evaluated the protective efficacy of probiotics supplementation against cigarette smoke-induced lung emphysema, inflammation, and loss of cilia in mice. Probiotics are known to promote mucosal tolerance and mitigate respiratory injuries. Twenty-four adult mice were randomly divided into three groups: control (Ctr), cigarette smoke (CS), and cigarette smoke + probiotics (CS+P). Probiotics were given for 7 days before exposure to smoke in the CS+P group. Tissue samples of the trachea (goblet cell count and index, loss of cilia), lungs (airspace distention), and bronchoalveolar lavage fluid (BALF) were collected and processed. The results showed a significant increase in acidic and neutral goblet cells in the CS group compared to the Ctr and CS+P groups (P < 0.05). Overall, goblet cell number and index were lower in the CS+P group (41.71 ± 5.76, 0.67 ± 0.073) than CS group (56.28 ± 5.34, 1.31 ± 0.28). Inflammatory cells and loss of cilia significantly decreased in mice fed probiotics before exposure to cigarette smoke (P < 0.05). Lung emphysema was also significantly reduced in the CS+P group compared to the CS group (P < 0.05). In conclusion, dietary supplementation of probiotics reduced lung emphysema, inflammatory cells, goblet cell index, and loss of cilia under conditions of cigarette smoke exposure in mice.(AU)

O presente trabalho avaliou a eficácia da suplementação com probióticos contra a indução de enfisema, inflamação e perda de cílios por fumaça de cigarro em camundongos. Sabe-se que os probióticos promovem a tolerância da mucosa e mitigam as injúrias respiratórias. Vinte e quatro camundongos foram divididos, ao acaso, em três grupos: controle (CTR), fumaça de cigarro (CS) e fumaça de cigarro + probióticos (CS+P). Os probióticos foram fornecidos por sete dias antes da exposição à fumaça no grupo CS+P. Foram colhidas e processadas amostras de tecidos da traqueia (contagem de células caliciformes e index, perda de cílios), pulmões (distensão do espaço aéreo) e fluido de lavagem broncoalveolar. Os resultados obtidos revelaram um aumento significativo em células caliciformes acidificadas e neutralizadas no grupo CS quando comparado aos grupos Ctr e CS+P (P<0,05). Os números global e o índice de células caliciformes foram menores no grupo CS+P (41,71+ 5,76; 0,67+ 0,073) que no grupo CS (56,28+ 5,34 e 1,131+ 0,28). As células inflamatórias e a perda de cílios decresceram em camundongos alimentados com probióticos antes da exposição à fumaça de cigarro (P<0,05). O enfisema pulmonar também foi significativamente reduzido no grupo CS+P quando comparado ao grupo CS (P<0,05). A conclusão obtida foi que o fornecimento de dieta suplementada com probióticos reduziu o enfisema pulmonar, as células inflamatórias, o índice de células caliciformes e a perda de cílios nos camundongos expostos à fumaça de cigarro.(AU)

Pancreatic cancer orthotopic graft in a murine model

Purpose: Pancreatic ductal adenocarcinoma (PDAC) is one of the deadliest cancers with increasing incidence. Even if progress have been made, the five-year overall survival remains lower than 10%. There is a desperate need in therapeutic improvements. In the last two decades, new in-vitro models have been developed and improved, including tridimensional-culture spheroids and organoids. However, animal studies remain mandatory in the upscaling before clinical studies. Orthotopic and syngeneic grafting is a robust model to test a drug efficiency in a tumor and its microenvironment. Methods: We described a method for orthotopic and syngeneic graft of KRAS mutated, p53 wildtype, 8305 cells in a C57BL/6J mouse model. Results: With this microsurgical method, 30 mice were grafted, 24 by a junior and six by a senior, resulting in 95,8 and 100% of (partial and total) successful tumoral implantation, respectively. Twenty mice underwent ultrasound follow-up. It was an efficient method for the tumoral growth evaluation. At day 16 after grafting, 85% of the tumors were detectable by ultrasound, and at day 22 all tumors were detected. Conclusions: The presented method appears to be a robust and reliable method for pre-clinical studies. A junior master student can provide positive results using this technique, which can be improved with training.

The effect of olsalazine of chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt in BALB/c mice

Purpose: To explore effect and mechanism of olsalazine of Chinese generic drugs on ulcerative colitis induced by dextran sulfate sodium salt (DSS) in BALB/c mice. Methods: The mouse model of ulcerative colitis was induced by free drinking of 3% (w/v) DSS aqueous solution for seven days. The mice were treated with olsalazine (0.6 g·kg-1) of Chinese generic drugs. The therapeutic effect of olsalazine on ulcerative colitis mice was evaluated by measuring disease activity index (DAI), colonic mucosal injury index (CMDI), histopathological score (HS), and detected the expression levels of interleukin (IL)-2, IL-10, tumor necrosis factor-α (TNF-α), interferon-γ (IFN-γ), IL-1ß in serum and IL-7, IL-17, IL-22, epidermal growth factor (EGF), transforming growth factor ß1 (TGF-ß1) in colonic homogenate of mice. Results: Olsalazine significantly increased the contents of IL-2, IL-10, IL-22, TGF and EGF in ulcerative colitis rats, and significantly decreased the scores of DAI, CMDI, HS and the contents in IL-7, IL-17, TNF-α, IL-1ß and IFN-γ when compared with the model group. It improved the degree of colonic lesion in ulcerative colitis mice. Conclusions: It was suggested that olsalazine has a therapeutic effect on ulcerative colitis induced by DSS in mice, and the mechanism may be related to the increase of IL-2, IL-10, IL-22, TGF, and EGF and the decrease of the expression of IL-7, IL-17, TNF-α, IL-1ß, and IFN-γ.

Taurine promotes axonal sprouting via Shh-mediated mitochondrial improvement in stroke

Purpose: Motor function is restored by axonal sprouting in ischemic stroke. Mitochondria play a crucial role in axonal sprouting. Taurine (TAU) is known to protect the brain against experimental stroke, but its role in axonal sprouting and the underlying mechanism are unclear. Methods: We evaluated the motor function of stroke mice using the rotarod test on days 7, 14, and 28. Immunocytochemistry with biotinylated dextran amine was used to detect axonal sprouting. We observed neurite outgrowth and cell apoptosis in cortical neurons under oxygen and glucose deprivation (OGD), respectively. Furthermore, we evaluated the mitochondrial function, adenosine triphosphate (ATP), mitochondrial DNA (mtDNA), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PCG-1α), transcription factor A of mitochondria (TFAM), protein patched homolog 1 (PTCH1), and cellular myelocytomatosis oncogene (c-Myc). Results: TAU recovered the motor function and promoted axonal sprouting in ischemic mice. TAU restored the neuritogenesis ability of cortical neurons and reduced OGD-induced cell apoptosis. TAU also reduced reactive oxygen species, stabilized mitochondrial membrane potential, enhanced ATP and mtDNA content, increased the levels of PGC-1α, and TFAM, and restored the impaired levels of PTCH1, and c-Myc. Furthermore, these TAU-related effects could be blocked using an Shh inhibitor (cyclopamine). Conclusion: Taurine promoted axonal sprouting via Shh-mediated mitochondrial improvement in ischemic stroke.

Antimicrobial and toxicological evaluation of Origanum vulgare: an in vivo study / Avaliação antimicrobiana e toxicológica de Origanum vulgare: um estudo in vivo

Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin along with marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.

Origanum vulgare tem despertado grande interesse na academia e na indústria farmacêutica devido às suas propriedades antioxidantes, antifúngicas e antitumorais. O presente estudo teve como objetivo encontrar o potencial anti-MRSA e avaliações de toxicidade in vivo de O. vulgare. O extrato de O. vulgare foi usado para monitorar a atividade anti-MRSA em camundongos. Após infecção estabelecida por MRSA em camundongos (Mus musculus), o tratamento com O. vulgare foi continuado por 7 dias. As autópsias foram realizadas e o reisolamento, pontuação das lesões grosseiras e carga bacteriana em vários órgãos foram medidos. Além disso, a amostra de sangue foi analisada para ensaios hematológicos. A avaliação da toxicidade do potencial de O. vulgare como medicamento foi feita com 200 mg / kg e 400 mg / kg, avaliando as funções hepática e renal. A carga bacteriana e as lesões graves nos pulmões e no coração foram significativamente baixas em comparação com o controle positivo após o tratamento com O. vulgare. Da mesma forma, os grupos tratados com O. vulgare apresentaram valores hematológicos, de neutrófilos e de TLC semelhantes aos grupos de controle. Aumento de AST, ALP e bilirrubina total juntamente com degeneração hepatocelular marcada e distorção ao redor da veia central, infiltração de células inflamatórias e vacuolização citoplasmática de células hepáticas foram observados em doses mais altas. Conclui-se que o extrato bruto de O. vulgare pode conter metabólitos secundários benéficos e, no futuro, pode ser explorado para a cura de doenças infecciosas.

Antimicrobial and toxicological evaluation of Origanum vulgare: an in vivo study / Avaliação antimicrobiana e toxicológica de Origanum vulgare: um estudo in vivo

Origanum vulgare has been of great interest in academia and pharma industry due to its antioxidant, antifungal and antitumor properties. The present study aimed to find the anti-MRSA potential and in vivo toxicity assessments of O. vulgare. O. vulgare extract was used to monitor anti-MRSA activity in mice. Following MRSA established infection in mice (Mus musculus), treatment with O. vulgare was continued for 7 days. Autopsies were performed and re-isolation, gross lesion scoring and bacterial load in various organs were measured. Additionally, blood sample was analysed for hematological assays. Toxicity assessment of O. vulgare potential as medicine was done at 200 mg/kg and 400 mg/kg by evaluating liver and kidney functions. Bacterial load and gross lesion in lungs and heart were significantly low compared to positive control following O. vulgare treatment. Likewise, O. vulgare treated groups had hematological, neutrophil and TLC values similar to control groups. Increased AST, ALP and total bilirubin along with marked hepatocellular degeneration and distortion around the central vein, inflammatory cell infiltration, and cytoplasmic vacuolization of hepatic cells was observed at higher dose. It is concluded that crude extract of O. vulgare may contain beneficial secondary metabolites and in future may be explored for curing infectious diseases.(AU)

Origanum vulgare tem despertado grande interesse na academia e na indústria farmacêutica devido às suas propriedades antioxidantes, antifúngicas e antitumorais. O presente estudo teve como objetivo encontrar o potencial anti-MRSA e avaliações de toxicidade in vivo de O. vulgare. O extrato de O. vulgare foi usado para monitorar a atividade anti-MRSA em camundongos. Após infecção estabelecida por MRSA em camundongos (Mus musculus), o tratamento com O. vulgare foi continuado por 7 dias. As autópsias foram realizadas e o reisolamento, pontuação das lesões grosseiras e carga bacteriana em vários órgãos foram medidos. Além disso, a amostra de sangue foi analisada para ensaios hematológicos. A avaliação da toxicidade do potencial de O. vulgare como medicamento foi feita com 200 mg / kg e 400 mg / kg, avaliando as funções hepática e renal. A carga bacteriana e as lesões graves nos pulmões e no coração foram significativamente baixas em comparação com o controle positivo após o tratamento com O. vulgare. Da mesma forma, os grupos tratados com O. vulgare apresentaram valores hematológicos, de neutrófilos e de TLC semelhantes aos grupos de controle. Aumento de AST, ALP e bilirrubina total juntamente com degeneração hepatocelular marcada e distorção ao redor da veia central, infiltração de células inflamatórias e vacuolização citoplasmática de células hepáticas foram observados em doses mais altas. Conclui-se que o extrato bruto de O. vulgare pode conter metabólitos secundários benéficos e, no futuro, pode ser explorado para a cura de doenças infecciosas.(AU)

Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice / Eugenol e seu nanocarreador à base de lipossoma reduzem a ansiedade ao inibir a expressão de glioxalase 1 em camundongos

The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.

A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.

Experimental model of nephropathy associated with diabetes mellitus in mice

Purpose: Nontransmissible chronic diseases, such as diabetes mellitus (DM) and nephropathy, affect a significant portion of the population, often treated due to injuries that require healing and regeneration. To create an experimental model of associated comorbidities, for healing and regeneration studies, protocols for induction of nephropathy by ischemia and reperfusion (I/R) and induction of DM by injection of streptozotocin (STZ) were associated. Methods: Sixty-four mice (Mus musculus), female, adult, Swiss strain, weighing approximately 20 g, were divided into four groups: G1: control (n = 24), G2: nephropathy group (N) (n = 7), G3, DM (n = 9), and G4: N+DM (n = 24). Arteriovenous stenosis (I/R) of the left kidney was performed as the first protocol. The animals received a hyperlipidemic diet for 7 days after the injection of STZ (150 mg/kg, via i.p.) and an aqueous glucose solution (10%) for 24 h. The animals in the G3 and G4 groups were observed for 14 days before receiving the diet and STZ. The evolution of nephropathy was observed using a urine test strip and the DM, through the analysis of blood glucose with a reagent strip on a digital monitor. Results: The ischemic induction protocols of nephropathy and DM with STZ, associated, were sustainable, low-cost, and without deaths. There were alterations compatible with initial renal alterations, in the first 14 days, such as increased urinary density, pH alteration, presence of glucose, proteins and leukocytes, when compared to the control group. DM was confirmed by the presence of hyperglycemia 7 days after induction and its evolution after 14 days. The animals in the G4 group showed constant weight loss when compared to the other groups. It was possible to observe morphological alterations in the kidneys submitted to I/R, regarding coloration, during surgery and after the end of the observation period, in the volume and size of the left kidney, when compared to the contralateral kidney. Conclusion: It was possible to induce nephropathy and DM associated in the same animal, in a simple way, confirmed with rapid tests, without losses, providing a basis for future studies.

Eugenol and its liposome-based nano carrier reduce anxiety by inhibiting glyoxylase-1 expression in mice / Eugenol e seu nanocarreador à base de lipossoma reduzem a ansiedade ao inibir a expressão de glioxalase 1 em camundongos

The most common form of psycho-social dysfunction is anxiety with depression being related closely without any age bar. They are present with combined state of sadness, confusion, stress, fear etc. Glyoxalase system contains enzyme named glyoxalase 1 (GLO1).It is a metabolic pathway which detoxifies alpha-oxo-aldehydes, particularly methylglyoxal (MG). Methylglyoxal is mainly made by the breakdown of the glycolytic intermediates, glyceraldehyde-3-phosphates and dihydroxyacetone phosphate. Glyoxylase-1 expression is also related with anxiety behavior. A casual role or GLO-1 in anxiety behavior by using viral vectors for over expression in the anterior cingulate cortex was found and it was found that local GLO-1 over expression increased anxiety behavior. The present study deals with the molecular mechanism of protective activity of eugenol against anxiolytic disorder. A pre-clinical animal study was performed on 42 BALB/c mice. Animals were given stress through conventional restrain model. The mRNA expression of GLO-1 was analyzed by real time RT-PCR. Moreover, the GLO-1 protein expression was also examined by immunohistochemistry in whole brain and mean density was calculated. The mRNA and protein expressions were found to be increased in animals given anxiety as compared to the normal control. Whereas, the expressions were decreased in the animals treated with eugenol and its liposome-based nanocarriers in a dose dependent manner. However, the results were better in animals treated with nanocarriers as compared to the compound alone. It is concluded that the eugenol and its liposome-based nanocarriers exert anxiolytic activity by down-regulating GLO-1 protein expression in mice.(AU)

A forma mais comum de disfunção psicossocial é a ansiedade intimamente relacionada com a depressão, sem qualquer barreira de idade. Elas estão presentes em um estado combinado de tristeza, confusão, estresse, medo etc. O sistema de glioxalase contém uma enzima chamada glioxalase 1 (GLO1). É uma via metabólica que desintoxica alfa-oxo-aldeídos, particularmente metilglioxal (MG). O metilglioxal é produzido principalmente pela quebra dos intermediários glicolíticos, gliceraldeído-3-fosfatos e fosfato de diidroxiacetona. A expressão da glioxalase 1 também está relacionada ao comportamento de ansiedade. Um papel casual ou GLO1 no comportamento de ansiedade usando vetores virais para superexpressão no córtex cingulado anterior foi encontrado e descobriu-se que a superexpressão local de GLO1 aumentava o comportamento de ansiedade. O presente estudo trata do mecanismo molecular da atividade protetora do eugenol contra o transtorno ansiolítico. Um estudo pré-clínico em animais foi realizado em 42 camundongos BALB / c. Os animais foram submetidos ao estresse por meio do modelo de contenção convencional. A expressão de mRNA de GLO1 foi analisada por RT-PCR em tempo real. Além disso, a expressão da proteína GLO1 também foi examinada por imuno-histoquímica em todo o cérebro e a densidade média foi calculada. Verificou-se que as expressões de mRNA e proteínas estavam aumentadas em animais que receberam ansiedade em comparação com o controle normal. Considerando que as expressões foram diminuídas nos animais tratados com eugenol e seus nanocarreadores baseados em lipossomas de forma dependente da dose. No entanto, os resultados foram melhores em animais tratados com nanocarreadores em comparação com o composto sozinho. Conclui-se que o eugenol e seus nanocarreadores baseados em lipossomas exercem atividade ansiolítica por regulação negativa da expressão da proteína GLO1 em camundongos.(AU)

Comparative evaluation of plant extract effects on peritoneal, medullary and J774 cells G8 macrophages / Avaliação comparativa do efeito de extratos de plantas em macrófagos peritoneais, medulares e da linhagem J774. G8

The use of medicinal plants as raw material for extracts production and pure substances isolation and subsequence development of new drugs represents a constantly growing area. However, some stages are indispensable before pharmacologically evaluating natural products such as medicines. Toxicity tests in mammalian cells are essential to initiate new drugs development or verify the substance's biocompatibility. Thus, we verified the toxicity of crude extracts and fractions with different polarities obtained from the leaves and stems of eight plant species. The toxic effect was evaluated on macrophages obtained from the bone marrow and peritoneal cavity of a Swiss webster mouse and J774 macrophages. G8 cell lineage. These macrophages were cultured in a 96-well plate, and the compounds were added at a concentration of 100 µg/mL for 24 hours. After this time, the supernatant was removed. The toxicity was evaluated for lactate dehydrogenase (LDH) release assay and the resazurin assay, which uses an indicator dye to measure oxidation-reduction reactions. The results showed a difference in the percentage of toxicity when comparing the same extract in different types of macrophages. This outcome indicates that these cells from different origins may exhibit different responses when exposed to the same natural compounds.

A utilização de plantas medicinais como matéria-prima para a produção de extratos e isolamento de substâncias puras para o desenvolvimento de novos fármacos representa uma área em constante crescimento. No entanto, existem processos a serem realizados antes de avaliar farmacologicamente produtos naturais como medicamentos. Os testes de toxicidade em células de mamíferos são fundamentais para iniciar o desenvolvimento de novas drogas ou verificar a biocompatibilidade de substâncias. Assim, verificamos a toxicidade de extratos brutos e frações com diferentes polaridades obtidos de folhas e caule de oito espécies de planta. Para comparar o efeito tóxico, os testes foram realizados em macrófagos obtidos da medula óssea e cavidade do peritônio de camundongo Swiss webster, bem como no macrófago da linhagem celular J774.G8. Esses macrófagos foram cultivados em placa de 96 poços e os compostos adicionados na concentração de 100 µg/mL por 24 horas. Após esse período o sobrenadante foi removido. A toxicidade foi avaliada pelos ensaios de detecção da enzima lactato-desidrogenase (LDH) e pelo ensaio de resazurina, que usa um corante indicador para medir as reações de oxidação-redução. Os resultados mostraram uma diferença na porcentagem de toxicidade quando comparamos o mesmo extrato em diferentes tipos de macrófagos. Este resultado indica que essas células de várias origens podem exibir respostas distintas quando expostas aos mesmos compostos naturais.

Columbianadin attenuates doxorubicin-induced cardiac injury, oxidative stress, and apoptosis via Sirt1/FOXO1 signaling pathway

Purpose: Oxidative stress and apoptosis contribute to the pathological basis of doxorubicin (DOX)-induced cardiotoxicity. Columbianadin (CBN) is one of the main bioactive constituents isolated from the root of Angelica pubescens. Herein, we intended to explore the potential role and molecular basis of CBN in DOX-induced cardiotoxicity. Methods: C57BL/6 mice were subjected to DOX (15 mg/kg/day, i.p.) to generate DOX-induced cardiotoxicity. CBN (10 mg/kg/day, i.p.) was administered for four week following DOX injection. Results: DOX administered markedly dampened cardiac function, increased cardiac injury, excessive reactive oxygen species (ROS) production, and cardiomyocyte loss. These alterations induced by DOX significantly alleviated by CBN treatment. Mechanistically, our results demonstrated that the CBN exerts cardioprotection role against DOX by up-regulating silent information regulator 1 (Sirt1) and decreasing acetylation of forkhead box O1 (FOXO1). Moreover, Sirt1 inhibition with Ex-527 significantly blunt the beneficial effect of CBN on DOX-induced cardiotoxicity, including cardiac dysfunction, ROS, and apoptosis. Conclusion: Collectively, CBN attenuated oxidative stress and cardiomyocyte apoptosis in DOX-induced cardiotoxicity through maintaining Sirt1/FOXO1 signaling pathway. Our results demonstrated that CBN might be used to treat DOX-related cardiotoxicity.

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.

Effect of Housing Design and Location on Production and Economic Performance of Broiler Chickens during Summer in Botswana

Botswana experiences long, hot summer periods which negatively affect broiler productivity and results in economic losses. To determine these negative effects, two parallel broiler production studies were conducted in the North eastern (NE) and South eastern (SE) regions. In each region, three large scale commercial broiler farms were randomly selected based on similarities in bird management and housing systems. In each farm, one house type (Gable, Hoop and See-saw) was selected for long term flock monitoring (1 to 35 days) over three production cycles. Results showed that the production performance of the broilers in the SE region was superior to that in the NE region, with temperatures on being average higher in the NE than in the SE. The European Production Efficiency Factor (EPEF) was significantly higher (p0.05) between the regions at 9.0% and 7.4% for the NE and SE, respectively. In the NE, the Gable structure had the highest profitability and economic efficiency and was thus superior in comparison to the other house structures.(AU)

In-house serological ELISA as a leishmaniosis diagnostic test: development and applications in canines from the western border of Brazil / ELISA "in house" para o diagnóstico de leishmaniose: desenvolvimento e aplicação em caninos da fronteira Oeste do Brasil

Leishmaniosis is a great public health problem affecting both humans and animals. The disease is caused by the protozoan Leishmania spp., which has a complex cycle involving a phlebotomine vector. The ELISA test (Enzyme-Linked Immunosorbent Assay) along with a chromatographic immunoassay was defined by the Brazil Health Ministry as the confirmatory screening protocol in 2011. Uruguaiana city is 630 km away from Porto Alegre, which makes it difficult to send samples and diagnose leishmaniasis, as well as receive quick results. In view of this, the present study evaluated an in-house indirect ELISA method compared to indirect immunofluorescence assay (IFA) and dual-path platform chromatographic immunoassay (DPP-BioManguinhos®) for the detection of an immune response to Leishmania spp. in canine species. The serological evaluation included 48 canines from the western border of Brazil (Uruguaiana and Barra do Quaraí city). Among the 48 canine samples tested, 18 were positive when using the ELISA technique, 19 were positive with IFA, and 17 were positive with rapid test DPP®. The ELISA technique showed a sensitivity/specificity of 83.3%/86.7% when compared to IFA and 100%/96.8% compared to DPP®. The present study showed a prevalence of 37.5%, demonstrating that the infection circulates in the studied population. It can be concluded that the ELISA technique was valuable for use in field conditions when performing screening tests in endemic areas.

A leishmaniose é um grande problema de saúde pública que afeta tanto humanos quanto animais. A doença é causada pelo protozoário Leishmania spp., que possui um ciclo complexo envolvendo um vetor flebotomíneo. O teste ELISA (Enzyme-Linked Immunosorbent Assay), juntamente com um imunoensaio cromatográfico, foi definido pelo Ministério da Saúde do Brasil como protocolo de triagem confirmatória em 2011. A cidade de Uruguaiana fica a 630 km de Porto Alegre, o que dificulta o envio de amostras e o diagnóstico da leishmaniose, além da demora para obter os resultados. Diante disso, o presente estudo teve como objetivo avaliar um método de ELISA indireto in-house comparado ao ensaio de imunofluorescência indireta (IFA) e imunoensaio cromatográfico de plataforma de dupla via (DPP-BioManguinhos®) para a detecção de uma resposta imune contra Leishmania spp. na espécie canina. A avaliação sorológica incluiu 48 caninos da fronteira oeste do Brasil (cidade de Uruguaiana e Barra do Quaraí). Das 48 amostras caninas testadas, 18 foram positivas na técnica de ELISA, 19 foram positivas com IFA e 17 foram positivas com o teste rápido DPP®. A técnica de ELISA apresentou sensibilidade/especificidade de 83,3%/86,7% quando comparada ao IFA e 100%/96,8% em relação ao DPP®. O presente estudo apresentou prevalência de 37,5%, demonstrando que a infecção circula na população estudada. Pode-se concluir que a técnica de ELISA foi valiosa para uso em condições de campo na realização de testes de triagem em áreas endêmicas.

Cyanidin-3-O-glucoside plays a protective role against renal ischemia/ reperfusion injury via the JAK/STAT pathway

Purpose: To investigate the role of cyanidin-3-O-glucoside (C3G) in renal ischemia/reperfusion (I/R) injury and the potential mechanisms. Methods: Mouse models were established by clamping the left renal vessels, and in vitro cellular models were established by hypoxic reoxygenation. Results: Renal dysfunction and tissue structural damage were significantly higher in the I/R group. After treatment with different concentrations of C3G, the levels of renal dysfunction and tissue structural damage decreased at different levels. And its protective effect was most pronounced at 200 mg/kg. The use of C3G reduced apoptosis as well as the expression of endoplasmic reticulum stress (ERS)-related proteins. Hypoxia/reoxygenation (H/R)-induced apoptosis and ERS are dependent on oxidative stress in vitro. In addition, both AG490 and C3G inhibited the activation of JAK/STAT pathway and attenuated oxidative stress, ischemia-induced apoptosis and ERS. Conclusions: The results demonstrated that C3G blocked renal apoptosis and ERS protein expression by preventing reactive oxygen species (ROS) production after I/R via the JAK/STAT pathway, suggesting that C3G may be a potential therapeutic agent for renal I/R injury.

Prevalence of bovine fascioliasis and economic losses in an abattoir located in the state of Espírito Santo, Brazil / Prevalência de fasciolose bovina e perdas econômicas em um abatedouro frigorífico localizado no estado do Espírito Santo, Brasil

Bovine fasciolosis is a neglected parasitic zoonosis that causes economic losses to beef production chains due to liver condemnation at abattoirs. Despite the characterization of Bovine fasciolosis in several areas of Brazil, an update on its prevalence in the states of Rio de Janeiro and Espirito Santo is lacking. Thus, fasciolosis prevalence from 2018 to 2021 is presented here according to cattle origin (municipalities of both states). In addition, the associated economic impact on an abbatoir was analyzed through liver condemnation of bovines from both states. The prevalence of fasciolosis in the state of Espírito Santo (10.4%) was significantly higher than Rio de Janeiro (3.6%) (P < 0.01), and resulted in an economic loss of US$12,678.60 for the abattoir. The following municipalities located in the state of Espírito Santo presented prevalences above the mean (10.3%) established in the study: Vargem Alta, Anchieta, Cachoeiro do Itapemirim, Castelo, Atilio Vivacqua, Apiacá and Ibitirama. Thus, majority of these municipalities are considered high-risk areas. Although, there is an aparrent reduction of fasciolosis prevalence, it continues to be a cause of economic losses in abattoirs especially in the state of Espírito Santo. Accordingly, prophylactic measures must still be adopted in cattle farms.

A fasciolose bovina é uma zoonose parasitária negligenciada que resulta em perdas econômicas para a cadeia produtiva da carne devido à condenação de fígado em abatedouros-frigoríficos. Essa doença é descrita em diversas áreas do Brasil, mas existe uma deficiência de informações atuais sobre a prevalência nos estados do Rio de Janeiro e Espírito Santo. Essa nota descreve a prevalência de fasciolose de 2018 a 2021 de acordo com o município de origem e o impacto econômico devido à condenação de fígados em um abatedouro que recebe animais de ambos os estados. A prevalência no Estado do Espírito Santo (10,4%) foi significativamente maior do que no Rio de Janeiro (3,6%) (P < 0,01) e resultou em uma perda econômica de R$ 64.636,00. Os municípios de Vargem Alta, Anchieta, Cachoeiro do Itapemirim, Castelo, Atilio Vivacqua, Apiacá e Ibitirama apresentaram prevalência superior à prevalência desse estudo (10,3%), sendo que esses municípios vem sendo reconhecidos como áreas de alto risco. Apesar de uma aparente redução na prevalência da enfermidade, a fasciolose persiste como uma causa de perdas econômicas aos abatedouros, especialmente no Estado do Espírito Santo, e medidas profiláticas ainda precisam ser adotadas nas fazendas.

Wild birds trade in Dera Ismael Khan and Bannu divisions of Khyber PakhtunKhwa (KPK) Province, Pakistan / Comércio de aves selvagens nas divisões Dera Ismail Khan e Bannu da província de Khyber Pakhtunkhwa (KPK), Paquistão

Abstract Wildlife trade is a profitable economic activity. Birds are among the most heavily traded animals worldwide, with numerous species threatened by pet trade. The present case study was stretched for period of one year to find out the status of wild birds' trade in Bannu and Dera Ismael Khan Divisions. The study was aimed to find out the types of species, commercial prices of bird, trade routes, overall income generated from birds' trade and the status of dealers whether licensed or not. Bimonthly visits were conducted to interview 52 bird dealers/pet shops owners/venders (23 in Dera Ismael Khan and 29 in Bannu). A sum of 16 conceivable sites were visited during the study period. Out of these, 8 sites were located in Dera Ismael Khan and 8 sites in Bannu Division. The highest priced species was Demoiselle crane (Grus virgo) and the lowest priced species was house sparrow (Passer domesticus). Total number of species traded in both regions were 8 and 14 while the income generated by bird trade was amounting to PkR 1,322,200 and 7,128,950 in Dera Ismael Khan and Bannu respectively. Majority of the birds were trapped locally with the exception of few from adjacent areas. Commercial activity led by illegal bird traders was found 75% and 100% species in Dera Ismael Khan and Bannu respectively. There was no significant difference between prices of birds, number of species sold and income generated by bird trade in two divisions.

Resumo O comércio de animais selvagens é uma atividade econômica lucrativa. Os pássaros estão entre os animais mais comercializados em todo o mundo, com inúmeras espécies ameaçadas pelo comércio de animais de estimação. O presente estudo de caso foi estendido por um período de um ano para descobrir a situação do comércio de aves selvagens nas Divisões Bannu e Dera Ismael Khan. O estudo teve como objetivo descobrir os tipos de espécies, os preços comerciais das aves, as rotas comerciais, a receita geral gerada pelo comércio de aves e o status dos negociantes, licenciados ou não. Visitas bimestrais foram realizadas para entrevistar 52 comerciantes de pássaros / proprietários / vendedores de pet shops (23 em Dera Ismael Khan e 29 em Bannu). Uma soma de 16 locais concebíveis foram visitados durante o período de estudo. Destes, 8 sites estavam localizados em Dera Ismael Khan e 8 sites na Divisão Bannu. A espécie com preço mais alto foi o guindaste Demoiselle (Grus virgo) e a espécie com preço mais baixo foi o pardal (Passer domesticus). O número total de espécies comercializadas em ambas as regiões foi de 8 e 14, enquanto a receita gerada pelo comércio de aves foi de PkR 1.322.200 e 7.128.950 em Dera Ismael Khan e Bannu, respectivamente. A maioria das aves foi capturada localmente, com exceção de algumas das áreas adjacentes. A atividade comercial liderada por comerciantes ilegais de aves foi encontrada com 75% e 100% de espécies em Dera Ismael Khan e Bannu, respectivamente. Não houve diferença significativa entre os preços das aves, o número de espécies vendidas e a receita gerada pelo comércio de aves nas duas divisões.

Effects of ortho-eugenol on anxiety, working memory and oxidative stress in mice / Efeitos do orto-eugenol na ansiedade, memória de trabalho e estresse oxidativo em camundongos

Ortho-eugenol is a synthetic derivative from eugenol, the major compound of clove essential oil, which has demonstrated antidepressant and antinociceptive effects in pioneering studies. Additionally, its effects appear to be dependent on the noradrenergic and dopaminergic systems. Depression and anxiety disorders are known to share a great overlap in their pathophysiology, and many drugs are effective in the treatment of both diseases. Furthermore, high levels of anxiety are related to working memory deficits and increased oxidative stress. Thus, in this study we investigated the effects of acute treatment of ortho-eugenol, at 50, 75 and 100 mg/kg, on anxiety, working memory and oxidative stress in male Swiss mice. Our results show that the 100 mg/kg dose increased the number of head-dips and reduced the latency in the hole-board test. The 50 mg/kg dose reduced malondialdehyde levels in the prefrontal cortex and the number of Y-maze entries compared to the MK-801-induced hyperlocomotion group. All doses reduced nitrite levels in the hippocampus. It was also possible to assess a statistical correlation between the reduction of oxidative stress and hyperlocomotion after the administration of ortho-eugenol. However, acute treatment was not able to prevent working memory deficits. Therefore, the present study shows that ortho-eugenol has an anxiolytic and antioxidant effect, and was able to prevent substance-induced hyperlocomotion. Our results contribute to the elucidation of the pharmacological profile of ortho-eugenol, as well as to direct further studies that seek to investigate its possible clinical applications.

Ortho-eugenol é um derivado sintético do eugenol, composto principal do óleo essencial de cravo, que demonstrou efeitos antidepressivos e antinociceptivos em estudos pioneiros. Além disso, seus efeitos parecem ser dependentes dos sistemas noradrenérgico e dopaminérgico. Sabe-se que os transtornos de depressão e ansiedade compartilham uma grande sobreposição em sua fisiopatologia, e muitas drogas são eficazes no tratamento de ambas as doenças. Além disso, altos níveis de ansiedade estão relacionados a déficits de memória de trabalho e aumento do estresse oxidativo. Assim, o presente estudo investigou os efeitos do tratamento agudo de orto-eugenol, nas doses de 50, 75 e 100 mg/kg, na ansiedade, memória de trabalho e estresse oxidativo em camundongos Swiss machos. Nossos resultados mostram que a dose de 100 mg/kg aumentou o número de mergulhos e reduziu a latência no teste da placa perfurada. A dose de 50 mg/kg reduziu os níveis de malondialdeído no córtex pré-frontal e o número de entradas no labirinto em Y em comparação com o grupo de hiperlocomoção induzida por MK-801. Todas as doses reduziram os níveis de nitrito no hipocampo. Também foi possível avaliar uma correlação estatística entre a redução do estresse oxidativo e a hiperlocomoção após a administração do orto-eugenol. No entanto, o tratamento agudo não foi capaz de prevenir os déficits de memória de trabalho. Portanto, o presente estudo mostra que o orto-eugenol tem efeito ansiolítico e antioxidante, sendo capaz de prevenir a hiperlocomoção induzida pela substância. Nossos resultados contribuem para a elucidação do perfil farmacológico do orto-eugenol, bem como para direcionar novos estudos que busquem investigar suas possíveis aplicações clínicas.

Amelioration potential of Moringa oleifera extracts against sodium arsenate induced embryotoxicity and genotoxicity in mouse (Mus musculus) / Potencial de melhoria de extratos de Moringa oleifera contra embriotoxicidade e genotoxicidade induzida por arseniato de sódio em camundongos (Mus musculus)

Previous studies have suggested that arsenic crosses the placenta and affects the fetus development. The study under consideration aims to show comparative ameliorative effect of Moringa oleifera leaf and flower extracts against sodium arsenate induced fetus toxicity of mice. Pregnant mice (N=44) were kept in lab and divided into eleven group from (A to K) and were orally administered the doses 6 mg/kg, 12 mg/kg for sodium arsenate, 150 mg/kg and 300 mg/kg for Moringa oleifera leaf extracts (MOLE) and 150 mg/kg and 300 mg/kg for Moringa oleifera flower extracts (MOFE) comparing with control. The investigation revealed evident reduction in the fetuses weight, hind limb, fore limb, tail and snout length, crown rump and head circumferences well as malformations in tail, feet, arms, legs, skin and eyes in the negative control group (only administered with sodium arsenate). Co-administration of sodium arsenate with MOLE and MOFE ameliorate the reversed effect of sodium arsenate on the shape, length, body weight and DNA damage of fetus significantly at 95% confidence interval. However, Moringa oleifera leaf extract showed more significant results in comparison to Moringa oleifera flower extract. Hence concluded that Moringa oleifera leaf extract ameliorated the embryo toxic effects of sodium arsenate and can be used against environmental teratogens.

Estudos anteriores sugeriram que o arsênio atravessa a placenta e afeta o desenvolvimento do feto. O estudo em consideração visa mostrar o efeito melhorador comparativo de extratos de folhas e flores de Moringa oleifera contra a toxicidade fetal induzida por arseniato de sódio em camundongos. Camundongos grávidas (N = 44) foram mantidos em laboratório e divididos em 11 grupos (de A a K) e foram administrados por via oral nas doses de 6 mg/kg, 12 mg/kg para arseniato de sódio, 150 mg/kg e 300 mg/kg para extratos de folhas de Moringa oleifera (MOLE) e 150 mg/kg e 300 mg/kg para extratos de flores de Moringa oleifera (MOFE) em comparação com o controle. A investigação revelou redução evidente no peso do feto, membro posterior, membro anterior, comprimento da cauda e focinho, coroa, nádega e circunferência da cabeça, bem como malformações na cauda, pés, braços, pernas, pele e olhos no grupo de controle negativo (apenas administrado com arseniato de sódio). A coadministração de arseniato de sódio com MOLE e MOFE melhora significativamente o efeito reverso do arseniato de sódio na forma, comprimento, peso corporal e dano ao DNA do feto, com intervalo de confiança de 95%. No entanto, o extrato da folha da Moringa oleifera apresentou resultados mais significativos em comparação ao extrato da flor da Moringa oleifera. Portanto, concluiu que o extrato da folha de Moringa oleifera melhorou os efeitos tóxicos do arseniato de sódio para o embrião e pode ser usado contra teratógenos ambientais.

Amelioration potential of Moringa oleifera extracts against sodium arsenate induced embryotoxicity and genotoxicity in mouse (Mus musculus) / Potencial de melhoria de extratos de Moringa oleifera contra embriotoxicidade e genotoxicidade induzida por arseniato de sódio em camundongos (Mus musculus)

Previous studies have suggested that arsenic crosses the placenta and affects the fetus development. The study under consideration aims to show comparative ameliorative effect of Moringa oleifera leaf and flower extracts against sodium arsenate induced fetus toxicity of mice. Pregnant mice (N=44) were kept in lab and divided into eleven group from (A to K) and were orally administered the doses 6 mg/kg, 12 mg/kg for sodium arsenate, 150 mg/kg and 300 mg/kg for Moringa oleifera leaf extracts (MOLE) and 150 mg/kg and 300 mg/kg for Moringa oleifera flower extracts (MOFE) comparing with control. The investigation revealed evident reduction in the fetuses weight, hind limb, fore limb, tail and snout length, crown rump and head circumferences well as malformations in tail, feet, arms, legs, skin and eyes in the negative control group (only administered with sodium arsenate). Co-administration of sodium arsenate with MOLE and MOFE ameliorate the reversed effect of sodium arsenate on the shape, length, body weight and DNA damage of fetus significantly at 95% confidence interval. However, Moringa oleifera leaf extract showed more significant results in comparison to Moringa oleifera flower extract. Hence concluded that Moringa oleifera leaf extract ameliorated the embryo toxic effects of sodium arsenate and can be used against environmental teratogens.(AU)

Estudos anteriores sugeriram que o arsênio atravessa a placenta e afeta o desenvolvimento do feto. O estudo em consideração visa mostrar o efeito melhorador comparativo de extratos de folhas e flores de Moringa oleifera contra a toxicidade fetal induzida por arseniato de sódio em camundongos. Camundongos grávidas (N = 44) foram mantidos em laboratório e divididos em 11 grupos (de A a K) e foram administrados por via oral nas doses de 6 mg/kg, 12 mg/kg para arseniato de sódio, 150 mg/kg e 300 mg/kg para extratos de folhas de Moringa oleifera (MOLE) e 150 mg/kg e 300 mg/kg para extratos de flores de Moringa oleifera (MOFE) em comparação com o controle. A investigação revelou redução evidente no peso do feto, membro posterior, membro anterior, comprimento da cauda e focinho, coroa, nádega e circunferência da cabeça, bem como malformações na cauda, pés, braços, pernas, pele e olhos no grupo de controle negativo (apenas administrado com arseniato de sódio). A coadministração de arseniato de sódio com MOLE e MOFE melhora significativamente o efeito reverso do arseniato de sódio na forma, comprimento, peso corporal e dano ao DNA do feto, com intervalo de confiança de 95%. No entanto, o extrato da folha da Moringa oleifera apresentou resultados mais significativos em comparação ao extrato da flor da Moringa oleifera. Portanto, concluiu que o extrato da folha de Moringa oleifera melhorou os efeitos tóxicos do arseniato de sódio para o embrião e pode ser usado contra teratógenos ambientais.(AU)